European Journal of Cardiovascular Medicine

Acute coronary syndrome (ACS) encompasses a spectrum of clinical presentations ranging from unstable angina to ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), representing one of the leading causes of morbidity and mortality globally (1). The timely and accurate diagnosis of ACS, coupled with appropriate risk stratification, remains paramount in determining optimal management strategies and improving patient outcomes. While traditional electrocardiographic parameters such as ST-segment elevation, pathological Q waves, and T-wave inversions have long served as cornerstone diagnostic and prognostic markers, emerging electrocardiographic phenomena continue to enhance our understanding of myocardial injury patterns and their clinical implications (2).

 

The fragmented QRS (fQRS) complex, characterized by various RSR' patterns including additional R waves, notching of R or S waves, or presence of multiple R' waves in two contiguous leads corresponding to major coronary territories, has emerged as a novel electrocardiographic marker reflecting heterogeneous ventricular depolarization (3). First systematically described by Das and colleagues, fQRS complexes are believed to arise from altered ventricular conduction around regions of myocardial scarring, fibrosis, or acute ischemia, resulting in delayed and fragmented electrical activation (4). Unlike bundle branch blocks which represent global conduction abnormalities, fQRS reflects localized conduction disturbances typically associated with structural myocardial damage.

 

The pathophysiological substrate underlying fQRS formation involves inhomogeneous electrical activation of the ventricles due to myocardial scar tissue, which creates regions of slow conduction and conduction block. Following myocardial infarction, the affected myocardium undergoes a healing process characterized by scar formation and fibrotic tissue deposition. This fibrotic tissue lacks electrical conductivity, forcing the activation wavefront to navigate around these non-conductive regions, thereby creating multiple depolarization vectors that manifest as fragmentation within the QRS complex (5). The presence of fQRS has been demonstrated to correlate with myocardial scarring detected by cardiac magnetic resonance imaging and single-photon emission computed tomography, establishing its validity as a marker of structural myocardial abnormalities (6).

 

In the context of ACS, fQRS complexes appear within hours to days following the acute ischemic event, with studies demonstrating their development in approximately 50-55% of patients with myocardial infarction (7). The temporal evolution of fQRS following ACS provides valuable prognostic information, with persistent fQRS associated with larger infarct size, more extensive myocardial damage, and increased risk of adverse cardiovascular events including heart failure, ventricular arrhythmias, and death (8). Several studies have established fQRS as an independent predictor of mortality in patients with ACS, with hazard ratios ranging from 1.68 to 2.79 depending on the study population and follow-up duration (9,10).

 

Coronary angiography remains the gold standard for anatomical assessment of coronary artery disease, providing detailed visualization of coronary anatomy, identification of culprit lesions, assessment of disease severity, and guidance for revascularization strategies. The extent and severity of coronary artery disease as determined by angiography, typically classified as single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD), represents a powerful prognostic indicator and influences treatment decisions regarding optimal medical therapy, percutaneous coronary intervention, or coronary artery bypass grafting (11). However, coronary angiography is an invasive procedure with inherent risks, costs, and limited availability in many healthcare settings, particularly in emergency scenarios.

The correlation between electrocardiographic findings and coronary angiographic anatomy has been a subject of considerable interest in cardiovascular medicine. While standard ST-segment changes provide general localization of ischemic territories, they lack specificity in predicting the precise culprit vessel or the extent of coronary artery disease (12). Recent investigations have suggested that fQRS patterns may offer superior correlation with angiographic findings compared to traditional electrocardiographic parameters. Guo and colleagues demonstrated that the frequency of fQRS complexes in specific electrocardiographic leads could identify culprit vessels in NSTEMI patients with sensitivities ranging from 68% to 83% depending on the affected coronary territory (13).

 

The clinical utility of fQRS extends beyond diagnostic accuracy to encompass prognostic value in risk stratification. Studies have consistently shown that patients with fQRS demonstrate higher rates of major adverse cardiac events (MACE) including death, reinfarction, heart failure, and ventricular arrhythmias compared to those without fQRS (14). The number of leads demonstrating fQRS fragmentation appears to correlate with the extent of myocardial damage and disease severity, with three or more leads showing fQRS associated with particularly poor prognosis (15). Furthermore, the location of fQRS has been shown to correspond to specific coronary territories, with anterior fQRS correlating with left anterior descending artery disease, inferior fQRS with right coronary artery or left circumflex involvement, and lateral fQRS with left circumflex disease.

Despite growing evidence supporting the diagnostic and prognostic utility of fQRS in ACS, several questions remain inadequately addressed. The precise correlation between fQRS patterns and specific angiographic findings, including the ability to identify culprit lesions and predict multivessel disease, requires further elucidation. Additionally, the incremental value of fQRS assessment over traditional risk stratification tools in guiding clinical decision-making remains to be established. Most existing studies have focused on either STEMI or NSTEMI populations separately, with limited data on the utility of fQRS across the entire spectrum of ACS presentations.

