Cardiac MRI measures as surrogate outcome for heart failure and atrial fibrillation: a Mendelian randomization analysis

Background drug development and disease prevention of heart failure (HF) and atrial fibrillation (AF) are impeded by a lack of robust early-stage surrogates. We determined to what extent cardiac magnetic resonance (CMR) measurements act as surrogates for the development of HF or AF in healthy individuals. Methods Genetic data was sourced on the association with 22 atrial and ventricular CMR measurements. Mendelian randomization was used to determine CMR associations with atrial fibrillation (AF), heart failure (HF), non-ischemic cardiomyopathy (CMP), and dilated cardiomyopathy (DCM). Additionally, for the CMR surrogates of AF and HF, we explored their association with non-cardiac traits. Results In total we found that 10 CMR measures were associated with the development of HF, 8 with development of non-ischemic CMP, 5 with DCM, and 11 with AF. Left-ventricular (LV) ejection fraction (EF), and LV end diastolic volume (EDV) were associated with all 4 cardiac outcomes. Increased LV-MVR (mass to volume ratio) affected HF (odds ratio (OR) 0.83, 95%CI 0.79; 0.88), DCM (OR 0.26, 95%CI 0.20; 0.34), non-ischemic CMP (OR 0.44 95%CI, 0.35; 0.57). We were able to identify 9 CMR surrogates for HF and AF (including LV-MVR, biventricular EDV, right-ventricular EF, and left-atrial maximum volume) which associated with non-cardiac traits such as blood pressure, cardioembolic stroke, diabetes, and late-onset Alzheimer’s disease. Conclusion CMR measurements may act as surrogate endpoints for the development of HF (including non-ischemic CMP and DCM) or AF. Additionally, we show that changes in cardiac function and structure measured through CMR, may affect diseases of other organs leading to diabetes and late-onset Alzheimer’s disease.