Etiology-Related Differences in Left Ventricular Remodeling and Left Atrial Function in Patients with Heart Failure and Reduced Ejection Fraction Referred for ICD/CRT Implantation

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Abstract
Background: Heart failure with reduced ejection fraction (HFrEF) may be caused by various factors. The etiology of HFrEF may influence prognosis and further management. Objectives: In this study we aimed to assess differences between ischemic and non-ischemic etiology in the context of clinical features, hemodynamic evaluation, and left ventricular (LV) and left atrial (LA) remodeling in a selected cohort of patients referred for device implantation. Methods: This prospective single-center study included 86 patients with HFrEF in sinus rhythm, without a history of atrial fibrillation, referred for ICD or CRT implantation. All patients underwent comprehensive echocardiography, electrocardiography, impedance cardiography and laboratory testing. This was a cross-sectional analysis without clinical follow-up. The pre-specified question was whether the two etiological groups differed in LV remodeling and LA function. All regression analyses were exploratory. Guideline-directed medical therapy was recorded in all patients. Results: Among 86 patients, 58 had ischemic and 28 had non-ischemic HFrEF. Patients with ischemic etiology were older, had worse renal function, and had higher N-terminal pro–B-type natriuretic peptide levels. They also exhibited lower left ventricular mass index (LVMI), left atrial reservoir strain (LASr), left atrial emptying fraction (LAEF), and higher left atrial stiffness index (LASI). Among myocardial work parameters, only global wasted work (GWW) differed significantly, with higher values in the non-ischemic group. Patients with ischemic HFrEF also had a higher Heather index (HI) in impedance cardiography. The two groups did not differ in guideline-directed medical therapy. In univariable logistic regression, older age, lower LVMI, reduced LASr and LAEF, higher LASI, higher HI, and lower eGFR were associated with ischemic HFrEF etiology. In the multivariable model, older age, lower LVMI, and reduced LASr remained independently associated with ischemic HFrEF (area under the ROC curve 0.82). Conclusions: Patients with ischemic and non-ischemic HFrEF referred for device implantation differ in LV remodeling and LA function. The between-group differences were small in absolute terms, with widely overlapping distributions, and the study was not designed to test whether echocardiography can replace established methods of establishing HFrEF etiology. These exploratory findings are hypothesis-generating and require confirmation in larger, independent cohorts.

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