 

The demographic and clinical characteristics associated with fQRS in ACS populations also warrant investigation. Previous studies have suggested higher prevalence of fQRS in elderly patients and those with diabetes mellitus, potentially reflecting greater burden of underlying coronary artery disease and myocardial dysfunction in these populations (13). Understanding these associations may help identify patient subgroups who would benefit most from fQRS assessment and aggressive therapeutic interventions.

 

The integration of fQRS assessment into routine clinical practice for ACS management could provide several advantages. First, electrocardiography is universally available, inexpensive, non-invasive, and can be performed rapidly at the bedside, making it an ideal screening tool. Second, fQRS detection requires no specialized equipment beyond standard electrocardiography and can be readily incorporated into existing clinical workflows. Third, early identification of high-risk patients through fQRS assessment could facilitate timely referral for coronary angiography and appropriate revascularization strategies. Finally, fQRS may help identify patients at risk for complications who require more intensive monitoring and aggressive medical management.

 

However, several limitations must be acknowledged regarding fQRS assessment. The interpretation of fQRS requires careful attention to avoid false-positive findings from artifact, muscle tremor, or baseline wander. Additionally, certain conditions including bundle branch blocks, ventricular hypertrophy, and pre-excitation syndromes may confound fQRS interpretation. Standardized criteria for fQRS definition and rigorous quality control in electrocardiographic acquisition and interpretation are essential for reliable clinical application.

Given the potential clinical utility of fQRS in ACS management and the need for better understanding of its correlation with angiographic findings, we conducted this prospective observational study to comprehensively evaluate the relationship between fQRS complexes and coronary angiographic findings in patients presenting with acute coronary syndrome. Our study specifically aimed to determine the prevalence of fQRS across different ACS presentations, assess the correlation between fQRS location and corresponding culprit vessels on angiography, evaluate the association between fQRS presence and extent of coronary artery disease, and determine the prognostic significance of fQRS for short-term clinical outcomes. By addressing these objectives, we sought to provide evidence-based insights that could enhance risk stratification and optimize management strategies for ACS patients in clinical practice.

 

AIMS AND OBJECTIVES

Primary Objectives:

1. To determine the prevalence of fragmented QRS complexes in patients presenting with acute coronary syndrome
2. To evaluate the correlation between the presence and location of fQRS and angiographic findings including identification of culprit lesions
3. To assess the relationship between fQRS and the extent of coronary artery disease (single-vessel, double-vessel, or triple-vessel disease) on coronary angiography

Secondary Objectives:

1. To analyze the association between fQRS and various clinical parameters including age, gender, cardiovascular risk factors, and troponin I levels
2. To determine the prognostic significance of fQRS for 30-day clinical outcomes including mortality and major adverse cardiac events
3. To compare baseline demographic, clinical, and laboratory characteristics between patients with and without fQRS
4. To evaluate the correlation between specific fQRS lead distribution patterns and corresponding coronary artery territories

