Adenosine-induced vasodilation is impaired and may be a therapeutic target in HFpEF
Contributor: Seyedeh Maryam Hosseini, MD
Heart failure with preserved ejection fraction is characterized by impaired cardiovascular reserve and coronary microvascular dysfunction. Tissue hypoxia activates endogenous adenosine secretion leading to vasodilation of the myocardial microvasculature. By increasing tissue perfusion in working myocardium, adenosine responds to increased metabolic demand. Davila et al. demonstrate that this adenosine vasodilation mechanism is impaired in HFpEF due to up-regulation of the adenosine kinase (ADK) enzyme gene. ADK changes adenosine to its inactive form. Increasing endogenous adenosine by inhibiting the ADK enzyme pharmacologically may have therapeutic potential to improve coronary vasodilation, myocardial perfusion and LV diastolic dysfunction in HFpEF.
VITALITY-HFpEF: Designed to test the hypothesis that vericiguat may improve physical functioning in patients with HFpEF
Contributor: Emily Cendrowski
VITALITY-HFPEF is a trial underway which will evaluate the efficacy of vericiguat in HFpEF patients by using the KCCQ-PLS (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score) as a primary endpoint. The choice of this primary endpoint will make it the first HF trial utilizing a quality of life, patient-reported outcome (PRO) as a primary endpoint. There remains a need for medications which improve mortality and functional status for patients with HFpEF. An ongoing area of research involves the cyclic guanosine monophosphate (cGMP) pathway.
Proenkephalin: a novel marker of renal dysfunction in heart failure
Contributor: Nicole Smith
Is the opioid system responsible for deteriorating renal function in heart failure?
In a large chronic HF study population, Emmens and colleagues demonstrated higher levels of the opioid surrogate proenkephalin (PENK) are associated with worse HF and deterioration of kidney function. Could PENK be the next renal biomarker in heart failure?