Cover Story

HFpEF: Prevalence, research on effective treatment options continue to grow

About 6.5 million U.S. adults have HF, according to the most recent report from the American Heart Association. It is estimated that more than half of all HF cases in the United States are HF with preserved ejection fraction, commonly known as HFpEF in the cardiology community. Experts told Cardiology Today the prevalence of HFpEF may continue to rise, especially in women and partially driven by the aging population.

Despite the increase in HFpEF, lack of an established medical treatment for the condition has prompted many efforts to pursue potential therapies and has ultimately raised awareness.

“Awareness is set; it is quite probable that HFpEF will become the dominant variant of HF soon,” Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, vice dean of diversity and inclusion, Magerstadt professor of medicine, professor of medical social sciences and chief of the division of cardiology at Northwestern University Feinberg School of Medicine, said in an interview. “This will require even more focused efforts to elucidate effective therapies. The entire community of investigators — basic and clinical academic scientists, industry-based scientists and device-based innovators — should be engaged to study this condition and search for new pathways of care.”

“HFpEF is an unmet need,” Randall C. Starling, MD, MPH, professor of medicine in the section of heart failure and cardiac transplant medicine; medical director of the Kaufman Center for Heart Failure; staff cardiologist in the Robert and Suzanne Tomsich department of cardiovascular medicine; and vice chairman of cardiovascular medicine operations at Cleveland Clinic, said. “All of the major [cardiology] societies have recognized this condition.”

Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, from Northwestern University Feinberg School of Medicine, said HFpEF may one day become the dominant form of HF.
Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, from Northwestern University Feinberg School of Medicine, said HFpEF may one day become the dominant form of HF.

Photo credit: Northwestern Medicine; reprinted with permission.

While research on the optimal therapy for HFpEF continues, cardiologists can help treat patients with the condition by treating the comorbidities.

“The emphasis should be on the importance of optimally treating comorbid conditions: control BP; treat obstructive sleep apnea; encourage exercise and ideal body weight targets; and make sure CAD, if present, is treated,” Starling said.

‘Explosion of new findings’

As more people are diagnosed with HFpEF, understanding of the pathophysiology of HFpEF has also grown. However, the presence of other comorbidities, the possibility of substantial pathophysiologic heterogeneity among patients with HFpEF and the interaction of various risk factors makes decoding the pathophysiology complex.

“There has been an explosion of new findings and new considerations about HFpEF,” Yancy, who is also associate director of the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital and a past president of the AHA, said. “Fundamental discoveries have made clear that cardiac fibrosis, likely driven by collagen cross-linkages, is a core component of left ventricular dysfunction. We now think the cascade begins with an imbalance of the redox potential likely driven by an inflammatory burden, the consequence of certain important metabolic components, especially diabetes and obesity. The increase in interleukins and C-reactive protein is now postulated to lead to a reduction in nitric oxide and creates a pro-fibrotic state. Concomitantly, we now recognize that CAD is a frequent comorbidity and chronic ischemia may participate in the pathophysiology as well.”

A recent study published in the American Journal of Medicine examined national trends in patients with HFpEF in a U.S. Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project database of more than 5 million hospitalizations from 2003 to 2012. Patients with HFpEF were older, more frequently women, and more likely to have anemia, atrial fibrillation, chronic lung disease, chronic renal failure and hypertension compared with patients with HF with reduced EF.

In a retrospective cohort study of prognostic factors in 800 Ethiopian patients, published in November in BMC Cardiovascular Disorders, more than half of those with HF (53%) had HFpEF. About 76% of those with HFpEF were women. Patients with HFpEF had etiologies of valvular and hypertensive heart diseases, and treatment with anticoagulants and calcium channel blockers was common. Mortality was similar between patients with HFpEF and HFrEF.

“Breakthrough research has suggested that with more complete characterization of patients with HFpEF (ie, ‘deep phenotyping’) we can discriminate risk among patients with HFpEF and should be able to eventually align therapies along a best fit model,” Yancy told Cardiology Today.

