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Research Article: The C-reactive protein–albumin–lymphocyte index is associated with ventricular functional improvement and long-term outcomes after cardiac resynchronization therapy

Date Published: 2026-09-18

Abstract:
Inflammation, malnutrition, and immune dysfunction are closely linked to adverse outcomes in heart failure. The C-reactive protein–albumin–lymphocyte (CALLY) index integrates these biological domains, but its clinical relevance in patients undergoing cardiac resynchronization therapy (CRT) remains insufficiently characterized. We investigated whether CALLY is associated with left ventricular ejection fraction (LVEF) improvement and long-term clinical outcomes after CRT. In this multicenter retrospective cohort study, 213 consecutive patients who underwent CRT implantation between January 2015 and August 2025 were enrolled. The CALLY index was analyzed primarily as a log2-transformed continuous variable. The primary endpoint was time to first major adverse cardiovascular event (MACE), defined as all-cause mortality, heart transplantation, left ventricular assist device implantation, or heart-failure rehospitalization. Echocardiographic response was evaluated in 191 patients with follow-up imaging. Multivariable Cox and linear regression were used to assess associations with MACE and absolute change in LVEF, respectively. Sensitivity analyses addressed baseline LVEF, pacemaker upgrade status, calendar era, and alternative handling of CR p values at the lower detection limit. During a median follow-up of 18?months, 56 patients (26.3%) experienced MACE, including 48 heart-failure rehospitalizations and 8 deaths. Each doubling of baseline CALLY was associated with a lower hazard of MACE (hazard ratio, 0.751; 95% confidence interval, 0.664–0.850; p <?0.001) and greater LVEF improvement ( ? =?0.949 percentage points; 95% confidence interval, 0.313–1.586; p =?0.004). Addition of CALLY to a parsimonious clinical model increased the Harrell C-index from 0.672 to 0.738; the optimism-corrected C-index was 0.705. Time-dependent AUCs were 0.773 and 0.759 at 12 and 18?months, respectively. The findings remained consistent after restriction to patients with LVEF ?35%, exclusion of pacemaker-upgrade patients, adjustment or stratification by calendar era, and alternative approaches to CR p values at the lower detection limit, with no significant interactions by baseline LVEF or calendar era. A higher baseline CALLY index was independently associated with greater LVEF improvement and a lower hazard of adverse cardiovascular outcomes after CRT. CALLY may provide complementary prognostic information in patients undergoing CRT, although prospective external validation is required before clinical implementation.

Introduction:
Inflammation, malnutrition, and immune dysfunction are closely linked to adverse outcomes in heart failure. The C-reactive protein–albumin–lymphocyte (CALLY) index integrates these biological domains, but its clinical relevance in patients undergoing cardiac resynchronization therapy (CRT) remains insufficiently characterized. We investigated whether CALLY is associated with left ventricular ejection fraction (LVEF) improvement and long-term clinical outcomes after CRT.

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