If nothing else, TOPCAT’s results further solidified spironolactone’s role as a reasonably safe drug for blood pressure lowering in HFPEF patients who are also hypertensive. Hypertension control is a must for patients with HFPEF as it’s believed to significantly contribute to HFPEF in most patients. "Hypertension is the most common underlying cause of HFPEF," said Dr. John R. Teerlink, professor of medicine and director of the heart failure program at the San Francisco Veterans Affairs Medical Center.
Dr. Sanjiv J. Shah
When it comes to treating hypertension in HFPEF patients, "unless there is a contraindication, spironolactone should be one of the first drugs to try, but I’m not sure you can say it’s the first choice" based on current evidence, Dr. Borlaug said.
A diuretic is an obvious antihypertensive for HFPEF patients with fluid overload. And there were suggestions of benefit from the ACE inhibitor perindopril in elderly patients in the PEP-CHF trial (Eur. Heart J. 2006;27:2338-45), another large HFPEF-treatment trial that failed to show significant benefit for the primary endpoint with perindopril treatment but had positive results in some secondary endpoints.
Patients "get these drugs to treat their hypertension, but we believe they may also help their heart failure. It’s a belief system. My colleagues and I already use a lot of spironolactone to treat hypertension, and the TOPCAT results won’t change my practice. I’m not comfortable telling people that you should use an aldosterone antagonist because of TOPCAT," Dr. Teerlink said in an interview.
"An angiotensin-converting enzyme inhibitor will probably work; spironolactone probably works if you get the diagnosis right; we don’t know about beta-blockers; and there is some evidence for using digoxin," said Dr. John G.F. Cleland, professor of cardiology at the University of Hull, Kingston-upon-Hull, England. "There must also be good treatment of hypertension, and judicious use of diuretics."
"I’m careful with beta-blockers; I’ve had some patients who felt miserable on them," said Dr. Borlaug. "Some HFPEF patients don’t have a stroke volume, they don’t have diastole, all they have is heart rate, and if you take that away they are left with no cardiac output."
Aside from controlling blood pressure, experts advise good management of other comorbidities such as coronary disease, atrial fibrillation, diabetes, sleep disordered breathing, and renal disease. "Clinicians should make sure that they are not missing severe coronary artery disease, infiltrative cardiomyopathy, constrictive pericarditis, or other causes of HFPEF that have specific treatments," said Dr. Shah. Some drugs have shown promise in early-phase studies – such as ivabradine and neprilysin – but phase III trials are needed. "My advice on how to manage patients with HFPEF is to make every effort to enroll them in a randomized clinical trial," said Dr. Fonarow.
Dr. Burkert M. Pieske
Another key is making the diagnosis, ideally to prevent development of irreversible cardiovascular damage. "HFPEF is difficult to diagnose with certainty unless you do a cardiac catheterization to measure filling pressures, but in patients with early-stage HFPEF, even their invasive hemodynamics look pretty normal," said Dr. Borlaug. Another approach is an exercise echo, which is noninvasive and can identify stress-induced diastolic dysfunction, but the sensitivity and specificity of this approach remains uncertain, he said. And an elevated natriuretic peptide level can help nail the HFPEF diagnosis in some patients but many other patients have levels within the normal range.
To find HFPEF patients, apply a low index of suspicion and look for breathlessness, loss of functional capacity, signs of congestion, lung crackles, echocardiographic signs, pulmonary artery hypertension, and an enlarged left atrium, he suggested.
"Finding patients is a big challenge," said Dr. Pieske. HFPEF patients tend to be elderly, women, and people who are obese who have hypertension and perhaps diabetes. "They complain of dyspnea and fatigue and many physicians think this is just how it is. They will not consider that there is a true diagnosis behind these symptoms and complaints," especially if the patient has preserved left ventricular ejection fraction and a normal natriuretic peptide level." A diastolic stress test using exercise and an echo exam may identify stable patients with early-stage diastolic dysfunction but this requires confirmation, he said.
HFPEF dominates heart failure, lacks good treatment
Experts say the onus on physicians to diagnose and manage HFPEF will grow substantially, since HFPEF is not only highly prevalent but also increasing faster than heart failure with reduced ejection fraction (HFREF). Results from 13 community-based studies published during 1997-2006 showed that HFPEF represented an average of 55% of all heart failure cases, Dr. Carolyn S.P. Lam said last November during a talk at the American Heart Association’s scientific sessions.