Dear Editor,
We read with great interest the recent article about the cardiac contractility modulation and symptomatic heart failure with reduced ejection fraction (HFrEF). The authors provided valuable evidence supporting the clinical benefits of cardiac contractility modulation (CCM) in patients with symptomatic HFrEF [1]. The reported improvements in exercise capacity, functional status, and quality of life are encouraging, and they highlight CCM as a promising therapeutic adjunct in this challenging population. However, whether CCM can fully replace guideline‐directed medical therapy (GDMT) remains an important clinical question.
Despite its advantages, we believe CCM cannot currently be considered a substitute for GDMT, for several reasons:
First, the existing evidence demonstrates symptomatic and functional improvement, but it does not establish CCM as a comprehensive disease‐modifying therapy. GDMT—including β‐blockers, ACEI/ARB/ARNI, MRA, and SGLT2 inhibitors—has robust randomized evidence for reducing mortality and hospitalization, whereas similar long‐term prognostic data on CCM remain limited [2].
Second, CCM does not directly target key neurohormonal pathways involved in HF progression. While it enhances contractile performance, it does not modulate renin–angiotensin–aldosterone activation, sympathetic overdrive, or inflammatory remodeling, which are central to the pathophysiology of HFrEF [3]. Therefore, CCM alone is unlikely to halt disease progression.
Third, current studies are limited by relatively small sample sizes, non‐randomized designs, and short follow‐up durations. Until large‐scale randomized controlled trials with hard endpoints (mortality and HF hospitalization) are available, CCM should be viewed as an adjunct rather than a replacement therapy.
Lastly, CCM is most suitable for a specific patient subgroup—those with persistent symptoms despite GDMT and not eligible for CRT. Its targeted indications further support the concept of complementarity rather than substitution.
In summary, CCM offers important symptomatic benefits and represents an exciting addition to the therapeutic armamentarium for HFrEF. However, based on current evidence, it should complement rather than replace established medical therapy. We look forward to future randomized trials that may clarify its long‐term prognostic impact and broader therapeutic role.
Conflicts of Interest
The authors declare no conflicts of interest.
References
- 1. Suruagy‐Motta R. F. O., Fukunaga C. K., da Silva E. V. B., et al., “Cardiac Contractility Modulation in Symptomatic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Single‐Arm Meta‐Analysis,” Journal of Cardiovascular Electrophysiology 36, no. 10 (October 2025): 2544–2555. [DOI] [PubMed] [Google Scholar]
- 2. Oates C. P., Santos‐Gallego C. G., Smith A., et al., “SGLT2 Inhibitors Reduce Sudden Cardiac Death Risk in Heart Failure: Meta‐Analysis of Randomized Clinical Trials,” Journal of Cardiovascular Electrophysiology 34, no. 5 (May 2023): 1277–1285. [DOI] [PubMed] [Google Scholar]
- 3. Lin L. Y., Lin J. L., Du C. C., et al., “Reversal of Deteriorated Fractal Behavior of Heart Rate Variability by Beta‐Blocker Therapy in Patients With Advanced Congestive Heart Failure,” Journal of Cardiovascular Electrophysiology 12, no. 1 (January 2001): 26–32. [DOI] [PubMed] [Google Scholar]