New research has also shed light on possible mechanisms for HFpEF. An excess of collagen in the myocardium is a known common thread in patients with HFpEF, but other factors are being uncovered.

“We have appropriately focused on collagen, but the emergence of titin as another fundamental perturbation in HFpEF opens up new considerations,” Yancy said.

More common in women

HFpEF is more common in women than men, but, to date, researchers have been unable to pinpoint why.

“We do not know for sure why HFpEF impacts more women than men. It is often very difficult to separate HFpEF from HF with hypertension, for example,” Starling said. “Due to the high frequency of comorbidities, there is clearly overlap in making the diagnosis.”

Age may also play a role, according to Mary Norine Walsh, MD, FACC, medical director of HF and cardiac transplantation and director of nuclear cardiology at St. Vincent Heart Center in Indianapolis.

Paul J. Mather, MD, FACC, FAHA, FHFSA, FESC, FACP
Paul J. Mather

“One of the reasons that women are affected is that HFpEF is a disease associated with longstanding hypertension and diabetes,” said Walsh, a Cardiology Today Editorial Board member and current president of the American College of Cardiology. “These conditions are prevalent in women as they age, and HFpEF accounts for the majority of HF in the elderly population.”

Mary Norine Walsh, MD, FACC
Mary Norine Walsh

Paul J. Mather, MD, FACC, FAHA, FHFSA, FESC, FACP, said, “The easy answer is that women live longer, but that is only a small part of the equation.

“Women tend to have more impaired ventricular [and] vascular compliance, and also tend to have more concentric LV hypertrophy and less LV dilatation, which can cause increased stiffness,” said Mather, professor of clinical medicine in the Heart Failure–Transplant Program at Perelman School of Medicine, University of Pennsylvania.

Focus on prevention, control

A major focus for cardiologists remains on prevention and controlling risk factors of HFpEF.

“Prevention is the key, so with growing awareness we may be able to decrease the numbers of patients affected by treatment of risk factors,” Walsh said. “Prevention of HFpEF involves controlling risk factors: keeping BP and diabetes well-treated and maintaining a healthy body weight,” she said.

Because of the heterogeneity and complexity of HFpEF, it is unlikely that one agent will be able to successfully treat all patients who have it, which may “result in several treatment options aligned with several nuanced phenotypes,” Yancy said.

Prevention, however, is “less complicated,” he said. “New considerations in the treatment of hypertension that result in a reduction in the incidence of HF will soon become paramount in our prevention strategies.”

A key part of any prevention strategy should be exercise, experts said.

“One of the most important things for prevention is early and aggressive BP control and better exercise tolerance,” Mather told Cardiology Today. “Many [patients with HFpEF] have abnormal exercise-mediated vasodilation and they also have chronotropic incompetence ... and that can be part of the conditioning. Exercise also would help with obesity, a risk factor for HFpEF.”

Diagnosis, management are key

Currently, diagnosis and management recommendations are based on professional guidelines, consensus of opinion and individualization of therapy. Recommendations generally focus on treatment of hypertension and maintenance of appropriate intravascular volume.

“Recognition that a specific diagnosis might be present is essential,” Starling said. “Treating HFpEF with diuretic therapy and not recognizing underlying coronary disease will result in poor outcomes. Clinicians should search for specific diagnoses, including amyloid, sleep apnea [and] valve disease.”

As HF and hypertension are closely linked, use of appropriate antihypertensive medications can be beneficial in patients with HFpEF, experts said.

“There are no guidelines that say one particular therapy is good for HFpEF. But there are guidelines that say: If people have hypertension, these drugs work well, and that might reduce HFpEF,” Mather said. “There is no evidence in randomized trials that ACE inhibitors, [angiotensin receptor blockers] and calcium channel blockers can improve mortality, but there are studies [showing angiotensin receptor blockers] can decrease [LV] hypertrophy and [LV] mass, and overall should be of benefit in HFpEF therapy.”

