Introduction

The surface electrocardiogram, as one of the most accessible cardiovascular diagnostic tools, continues to attract attention for its potential to provide incremental etiologic information beyond basic rhythm analysis [1].

The 12‑lead electrocardiogram reflects the summation of myocardial depolarization and repolarization vectors and offers indirect insight into myocardial structure, perfusion, and electrical heterogeneity. While traditional ECG markers such as pathologic Q waves, ST‑segment deviations, and bundle branch blocks have long been associated with ischemic heart disease, their sensitivity and specificity for distinguishing ischemic from non‑ischemic cardiomyopathy are limited. Many patients with advanced non‑ischemic cardiomyopathy may exhibit Q waves or ST‑T abnormalities unrelated to coronary artery disease, whereas patients with ischemic cardiomyopathy may lack classic ECG signs, particularly in the chronic phase. This overlap reduces the diagnostic utility of conventional ECG interpretation when used in isolation. As a result, contemporary research has increasingly focused on less emphasized ECG components, including vector‑specific leads and subtle repolarization patterns, that may better reflect the underlying etiology of myocardial dysfunction. Among these, lead aVR has emerged as a potentially informative yet historically neglected lead [2].

Lead aVR occupies a unique spatial orientation, viewing the heart from the right upper aspect and recording electrical activity directed toward the right shoulder. For decades, it was considered a “forgotten lead,” often ignored in routine ECG interpretation due to the predominance of negative deflections in normal individuals. However, accumulating evidence has challenged this perception, demonstrating that lead aVR can provide valuable diagnostic and prognostic information in a variety of cardiovascular conditions, including acute coronary syndromes, left main coronary artery disease, and global sub endocardial ischemia. The distinctive vector alignment of lead aVR makes it particularly sensitive to changes in the basal interventricular septum and the right ventricular outflow tract, regions that are often involved in ischemic processes. As such, abnormalities in this lead may capture ischemia‑related electrical alterations that are not readily apparent in other leads, thereby offering a unique window into myocardial pathology [3].

The T wave represents ventricular repolarization and is influenced by myocardial action potential duration, regional heterogeneity of repolarization, autonomic tone, electrolyte balance, and ischemia. Alterations in T‑wave morphology and amplitude are common in cardiomyopathy and have traditionally been interpreted as nonspecific findings. Nevertheless, the spatial distribution of repolarization abnormalities may carry important etiologic implications. In ischemic cardiomyopathy, chronic hypo perfusion and scar formation lead to altered repolarization gradients, particularly in regions supplied by diseased coronary arteries. These changes may manifest as flattening, inversion, or normalization of the T wave in specific leads, depending on the direction of the resultant repolarization vector. In non‑ischemic cardiomyopathy, repolarization abnormalities are more often diffuse and related to global myocardial remodeling rather than regional ischemia. This fundamental difference provides a theoretical basis for using T‑wave characteristics in strategically oriented leads, such as aVR, to distinguish ischemic from non‑ischemic myocardial disease [4].

Recent studies have suggested that the polarity and amplitude of the T wave in lead aVR may be particularly informative. In healthy individuals, the T wave in aVR is typically negative, reflecting the normal direction of ventricular repolarization away from the right upper quadrant. Deviations from this pattern, including isoelectric or positive T waves, may indicate significant alterations in repolarization vectors. Such changes have been associated with severe coronary artery disease, left main or proximal left anterior descending artery involvement, and extensive myocardial ischemia. Importantly, these patterns may persist in chronic ischemic cardiomyopathy, reflecting long‑standing electrical remodeling rather than transient ischemic episodes. In contrast, patients with non‑ischemic cardiomyopathy may retain the expected negative T‑wave pattern in aVR despite marked systolic dysfunction, suggesting a relative preservation of normal repolarization orientation [5].

The potential diagnostic value of lead aVR becomes particularly relevant in patients with established left ventricular systolic dysfunction, in whom the differentiation between ischemic and non‑ischemic cardiomyopathy has direct therapeutic implications. Identifying an ischemic etiology may prompt coronary angiography, revascularization, and intensified secondary prevention strategies, whereas a non‑ischemic diagnosis may shift the focus toward genetic evaluation, immunomodulatory therapy, or device‑based interventions. Although advanced imaging techniques such as cardiac magnetic resonance with late gadolinium enhancement provide high diagnostic accuracy, their availability, cost, and contraindications limit universal application. In this context, an ECG‑based marker capable of raising or lowering suspicion for ischemic cardiomyopathy could serve as a valuable triage tool, guiding further diagnostic pathways and optimizing resource utilization [6].

Despite growing interest, the role of T‑wave amplitude in lead aVR has not been fully elucidated in the setting of chronic cardiomyopathy. Much of the existing literature has focused on acute coronary syndromes or short‑term prognostic outcomes, with relatively few studies addressing its diagnostic performance in stable patients with established myocardial dysfunction. Moreover, previous investigations have often grouped repolarization abnormalities broadly, without stratifying T‑wave amplitude into clinically meaningful categories. This gap in knowledge underscores the need for focused analyses that examine whether specific T‑wave patterns in lead aVR are preferentially associated with ischemic versus non‑ischemic etiologies, independent of the severity of systolic dysfunction. Such analyses may help clarify whether lead aVR provides etiologic rather than merely prognostic information in cardiomyopathy [7].

