Heart Failure

An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.

An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.

An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.

Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.

Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.

About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.

Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.

“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”

Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.

Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.

A U.S. disease

Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.

The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.

Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”

Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.

Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”

Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.

“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.

Treatment options

No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).

Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.

“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.

The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.

“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”

Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).

Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.

“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.

Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”

Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.

“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.

“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”

“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”

Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.

The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.

“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”

Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.

Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.

About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.

Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.

“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”

Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.

Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.

A U.S. disease

Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.

The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.

Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”

Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.

Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”

Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.

“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.

Treatment options

No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).

Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.

“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.

The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.

“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”

Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).

Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.

“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.

Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”

Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.

“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.

“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”

“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”

Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.

The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.

“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”

Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.

Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.

About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.

Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.

“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”

Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.

Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.

A U.S. disease

Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.

The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.

Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”

Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.

Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”

Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.

“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.

Treatment options

No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).

Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.

“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.

The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.

“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”

Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).

Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.

“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.

Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”

Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.

“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.

“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”

“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”

Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.

The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.

“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”

ORLANDO – Optimal blood pressure in patients with asymptomatic mild to moderate aortic stenosis is 140-159 mm Hg for systolic and 70-89 mm Hg for diastolic, according to an analysis of all-cause mortality in the world’s largest data set of such patients with longitudinal follow-up and endpoint evaluation.

Within those target blood pressure ranges, the nadir in terms of all-cause mortality – and thus the true optimal blood pressure – is about 145/82 mm Hg, Dr. Kristian Wachtell reported at the American Heart Association scientific sessions.

Bruce Jancin/Fronltine Medical News

He presented an analysis of 1,873 asymptomatic patients with mild to moderate aortic stenosis (AS) and a peak aortic-jet velocity of 2.5-4.0 M/sec upon enrollment in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) trial. SEAS was a double-blind, multicenter study in which participants were randomized to 40 mg of simvastatin plus 10 mg of ezetimibe per day or placebo and followed for a mean of 4.3 years. Half of them had a history of hypertension at baseline.

As previously reported (N Engl J Med. 2008 Sep 25;359[13]:1343-56), SEAS was a negative trial. Lipid-lowering therapy didn’t affect AS progression or aortic valve–related outcomes. On the plus side, the SEAS cohort is the world’s largest population of patients with asymptomatic AS followed prospectively for clinical endpoints, noted Dr. Wachtell of Oslo University.

He and his coinvestigators decided to plot all-cause mortality versus average blood pressure in the SEAS cohort because of the paucity of data regarding blood pressure and antihypertensive therapy in patients with asymptomatic AS. Neither the 2014 ACC/AHA guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643) nor the European guidelines provide recommendations for optimal blood pressure targets in patients with asymptomatic AS, even though AS is the third most common cardiac disease, behind hypertension and coronary artery disease.

Moreover, nearly 100,000 aortic valve replacements are done per year in the United States as a consequence of AS. And AS and hypertension go hand in hand, with the prevalence of hypertension among patients with AS cited as 50% or more in multiple studies, the cardiologist continued.

In a multivariate analysis adjusted for aortic valve area index and peak velocity, heart failure, MI, and aortic valve replacement during follow-up, all-cause mortality showed a U-shaped relationship with blood pressure. A systolic blood pressure below 120 mm Hg was associated with a 5-fold increased risk of mortality, a systolic of 120-139 mm Hg carried a 1.5-fold increased risk, and a diastolic blood pressure of 90 mm Hg or more was associated with a 1.9-fold increased risk.

“Patients with low systolic blood pressure had an increased mortality risk and should probably undertake individual clinical assessment for blood pressure control and evaluation of their AS,” Dr. Wachtell said.

The first question audience members asked was, “What about SPRINT?” The SPRINT trial, presented elsewhere at the meeting, was a practice-changing study that was the talk of the conference. It redefined the systolic blood pressure treatment target as less than 120 mm Hg instead of less than 140 mm Hg in hypertensive patients (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939).

“I think it’s most likely that for blood pressure, one size does not fit all,” Dr. Wachtell replied. “The extent of target organ damage – and you could say that aortic stenosis is actually target organ damage, like atrial fibrillation or left ventricular hypertrophy – warrants a different level of blood pressure.”

He added, however, that the SEAS analysis was based on observational data, and that’s a limitation.

“This is a qualified guess as to what blood pressures should be in patients with aortic stenosis,” he cautioned.

Dr. Wachtell reported having no conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

ORLANDO – Optimal blood pressure in patients with asymptomatic mild to moderate aortic stenosis is 140-159 mm Hg for systolic and 70-89 mm Hg for diastolic, according to an analysis of all-cause mortality in the world’s largest data set of such patients with longitudinal follow-up and endpoint evaluation.

