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Published on: June 10, 2025
Risk stratification and prevention of sudden death in patients with heart failure
Moustafa Banna1, Julia H Indik
1Sarver Heart Center, The University of Arizona College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ, 85724-5037, USA, moustafa.banna@gmail.com.
Insights
Current sudden cardiac death prevention relies on left ventricular ejection fraction (LVEF), but new methods are needed. Myocardial fibrosis markers show promise for identifying high-risk patients, including those with LVEF >35%.
Area of Science:
- Cardiology
- Biomarkers
- Sudden Cardiac Death
Background:
- Current guidelines for implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD) primarily use left ventricular ejection fraction (LVEF) ≤35%.
- This approach leads to over-implantation as many patients do not experience life-threatening events.
- A significant number of sudden cardiac arrests occur in individuals without heart failure or significant left ventricular dysfunction.
Purpose of the Study:
- To address the need for improved risk stratification methods beyond LVEF for identifying patients at risk of sudden cardiac death.
- To explore novel markers for predicting arrhythmic events and total mortality.
Main Methods:
- Review of existing risk stratification criteria, including autonomic tone markers (heart rate turbulence, QT dynamicity) and microvolt T-wave alternans.
- Focus on newer markers based on myocardial fibrosis detection, such as collagen turnover and cardiac MRI quantification of myocardial scar.
Main Results:
- Autonomic tone markers predict total mortality but not specifically arrhythmic events.
- Microvolt T-wave alternans has not shown predictive value in large trials.
- Myocardial fibrosis markers, including collagen turnover and MRI scar quantification, show potential for improved risk identification.
Conclusions:
- LVEF is insufficient for comprehensive sudden cardiac death risk stratification.
- Myocardial fibrosis markers represent a promising avenue for identifying high-risk individuals, potentially including those with LVEF >35% not currently eligible for ICDs.
- Further research into fibrosis markers could refine sudden cardiac death prevention strategies.
Opinion Statement:
For almost the past decade, recommendations for the use of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death have been based upon the left ventricular ejection fraction (LVEF). Current guidelines recommend an ICD for heart failure patients with LVEF ≤35% and NYHA functional class of II or III; however, because the majority of heart failure patients who qualify for ICD implantation based on these criteria will never have an event requiring ICD therapy over several years of follow-up, additional methods of risk stratification for sudden death are clearly needed. Additionally, most of the nearly 300,000 cardiac arrests that occur each year occur in patients without heart failure or significant left ventricular dysfunction. To improve the identification of patients at risk for sudden death, several criteria other than ejection fraction have been proposed and studied. Markers of autonomic tone, including heart rate turbulence and QT dynamicity, have shown some ability to predict total mortality but not arrhythmic events. Microvolt T-wave alternans testing was initially thought to be highly predictive of life-threatening arrhythmias, but prospective large sub-studies of the MADIT II and SCD-HeFT trials have failed to show a predictive value for T-wave alternans testing. Newer markers for risk are based upon the detection of myocardial fibrosis, which forms the substrate for re-entrant and malignant ventricular tachyarrhythmias. Markers of collagen turnover or quantification of myocardial scar by MRI may hold the best promise for identifying patients at highest risk for sudden cardiac death and may also identify patients at high risk but with an ejection fraction above 35%, who are not currently recommended for ICD implantation.
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