However, certain therapies should not be used excessively, according to Mather.

“We shouldn’t use venodilators or overuse diuretics, because we need to have a certain amount of fluid in patients. If we dehydrate them too much, that also can push them into trouble,” he said. “Using therapies to slow the heart rate with beta-blockers, control the BP and decrease [LV hypertrophy], though [without a] mortality benefit, may have a morbidity benefit and decrease hospitalizations, and thus improve the quality of life.”

The spironolactone saga

Marc A. Pfeffer, MD, PhD, FACC, FAHA, FHFSA
Marc A. Pfeffer

While several medical therapies have been studied for possible benefit in patients with HFpEF (see Sidebar below), spironolactone has garnered the most attention recently.

Results of the TOPCAT trial were reported in November 2013 at the AHA Scientific Sessions by Marc A. Pfeffer, MD, PhD, FACC, FAHA, FHFSA, the Dzau professor of medicine at Harvard Medical School and senior physician in the cardiovascular division of Brigham and Women’s Hospital. The large, randomized, double blind, placebo-controlled study compared treatment with the mineralocorticoid receptor antagonist spironolactone vs. placebo in patients with HFpEF. Participants were enrolled from six countries: Argentina, Brazil, Canada, Russia, the Republic of Georgia and the United States.

Available treatment options for HFpEF

The overall TOPCAT results yielded no reduced risk for the composite primary outcome of CV death, HF hospitalization or aborted cardiac arrest with spironolactone vs. placebo. However, subgroup analysis showed a benefit of spironolactone treatment when only participants from the Americas were included. Further, spironolactone was associated with a lower rate of the primary outcome in participants from the Americas (HR = 0.82; 95% CI, 0.69-0.98), but not in participants from Georgia and Russia (HR = 1.1; 95% CI, 0.79-1.51). Participants in the Americas assigned spironolactone also exhibited reductions in CV death (HR = 0.74; 95% CI, 0.57-0.97) and HF hospitalization (HR = 0.82; 95% CI, 0.67-0.99) compared with participants in the Americas assigned placebo.

“In the absence of any other data, it is extremely important for us to take note of this,” Pfeffer told Cardiology Today.

Walsh, an investigator on the TOPCAT trial, agreed, noting that “spironolactone is a very reasonable alternative for patients with HFpEF if they don’t have contraindications such as renal insufficiency or hyperkalemia.”

Therefore, given a lack of current alternatives, some cardiologists treating patients with HFpEF have turned to spironolactone.

“We believe, based on the data in the TOPCAT cohort [in the Americas], that the use of spironolactone should be strongly considered in patients with HFpEF [who] are eligible to receive the drug,” Starling said. “Elevation of creatinine and/or potassium will preclude [its use in] some patients. The drug is safe in appropriate patients and may provide benefit.”

Randall C. Starling, MD, MPH
Randall C. Starling

Periodic monitoring of electrolytes and creatinine must be conducted to detect occasional development of hyperkalemia and renal dysfunction, Pfeffer and colleagues wrote in a Viewpoint published in the April 2016 issue of JAMA Cardiology.

“The most relevant data from TOPCAT is from the Americas and, even though it is not definitive, in the absence of any further data, when somebody really has HFpEF it would be a shame not to consider spironolactone — which comes with the responsibility of monitoring the patient for potassium,” Pfeffer told Cardiology Today.

Spironolactone should not be administered to any patient with HFpEF without careful consideration and discussion with the patient, Yancy said.

“We would argue that the TOPCAT trial was an informative study and that the Americas population does provide a template that practitioners may choose to follow in patients who are similar to those studied in the Americas,” he said. “This will require a very well-informed, patient-centered, shared decision-making discussion, as adopting this strategy cannot be embraced with much conviction.”

