New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

Abstract

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

“…Patofizjologia leżąca u podłoża HFpEF i HFmrEF jest złożona, a obraz kliniczny różnorodny, w tym związany jest z występowaniem licznych chorób współistniejących, zarów-no sercowo-naczyniowych (np. AF, CAD, nadciśnienie tętni-cze, nadciśnienie płucne), jak i nie sercowo-naczyniowych (cukrzyca, przewlekła choroba nerek [CKD], niedokrwistość, niedobór żelaza, POChP i otyłość) [303,304]. W porównaniu z chorymi z HFrEF zarówno hospitalizacje, jak i zgony w grupie osób z HFmrEF/HFrEF mają często podłoże nie sercowo-naczyniowe [305,306].…”

InterAtrial Shunt Device (IASD®) implantation — a novel treatment method for heart failure with preserved ejection fraction

“…Many co-morbidities (i.e. arterial hypertension, atrial fibrillation, coronary artery disease, diabetes, obesity, chronic kidney disease, anaemia, chronic obstructive pulmonary disease) contribute to the clinical profile and symptom development in patients with HFpEF [17][18][19][20]. According to the current guidelines, HFpEF can be diagnosed if LVEF is equal to or more than 50% (the most recent European Society of Cardiology guidelines on HF defined "mid-range" HF in patients with LVEF 40-49%); however, most of the HFpEF trials included patients with LVEF ≥ 40% [21].…”

Definition and Classification of Heart Failure

“…Unfortunately, subclinical forms of heart failure remain unnoticed and are frequently underdiagnosed [12]. For these reasons, given the heterogeneity of heart failure phenotypes [13], classification systems and diagnostic algorithms have been developed.…”