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H EART FAILURE WITH preserved ejection fraction (HFpEF), for- merly known as diastolic heart failure, accounts for more than 50 percent of heart failure. 1 Patients with HFpEF are older, often female and more obese than those with heart failure with reduced ejection fraction (HFrEF). They are also less likely to have coronary heart disease and more likely to have hypertension and atrial fibrillation. 2 In a cohort study of veterans, patients with HFpEF had similar hospitalization and mortality rates as those with HFrEF, but HFpEF patients were more likely to be admitted for noncardiac conditions. 3 Diagnosis of HFpEF includes dem- onstrating a clinical syndrome of heart failure — such as volume overload, dyspnea or exertional intolerance — documenting preserved systolic function and evidence of diastolic dysfunction. Diastolic dysfunction can be assessed invasively with left/right heart catheterization (wedge pressure>12mmHg, LVEDP>16mmHG) or noninvasively by echo- cardiography (Doppler techniques). Elevated natriuretic peptides (BNP, proBNP), left atrial dilation and left ventricular hypertrophy provide additional supportive criteria. 4 Pulmonary hypertension is very commonly seen in HFpEF. In a study of 244 patients with HFpEF, 83 percent had pulmonary hypertension by Doppler echocardiography, and this strongly predicted mortality. 5 American College of Cardiology/American Heart Association Guidelines for Heart Failure 2013 define the following goals of treatment of HFpEFs: + Lowering dia stolic f illing pres- sures — diuretics, long-acting nitrates, salt restriction + Blood pressure control — no specific agent recommended, based on lack of clinical trial data + Controlling heart rate in patients with atrial fibrillation These recommendations are somewhat sparse compared with recommendations for patients with HFrEF (beta blockers, ACE-I, spironolactone, device therapy), illustrating the lack of clear, evidence-based treatment. Clinical Trials in HFpEF 6 + CHARM: A preserved trial in which clinicians randomized 3,023 patients to candesartan versus placebo. No signifi- cant effect on cardiovascular death, but fewer hospitalizations due to heart failure (HF) in candesartan-treated patients. + I-PRESERVE: Researchers enrolled 4,128 patients and randomly assigned them to irbesartan or placebo. No changes in mortality or rates of hospi- talizations for cardiovascular causes were observed. + PEP-CHF: This trial compared perindo- pril with placebo and found no overall difference in mortality and/or need for HF hospitalizations + SENIORS trial: Results suggested beta-blocker (nebivolol) benefit in HF regardless of EF, but there was not a large number of patients with truly "normal" EF (50–55 percent). + ALDO-CHF: Spironolactone did not improve exercise capacity or quality of life in patients with HFpEF compared with placebo. + PARAMOUNT trial: In this promising trial, LCZ696, an angiotensin recep- tor/neprilysin inhibitor (ARNI) dual agent, reduced NT-proBNP to a greater extent than did valsartan at 12 weeks. Neprilysin is an enzyme that breaks down endogenous natriuretic peptides. + RELAX Trial: Treatments with phos- phodiesterase-5 inhibition (sildenafil) for 24 weeks did not improve median peak oxygen consumption or exercise capacity compared with placebo in a study of 216 HFPEF patients. The importance of HFpEF should increasingly be recognized, especially as our population ages. However, more positive clinical trial data are needed to help address its management. Dr. Kshatriya practices at Heartland Cardiolog y; for more information or to reach her, please call 316-686-5300 or visit heartlandcardiology.com. ■ References: 1. Smith GL, et al. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. JACC 2003; 41:1510e8). 2. Hogg K, et al. J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. JACC 2004; 43:317–327.) 3. Ather et al. Impact of Noncardiac Comorbidities on Morbidity and Mortality in a Predominantly Male Population with Heart Failure and Preserved Ejection Fraction JACC 2012: 998-1005 4. Paulus et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection frac- tion by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct; 28(20):2539-50). 5. Lam et al Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction. JACC 2009 6. Lam et al.Patient Selection in Heart Failure with Preserved Ejection Fraction Clinical Trials. JACC 2015 Shilpa Kshatriya, MD ++++++++++++++++++++++ +++ + +++ + ++++++++++++++++++++++ ❮ CARDIO CORNER Preserved Ejection Fraction By Shilpa Kshatriya, MD HEART FAILURE with M D N E W S . CO M ■ MD NEWS Greater Kansas | 1 5