The risk of obesity and the association of body mass index on all-cause mortality after cardiac resynchronization therapy

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union. BACKGROUND: Overweight and obese people have a higher risk of acquiring heart failure, however these patients tend to have more favorable outcome, a phenomenon known as the obesity paradox. PURPOSE: We aimed to investigate the risk of obesity and the association of body mass index (BMI) on all-cause mortality in heart failure CRT patients at long-term. METHODS: We examined retrospectively 1585 patients undergoing CRT implantation at our clinic between 2000-2020 with their BMI available at baseline. Patients were sorted into three groups: normal weight (BMI ‹25), overweight (BMI 25-29.9) and obese (BMI≥30). The composite primary endpoint was all-cause mortality, heart transplantation or implantation of a left ventricular assist device. Time-to-event data was studied by log-rank and multivariate Cox regression analysis. We studied peri-procedural complication rates, and reverse remodeling, defined as a ≥15% relative increase in left ventricular ejection fraction (LVEF) within 6 months after CRT implantation. RESULTS: During our mean follow-up time of 5.1 years, 973 (61%) reached our primary endpoint, 302 (66%) in the BMI ‹25 group, 389 (61%) in the BMI 25-29.9 group and 282 (58%) in the BMI≥30 group. Obese patients showed mortality benefit over normal-weighed patients (HR 0.78; 95%CI 0.66-0.92; p=0.003), with only a trend in overweight patients over normal-weighed patients (HR 0.86; 95%CI 0.74-1.00; p=0.05). At multivariate analysis, BMI ‹25 patients showed a 19% higher risk of all-cause mortality compared to overweight and obese patients (HR 1.19; 95%CI 1.03-1.38; p=0.02) after adjusting for age, sex, NYHA class, diabetes, hypertension, myocardial infarction and atrial fibrillation. Obese and overweight patients were younger than normal-weighed patients (68yrs. vs. 69yrs. vs. 70 yrs.; p‹0.0001), similar sex distribution can be seen. Diabetes (BMI ‹25 48% vs. BMI 25-29.9 37% vs. BMI≥30 26%; p‹0.0001) and hypertension (BMI ‹25 82% vs. BMI 25-29.9 74% vs. BMI≥30 71%; p‹0.001) occurred more frequently in obese and overweight patients. Obese and overweight patients had a higher LVEF than in the normal weight group (30% vs. 28% vs. 27%; p‹0.001), respectively. Peri-procedural complication rates did not differ in the three groups. In all patient groups, a significant improvement in LVEF at 6 months was seen (BMI ‹25 ∆-EF 7%, BMI 25-29.9 ∆-EF 7.5%, and BMI ≥30 ∆-EF 6; p<0.001). No difference was seen in the proportion of developing reverse remodeling (BMI ‹25 58% vs. BMI 25-29.9 61% vs. BMI≥30 57%; p=0.75). CONCLUSIONS: Despite having more co-morbidities like diabetes or hypertension, obese patients showed mortality benefit over normal-weighed patients proving, that the obesity paradox was present in our CRT patient cohort at long-term. Peri-procedural complications did not occur more frequently in obese or overweight patients. Echocardiographic response did not vary, similar reverse remodeling was observed across the patient groups.