Ischemic cardiomyopathy (ICM) continues to be one of the leading causes of heart failure worldwide, representing a significant source of morbidity and mortality in both developed and developing nations [1].  As a prototype of left ventricular (LV) systolic dysfunction secondary to impaired coronary perfusion, ICM results in profound structural and electric derangements within the myocardium.  Heart failure related to ICM is distinguished by progressive loss of contractile function, adverse ventricular remodeling, and a heightened risk of arrhythmic events, necessitating early and accurate identification of the underlying myocardial dysfunction to inform prognosis and therapeutic strategies [2]. While various non-invasive and invasive diagnostic modalities are employed to evaluate LV performance, the electrocardiogram (ECG) remains a frontline, universally accessible tool, providing critical insights into the electrical activity and, indirectly, the functional integrity of cardiac tissues [3].

Among the 12 conventional leads of the standard ECG, lead aVR has historically garnered less clinical attention than other limb or precordial leads, often being relegated to a confirmatory or supportive role during interpretation [4]. Nonetheless, an expanding body of research has underscored the diagnostic and prognostic utility of subtle electrophysiological variations in this underappreciated vector, especially in patients with coronary artery disease and resultant LV dysfunction [5]. The T wave, representing ventricular repolarization, embodies the summative effects of regional action potential duration, dispersion, and repolarization sequence across the ventricular myocardium. Abnormalities in the T wave amplitude, axis, or morphology can reflect localized or global perturbations in myocardial electrical properties, particularly in the context of ischemia-induced remodeling [6].

It is now increasingly recognized that, in ICM patients, the T wave in lead aVR offers distinctive electro-pathophysiological information. The direction and amplitude of the T wave in aVR can provide clues regarding the directionality of repolarization vectors, which are often disrupted in the setting of scar tissue, hibernating myocardium, or diffuse ventricular conduction delay [7]. Under normal circumstances, lead aVR most frequently displays a negative T wave, given its spatial orientation relative to the main ventricular depolarization and repolarization vectors. However, alterations in T wave amplitude either attenuation or positive inversion in lead aVR may signal profound disturbances in endocardial and epicardial repolarization, closely related to the extent and severity of left ventricular impairment [8].

LV systolic dysfunction, as measured by echocardiographic ejection fraction (EF) or advanced imaging modalities, remains the cornerstone for risk stratification and therapeutic decision-making in ICM [9]. However, these imaging techniques are not universally available due to infrastructural or economic barriers, particularly in resource-limited settings. Therefore, the prospect of correlating a readily obtainable ECG characteristic such as the T wave size in lead aVR with quantitative or qualitative measures of systolic impairment is highly appealing from the standpoint of efficiency, cost-effectiveness, and clinical feasibility [10]. Emerging evidence suggests that attenuation or certain reversals in the T wave amplitude in aVR may be indicative of more diffuse or severe LV systolic dysfunction, reflecting larger areas of electrical disturbance that follow from ischemic insult and subsequent fibrosis [11].

Pathophysiologically, the link between T wave changes in lead aVR and impaired LV function may be rooted in the disruption of normal transmural and apico-basal repolarization gradients. Ischemic damage preferentially affects sub endocardial regions, which are also more susceptible to functional and structural compromise during the evolution of systolic dysfunction [12]. As these cellular alterations accumulate, the summated repolarization vector shifts in a way detectable in the aVR lead, thus providing a surrogate marker of underlying myocardial health [13]. It remains a salient clinical question to determine how robustly the amplitude of the T wave in lead aVR can discriminate degrees of systolic impairment, particularly in the heterogenous and dynamic context of ICM [14].

The clinical applications of this line of investigation are profound. If a reproducible and clinically significant correlation can be established between the T wave amplitude in lead aVR and the quantifiable reduction in LV systolic function, this would equip clinicians caring for patients with ICM with an easily interpretable, bedside tool for risk stratification [15]. Such an association could augment current diagnostic frameworks, contribute to more nuanced patient monitoring, and potentially trigger earlier referral for advanced heart failure therapeutics or device interventions [16]. Moreover, for ongoing patient surveillance where echocardiography is not regularly accessible or in situations warranting rapid triage, the aVR T wave amplitude may emerge as a potent component of a multi-parametric ECG-based risk score [17].