Within those target blood pressure ranges, the nadir in terms of all-cause mortality – and thus the true optimal blood pressure – is about 145/82 mm Hg, Dr. Kristian Wachtell reported at the American Heart Association scientific sessions.

Bruce Jancin/Fronltine Medical News

He presented an analysis of 1,873 asymptomatic patients with mild to moderate aortic stenosis (AS) and a peak aortic-jet velocity of 2.5-4.0 M/sec upon enrollment in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) trial. SEAS was a double-blind, multicenter study in which participants were randomized to 40 mg of simvastatin plus 10 mg of ezetimibe per day or placebo and followed for a mean of 4.3 years. Half of them had a history of hypertension at baseline.

As previously reported (N Engl J Med. 2008 Sep 25;359[13]:1343-56), SEAS was a negative trial. Lipid-lowering therapy didn’t affect AS progression or aortic valve–related outcomes. On the plus side, the SEAS cohort is the world’s largest population of patients with asymptomatic AS followed prospectively for clinical endpoints, noted Dr. Wachtell of Oslo University.

He and his coinvestigators decided to plot all-cause mortality versus average blood pressure in the SEAS cohort because of the paucity of data regarding blood pressure and antihypertensive therapy in patients with asymptomatic AS. Neither the 2014 ACC/AHA guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643) nor the European guidelines provide recommendations for optimal blood pressure targets in patients with asymptomatic AS, even though AS is the third most common cardiac disease, behind hypertension and coronary artery disease.

Moreover, nearly 100,000 aortic valve replacements are done per year in the United States as a consequence of AS. And AS and hypertension go hand in hand, with the prevalence of hypertension among patients with AS cited as 50% or more in multiple studies, the cardiologist continued.

In a multivariate analysis adjusted for aortic valve area index and peak velocity, heart failure, MI, and aortic valve replacement during follow-up, all-cause mortality showed a U-shaped relationship with blood pressure. A systolic blood pressure below 120 mm Hg was associated with a 5-fold increased risk of mortality, a systolic of 120-139 mm Hg carried a 1.5-fold increased risk, and a diastolic blood pressure of 90 mm Hg or more was associated with a 1.9-fold increased risk.

“Patients with low systolic blood pressure had an increased mortality risk and should probably undertake individual clinical assessment for blood pressure control and evaluation of their AS,” Dr. Wachtell said.

The first question audience members asked was, “What about SPRINT?” The SPRINT trial, presented elsewhere at the meeting, was a practice-changing study that was the talk of the conference. It redefined the systolic blood pressure treatment target as less than 120 mm Hg instead of less than 140 mm Hg in hypertensive patients (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939).

“I think it’s most likely that for blood pressure, one size does not fit all,” Dr. Wachtell replied. “The extent of target organ damage – and you could say that aortic stenosis is actually target organ damage, like atrial fibrillation or left ventricular hypertrophy – warrants a different level of blood pressure.”

He added, however, that the SEAS analysis was based on observational data, and that’s a limitation.

“This is a qualified guess as to what blood pressures should be in patients with aortic stenosis,” he cautioned.

Dr. Wachtell reported having no conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

ORLANDO – Optimal blood pressure in patients with asymptomatic mild to moderate aortic stenosis is 140-159 mm Hg for systolic and 70-89 mm Hg for diastolic, according to an analysis of all-cause mortality in the world’s largest data set of such patients with longitudinal follow-up and endpoint evaluation.

Within those target blood pressure ranges, the nadir in terms of all-cause mortality – and thus the true optimal blood pressure – is about 145/82 mm Hg, Dr. Kristian Wachtell reported at the American Heart Association scientific sessions.

Bruce Jancin/Fronltine Medical News

He presented an analysis of 1,873 asymptomatic patients with mild to moderate aortic stenosis (AS) and a peak aortic-jet velocity of 2.5-4.0 M/sec upon enrollment in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) trial. SEAS was a double-blind, multicenter study in which participants were randomized to 40 mg of simvastatin plus 10 mg of ezetimibe per day or placebo and followed for a mean of 4.3 years. Half of them had a history of hypertension at baseline.

As previously reported (N Engl J Med. 2008 Sep 25;359[13]:1343-56), SEAS was a negative trial. Lipid-lowering therapy didn’t affect AS progression or aortic valve–related outcomes. On the plus side, the SEAS cohort is the world’s largest population of patients with asymptomatic AS followed prospectively for clinical endpoints, noted Dr. Wachtell of Oslo University.

