Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

Abstract

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.

Sacubitril/valsartan Inhibits Obesity-associated Diastolic Dysfunction through Suppression of Ventricular-vascular Stiffness

“…Childhoodadolescent overweight and obesity are major health burdens around the globe and the presence of DD has significant impact as a risk factor for the progression of CVD [6,7]. However, drugs targeting systolic dysfunction are not usually considered as effective in the management of DD, thereby necessitating the need to develop drugs that specifically target DD, especially in the setting of obesity [34,35]. In this regard, obesity-induced DD is associated with multiple abnormalities, including inappropriate activation of tissue renin-angiotensin-aldosterone system (RAAS) [24,36,37], as well as, normal or subnormal responses to ANP in the early stages of the disease or enhanced ANP responsiveness at later stages [23].…”

<p>Diagnosis and Management of Patients with Heart Failure with Preserved Ejection Fraction (HFpEF): Current Perspectives and Recommendations</p>

“…Fluid retention in patients with HFpEF cause dyspnea and peripheral oedema and can lead to hospitalization due to cardiac decompensation and in sum worse the prognosis. Since every hospitalization in patients with HF make the prognosis worse and associated with higher mortality risk 101,102 remote monitoring strategies have been developed to improve ambulatory care of heart failure patients and reduce heart failure hospitalizations. 103 The most significant advancement in the arena of implantable hemodynamic monitoring capabilities was taken with a novel, wireless, battery-free, pulmonary artery pressure monitoring system called the CardioMEMS HF System (CardioMEMS).…”

Medikamentöse Therapie bei Herzinsuffizienz mit erhaltener Pumpfunktion

“…MicroRCAs sind kleine, nicht kodierende Ribonukleinsäuren, die über Boten-RNA, die sogenannte Messenger-RNA oder mRNA, mit der Expression bestimmter Gene interagieren. Während davon ausgegangen werden kann, dass auch in der HFpEF bestimmte Mirco-RNA-Signaturen spezifisch verändert sind, ist es bisher (noch) nicht gelungen, dies in einen klinisch relevanten und erfolgreichen Ansatz zu übersetzen [19,20]. Auch das komplexe Feld einer Zelltherapie zielt darauf ab, myokardiale Inflammation und Fibrose bei HFpEF-Patienten zu adressieren.…”

“…Dazu werden aus dem Körper gewonnene bzw. programmierte Zellen zielgerichtet verabreicht, um therapeutische Effekte zu erzielen [19,20]. Jedoch sind die klinischen Effekte auch im Feld der Zelltherapie bisher nicht als bahnbrechend zu bezeichnen.…”