Another important consideration is the simplicity and reproducibility of ECG‑based markers. T‑wave amplitude in lead aVR can be readily assessed on standard ECG recordings without the need for advanced software or complex measurements. This makes it particularly attractive for use in routine clinical practice and in settings with limited access to specialized cardiovascular diagnostics. Furthermore, incorporating lead aVR into systematic ECG interpretation may enhance diagnostic yield without increasing cost or patient burden. However, before such an approach can be recommended, its diagnostic relevance must be established through methodologically sound studies that account for confounding factors such as age, sex, comorbidities, and medication use [8].

In light of these considerations, investigating the diagnostic role of the T wave in lead aVR in differentiating ischemic from non‑ischemic cardiomyopathy is both timely and clinically meaningful. Understanding whether specific T‑wave amplitude patterns are preferentially associated with ischemic myocardial disease could contribute to more nuanced ECG interpretation and improve etiologic assessment in patients with cardiomyopathy. By focusing on a frequently overlooked lead and a readily measurable ECG parameter, such research aligns with the broader goal of maximizing the diagnostic potential of existing, low‑cost tools. Ultimately, elucidating the relationship between lead aVR T‑wave characteristics and cardiomyopathy etiology may help bridge the gap between surface electrocardiography and underlying myocardial pathology, reinforcing the enduring relevance of the ECG in modern cardiovascular medicine.

Material and methods

Study Design: The present investigation was designed as a retrospective cross‑sectional study. It was conducted at Shahid Madani Heart Center, a tertiary referral cardiovascular hospital affiliated with Tabriz University of Medical Sciences, Tabriz, Iran. Patient data were collected over a one‑year period corresponding to the beginning through the end of the Iranian calendar year 1402. The study focused on individuals diagnosed with cardiomyopathy who had been evaluated and managed within this center during the specified timeframe.

Sampling Method and Sample Size: A census sampling strategy was employed to include all eligible patients who met the predefined inclusion criteria during the study period. This approach was selected to minimize selection bias and to ensure comprehensive representation of the target population. A total of 315 patients were ultimately enrolled in the study and included in the final analysis.

Inclusion and Exclusion Criteria: Patients were eligible for inclusion if they had a confirmed diagnosis of cardiomyopathy based on clinical evaluation and echocardiographic findings, had documented left ventricular systolic dysfunction, and possessed complete medical records including a standard 12‑lead electrocardiogram suitable for analysis. Both ischemic and non‑ischemic etiologies were considered, with ischemic cardiomyopathy defined according to documented evidence of coronary artery disease and non‑ischemic cardiomyopathy diagnosed in the absence of significant obstructive coronary lesions. Exclusion criteria comprised a history of acute coronary syndrome within the recent period prior to ECG acquisition, prior cardiac surgery or device implantation affecting ECG interpretation, significant valvular heart disease as the primary pathology, congenital heart disease, paced rhythms, bundle branch blocks or arrhythmias that interfered with accurate T‑wave assessment, electrolyte imbalances at the time of ECG recording, and incomplete or poor‑quality clinical, echocardiographic, or electrocardiographic data.

Study Procedure: Clinical and demographic information, including age, sex, cardiovascular risk factors, comorbid conditions, and relevant medical history, were extracted from hospital electronic medical records and archived patient files. Etiologic classification into ischemic or non‑ischemic cardiomyopathy was performed based on documented coronary angiography reports, prior medical diagnoses, and cardiology consultation notes, in accordance with accepted clinical definitions.

Standard resting 12‑lead electrocardiograms recorded at a paper speed of 25 mm/s and calibration of 10 mm/mV were reviewed retrospectively. All ECGs were obtained during a clinically stable condition. The T‑wave amplitude in lead aVR was carefully evaluated and categorized according to predefined criteria as negative, isoelectric, or positive. ECG interpretation was performed by trained investigators who were blinded to the etiologic classification to reduce observer bias.

Transthoracic echocardiographic data were reviewed to assess left ventricular systolic function. Left ventricular ejection fraction was measured using standard echocardiographic techniques and used to confirm systolic dysfunction. The degree of systolic impairment was recorded and later analyzed in relation to T‑wave amplitude categories in lead aVR. All collected data were anonymized prior to analysis.

Statistical Analysis: Statistical analyses were performed using appropriate statistical software. Categorical variables were expressed as frequencies and percentages, while continuous variables were presented as means with standard deviations. Comparisons between ischemic and non‑ischemic cardiomyopathy groups were conducted using the chi‑square test or Fisher’s exact test for categorical variables and independent‑sample t‑tests for continuous variables, as appropriate. The association between T‑wave amplitude categories in lead aVR and cardiomyopathy etiology, as well as the degree of left ventricular systolic dysfunction, was evaluated using comparative statistical methods. A two‑sided P value of less than 0.05 was considered statistically significant.

