Improving treatment outcomes of HF with preserved ejection fraction according to JACC: What does the success of gliflozins mean for the future?
The Journal of the American College of Cardiology (JACC) recently issued a scientific statement in which the authors thoroughly examined current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction of the left ventricle (HFpEF). Recent studies in this heterogeneous disease suggest the importance of carefully determining the HFpEF phenotype in a given patient based on pathophysiology, which enables better individualization of treatment. The authors also reflect on the success of gliflozins in treating HFpEF and how HFpEF pharmacotherapy can be further improved.
HFpEF – one of the most urgent challenges in contemporary medicine
The American College of Cardiology (ACC) elucidates its release of a statement on the diagnosis and treatment of HFpEF with the following facts. The incidence and prevalence of HFpEF continue to rise with the aging population, prevalence of obesity, sedentary lifestyle, and cardiometabolic disorders. Although understanding of its pathophysiological impacts on the heart, lungs, and other tissues is deepening, and diagnostic capabilities have advanced, in everyday practice, HFpEF remains underdiagnosed. There is, however, highly effective modern treatment based on pharmacotherapy and lifestyle changes that can improve the clinical condition and reduce morbidity and mortality in patients with HFpEF.
HFpEF is becoming a more common cause of exercise intolerance associated with obesity and a sedentary lifestyle. The authors of the scientific statement identify HFpEF as one of the most urgent diagnostic and therapeutic challenges in contemporary clinical medicine due to its rising prevalence, underdiagnosis, poor prognosis, limited therapeutic options, and significant burden on healthcare systems worldwide.
Current treatability of HFpEF
JACC highlights the success of recent studies with sodium-glucose cotransporter 2 inhibitors (SGLT2i, i.e., gliflozins), specifically DELIVER with dapagliflozin and EMPEROR-Preserved with empagliflozin, which demonstrated that HFpEF is treatable. Administration of gliflozins was associated with an 18-21% reduction in the risk of the composite primary endpoint, including heart failure hospitalizations or cardiovascular death in patients with heart failure and LVEF > 40%. These benefits were seen regardless of the presence of diabetes and across the spectrum of ejection fraction values. However, the absolute risk reduction of the primary endpoint was only 3%, due to a reduction in heart failure hospitalizations and not cardiovascular mortality – this indicates, according to JACC, the necessity of improving both diagnostics and treatment of HFpEF.
Today, treating HFpEF, according to the authors of this statement, involves the administration of SGLT2i, with diuretics added in cases of fluid overload. Additionally, optimal treatment of all comorbidities is necessary, including hypertension, iron deficiency, diabetes, ischemic heart disease, atrial fibrillation, obesity, chronic kidney disease, pulmonary disease, and obstructive sleep apnea.
The success of targeting multiple organs
HFpEF is a systemic disease affecting multiple organs, not just the heart. This is related to the expansion of potential treatment options beyond conventional therapeutic approaches for HF with procedures that have beneficial multi-organ effects. The probable reason for the broad success of SGLT2i is the ability to positively influence metabolism in various organs while simultaneously promoting renoprotective diuresis. Therefore, future successful therapeutic strategies will likely fall into two categories – broadly applicable drugs like SGLT2i and individually tailored approaches specifically targeting HFpEF subtypes (in line with precision medicine principles). Emphasis is to be placed on HFpEF phenotypes.
The authors conclude their statement by noting that ongoing extensive studies of HFpEF pathophysiology, increasing translational research, and numerous clinical trials of new HFpEF therapeutic options offer hope that HFpEF prevalence and associated morbidity and mortality will decrease in the future.
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Source: Borlaug B. A., Sharma K., Shah S. J., Ho J. E. Heart failure with preserved ejection fraction. JACC scientific statement. JACC 2023 May; 81: 1810–1834, doi: 10.1016/j.jacc.2023.01.049.
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