Korean Circ J.  2022 Apr;52(4):251-264. 10.4070/kcj.2021.0420.

Sudden Death and Ventricular Arrhythmias in Heart Failure With Preserved Ejection Fraction

• Cho JH

• KMID: 2528020
• DOI: http://doi.org/10.4070/kcj.2021.0420

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 cardioverterdefibrillator 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.

Keyword

Heart failure; diastolic; Sudden death; Cardiac arrhythmias; Cardiac hypertrophy; Action potential

Figure

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  Figure 1 Mode of death in HFrEF and HFpEF patients.HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction.

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  Figure 2 Cardiac arrest in HFrEF and HFpEF patients.HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction.

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  Figure 3 Ventricular hypertrophy in HFpEF reduces the conduction velocity and provides substrates for re-entry.HFpEF = heart failure with preserved ejection fraction.

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  Figure 4 Delayed repolarization of HFpEF is caused by down-regulations of various potassium channels (transient outward and rapid component delayed rectifier potassium channels in this figure) and provides a window for EAD to initiate ventricular arrhythmias. Calcium leakeage caused by altered EC copling in HFpEF can trigger DAD and initiate ventricular arrhythmias.AP = action potential; DAD = delayed afterdepolarization; EAD = early afterdepolarization; HFpEF = heart failure with preserved ejection fraction.

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  Figure 5 Ventricular fibrosis present in HFpEF hearts can provide substrates for re-entry.HFpEF = heart failure with preserved ejection fraction.

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  Figure 6 Mechanisms of ventricular arrhythmias in HFpEF.DAD = delayed afterdepolarization; EAD = early afterdepolarization; HFpEF = heart failure with preserved ejection fraction; RyR2 = ryanodine receptor 2.

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