{"title":"Letter to the Editor: Regarding Electrocardiographic Predictors of Major Adverse Cardiovascular Events in Women With INOCA","authors":"Oguz Kaan Kaya","doi":"10.1111/anec.70191","DOIUrl":"10.1111/anec.70191","url":null,"abstract":"<p>We read with great interest the recent article by Dungan et al. (<span>2026</span>) evaluating electrocardiographic predictors of major adverse cardiovascular events (MACE) in women with ischemia and no obstructive coronary artery disease (INOCA). The authors should be commended for addressing an important and often underrecognized clinical entity. The use of readily available electrocardiographic (ECG) parameters to improve risk stratification in this population is particularly appealing from a practical standpoint.</p><p>However, several aspects of the study merit further consideration.</p><p>First, although resting heart rate (RHR) emerged as an independent predictor of MACE, the magnitude of its effect appears modest (hazard ratio 1.018), and the observed values largely remained within the normal physiological range. This raises the question of whether RHR represents a causal factor or rather a surrogate marker reflecting autonomic imbalance, comorbidity burden, or overall disease severity. Indeed, prior large-scale analyses suggest that the prognostic value of RHR is often mediated through underlying risk profiles rather than direct pathophysiological mechanisms (Zhang et al. <span>2016</span>).</p><p>Second, it is noteworthy that traditional ECG parameters such as QTc interval, QRS duration, and ST–T abnormalities were not independently associated with outcomes in the final model. This finding contrasts with prior evidence demonstrating the prognostic relevance of repolarization abnormalities in various cardiovascular populations (O'Neal et al. <span>2017</span>), and may reflect the limited sensitivity of resting ECG in capturing the underlying pathophysiology of INOCA, which is predominantly driven by coronary microvascular dysfunction and subendocardial ischemia (Pepine <span>2023</span>).</p><p>In this context, advanced imaging modalities may provide incremental value beyond ECG. Techniques such as speckle-tracking echocardiography and global longitudinal strain (GLS) offer superior sensitivity for detecting early subclinical myocardial dysfunction, particularly at the subendocardial level (Yingchoncharoen et al. <span>2013</span>). Given the central role of microvascular impairment in INOCA, integration of myocardial deformation parameters into future risk models may improve prognostic accuracy and provide a more comprehensive assessment of myocardial involvement.</p><p>Finally, although the exclusive inclusion of women is appropriate given the epidemiology of INOCA, it may limit the generalizability of the findings. In addition, the relatively high number of covariates in relation to the number of events raises the possibility of model overfitting.</p><p>In conclusion, this study provides valuable insights into the prognostic role of simple ECG parameters in INOCA. However, the modest predictive strength of RHR and the absence of other ECG markers highlight the need for more sensitive tools. Future studies integrating ECG with adva","PeriodicalId":8074,"journal":{"name":"Annals of Noninvasive Electrocardiology","volume":"31 3","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the Editor Regarding The Effects of Supraphysiological Estrogen Levels Observed During In Vitro Fertilization Treatment on Cardiac Electrophysiology","authors":"Yongchao Huang","doi":"10.1111/anec.70192","DOIUrl":"10.1111/anec.70192","url":null,"abstract":"<p>We read with interest the recent study by Savaş et al. (<span>2026</span>) which prospectively evaluated electrocardiographic changes during controlled ovarian hyperstimulation in women undergoing in vitro fertilization. The authors should be commended for addressing a clinically relevant and insufficiently studied question. Their paired within-subject design also provides useful preliminary data on short-term changes in atrial conduction and ventricular repolarization during the stimulation phase. However, several aspects of the interpretation warrant further consideration.</p><p>First, the observed electrocardiographic changes may have been attributed too specifically to estradiol. Although estradiol increased markedly during stimulation, the study design does not isolate estradiol from other concurrent physiological changes related to controlled ovarian hyperstimulation. Several laboratory variables also changed significantly, including luteinizing hormone, sodium, hemoglobin, hematocrit, blood urea nitrogen, creatinine, thyroid-stimulating hormone, and white blood cell count (Savaş et al. <span>2026</span>). The authors further note that some of these changes may reflect fluid retention and hemodilution. In addition, the stimulation protocol was not completely uniform, as participants received either recombinant FSH alone or recombinant FSH combined with hMG. Under these conditions, the reported ECG changes may be more appropriately interpreted as reflecting the overall physiological state associated with ovarian stimulation rather than a specific estradiol-mediated effect.</p><p>Second, the mechanistic inference would have been more convincing if the analysis had demonstrated a direct relationship between the magnitude of estradiol change and the degree of ECG change. Although correlation analyses were described in the statistical methods, the manuscript does not report whether changes in estradiol were associated with changes in QTc, Tp-e, J-Tp, or PR interval (Savaş et al. <span>2026</span>). Without such analyses, the argument for estradiol-specific mediation remains indirect. This point is particularly relevant because the electrophysiological effects of sex hormones are likely to be interactive rather than unidirectional, and may also be influenced by methodological choices such as interval correction (Sedlak et al. <span>2012</span>; Naderi et al. <span>2025</span>).</p><p>Third, the clinical implications may be stated too strongly. Although QTc and Tp-e increased significantly, all QTc values remained within the conventional normal range for women, and no overt arrhythmic events were reported (Savaş et al. <span>2026</span>). Moreover, the study population consisted of otherwise healthy women without obesity, cardiovascular disease, or a family history of sudden cardiac death, whereas the discussion extends the findings to higher-risk IVF populations. These observations may justify further investigation in such groups, but they do ","PeriodicalId":8074,"journal":{"name":"Annals of Noninvasive Electrocardiology","volume":"31 3","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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