Unanswered questions

Numerous challenges remain in treating patients with HFpEF.

“We need to embark on large, randomized trials of therapies in this population as we have in the past for the HFrEF population,” Walsh said. “Defining the disease has been difficult, and the patients affected often have other comorbid conditions. We can’t let this complexity stop us from discovering therapies that work to improve the quality of patients’ lives.”

Device therapy should also be explored, Yancy said.

“We should also consider the newer devices: The potential for chronic pulmonary artery monitoring to modify the natural history of symptomatic HFpEF is intriguing and could fundamentally change care, while also lessening the hospitalization burden,” he said.

The need for more research is urgent, as the prevalence of HFpEF continues to grow, according to Yancy.

“There can never be enough research in this field,” he said. “We still don’t have a treatment ... and most worrisome, more and more patients are affected with this condition. We still don’t understand fully what makes a patient vulnerable and, though we are hopeful regarding prevention, proof that we can actually decrease the incidence of the HFpEF phenotype per se is still an unanswered hypothesis.” – by Suzanne Reist

Disclosures: Pfeffer reports consulting for Aastrom, Abbott Vascular, Amgen, Cerenis, Concert, Daiichi Sankyo, Fibrogen, Genzyme, Glaxo-SmithKline, Hamilton Health Sciences, Medtronic, Merck, Novo Nordisk, Roche, Salix, Sanderling, Sanofi-Aventis, Serono, Servier and Teva; receiving research grants from Amgen, Celladon, New England Research Institute via subcontract from the NIH, Novartis and Sanofi-Aventis; and being a co-inventor on a patent held by Brigham and Women’s Hospital and licensed to Novartis, for which his share is transferred to charity. Starling reports serving on the steering committee of ROADMAP trial sponsored by Thoratec and the INOVATE HF trial sponsored by BioControl and serving as an investigator on the PARADIGM-HF trial sponsored by Novartis, but receiving no honoraria. Mather, Walsh and Yancy report no relevant financial disclosures.

About 6.5 million U.S. adults have HF, according to the most recent report from the American Heart Association. It is estimated that more than half of all HF cases in the United States are HF with preserved ejection fraction, commonly known as HFpEF in the cardiology community. Experts told Cardiology Today the prevalence of HFpEF may continue to rise, especially in women and partially driven by the aging population.

Despite the increase in HFpEF, lack of an established medical treatment for the condition has prompted many efforts to pursue potential therapies and has ultimately raised awareness.

“Awareness is set; it is quite probable that HFpEF will become the dominant variant of HF soon,” Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, vice dean of diversity and inclusion, Magerstadt professor of medicine, professor of medical social sciences and chief of the division of cardiology at Northwestern University Feinberg School of Medicine, said in an interview. “This will require even more focused efforts to elucidate effective therapies. The entire community of investigators — basic and clinical academic scientists, industry-based scientists and device-based innovators — should be engaged to study this condition and search for new pathways of care.”

“HFpEF is an unmet need,” Randall C. Starling, MD, MPH, professor of medicine in the section of heart failure and cardiac transplant medicine; medical director of the Kaufman Center for Heart Failure; staff cardiologist in the Robert and Suzanne Tomsich department of cardiovascular medicine; and vice chairman of cardiovascular medicine operations at Cleveland Clinic, said. “All of the major [cardiology] societies have recognized this condition.”

Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, from Northwestern University Feinberg School of Medicine, said HFpEF may one day become the dominant form of HF.
Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, from Northwestern University Feinberg School of Medicine, said HFpEF may one day become the dominant form of HF.

Photo credit: Northwestern Medicine; reprinted with permission.

While research on the optimal therapy for HFpEF continues, cardiologists can help treat patients with the condition by treating the comorbidities.

“The emphasis should be on the importance of optimally treating comorbid conditions: control BP; treat obstructive sleep apnea; encourage exercise and ideal body weight targets; and make sure CAD, if present, is treated,” Starling said.

