How excess fat affects cardiac electrophysiology: preclinical obesity, clinical obesity with cardiac arrhythmias and ECG features

Background Obesity has been associated with increased risk of arrhythmias. However, current BMI-based diagnostic paradigm is unable to capture the complexity of obesity. The Lancet Diabetes & Endocrinology Commission has recently proposed a novel obesity classification framework. The effects of different obesity stages on arrhythmias remain unknown. Purpose To compare the risk of arrhythmias and ECG features among individuals with different obesity status. Methods This study analyzed data from UK Biobank participants with available data for obesity classification and without prior arrhythmias. Participants were stratified into non-obesity, preclinical obesity, and clinical obesity groups using The Lancet definitions. The co-primary outcomes were new-onset any arrhythmias, supraventricular arrhythmias (SVA), bradyarrhythmias, and ventricular arrhythmias (VA). Individual components of the primary outcomes were analyzed as secondary endpoints. Multivariable Cox models were applied to evaluate the associations between obesity status with arrhythmias. Results This study included 428562 participants, with 157787 classified as non-obesity, 86400 as preclinical obesity, and 184375 as clinical obesity. Over a median follow-up of 14.6 years, compared to non-obesity, preclinical obesity was associated with increased risk of any arrhythmias (adjusted HR 1.06, P<0.001), SVA (aHR 1.09, P<0.001), atrial fibrillation (aHR 1.10, P<0.001), and cardiac block (aHR 1.08, P<0.001) (Figure 1). Compared to non-obesity, clinical obesity significantly increased the risk of any arrhythmias (aHR 1.28, P<0.001), SVA (aHR 1.31, P<0.001), bradyarrhythmias (aHR 1.24, P<0.001), VA (aHR 1.16, P<0.001), AF (aHR 1.34, P<0.001), cardiac block (aHR 1.28, P<0.001), pacemaker insertion (aHR 1.18, P<0.001), ventricular tachycardia (aHR 1.22, P<0.001), implantable cardioverter defibrillator insertion (aHR 1.44, P<0.001), and cardiac arrest (aHR 1.16, P=0.009) (Figure 1). When compared to preclinical obesity, clinical obesity was associated with significantly higher risk of any arrhythmias, SVA, bradyarrhythmias, VA, AF, supraventricular tachycardia, cardiac block, sinus node dysfunction, pacemaker insertion, premature ventricular beats, VT, and cardiac arrest (all p<0.05) (Figure 2). Additionally, clinical obesity exhibited significant correlations with ECG alterations, including prolonged P-wave duration, PR interval, QTc interval, and QRS duration, accompanied by shortened RR interval, elevated ventricular rate, significant altered P-wave axis and R-wave axis (all P<0.05), compared to preclinical obesity (Figure 2). Conclusions Both preclinical and clinical obesity confer elevated arrhythmia risks, with clinical obesity demonstrating particularly pronounced associations across atrial, ventricular, and conduction system arrhythmias and presenting with significant proarrhythmic electrophysiological shifts.Figure 1 Figure 2