Gaps in Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction
The management of HFrEF has made substantial gains over the past three decades. In contrast, despite the high prevalence, mortality and morbidity of HFpEF, little progress has been made in establishing unified diagnostic criteria.59 The treatment of HFpEF remains largely opinion-based with little good evidence to guide therapy. Though promising in theory, trials of beta-blocker, ACEI, ARB, aldosterone antagonists, digoxin and phosphodiesterase type 5 (PDE-5) inhibitors have all shown largely disappointing results.60 Establishing broadly applicable therapies is hampered by the heterogeneity of the syndrome. LCZ696, discussed previously in HFrEF, was found to reduce N-terminal pro-brain natriuretic (NT-proBNP) and left atrial size in patients with HFpEF when compared with valsartan in a phase II RCT.61 The followup phase III trial powered to evaluate mortality has recently started recruiting patients (NCT01920711). Future studies should more distinctly subclassify different clinical phenotypes of HFpEF to target the dominant pathophysiology. And while mortality and hospitalisation are important clinical endpoints, they may be too insensitive for this heterogeneous population with multiple co-morbidities. There should be more focus on using health-related quality of life and other measures of health status as part of clinical trial endpoints to elicit meaningful results.
Additional ambiguity is seen in the intermediate group with EF between 40 and 50 %. These patients are often treated with therapy recommended for patients with HFrEF despite being underrepresented or excluded from most HFrEF trials.1 Finally, patients with a history of HFrEF where EF have recovered represent another subset where little is known about the natural history and prognosis. They likely represent a distinct phenotype in the spectrum of HFrEF and HFpEF and need further characterisation to determine the need for continued therapies.62