Study Design and Setting This was a prospective observational study conducted in the Department of General Medicine and Department of Cardiology at Karnataka Institute of Medical Sciences (KIMS), Hubballi, Karnataka, India. The study was conducted over a period of 18 months from January 2023 to June 2024. All patients presenting to the emergency department or cardiology outpatient department with suspected or confirmed acute coronary syndrome were screened for eligibility. The study protocol was approved by the Institutional Ethics Committee of Karnataka Institute of Medical Sciences, and written informed consent was obtained from all participants before enrollment. Study Population The study included consecutive patients presenting with acute coronary syndrome defined according to current guidelines as the presence of symptoms suggestive of myocardial ischemia along with either electrocardiographic changes consistent with myocardial ischemia or elevation of cardiac biomarkers. A total of 147 patients who met the inclusion criteria and provided informed consent were enrolled in the study. Inclusion Criteria Patients were included in the study if they met all of the following criteria: 1. Age 18 years or older 2. Clinical presentation consistent with acute coronary syndrome including chest pain, dyspnea, or anginal equivalents 3. Electrocardiographic changes suggestive of myocardial ischemia or infarction 4. Willingness to undergo coronary angiography as part of standard clinical care 5. Ability to provide written informed consent Exclusion Criteria Patients were excluded from the study if they had any of the following: 1. Complete or incomplete bundle branch block (QRS duration ≥120 milliseconds) 2. Pre-existing permanent pacemaker or implantable cardioverter-defibrillator 3. Ventricular pre-excitation syndromes (Wolff-Parkinson-White syndrome) 4. Previous coronary artery bypass grafting 5. Significant valvular heart disease (moderate to severe stenosis or regurgitation) 6. Congenital heart disease 7. Chronic total occlusion on previous angiography 8. Inability to undergo coronary angiography due to medical contraindications 9. Refusal to participate or provide informed consent 10. Poor electrocardiographic quality preventing reliable assessment of QRS morphology Clinical Assessment All enrolled patients underwent comprehensive clinical evaluation at the time of admission. Detailed medical history was obtained including presenting symptoms (chest pain, breathlessness, sweating, nausea, vomiting), duration of symptoms, cardiovascular risk factors (diabetes mellitus, hypertension, dyslipidemia, smoking history, family history of coronary artery disease), and past medical history. Physical examination was performed with particular attention to vital signs, cardiovascular examination, and assessment for signs of heart failure. Body mass index was calculated based on measured height and weight. Electrocardiographic Assessment Standard 12-lead electrocardiography was performed on all patients at the time of presentation using a standardized protocol with paper speed of 25 millimeters per second and calibration of 10 millimeters per millivolt. Electrocardiograms were obtained with patients in the supine position after a brief period of rest. All electrocardiograms were independently reviewed by two experienced cardiologists blinded to clinical and angiographic data. Discrepancies were resolved through consensus discussion. Fragmented QRS was defined according to criteria established by Das and colleagues. Specifically, fQRS was defined as the presence of various RSR' patterns including: • Additional R wave (R') • Notching of the R wave • Notching of the S wave • Presence of more than one R' wave These patterns had to be present in two or more contiguous leads corresponding to a major coronary artery territory, with QRS duration less than 120 milliseconds in the absence of typical bundle branch block patterns. The electrocardiographic leads were categorized into territories as follows: • Anterior leads: V1, V2, V3, V4 • Lateral leads: I, aVL, V5, V6 • Inferior leads: II, III, aVF ST-segment elevation was defined as new ST elevation at the J point in two contiguous leads with the cut-points: ≥1 millimeter in all leads other than V2-V3 where the following cut points applied: ≥2 millimeters in men ≥40 years, ≥2.5 millimeters in men <40 years, or ≥1.5 millimeters in women. NSTEMI was diagnosed based on elevated cardiac biomarkers without ST-segment elevation. Laboratory Investigations Blood samples were collected from all patients at the time of admission for measurement of complete blood count, renal function tests (blood urea, serum creatinine), electrolytes (sodium, potassium, magnesium), fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), fasting blood glucose, and glycosylated hemoglobin (HbA1c). Cardiac biomarker assessment included high-sensitivity troponin I measured at presentation. Troponin I levels were classified as elevated if >0.3 nanograms per milliliter. Echocardiographic Assessment Transthoracic echocardiography was performed on all patients within 24 hours of admission using standard techniques. Two-dimensional and Doppler echocardiographic examinations were conducted by experienced echocardiographers following standardized protocols. Left ventricular ejection fraction was calculated using the modified biplane Simpson's method. Regional wall motion abnormalities were assessed systematically in all myocardial segments according to the 16-segment model recommended by the American Society of Echocardiography. Wall motion was graded as normal, hypokinetic, akinetic, or dyskinetic. Coronary Angiography Coronary angiography was performed in all study participants as part of standard clinical care. The timing of angiography was determined based on clinical presentation and institutional protocols, with most patients undergoing angiography within 72 hours of presentation. Angiography was performed via either femoral or radial artery approach at the discretion of the interventional cardiologist. Standard coronary views were obtained for visualization of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery along with their major branches. Angiographic findings were analyzed by experienced interventional cardiologists who were blinded to electrocardiographic findings regarding fQRS presence. Significant coronary artery disease was defined as luminal diameter stenosis ≥50% in any major epicardial coronary artery. The extent of coronary artery disease was classified as: • Normal or recanalized: No significant stenosis or previously revascularized vessels with TIMI grade 3 flow • Single-vessel disease: Significant stenosis in one major epicardial coronary artery • Double-vessel disease: Significant stenosis in two major epicardial coronary arteries • Triple-vessel disease: Significant stenosis in all three major coronary territories (left anterior descending, left circumflex, right coronary artery) The culprit lesion was identified based on angiographic characteristics including presence of thrombus, ulceration, irregularity, and correlation with electrocardiographic and echocardiographic findings. The affected coronary artery territory was documented for correlation with electrocardiographic lead distribution of fQRS. Follow-up and Outcome Assessment All patients were followed during their hospital stay and for 30 days after discharge. Follow-up information was obtained through telephone contact with patients or family members. Clinical outcomes assessed included: • All-cause mortality • Cardiovascular mortality • Reinfarction • Heart failure requiring hospitalization • Malignant ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation) • Major bleeding complications Major adverse cardiac events (MACE) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, and urgent revascularization. Statistical Analysis Data were entered into Microsoft Excel spreadsheets and analyzed using Statistical Package for Social Sciences (SPSS) version 23.0. Continuous variables were expressed as mean ± standard deviation for normally distributed data or median with interquartile range for non-normally distributed data. Categorical variables were expressed as frequencies and percentages. Normality of distribution was assessed using the Kolmogorov-Smirnov test. Comparison between patients with and without fQRS was performed using independent samples t-test for normally distributed continuous variables, Mann-Whitney U test for non-normally distributed continuous variables, and chi-square test or Fisher's exact test (when expected cell frequency was <5) for categorical variables. Correlation between fQRS presence and various clinical parameters was assessed using Pearson or Spearman correlation coefficients as appropriate. A p-value of <0.05 was considered statistically significant. Odds ratios with 95% confidence intervals were calculated to assess the strength of association between fQRS and clinical outcomes.