Heart Failure with Preserved Ejection Fraction

Half of all individuals with heart failure have what appears to be fairly normal contractile function, typically assessed from the ejection fraction.  This syndrome is now known as heart failure with preserved ejection fraction, or HFpEF.  HFpEF patients have marked morbidity and mortality, and there is now only one approved treatment that is a repurposed diabetes medication. In the past two decades, HFpEF evolved from a syndrome where cardiac hypertrophy with hypertension were the prominent comorbidities, to a syndrome where severe obesity and cardio metabolic syndrome are most common.  In my lab, we are trying to dissect how obesity has impacted HFpEF, what the impact is on molecular signaling, metabolic substrate use, and underlying function of the sarcomeres. The scope is broad, from very novel mechanisms underlying abnormal protein translation and metabolism, to why obesity has depressed sarcomere systolic performance in human HFpEF myocytes. We use multiple molecular methods, cellular and in vivo mouse models often with gene-modulation, and importantly human myocardial tissue, to determine what are the underlying defects in HFpEF, and what we might target for impactful treatment.