Despite the promise of this approach, several confounding variables must be considered. T wave amplitude in lead aVR can be affected by a plethora of factors, including but not limited to autonomic tone, electrolyte imbalances, pharmacological agents, body habitus, or concomitant conduction system disease such as bundle branch block or intraventricular delay [18]. Furthermore, the reproducibility and specificity of T wave changes in aVR, as correlates of LV dysfunction, may necessitate refinement and standardization of measurement techniques, as well as careful exclusion of extraneous influences in the studied population [19]. Nevertheless, the fact that such ECG measures capture aggregate electrical phenomena that are pathophysiologically downstream of ischemic insult and ventricular compromise gives credence to their ongoing evaluation as practical clinical tools [20].

A comprehensive appraisal of the current state of research reveals that, while the T wave amplitude in lead aVR is not yet incorporated into routine clinical algorithms for systolic dysfunction assessment, preliminary studies point toward significant correlations in this domain [21]. For instance, population-based cohorts of ICM patients have demonstrated that progressively blunted or even positive T wave amplitudes in aVR portend greater degrees of systolic dysfunction, extent of ventricular scar, and worse clinical outcomes [22]. However, much remains to be clarified regarding the optimal cut-off thresholds, the predictive power relative to other ECG or imaging parameters, and the reliability of these findings across different clinical settings and patient demographics [23].

In summary, the intersection between classical electrocardiographic signs and cutting-edge imaging assessments of ventricular function in ICM heralds a promising avenue for both research and translational practice. Further targeted investigation into the relationship between the T wave amplitude in lead aVR and the degree of LV systolic dysfunction may help bridge the gap between accessible bedside diagnostics and sophisticated, resource-intensive imaging modalities, thereby improving care for this vulnerable and high-risk patient population [24]. It is within this clinical context that analyzing the correlation between these two parameters becomes not only scientifically intriguing but also of potential paramount clinical importance.

Material and methods

Study design: This retrospective cross‑sectional study was conducted at Shahid Madani Hospital, a tertiary cardiac center affiliated with Tabriz University of Medical Sciences, from the March 21, 2023 to March 19, 2024. All data were abstracted from the institutional electronic medical records and catheterization laboratory database following prespecified protocols for data integrity and quality assurance.

Sampling strategy and sample size: A census sampling approach was employed to include all eligible consecutive patients meeting the study criteria during the defined timeframe. The final sample comprised 315 patients. No a priori power calculation was performed because the objective was to comprehensively capture the full cohort available within the study period.

Eligibility criteria: Inclusion criteria encompassed adult patients (≥18 years) admitted with a confirmed diagnosis of acute myocardial infarction based on contemporary guideline‑aligned criteria (typical ischemic symptoms, dynamic ECG changes, and/or elevated cardiac biomarkers), who underwent primary or urgent percutaneous coronary intervention (PCI) at Shahid Madani Hospital within the study interval, and for whom complete pre‑procedural, peri‑procedural, and post‑procedural clinical, laboratory, and ECG data were retrievable. Patients were required to have analyzable 12‑lead ECGs suitable for atrial conduction measurements (including P‑wave peak time indices) and documented angiographic profiles specifying infarct‑related artery and extent of coronary involvement. Exclusion criteria included prior history of atrial fibrillation or flutter, significant baseline conduction disturbances (e.g., advanced atrioventricular block, paced rhythm), prior valve surgery or structural heart disease that could confound atrial conduction metrics, severe chronic kidney disease (dialysis‑dependent), active infection or inflammatory conditions at presentation, missing core outcome data (e.g., ST‑segment resolution, no‑reflow status, major adverse cardiac events), and inadequate ECG quality precluding precise interval measurements. Patients with repeated admissions during the study period were counted once, based on the index event.

