Heart Failure

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

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Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY