Heart Failure

For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.

“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.

©Fuse/Thinkstock

Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.

“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.

Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.

The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).

Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m²,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).

Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.

Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.

Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.

“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.

This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.

For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.

“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.

©Fuse/Thinkstock

Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.

“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.

Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.

The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).

Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m²,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).

Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.

Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.

Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.

“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.

This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.

For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.

“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.

©Fuse/Thinkstock

Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.

“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.

Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.

The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).

Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m²,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).

Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.

Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.

Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.

“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.

This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.

Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.

The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).

©Kimberly Pack/Thinkstock.com

Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.

The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.

The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.

Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.

“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.

Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.

The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.

The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.

Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.

The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).

©Kimberly Pack/Thinkstock.com

Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.

The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.

The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.

Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.

“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.

Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.

The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.

The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.

Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.

The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).

©Kimberly Pack/Thinkstock.com

Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.

The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.

The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.

Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.

“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.

Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.

The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.

The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

Mitchel L. Zoler/Frontline Medical News

As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

Mitchel L. Zoler/Frontline Medical News

According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

Mitchel L. Zoler/Frontline Medical News

As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

Mitchel L. Zoler/Frontline Medical News

According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

Mitchel L. Zoler/Frontline Medical News

As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

Mitchel L. Zoler/Frontline Medical News

According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

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