‘Explosion of new findings’

As more people are diagnosed with HFpEF, understanding of the pathophysiology of HFpEF has also grown. However, the presence of other comorbidities, the possibility of substantial pathophysiologic heterogeneity among patients with HFpEF and the interaction of various risk factors makes decoding the pathophysiology complex.

“There has been an explosion of new findings and new considerations about HFpEF,” Yancy, who is also associate director of the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital and a past president of the AHA, said. “Fundamental discoveries have made clear that cardiac fibrosis, likely driven by collagen cross-linkages, is a core component of left ventricular dysfunction. We now think the cascade begins with an imbalance of the redox potential likely driven by an inflammatory burden, the consequence of certain important metabolic components, especially diabetes and obesity. The increase in interleukins and C-reactive protein is now postulated to lead to a reduction in nitric oxide and creates a pro-fibrotic state. Concomitantly, we now recognize that CAD is a frequent comorbidity and chronic ischemia may participate in the pathophysiology as well.”

A recent study published in the American Journal of Medicine examined national trends in patients with HFpEF in a U.S. Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project database of more than 5 million hospitalizations from 2003 to 2012. Patients with HFpEF were older, more frequently women, and more likely to have anemia, atrial fibrillation, chronic lung disease, chronic renal failure and hypertension compared with patients with HF with reduced EF.

In a retrospective cohort study of prognostic factors in 800 Ethiopian patients, published in November in BMC Cardiovascular Disorders, more than half of those with HF (53%) had HFpEF. About 76% of those with HFpEF were women. Patients with HFpEF had etiologies of valvular and hypertensive heart diseases, and treatment with anticoagulants and calcium channel blockers was common. Mortality was similar between patients with HFpEF and HFrEF.

PAGE BREAK

“Breakthrough research has suggested that with more complete characterization of patients with HFpEF (ie, ‘deep phenotyping’) we can discriminate risk among patients with HFpEF and should be able to eventually align therapies along a best fit model,” Yancy told Cardiology Today.

New research has also shed light on possible mechanisms for HFpEF. An excess of collagen in the myocardium is a known common thread in patients with HFpEF, but other factors are being uncovered.

“We have appropriately focused on collagen, but the emergence of titin as another fundamental perturbation in HFpEF opens up new considerations,” Yancy said.

More common in women

HFpEF is more common in women than men, but, to date, researchers have been unable to pinpoint why.

“We do not know for sure why HFpEF impacts more women than men. It is often very difficult to separate HFpEF from HF with hypertension, for example,” Starling said. “Due to the high frequency of comorbidities, there is clearly overlap in making the diagnosis.”

Age may also play a role, according to Mary Norine Walsh, MD, FACC, medical director of HF and cardiac transplantation and director of nuclear cardiology at St. Vincent Heart Center in Indianapolis.

Paul J. Mather, MD, FACC, FAHA, FHFSA, FESC, FACP
Paul J. Mather

“One of the reasons that women are affected is that HFpEF is a disease associated with longstanding hypertension and diabetes,” said Walsh, a Cardiology Today Editorial Board member and current president of the American College of Cardiology. “These conditions are prevalent in women as they age, and HFpEF accounts for the majority of HF in the elderly population.”

Mary Norine Walsh, MD, FACC
Mary Norine Walsh

Paul J. Mather, MD, FACC, FAHA, FHFSA, FESC, FACP, said, “The easy answer is that women live longer, but that is only a small part of the equation.

“Women tend to have more impaired ventricular [and] vascular compliance, and also tend to have more concentric LV hypertrophy and less LV dilatation, which can cause increased stiffness,” said Mather, professor of clinical medicine in the Heart Failure–Transplant Program at Perelman School of Medicine, University of Pennsylvania.

Focus on prevention, control

A major focus for cardiologists remains on prevention and controlling risk factors of HFpEF.

