Obesity paradox in patients with reduced ejection fraction eligible for device implantation - an observational study

Patients with obesity have an overall higher cardiovascular risk, at the same time obesity could be associated with a better outcome in a certain subgroup of patients, a phenomenon known as the obesity paradox. Data are scarce in candidates for cardiac resynchronization therapy (CRT). We aimed to investigate the association between body mass index (BMI) and all-cause mortality in patients eligible for CRT.

Altogether 1,585 patients underwent cardiac resynchronization therapy between 2000-2020 and were categorized based on their BMI, 459 (29%) patients with normal weight (BMI < 25 kg/m2), 641 (40%) patients with overweight (BMI 25- < 30 kg/m2) and 485 (31%) with obesity (BMI ≥ 30 kg/m2). The primary endpoint was all-cause mortality, heart transplantation, and left ventricular assist device implantation. We assessed periprocedural complications and 6-month echocardiographic response.

Normal-weight patients were older compared to patients with overweight or obesity (70 years vs. 69 years vs. 68 years; P ‹0.001), respectively. Sex distribution, ischaemic aetiology, and CRT-D implantation rates were similar in the three patient groups. Diabetes mellitus (BMI < 25 kg/m² 26% vs. BMI 25- < 30 kg/m² 37% vs. BMI ≥ 30 kg/m² 48%; P ‹0.001) and hypertension (BMI < 25 kg/m² 71% vs. BMI 25- < 30 kg/m² 74% vs. BMI ≥ 30 kg/m² 82%; P ‹0.001) were more frequent in patients with overweight and obesity. During the mean follow-up time of 5.1 years, 973 (61%) reached the primary endpoint, 66% in the BMI < 25 kg/m² group, 61% in the BMI 25- < 30 kg/m² group and 58% in the BMI ≥ 30 kg/m² group (log-rank P‹0.05). Patients with obesity showed mortality benefit over normal-weight patients (HR 0.78; 95%CI 0.66-0.92; P = 0.003). The obesity paradox was present in patients free from diabetes, atrial fibrillation, and ischemic events. Periprocedural complication rates did not differ in the three groups (BMI < 25 kg/m² 25% vs. BMI 25- < 30 kg/m² 28% vs. BMI ≥ 30 kg/m² 26%; P = 0.48). Left ventricular ejection fraction improved significantly in all patient groups (BMI < 25 kg/m² median $$ -LVEF 7% vs. BMI 25- < 30 kg/m² median $$ -LVEF 7.5% vs. BMI ≥ 30 kg/m² median $$ -LVEF 6%; P < 0.0001) with a similar proportion of developing reverse remodeling (BMI < 25 kg/m² 58% vs. BMI 25- < 30 kg/m² 61% vs. BMI ≥ 30 kg/m² 57%; P = 0.48); P = 0.75).

The obesity paradox was present in our HF cohort at long-term, patients underwent CRT implantation with obesity and free of comorbidities showed mortality benefit compared to normal weight patients. Patients with obesity showed similar echocardiographic response and safety outcomes compared to normal weight patients.