Advances in extracardiac mechanisms for heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with highly heterogeneous clinical symptoms, and its incidence has been increasing in recent years. Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF has a worse prognosis. Traditional therapies targeting the internal mechanisms of the heart show limited or inefficacy on HFpEF, and new therapeutic targets for HFpEF are expected to be found by focusing on the extracardiac mechanisms. Recent studies have shown that cardiopulmonary pathophysiological interaction exacerbates the progression of HFpEF. Hypertension, systemic vascular injury, and inflammatory response lead to coronary microvascular dysfunction, myocardial hypertrophy, and coronary microvascular remodeling. Acute kidney injury affects myocardial energy production, induces oxidative stress and catabolism of myocardial protein, which leads to myocardial dysfunction. Liver fibrosis mediates heart injury by abnormal protein deposition and inflammatory factors production. Skeletal muscle interacts with the sympathetic nervous system by metabolic signals. It also produces muscle factors, jointly affecting cardiac function. Metabolic syndrome, gut microbiota dysbiosis, immune system diseases, and iron deficiency promote the occurrence and development of HFpEF through metabolic changes, oxidative stress, and inflammatory responses. Therefore, the research on the extracardiac mechanisms of HFpEF has certain implications for model construction, mechanism research, and treatment strategy formulation.