“Prevention is the key, so with growing awareness we may be able to decrease the numbers of patients affected by treatment of risk factors,” Walsh said. “Prevention of HFpEF involves controlling risk factors: keeping BP and diabetes well-treated and maintaining a healthy body weight,” she said.

Because of the heterogeneity and complexity of HFpEF, it is unlikely that one agent will be able to successfully treat all patients who have it, which may “result in several treatment options aligned with several nuanced phenotypes,” Yancy said.

Prevention, however, is “less complicated,” he said. “New considerations in the treatment of hypertension that result in a reduction in the incidence of HF will soon become paramount in our prevention strategies.”

A key part of any prevention strategy should be exercise, experts said.

PAGE BREAK

“One of the most important things for prevention is early and aggressive BP control and better exercise tolerance,” Mather told Cardiology Today. “Many [patients with HFpEF] have abnormal exercise-mediated vasodilation and they also have chronotropic incompetence ... and that can be part of the conditioning. Exercise also would help with obesity, a risk factor for HFpEF.”

Diagnosis, management are key

Currently, diagnosis and management recommendations are based on professional guidelines, consensus of opinion and individualization of therapy. Recommendations generally focus on treatment of hypertension and maintenance of appropriate intravascular volume.

“Recognition that a specific diagnosis might be present is essential,” Starling said. “Treating HFpEF with diuretic therapy and not recognizing underlying coronary disease will result in poor outcomes. Clinicians should search for specific diagnoses, including amyloid, sleep apnea [and] valve disease.”

As HF and hypertension are closely linked, use of appropriate antihypertensive medications can be beneficial in patients with HFpEF, experts said.

“There are no guidelines that say one particular therapy is good for HFpEF. But there are guidelines that say: If people have hypertension, these drugs work well, and that might reduce HFpEF,” Mather said. “There is no evidence in randomized trials that ACE inhibitors, [angiotensin receptor blockers] and calcium channel blockers can improve mortality, but there are studies [showing angiotensin receptor blockers] can decrease [LV] hypertrophy and [LV] mass, and overall should be of benefit in HFpEF therapy.”

However, certain therapies should not be used excessively, according to Mather.

“We shouldn’t use venodilators or overuse diuretics, because we need to have a certain amount of fluid in patients. If we dehydrate them too much, that also can push them into trouble,” he said. “Using therapies to slow the heart rate with beta-blockers, control the BP and decrease [LV hypertrophy], though [without a] mortality benefit, may have a morbidity benefit and decrease hospitalizations, and thus improve the quality of life.”

The spironolactone saga

Marc A. Pfeffer, MD, PhD, FACC, FAHA, FHFSA
Marc A. Pfeffer

While several medical therapies have been studied for possible benefit in patients with HFpEF (see Sidebar below), spironolactone has garnered the most attention recently.

Results of the TOPCAT trial were reported in November 2013 at the AHA Scientific Sessions by Marc A. Pfeffer, MD, PhD, FACC, FAHA, FHFSA, the Dzau professor of medicine at Harvard Medical School and senior physician in the cardiovascular division of Brigham and Women’s Hospital. The large, randomized, double blind, placebo-controlled study compared treatment with the mineralocorticoid receptor antagonist spironolactone vs. placebo in patients with HFpEF. Participants were enrolled from six countries: Argentina, Brazil, Canada, Russia, the Republic of Georgia and the United States.

Available treatment options for HFpEF

The overall TOPCAT results yielded no reduced risk for the composite primary outcome of CV death, HF hospitalization or aborted cardiac arrest with spironolactone vs. placebo. However, subgroup analysis showed a benefit of spironolactone treatment when only participants from the Americas were included. Further, spironolactone was associated with a lower rate of the primary outcome in participants from the Americas (HR = 0.82; 95% CI, 0.69-0.98), but not in participants from Georgia and Russia (HR = 1.1; 95% CI, 0.79-1.51). Participants in the Americas assigned spironolactone also exhibited reductions in CV death (HR = 0.74; 95% CI, 0.57-0.97) and HF hospitalization (HR = 0.82; 95% CI, 0.67-0.99) compared with participants in the Americas assigned placebo.

