Sudden Death and Ventricular Arrhythmias in Heart Failure With Preserved Ejection Fraction.
Publication Year:
2022
PubMed ID:
35388994
Funding Grants:
Public Summary:
Heart failure with preserved ejection fraction (HFpEF) is a common type of heart failure, especially in older people with conditions like high blood pressure, diabetes, and obesity. Unlike other heart failures, it’s harder to treat and traditional medicines don’t improve survival. Many patients with HFpEF die suddenly, but the exact reasons aren’t well understood. While abnormal heart rhythms in the lower heart chambers (ventricular arrhythmias) often cause sudden death in heart failure, they may play a smaller role in HFpEF. In HFpEF, changes in the heart include slower electrical signals due to thickened heart muscle, delays in how the heart resets electrically, calcium leaks inside heart cells, and increased scarring caused by inflammation. These changes can create conditions that trigger dangerous heart rhythms. More research is needed to fully understand how these electrical problems cause sudden death in HFpEF and how to prevent them.
Scientific Abstract:
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure (HF) cases. The prevalence of HFpEF is increasing due to an aging population with hypertension, diabetes mellitus, and obesity. HFpEF remains a challenging clinical entity due to a lack of effective treatment options. Traditional HF medications have not been shown to reduce mortality of patients with HFpEF, and an implantable cardioverter-defibrillator is not indicated due to normal ejection fraction. Sudden death is the most common mode of death in patients with HFpEF; however, the underlying mechanisms of sudden death are not fully elucidated. Although ventricular arrhythmias are responsible for the majority of sudden deaths in general, their contribution to sudden deaths in HFpEF patients is likely less significant. The mechanisms of ventricular arrhythmias in HFpEF are 1) reduced conduction velocity due to ventricular hypertrophy, 2) delayed repolarization due to potassium current down-regulation, 3) calcium leakage due to altered excitation-contraction coupling, and 4) increased ventricular fibrosis caused by systemic inflammation. Hypertension and subsequent ventricular hypertrophy reduce the conduction velocity in HFpEF hearts via heterogeneous distribution of connexin 43. Delayed repolarization caused by potassium current down-regulation in HFpEF hearts provides a window for early afterdepolarization to trigger ventricular arrhythmias. Altered excitation-contraction coupling in HFpEF can cause calcium to leak and trigger delayed afterdepolarization. Increased systemic inflammation and subsequent ventricular fibrosis provide substrates for re-entry. Further research is warranted to investigate the detailed mechanisms of ventricular arrhythmias in HFpEF.