He and his coinvestigators decided to plot all-cause mortality versus average blood pressure in the SEAS cohort because of the paucity of data regarding blood pressure and antihypertensive therapy in patients with asymptomatic AS. Neither the 2014 ACC/AHA guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643) nor the European guidelines provide recommendations for optimal blood pressure targets in patients with asymptomatic AS, even though AS is the third most common cardiac disease, behind hypertension and coronary artery disease.

Moreover, nearly 100,000 aortic valve replacements are done per year in the United States as a consequence of AS. And AS and hypertension go hand in hand, with the prevalence of hypertension among patients with AS cited as 50% or more in multiple studies, the cardiologist continued.

In a multivariate analysis adjusted for aortic valve area index and peak velocity, heart failure, MI, and aortic valve replacement during follow-up, all-cause mortality showed a U-shaped relationship with blood pressure. A systolic blood pressure below 120 mm Hg was associated with a 5-fold increased risk of mortality, a systolic of 120-139 mm Hg carried a 1.5-fold increased risk, and a diastolic blood pressure of 90 mm Hg or more was associated with a 1.9-fold increased risk.

“Patients with low systolic blood pressure had an increased mortality risk and should probably undertake individual clinical assessment for blood pressure control and evaluation of their AS,” Dr. Wachtell said.

The first question audience members asked was, “What about SPRINT?” The SPRINT trial, presented elsewhere at the meeting, was a practice-changing study that was the talk of the conference. It redefined the systolic blood pressure treatment target as less than 120 mm Hg instead of less than 140 mm Hg in hypertensive patients (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939).

“I think it’s most likely that for blood pressure, one size does not fit all,” Dr. Wachtell replied. “The extent of target organ damage – and you could say that aortic stenosis is actually target organ damage, like atrial fibrillation or left ventricular hypertrophy – warrants a different level of blood pressure.”

He added, however, that the SEAS analysis was based on observational data, and that’s a limitation.

“This is a qualified guess as to what blood pressures should be in patients with aortic stenosis,” he cautioned.

Dr. Wachtell reported having no conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

ORLANDO – Three simple, routinely collected measurements together provide a lot of insight into the risk faced by community-dwelling patients hospitalized for acute decompensated heart failure, according to data collected from 3,628 patients at one U.S. center.

The three measures are blood urea nitrogen (BUN), systolic blood pressure, and serum creatinine. Using dichotomous cutoffs first calculated a decade ago, these three parameters distinguish up to an eightfold range of postdischarge mortality during the 30 or 90 days following an index hospitalization, and up to a fourfold range of risk for rehospitalization for heart failure during the ensuing 30 or 90 days, Dr. Sithu Win said at the American Heart Association scientific sessions.

Applying this three-measure assessment to patients hospitalized with acute decompensated heart failure “may guide care-transition planning and promote efficient allocation of limited resources,” said Dr. Win, a cardiologist at the Mayo Clinic in Rochester, Minn. The next step is to try to figure out the best way to use this risk prognostication in routine practice, he added.

Researchers published the original analysis that identified BUN, systolic BP, and serum creatinine as key prognostic measures in 2005 using data taken from more than 65,000 U.S. heart failure patients enrolled in ADHERE (Acute Decompensated Heart Failure National Registry) (JAMA. 2005 Feb 2;293[5]:572-80). Using a classification and regression tree analysis, the 2005 study verified dichotomous cutoffs for these three parameters that identified patients at highest risk for in-hospital mortality.

The 2005 study prioritized the application of these cutoffs to define in-hospital mortality risk: first BUN, then the systolic BP criterion, and lastly the serum creatinine criterion. This resulted in five risk levels: Highest-risk patients had a BUN of at least 43 mg/dL, a systolic BP of less than 115 mm Hg, and a serum creatinine of at least 2.75 mg/dL. Lowest-risk patients had a BUN of less than 43 mg/dL and a systolic BP of more than 115 mm Hg. (In lower-risk patients, serum-creatinine level dropped out as a risk determinant.) The analysis also created three categories of patients with intermediate risk based on various combinations of the three measures.

The new study run by Dr. Win and his associates evaluated how this risk-assessment tool developed to predict in-hospital mortality performed for predicting event rates among community-based heart failure patients who had a total of 5,918 hospitalizations for acute decompensated heart failure at the Mayo Clinic during 2000-2013. They averaged 78 years old, half were women, and 48% had heart failure with preserved ejection fraction.

The risk-level distribution of the 3,628 Mayo patients closely matched the pattern seen in the original ADHERE registry: 63% were low risk, 17% were at intermediate level 3 (the lowest risk level in the intermediate range), 13% were at intermediate level 2, 5% at intermediate level 1, and 2% were categorized as high risk.

