Resting Heart Rate Alone May Not Fully Capture Electrocardiographic Risk in Women With INOCA

Abstract

We read with great interest the article by Dungan et al. investigating electrocardiographic predictors of major adverse cardiovascular events (MACE) in women with ischemia and no obstructive coronary artery disease (INOCA). The authors should be congratulated for addressing an important and increasingly recognized cardiovascular condition and for identifying resting heart rate (RHR) as an independent predictor of adverse outcomes.

Nevertheless, several issues deserve further discussion.

First, although RHR emerged as the only electrocardiographic predictor in the final multivariable model, the observed effect size was relatively modest. While statistically significant, RHR may represent a surrogate marker reflecting autonomic dysfunction, systemic inflammation, physical conditioning, or medication effects rather than a direct indicator of electrical instability. Previous large-scale studies have demonstrated an association between elevated resting heart rate and cardiovascular mortality; however, the incremental prognostic value beyond established clinical and electrocardiographic variables remains debated (Benetos et al. 1999; Zhang et al. 2016).

Second, earlier analyses from the Women's Ischemia Syndrome Evaluation (WISE) cohort identified several electrocardiographic markers, including prolonged QTc interval, widened QRS duration, and abnormal QRS-T angle, as predictors of adverse cardiovascular outcomes (Triola et al. 2005; Mehta et al. 2017). The lack of significance of these parameters in the present analysis may reflect differences in model construction, endpoint definitions, or statistical power and warrants further clarification.

Third, contemporary electrocardiographic risk assessment extends beyond conventional intervals and rhythm analysis. Emerging markers such as fragmented QRS, Tpeak–Tend (Tp-e) interval, Tp-e/QT ratio, and P-wave dispersion have been associated with ventricular arrhythmogenesis, autonomic dysfunction, myocardial fibrosis, and adverse cardiovascular outcomes in various clinical settings (Das et al. 2006; Gupta et al. 2008; Kors et al. 1998; Dilaveris and Gialafos 2001). Incorporating these parameters may provide additional mechanistic insight into risk stratification among women with INOCA.

Finally, coronary microvascular dysfunction and autonomic dysregulation are increasingly recognized as central mechanisms in INOCA. Future studies integrating advanced electrocardiographic markers with coronary functional testing and multimodality imaging may improve prognostic assessment beyond resting heart rate alone.

We congratulate the authors for their valuable contribution and believe that further exploration of novel electrocardiographic markers may refine risk stratification in this challenging population.

C.K. conceived the idea for the manuscript, performed the literature review, and drafted the initial version of the letter. B.G. critically revised the manuscript for important intellectual content and provided expert supervision. Both authors contributed to the final version of the manuscript and approved it for publication.

The authors have nothing to report.

The authors declare no conflicts of interest.

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.