PAGE BREAK

“In the absence of any other data, it is extremely important for us to take note of this,” Pfeffer told Cardiology Today.

Walsh, an investigator on the TOPCAT trial, agreed, noting that “spironolactone is a very reasonable alternative for patients with HFpEF if they don’t have contraindications such as renal insufficiency or hyperkalemia.”

Therefore, given a lack of current alternatives, some cardiologists treating patients with HFpEF have turned to spironolactone.

“We believe, based on the data in the TOPCAT cohort [in the Americas], that the use of spironolactone should be strongly considered in patients with HFpEF [who] are eligible to receive the drug,” Starling said. “Elevation of creatinine and/or potassium will preclude [its use in] some patients. The drug is safe in appropriate patients and may provide benefit.”

Randall C. Starling, MD, MPH
Randall C. Starling

Periodic monitoring of electrolytes and creatinine must be conducted to detect occasional development of hyperkalemia and renal dysfunction, Pfeffer and colleagues wrote in a Viewpoint published in the April 2016 issue of JAMA Cardiology.

“The most relevant data from TOPCAT is from the Americas and, even though it is not definitive, in the absence of any further data, when somebody really has HFpEF it would be a shame not to consider spironolactone — which comes with the responsibility of monitoring the patient for potassium,” Pfeffer told Cardiology Today.

Spironolactone should not be administered to any patient with HFpEF without careful consideration and discussion with the patient, Yancy said.

“We would argue that the TOPCAT trial was an informative study and that the Americas population does provide a template that practitioners may choose to follow in patients who are similar to those studied in the Americas,” he said. “This will require a very well-informed, patient-centered, shared decision-making discussion, as adopting this strategy cannot be embraced with much conviction.”

Unanswered questions

Numerous challenges remain in treating patients with HFpEF.

“We need to embark on large, randomized trials of therapies in this population as we have in the past for the HFrEF population,” Walsh said. “Defining the disease has been difficult, and the patients affected often have other comorbid conditions. We can’t let this complexity stop us from discovering therapies that work to improve the quality of patients’ lives.”

Device therapy should also be explored, Yancy said.

“We should also consider the newer devices: The potential for chronic pulmonary artery monitoring to modify the natural history of symptomatic HFpEF is intriguing and could fundamentally change care, while also lessening the hospitalization burden,” he said.

The need for more research is urgent, as the prevalence of HFpEF continues to grow, according to Yancy.

“There can never be enough research in this field,” he said. “We still don’t have a treatment ... and most worrisome, more and more patients are affected with this condition. We still don’t understand fully what makes a patient vulnerable and, though we are hopeful regarding prevention, proof that we can actually decrease the incidence of the HFpEF phenotype per se is still an unanswered hypothesis.” – by Suzanne Reist

Disclosures: Pfeffer reports consulting for Aastrom, Abbott Vascular, Amgen, Cerenis, Concert, Daiichi Sankyo, Fibrogen, Genzyme, Glaxo-SmithKline, Hamilton Health Sciences, Medtronic, Merck, Novo Nordisk, Roche, Salix, Sanderling, Sanofi-Aventis, Serono, Servier and Teva; receiving research grants from Amgen, Celladon, New England Research Institute via subcontract from the NIH, Novartis and Sanofi-Aventis; and being a co-inventor on a patent held by Brigham and Women’s Hospital and licensed to Novartis, for which his share is transferred to charity. Starling reports serving on the steering committee of ROADMAP trial sponsored by Thoratec and the INOVATE HF trial sponsored by BioControl and serving as an investigator on the PARADIGM-HF trial sponsored by Novartis, but receiving no honoraria. Mather, Walsh and Yancy report no relevant financial disclosures.