For 30-day mortality post hospitalization, patients at the highest risk level had a mortality rate eightfold higher than did the lowest-risk patients, those rated intermediate level 1 had a fivefold higher mortality rate, intermediate level 2 patients had a threefold higher rate, and those at intermediate 3 had a 50% higher rate, Dr. Win reported. During the 90 days after discharge, mortality rates relative to the lowest risk level ranged from a sixfold higher rate among the highest-risk patients to a 50% higher rate among patients with an intermediate 3 designation.

Analysis of rehospitalizations for heart failure showed that, by 30 days after hospitalization, the readmission rate ran threefold higher in the highest-risk patients, compared with those at the lowest risk and fourfold higher among those at intermediate risk level 1. Heart failure readmissions by 90 days following the index hospitalization ran threefold higher for both the highest-risk patients as well as those at intermediate level 1, compared with the patients at lowest risk.

The new analyses also showed that roughly similar risk patterns occurred regardless of whether patients had heart failure with reduced or preserved ejection fraction during their index hospitalization, although the relatively increased rate of 30-day mortality with a worse risk profile was most dramatic among patients with reduced ejection fraction. Age, sex, and comorbidity severity did not have a marked effect on the relationships between event rates and risk levels, Dr. Win said.

Dr. Win had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ORLANDO – Three simple, routinely collected measurements together provide a lot of insight into the risk faced by community-dwelling patients hospitalized for acute decompensated heart failure, according to data collected from 3,628 patients at one U.S. center.

The three measures are blood urea nitrogen (BUN), systolic blood pressure, and serum creatinine. Using dichotomous cutoffs first calculated a decade ago, these three parameters distinguish up to an eightfold range of postdischarge mortality during the 30 or 90 days following an index hospitalization, and up to a fourfold range of risk for rehospitalization for heart failure during the ensuing 30 or 90 days, Dr. Sithu Win said at the American Heart Association scientific sessions.

Applying this three-measure assessment to patients hospitalized with acute decompensated heart failure “may guide care-transition planning and promote efficient allocation of limited resources,” said Dr. Win, a cardiologist at the Mayo Clinic in Rochester, Minn. The next step is to try to figure out the best way to use this risk prognostication in routine practice, he added.

Researchers published the original analysis that identified BUN, systolic BP, and serum creatinine as key prognostic measures in 2005 using data taken from more than 65,000 U.S. heart failure patients enrolled in ADHERE (Acute Decompensated Heart Failure National Registry) (JAMA. 2005 Feb 2;293[5]:572-80). Using a classification and regression tree analysis, the 2005 study verified dichotomous cutoffs for these three parameters that identified patients at highest risk for in-hospital mortality.

The 2005 study prioritized the application of these cutoffs to define in-hospital mortality risk: first BUN, then the systolic BP criterion, and lastly the serum creatinine criterion. This resulted in five risk levels: Highest-risk patients had a BUN of at least 43 mg/dL, a systolic BP of less than 115 mm Hg, and a serum creatinine of at least 2.75 mg/dL. Lowest-risk patients had a BUN of less than 43 mg/dL and a systolic BP of more than 115 mm Hg. (In lower-risk patients, serum-creatinine level dropped out as a risk determinant.) The analysis also created three categories of patients with intermediate risk based on various combinations of the three measures.

The new study run by Dr. Win and his associates evaluated how this risk-assessment tool developed to predict in-hospital mortality performed for predicting event rates among community-based heart failure patients who had a total of 5,918 hospitalizations for acute decompensated heart failure at the Mayo Clinic during 2000-2013. They averaged 78 years old, half were women, and 48% had heart failure with preserved ejection fraction.

The risk-level distribution of the 3,628 Mayo patients closely matched the pattern seen in the original ADHERE registry: 63% were low risk, 17% were at intermediate level 3 (the lowest risk level in the intermediate range), 13% were at intermediate level 2, 5% at intermediate level 1, and 2% were categorized as high risk.

For 30-day mortality post hospitalization, patients at the highest risk level had a mortality rate eightfold higher than did the lowest-risk patients, those rated intermediate level 1 had a fivefold higher mortality rate, intermediate level 2 patients had a threefold higher rate, and those at intermediate 3 had a 50% higher rate, Dr. Win reported. During the 90 days after discharge, mortality rates relative to the lowest risk level ranged from a sixfold higher rate among the highest-risk patients to a 50% higher rate among patients with an intermediate 3 designation.