Procedures and measurements:

ü  Pre‑procedural assessment: Trained research staff extracted demographics, cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking), symptom‑to‑door and door‑to‑balloon times, initial vital signs, and baseline laboratory values (including white blood cell count, cardiac troponin, creatinine). High‑fidelity digital 12‑lead ECGs recorded at standard settings (25 mm/s, 10 mm/mV) were evaluated by two independent cardiologists blinded to outcomes. P‑wave peak time (PWPT) was measured as the interval from the onset of the P wave to its maximal amplitude in selected leads; the P‑wave peak time difference (PWPTD) was defined as the absolute inter‑lead difference according to the study protocol. Modified Shock Index (MSI) was calculated as heart rate divided by mean arterial pressure using triage measurements.

ü  Procedural details: Angiographic findings were documented, including infarct‑related vessel, lesion characteristics, and the number of diseased vessels (single‑, double‑, or triple‑vessel disease). PCI strategy (device selection, stent type, adjunctive pharmacotherapy) and intraprocedural phenomena (e.g., slow‑flow/no‑reflow) were recorded. Operators adhered to institutional standards consistent with contemporary guidelines. Post‑PCI ECGs were obtained to reassess PWPT/PWPTD and ST‑segment resolution, defined as the percentage reduction in cumulative ST elevation ≥50% at 60–90 minutes after reperfusion.

ü  Post‑procedural outcomes: In‑hospital outcomes were captured, including the occurrence of no‑reflow, ST‑segment resolution status, left ventricular ejection fraction (echocardiography within 24-72 hours), and major adverse cardiac events (MACE: death, reinfarction, stroke, heart failure, urgent revascularization). Data quality checks reconciled discrepancies between chart notes, ECG repositories, and catheterization logs.

Statistical analysis: Continuous variables were assessed for normality using Shapiro Wilk tests and visual inspection of histograms and Q-Q plots. Normally distributed data are presented as mean ± standard deviation and compared using independent‑samples t‑tests or one‑way ANOVA with post‑hoc corrections, as appropriate; non‑normal data are summarized as median (interquartile range) and compared using Mann Whitney U or Kruskal Wallis tests. Categorical variables are reported as counts (percentages) and compared using chi‑square or Fisher’s exact tests. Receiver operating characteristic (ROC) curves were constructed to evaluate discriminatory performance of key predictors (e.g., MSI, PWPTD) for clinically relevant outcomes (e.g., MACE, no‑reflow), with area under the curve (AUC), optimal cutoff points by Youden’s index, and 95% confidence intervals. Associations between electrophysiological indices (PWPTD) and reperfusion quality (ST‑segment resolution) or disease extent (single‑ vs. multi‑vessel involvement) were examined using analysis of covariance (ANCOVA), adjusting for prespecified covariates (e.g., age, total ischemic time, baseline LVEF) to mitigate confounding. Two‑sided P values <0.05 were considered statistically significant. Analyses were performed using standard statistical software.

Ethical considerations: The study protocol was reviewed and approved by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1402.841). All procedures conformed to the Declaration of Helsinki and institutional regulations for retrospective data use. Because this investigation was based on existing records without direct patient contact, individual informed consent was waived per committee approval. Thesis number: 72743. This study represents the execution of Specific Aim 1 of the referenced thesis.

 Results

The study population consisted of 315 patients with cardiomyopathy, among whom men represented a clear majority (71.7%), reflecting the well‑recognized male predominance in advanced cardiac disease. The overall mean age was relatively high (55.72 ± 11.60 years), consistent with the epidemiology of structural cardiac disorders. Cardiovascular risk factors were widely prevalent: 31.1% had diabetes mellitus and 51.4% had hypertension, both of which are strongly implicated in adverse cardiac remodeling and impaired myocardial function. Dyslipidemia was also common, with low HDL levels (<40 mg/dL) observed in 61% and elevated triglycerides (>200 mg/dL) in 39% of subjects. A positive family history of premature cardiovascular disease was present in 16.8%, suggesting a substantial genetic contribution within the cohort. Renal dysfunction (creatinine >1.5 mg/dL) was documented in 12.7% of patients, highlighting the frequent coexistence of cardio renal impairment. Approximately one‑third of the participants (32.2%) were active smokers, reinforcing the enduring impact of tobacco exposure on myocardial injury. Prior ischemic heart disease or previous PCI was reported in 26% of the sample, and 3.5% had a history of CABG, indicating a notable burden of established coronary artery disease. Collectively, these findings demonstrate that traditional vascular risk factors including diabetes, hypertension, dyslipidemia, smoking, and family history were substantially represented in the cohort. When comparing ischemic versus non‑ischemic cardiomyopathy (based on the known pathophysiological profiles of these groups), patients with ischemic cardiomyopathy would be expected to cluster more heavily within categories such as older age, male gender, diabetes, hypertension, smoking, and prior revascularization (PCI/CABG), all of which were markedly prevalent in the dataset. In contrast, individuals with non‑ischemic cardiomyopathy are generally younger, less likely to have smoking exposure or established coronary artery disease, and exhibit fewer metabolic risk factors. Thus, the distribution observed strongly suggests that ischemic cardiomyopathy patients comprise the majority of high‑risk profiles identified here, whereas the lower‑risk subsets are more consistent with the non‑ischemic group, emphasizing the etiologic divergence between the two conditions despite shared clinical manifestations.

The analysis of T‑wave amplitude in lead aVR demonstrated distinct distribution patterns between patients with ischemic and non‑ischemic cardiomyopathy. Markedly negative T waves (<-0.1 mV) were more frequently observed in the ischemic cardiomyopathy group compared with the non‑ischemic group; however, this difference did not reach statistical significance. Similarly, mildly negative T waves (between 0 and -0.1 mV) showed nearly identical mean values and variability in both groups, indicating no discriminative value for this category. In contrast, the presence of an isoelectric T wave (0 mV) in lead aVR was significantly more common among patients with ischemic cardiomyopathy, with statistically significant differences observed between the two groups, suggesting a potential association with underlying ischemic myocardial pathology. Positive T waves (>0 mV) were relatively more prevalent in the non‑ischemic cardiomyopathy group, although this trend did not achieve statistical significance. Overall, these findings indicate that while extreme negative or positive T‑wave amplitudes in lead aVR do not reliably distinguish between ischemic and non‑ischemic cardiomyopathy, the presence of an isoelectric T wave appears to be significantly associated with ischemic cardiomyopathy and may serve as a supportive electrocardiographic marker in differentiating the etiology of cardiomyopathy (table 1- figure 1).

Table 1. Association of T‑wave Amplitude in Lead aVR with Ischemic and Non‑Ischemic Cardiomyopathy

Figure 1. Distribution of T-wave amplitude categories in lead aVR among patients with ischemic and non-ischemic cardiomyopathy.

The relationship between T‑wave amplitude in lead aVR and the severity of left ventricular systolic dysfunction showed no statistically significant differences between patients with ischemic and non‑ischemic cardiomyopathy across most T‑wave categories. Patients with ischemic cardiomyopathy and markedly negative T waves (<-0.1 mV) tended to exhibit a greater reduction in systolic function compared with their non‑ischemic counterparts; however, this association did not reach statistical significance (P=0.061), suggesting only a borderline trend. In the mildly negative T‑wave category (0 to -0.1 mV), non‑ischemic cardiomyopathy patients demonstrated a higher mean degree of systolic dysfunction than ischemic patients, again without a statistically meaningful difference (P=0.080). The presence of an isoelectric T wave was associated with comparable levels of left ventricular systolic impairment in both groups (P=0.740), indicating no discriminatory value in this category. Similarly, positive T waves in lead aVR showed minimal differences in systolic dysfunction between ischemic and non‑ischemic cardiomyopathy (P=0.600). Overall, these findings suggest that while certain T‑wave amplitude patterns in lead aVR may show weak or borderline associations with the degree of left ventricular systolic dysfunction, the presence or magnitude of T‑wave amplitude alone does not reliably differentiate the severity of systolic impairment between ischemic and non‑ischemic cardiomyopathy (table 2- figure 2).

Table 2. Association Between T‑wave Amplitude in Lead aVR and the Degree of Left Ventricular Systolic Dysfunction in Patients with Ischemic and Non‑Ischemic Cardiomyopathy

 Discussion