Ethical Considerations: The study protocol was reviewed and approved by the Ethics Committee of Tabriz University of Medical Sciences under the ethics code IR.TBZMED.REC.1402.841. The study was conducted in accordance with the principles of the Declaration of Helsinki. Given the retrospective nature of the study, informed consent was waived. This research constitutes part of an approved medical thesis registered under thesis number 72743. All patient information was handled confidentially, and data were used solely for research purposes.

Results

The study population demonstrated a marked male predominance and a relatively advanced mean age, reflecting the typical demographic profile of patients with cardiomyopathy. Traditional cardiovascular risk factors were highly prevalent, with more than half of the patients affected by hypertension and nearly one‑third by diabetes mellitus and cigarette smoking. Dyslipidemia, particularly reduced HDL cholesterol levels, was observed in a substantial proportion of the cohort, underscoring the metabolic burden within this population. A prior history of ischemic heart disease or coronary revascularization was present in approximately one‑quarter of patients, suggesting a significant contribution of coronary pathology. When comparing ischemic and non‑ischemic cardiomyopathy, these risk factors are expected to cluster more prominently in the ischemic group, particularly male sex, diabetes, hypertension, dyslipidemia, smoking, chronic kidney disease, and previous ischemic heart disease or revascularization. In contrast, patients with non‑ischemic cardiomyopathy typically exhibit a lower prevalence of established atherosclerotic risk factors and coronary interventions, reflecting fundamental differences in disease mechanisms between the two etiologic categories (table 1).

 Table 1. Assessment of Demographic Characteristics and Coronary Artery Disease Risk Factors in Patients with Ischemic and Non‑Ischemic Cardiomyopathy

The in‑hospital clinical profile of the study population reflects a cohort with moderate hemodynamic stability and metabolic variability at the time of admission. Overall electrolyte levels and renal function indices showed considerable dispersion, indicating heterogeneity in disease severity and comorbid conditions. Cardiac troponin I levels were generally low but displayed wide variability, suggesting that while acute myocardial injury was not prominent in all patients, it was more likely to be observed in those with ischemic cardiomyopathy. Similarly, renal function markers and blood urea nitrogen tended to be higher among ischemic patients, consistent with a greater burden of systemic atherosclerosis and cardiorenal interaction. Admission blood pressure and heart rate values did not demonstrate marked differences between groups, implying comparable initial hemodynamic status. However, patients with ischemic cardiomyopathy are typically expected to experience longer hospital stays, reflecting more complex clinical courses and the need for advanced diagnostic or interventional procedures compared ith those with non‑ischemic cardiomyopathy (table 2).

 Table 2. Evaluation of in‑Hospital Clinical Parameters in Patients with Ischemic and Non‑Ischemic Cardiomyopathy

Analysis of hospital length of stay across different T‑wave amplitude categories in lead aVR demonstrated no statistically significant association with hospitalization duration. Although a gradual increase in mean length of stay was observed from patients with clearly negative T waves to those with isoelectric and positive T waves, this trend did not reach statistical significance. When ischemic and non‑ischemic cardiomyopathy groups were considered, similar patterns were observed, indicating that T‑wave amplitude in lead aVR did not meaningfully differentiate the clinical course in terms of hospitalization duration between the two etiologies. These findings suggest that while T‑wave characteristics in lead aVR may reflect underlying electrophysiological or etiologic differences, they do not appear to independently influence short‑term in‑hospital outcomes such as length of stay in either ischemic or non‑ischemic cardiomyopathy (table 3).

Table 3. Association Between T‑Wave Amplitude in Lead aVR and Length of Hospital Stay in Patients with Ischemic and Non‑Ischemic Cardiomyopathy

Evaluation of in‑hospital mortality and adverse clinical outcomes across different T‑wave amplitude categories in lead aVR demonstrated no statistically significant association, as reflected by a non‑significant P‑value. The majority of patients in all T‑wave groups experienced an uncomplicated hospital course, with the highest proportion observed among those with markedly negative and positive T waves. In‑hospital mortality was rare and occurred only in patients with mildly negative or isoelectric T waves, while no deaths were recorded in the markedly negative or positive T‑wave categories. Similarly, non‑fatal adverse events such as stroke, arrhythmia, and recurrent myocardial infarction or acute coronary syndrome were infrequent and distributed without a consistent pattern across T‑wave amplitudes. When comparing ischemic and non‑ischemic cardiomyopathy, these outcomes followed comparable trends, indicating that T‑wave amplitude in lead aVR did not significantly differentiate short‑term in‑hospital prognosis between the two etiologic groups. Overall, the absence of statistical significance suggests that, despite its potential diagnostic value, T‑wave amplitude in lead aVR does not independently predict in‑hospital mortality or major adverse events in patients with either ischemic or non‑ischemic cardiomyopathy (table 4).

Table 4. Association Between T‑Wave Amplitude in Lead aVR and in‑Hospital Mortality and Adverse Outcomes in Patients with Ischemic and Non‑Ischemic Cardiomyopathy