Analysis of rehospitalizations for heart failure showed that, by 30 days after hospitalization, the readmission rate ran threefold higher in the highest-risk patients, compared with those at the lowest risk and fourfold higher among those at intermediate risk level 1. Heart failure readmissions by 90 days following the index hospitalization ran threefold higher for both the highest-risk patients as well as those at intermediate level 1, compared with the patients at lowest risk.

The new analyses also showed that roughly similar risk patterns occurred regardless of whether patients had heart failure with reduced or preserved ejection fraction during their index hospitalization, although the relatively increased rate of 30-day mortality with a worse risk profile was most dramatic among patients with reduced ejection fraction. Age, sex, and comorbidity severity did not have a marked effect on the relationships between event rates and risk levels, Dr. Win said.

Dr. Win had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ORLANDO – Three simple, routinely collected measurements together provide a lot of insight into the risk faced by community-dwelling patients hospitalized for acute decompensated heart failure, according to data collected from 3,628 patients at one U.S. center.

The three measures are blood urea nitrogen (BUN), systolic blood pressure, and serum creatinine. Using dichotomous cutoffs first calculated a decade ago, these three parameters distinguish up to an eightfold range of postdischarge mortality during the 30 or 90 days following an index hospitalization, and up to a fourfold range of risk for rehospitalization for heart failure during the ensuing 30 or 90 days, Dr. Sithu Win said at the American Heart Association scientific sessions.

Applying this three-measure assessment to patients hospitalized with acute decompensated heart failure “may guide care-transition planning and promote efficient allocation of limited resources,” said Dr. Win, a cardiologist at the Mayo Clinic in Rochester, Minn. The next step is to try to figure out the best way to use this risk prognostication in routine practice, he added.

Researchers published the original analysis that identified BUN, systolic BP, and serum creatinine as key prognostic measures in 2005 using data taken from more than 65,000 U.S. heart failure patients enrolled in ADHERE (Acute Decompensated Heart Failure National Registry) (JAMA. 2005 Feb 2;293[5]:572-80). Using a classification and regression tree analysis, the 2005 study verified dichotomous cutoffs for these three parameters that identified patients at highest risk for in-hospital mortality.

The 2005 study prioritized the application of these cutoffs to define in-hospital mortality risk: first BUN, then the systolic BP criterion, and lastly the serum creatinine criterion. This resulted in five risk levels: Highest-risk patients had a BUN of at least 43 mg/dL, a systolic BP of less than 115 mm Hg, and a serum creatinine of at least 2.75 mg/dL. Lowest-risk patients had a BUN of less than 43 mg/dL and a systolic BP of more than 115 mm Hg. (In lower-risk patients, serum-creatinine level dropped out as a risk determinant.) The analysis also created three categories of patients with intermediate risk based on various combinations of the three measures.

The new study run by Dr. Win and his associates evaluated how this risk-assessment tool developed to predict in-hospital mortality performed for predicting event rates among community-based heart failure patients who had a total of 5,918 hospitalizations for acute decompensated heart failure at the Mayo Clinic during 2000-2013. They averaged 78 years old, half were women, and 48% had heart failure with preserved ejection fraction.

The risk-level distribution of the 3,628 Mayo patients closely matched the pattern seen in the original ADHERE registry: 63% were low risk, 17% were at intermediate level 3 (the lowest risk level in the intermediate range), 13% were at intermediate level 2, 5% at intermediate level 1, and 2% were categorized as high risk.

For 30-day mortality post hospitalization, patients at the highest risk level had a mortality rate eightfold higher than did the lowest-risk patients, those rated intermediate level 1 had a fivefold higher mortality rate, intermediate level 2 patients had a threefold higher rate, and those at intermediate 3 had a 50% higher rate, Dr. Win reported. During the 90 days after discharge, mortality rates relative to the lowest risk level ranged from a sixfold higher rate among the highest-risk patients to a 50% higher rate among patients with an intermediate 3 designation.

Analysis of rehospitalizations for heart failure showed that, by 30 days after hospitalization, the readmission rate ran threefold higher in the highest-risk patients, compared with those at the lowest risk and fourfold higher among those at intermediate risk level 1. Heart failure readmissions by 90 days following the index hospitalization ran threefold higher for both the highest-risk patients as well as those at intermediate level 1, compared with the patients at lowest risk.

The new analyses also showed that roughly similar risk patterns occurred regardless of whether patients had heart failure with reduced or preserved ejection fraction during their index hospitalization, although the relatively increased rate of 30-day mortality with a worse risk profile was most dramatic among patients with reduced ejection fraction. Age, sex, and comorbidity severity did not have a marked effect on the relationships between event rates and risk levels, Dr. Win said.

Dr. Win had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler