European Journal of Cardiovascular Medicine

Left ventricular systolic dysfunction used synonymously with Heart failure with reduced ejection fraction defined as LVEF of < 40% (1), continues to be one of most challenging cardiovascular conditions responsible for significant mortality, morbidity, and health care burden. Introduction of GDMT has revolutionised the management of heart failure and significantly improved survival (2).

QRS complex duration on electrocardiogram is a simple measure of inter ventricular conduction delay, number studies have shown that prolonged QRS >120 msecduration on ECG is consistently associated with worse outcomes in heart failure, increased mortality associated with intraventricular dyssynchony and impaired left ventricular contraction (3,4). Recently Pooled analysis of landmark DAPA-HF and DELIVER trials on SGLT2 inhibitors showed no matter what the Ejection fraction was, patients with wider QRS > 120-149 msec or > 150 msec corresponded higher rates of cardiovascular deaths and worsening of heart failure compared to those with narrow QRS < 120 msec (5). Most studies have been conducted in resource-rich settings, with very limited prospective data available from rural India. In particular, there is a lack of research on patients with newly diagnosed left ventricular (LV) dysfunctionwho have not yet been influenced by long disease duration or prior therapy. Furthermore, the impact of QRS duration on the response to guideline-directed medical therapy (GDMT) in such populations is stillunder explored. Therefore, this study was designed to fill this important gap by comparing clinical outcomes in patients with newly diagnosed LV dysfunction, treated with full GDMT, stratified by narrow versus wide QRS duration in a rural North Indian population, while incorporating the most up-to-date evidence and treatment strategies

This was a prospective observational cohort study conducted in Department of Cardiology, Ayushman Hospital Shamli, Uttar Pradesh for a period of 1 year from August 2023 to September 2024. Patient were taken from hospital wards admitted with Diagnosis of Heart failure and from Outpatient department with clinical diagnosis of heart failure subsequently found to left ventricular systolic dysfunction on echocardiography. Patients aged ≥18 years with newly diagnosed left ventricular systolic dysfunction (LVSD), defined as a left ventricular ejection fraction (LVEF) ≤40% on echocardiography measured by Simpson’s method, were eligible for inclusion. Patients with prior heart failure therapy, significant valvular heart disease, congenital heart disease, prior history of acute coronary syndrome, or advanced COPD, renal/hepatic dysfunction, History of Alcoholic abuse and patients who werelost on follow up were excluded from study.

Electrocardiographic Assessment: A standard 12-lead electrocardiogram was obtained for all patients at baseline. QRS duration was measured manually, and patients were categorized into two groups:

• Narrow QRS group: QRS duration <120 ms(Group A)
• Wide QRS group: QRS duration ≥120 ms (Group B)

Other parameter considered was morphology of QRS whether left bundle branch block (LBBB) is present or not.

Guideline-Directed Medical Therapy (GDMT): All patients were initiated on GDMT in accordance with the latest ACC/AHA/ESC heart failure guidelines, included following class of drugs.

• Renin–angiotensin–aldosterone system inhibitors (ACE inhibitors or ARBs).
• Angiotensin receptor and neprilysin inhibitors (ARNIs).
• Beta-blockers.
• Sodium-Gulcose cotransporter 2 inhibitors (SGLT2 inhibitors).
• Mineralocorticoid receptor antagonists (MRAs).
• Loop diuretics for symptomatic relief
• Hydralazine + Isosorbide Dinitrate

Therapy was titrated to target doses as tolerated, with regular follow-up every 2–4 weeks for up-titration and monitoring of adverse effects.

Follow-up and Outcomes: Patients were followed for 12 months. The primary outcome was a composite of

1. All-cause mortality and
2. Heart failure hospitalization.

Secondary outcomes included:

1. Change in Left ventricular ejection fraction from baseline

1. NYHA functional class improvement

Definitions of Study Endpoints

1. Left Ventricular Systolic Dysfunction (LVSD): Defined as left ventricular ejection fraction (LVEF) ≤40%, measured by two-dimensional echocardiography using the modified Simpson’s method, in line with ACC/AHA and ESC HF guidelines (1).
2. All-Cause Mortality: Death from any cause during follow-up, irrespective of cardiovascular or non-cardiovascular etiology (1).
3. Heart Failure Hospitalisation: Admission for worsening heart failure symptoms, requiring at least intravenous diuretic therapy, inotropes, or vasodilators, consistent with prior HF trials. (6)
4. NYHA Functional Class Improvement: Improvement defined as ≥1 class reduction in NYHA functional classification from baseline to follow-up visit. (7)
5. Echocardiographic Response (Secondary Endpoint): Improvement in LVEF expressed as absolute percentage change from baseline, consistent with guideline-recommended definitions of reverse remodelling. (7)

Data Collection: Data was collected regarding the patients' Demographic profile consisting of Age, Gender, Comorbidities, NYHA functional class, NT-pro BNP levels whenever available, Echocardiographic data ( LV ejection fraction measured with modified Simpsons method  and Left ventricular End diastolic dimension in millimetres taken by anatomical M-mode ), ECG data were recorded at baseline and during follow-up visits. LVEF was assessed by two-dimensional echocardiography using the modified Simpson’s method. Adherence to therapy was assessed through patient interviews and prescription records on Opd follow up and telephonic conversation.

Statistical Analysis: Continuous variables were expressed as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables were expressed as counts and percentages. Comparisons between narrow and wide QRS groups were performed using Student’s t-test or Mann–Whitney U test for continuous variables and chi-square or Fisher’s exact test for categorical variables. Kaplan–Meier survival analysis was used to estimate event-free survival, and differences were compared using the log-rank test. Multivariable Cox proportional hazards regression was used to identify independent predictors of outcomes. A two-tailed p-value <0.05 was considered statistically significant. Statistical analyses were performed using (software SPSS v26).

We had total of 208 patients, around 30 patients were lost during follow up. Among the remaining 178 patients with diagnosis of Newly diagnosed LV systolic dysfunction92 patients (52%) had Narrow QRS ECG (< 120 msec) labelled as (Group A) and 86 patients have wide QRS ECG (>120 msec) labelled as (Group B). Baselines characteristics of Study patients in each Group are shown below (Table 1).

*Statistically Significant Difference (P-value<0.05)

Mean age of patients in Group A was 56.1+/-8.34 years and in Group B 58.2+/-7.89 years. Group A had 68.5% males and 65.1% in Group B. Mean Pro-BNP level pg/ml was 2153+/-973.1 pg/ml in Group A and 2341+/-1087.5 pg/ml in Group B. Mean QRS duration in Group A narrow QRS group 90.6 +/-12.4 msec and in Group B wide QRS group is 141.24 +/-34.7 msec. LBBB pattern on ECG was present in 17.39% in Group A and 67.44% in Group B. LV ejection fraction% at presentation was 29.8 +/-8.93% in Group A and 32.3 +/-10.14 % in Group B.

Patients were started on GDMT as per latest ACC/AHA guidelines. GDMT Adherence defined as receipt of recommended HF medications (ACE inhibitor/ARB, ARNIs, beta-blocker, SGLT2 inhibitors and mineralocorticoid receptor antagonist) at ≥50% of target dose, with no significant interruptions during follow-up (1). Below Table (2) shows percentage of different components of GDMT used in each group.

There were no significant differences in GDMT used in either Group. P valve (<0.05).During follow-up, most patients achieved target or maximally tolerated doses, with comparable up-titration between narrow and wide QRS groups.

Over a median follow up of 12 months, Primary outcome All cause Mortality occurred in patients (8.7%) of patients in Narrow QRS group (Group A) and 14% of patients in wide QRS group (Group B)(p-valve=0.267). Similarly, heart failure hospitalisation occurred in 17.4% of patients in Group A and 25.6% of patients in Group B (p-valve = 0.183).

In above Table (3) though there was not a statistically significant difference interms Primary Outcome between two groups, however overallcomposite primary outcomes endpoint events tend to occur more in Group B that is the wide QRS group.

Both Groups experienced significant improvement in LV ejection fraction on follow up. Mean LVEF% improvement was 8.3+/-3.42 % in Group A and 7.4 +/- 2.78 % in Group B(p-valve= 0.057). >1class improvement in NYHA functional status was observed in 67.4% of patients in Group A and 64% of patients in Group B (p-valve =0.629; table 4)

There was no statistically significant difference in secondary outcomes between two groups

This was a prospective observational studydone at Tertiary care institute from rural North India which showed both groups of patients with newly diagnosed left ventricular systolic dysfunction showed significant clinical and echocardiographic improvement following institution of comprehensive guideline-directed medical therapy (GDMT). However, patients with narrow QRS duration (Group A)showed a numerically greater improvement in left ventricular ejection fraction (LVEF) and functional class compared with those having wide QRS duration (Group B), despite comparable baseline characteristics and similar GDMT uptake. Although the between-group differences in mortality, heart failure (HF) hospitalisation, and EF recovery did not reach statistical significance, the trend consistently favoured the narrow QRS group, supporting the hypothesis that electrical remodellingchanges the extent of reverse remodelling under pharmacologic therapy. Our findings are concordant with previous evidence showing that QRS duration is a powerful marker of disease severity and outcome in HF. Prolonged QRS duration reflects greater myocardial fibrosis, conduction delay, and mechanical dyssynchrony, all of which attenuate response to pharmacologic therapy alone (8).In numerous registries and trails wideQRSespecially with left bundle branch block (LBBB)has been associated with reduced reverse remodelling, higher NT-proBNP levels, and increased hospitalisation risk despite GDMT. (4,9) In our study a higher prevalence of LBBB in the wide-QRS group (67.44% vs 17.39 1%, p<0.001) aligns with these mechanistic observations and likely explains the trend toward less improvement in LVEF and higher event rates in that group.

All patients in our study received optimized GDMT, these rates are substantially higher than those reported in many Indian and global real-world registrieshighlighting the feasibility of comprehensive GDMT implementation even in resource-limited, rural settings. (10,11). Recent randomised evidence, from DELIVER and DAPA-HF trials showed that rapid initiation of all four foundational drug classes produced meaningful clinical recovery across both QRS groups (12,13). While wide-QRS patients achieved symptomatic improvement, but their relatively lower EF gain (7.4±2.8% vs 8.3±3.4%, p=0.057) and numerically higher hospitalisation rate (25.6% vs 17.4%) suggest residual mechanical inefficiency that might not be fully addressed by medical therapy alone. Trails such asMADIT-CRT and COMPANION, show that in such patients, addition of cardiac resynchronisation therapy (CRT) can yield substantial reverse remodelling beyond pharmacologic limits. (4,14)

From a practical standpoint, GDMT stays the universal foundation of management for all newly diagnosed LV systolic dysfunction patients, irrespective of QRS duration. Early institution and up-titration of ARNI, beta-blockers, MRAs, and SGLT2 inhibitors should remain the priority. However, wide-QRS patients call for closer monitoring for incomplete recovery or persistent symptoms and should be reassessed early for device candidacy if optimal medical therapy does not achieve desired functional or structural improvement. Some important systemic barriers exposed by this study include rural access, drug affordability, and fragmented follow-up. Despite these, the observed adherence reinforces that with structured follow-up and local health-worker involvement, contemporary heart failure care can be successfully translated into rural practice. (11)

Limitations: The strengths of this study include its prospective design, inclusion of treatment-naïve patients, and real-world rural representation. Limitations include its non-randomised design, modest sample size, and short follow-up duration. The absence of mechanical dyssynchrony parameters or detailed QRS morphology analysis limits further stratification of wide-QRS phenotypes.

Among newly diagnosed patients with LV systolic dysfunction, early and comprehensive GDMT produced significant improvement in functional and structural outcomes in both narrow and wide QRS groups. However, patients with wide QRS duration especially those with LBBB showed numerically less reverse remodelling and higher event rates despite similar therapy. These findings suggest that baseline QRS duration is an important modifier of GDMT response, and patients with wide QRS may require earlier consideration of device-based therapy alongside continued pharmacologic optimisation. Expanding GDMT delivery and structured follow-up in rural regions could substantially improve the national heart failure care landscape

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