Changing Role of Implantable Cardioverter-Defibrillator Therapy in the Era of Optimized Heart Failure Management

Interview With Amin Yehya, MD, MS

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EP LAB DIGEST. 2025;25(4):ONLINE ONLY.

Interview by Jodie Elrod

In this interview, EP Lab Digest speaks with Amin Yehya MD, MS, about the contemporary role for implantable cardioverter-defibrillator (ICD) therapy in the era of improved guideline-directed medical therapy (GDMT), including the 4 pillars of GDMT for heart failure, how to use GDMT and when to use which pillar, and how this research impacts clinical practice. 

Can you start by summarizing your recent research¹? What key findings did your research uncover about the role of ICDs in the current era of GDMT?

Our manuscript re-examines the role of ICDs for primary prevention of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF) in the current era of GDMT. As contemporary GDMT significantly reduces the risk of SCD and ventricular arrhythmias, the indications for ICD implantation as primary prevention are being re-evaluated. The manuscript emphasizes shared decision-making (SDM) and the need to consider factors beyond left ventricular ejection fraction (LVEF), such as competing risks, cardiomyopathy reversibility, and novel risk stratification tools like cardiac magnetic resonance imaging (MRI) and genetic testing.

Despite these advances, residual SCD risk persists, necessitating a personalized approach to ICD use. The manuscript also discusses ongoing and future clinical trials investigating AI-driven risk models and biomarker-based strategies to refine patient selection. As the field evolves, these advancements may help ensure ICDs are used in those who derive the greatest benefit.

Can you briefly outline the 4 pillars of GDMT and their impact on HFrEF? How have these therapies improved survival and reduced risk of SCD?

The 4 pillars of GDMT—beta-blockers (BB), renin-angiotensin system (RAS) inhibitors (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 (SGLT2) inhibitors—have dramatically improved survival, reduced HF hospitalizations, and lowered SCD risk. Beta-blockers reduce arrhythmias and SCD risk, while RAS inhibitors and ARNI not only improve LV function but have also demonstrated mortality benefits, particularly in the PARADIGM-HF trial. MRAs significantly reduce SCD rates, and SGLT2 inhibitors have shown promising results in lowering both ventricular arrhythmias and overall cardiovascular mortality. However, despite these benefits, the real-world implementation of GDMT remains suboptimal, limiting the full potential of these therapies to mitigate SCD risk.

How should clinicians optimize the use of GDMT before considering ICD implantation? 

Before considering ICD implantation, clinicians should prioritize early initiation and dose uptitration of GDMT to ensure that patients receive the maximum benefit from the pharmacologic treatment. It is crucial to allow at least 3 months of therapy before reassessing LVEF for ICD eligibility. This period enables reverse remodeling in a substantial proportion of patients, potentially mitigating the need for device therapy. Beyond pharmacologic optimization, the etiology of cardiomyopathy should be considered as some cardiomyopathies are associated with increased risk of SCD (eg, arrhythmogenic right ventricular cardiomyopathy, genetic mutations that are associated with increased risk of SCD such as the LMNA gene encoding the lamin-A and -C nuclear envelope proteins, among others). Other risk stratification tools such as cardiac MRI can help identify patients who remain at high risk of SCD despite GDMT, particularly those with evidence of myocardial fibrosis, which has been associated with ventricular arrhythmias independent of LVEF. Other patient-specific factors, such as age, frailty, and chronic kidney disease, should also be considered. Finally, SDM should be an integral part of the process, ensuring that patients understand the potential benefits and risks of ICD implantation in the context of their response to GDMT. 

When deciding which pillar of GDMT to prioritize or adjust, what key clinical factors should guide therapy selection?

When selecting which pillar of GDMT to prioritize or adjust, clinicians must consider factors such as hemodynamic stability, renal function, electrolyte balance, risk of SCD, and the presence of comorbidities. Beta-blockers should be prioritized in patients with elevated sympathetic drive and tachycardia, but caution is needed in those with bradycardia. RAS inhibitors are central to ventricular remodeling but may need dose adjustments in patients with renal impairment or hyperkalemia. Hypotensive patients may require a lower initial dose of ARNI or beta-blockers, with gradual titration based on tolerance. MRAs are highly effective in reducing fibrosis, but require close monitoring of potassium levels particularly in those with chronic kidney disease (CKD). SGLT2 inhibitors provide significant cardiovascular and renal benefits, making them a preferred choice in patients with diabetes or CKD, as well as in those with volume overload due to their mild diuretic effect. Given the complexity of individual patient profiles, therapy selection should be highly personalized, integrating risk stratification tools, hemodynamic assessments, and SDM strategies to maximize the benefits of medical therapy while minimizing adverse effects.

Based on your research, how will this evolving landscape impact clinical practice and SDM around ICD therapy? How can electrophysiologists and HF specialists collaborate more effectively to personalize therapy in light of these findings?

The evolving landscape of GDMT and ICD therapy necessitates a shift in the mindset of clinical practice toward a more personalized, risk-based approach. Rather than using LVEF ≤35% as the sole determinant, patient selection should incorporate response to GDMT, cardiac imaging findings, and competing mortality risks. Collaboration between electrophysiologists and HF specialists is crucial in achieving this goal. For example, HF specialists should lead efforts in maximizing GDMT, while electrophysiologists can contribute expertise in arrhythmia risk stratification, device therapy, and alternative strategies such as wearable defibrillators for transient risk periods. Establishing these multidisciplinary teams can enhance patient care, bridging gaps in knowledge and improving outcomes. As data from ongoing trials continue to shape practice, a refined, patient-centered approach will be essential to ensure that ICD therapy is used effectively in the modern era of HF management.

Reference

1.     Yehya A, Lopez J, Sauer AJ, et al. Revisiting ICD therapy for primary prevention in patients with heart failure and reduced ejection fraction. JACC Heart Fail. 2025;13(1):1-13. doi:10.1016/j.jchf.2024.09.014