Background: Heart failure (HF) and diabetes mellitus promote atrial fibrillation (AF) and are associated with increased morbidity and mortality. Here, we aimed to study the relationship between these 2 common and intertwined diseases, and to explore the clinical utility of NT-proBNP in an unselected patient population with AF.

Methods: Patients with AF included in the present analysis were identified through search of electronic health records (between 07/2000 and 07/2019) of the Vienna General Hospital and Medical University of Vienna. The primary endpoint was all-cause death. We used cox regression models adjusted for age, sex, estimated glomerular filtration rate (eGFR), diabetes, HF, body mass index, prior myocardial infarction, hypertension, hypercholesterinemia, peripheral artery disease, and smoking.

Results: In total, 7,850 patients were included in the present analysis and followed over a median of 4.7 years. The patients’ median age was 70 years (interquartile range (IQR) 61 to 78), 3,110 (39.6%) were female, and the median eGFR was 65 ml/min/1.73m² (IQR 50 to 80). 1,393 (17.7%) patients had known diabetes and 1,493 (19.0%) patients had established HF; thereof 427 (5.4%) patients had both diabetes and HF.

NT-proBNP measurements were available in 4,218 patients. The median NT-proBNP levels were 743 pg/ml (IQR 220 to 1972), 1,376 pg/ml (IQR 532 to 1,972), 2,784 pg/ml (IQR 1,186 to 5,847), and 3,119 pg/ml (IQR 1,510 to 7,288) in patients without HF or diabetes, only diabetes, only HF, and those who had both, respectively.

Patients with either diabetes or HF had similar 5‑year Kaplan Meier event rates (diabetes: 41.6%, HF: 46.6%; p-logrank = 0.12), while patients with both, diabetes and HF, had significantly higher rates of death (59.7%, p‑logrank <0.001) [Fig A]. The magnitude of the relationship between death and diabetes (Adjusted (Adj.) hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30 to 1.63) and HF (Adj. HR 1.61, 95% CI 1.44 to 1.79), respectively, remained similar after adjustment for traditional clinical risk factors.

Moreover, there was a strong relationship between death and NT-proBNP (Adj. HR for 1-unit increase in standardized log-transformed biomarker 1.99, 95% CI 1.80 to 2.20) [Fig B]. NT-proBNP also showed good discriminatory performance (area under the curve (AUC) 0.78, 95% CI 0.77-0.80). The addition of NT-proBNP to the clinical covariates used for adjustment resulted in a significant improvement of the AUC (Δ=0.04, P=0.001).

Conclusion: AF patients with diabetes and/or HF are at very high risk of death. Patients with either diabetes or heart failure had similar event rates, while the combination of both diseases magnified the risk of death. Measurement of NT-proBNP may provide improved risk assessment in an unselected AF patient population.

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