Low Serum Magnesium is Associated with Increased Mortality and Cardiac Allograft Vasculopathy Following Heart Transplantation

Abstract

Purpose Hypomagnesemia is commonly observed in heart transplant (HT) recipients treated with calcineurin inhibitors. Low serum magnesium (s-Mg) is associated with inflammation and disturbances in the regulation of vascular tone and endothelial function and has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, atrial and ventricular arrhythmias and sudden cardiac death. We therefore investigated the association between s-Mg and HT outcomes. Methods Between 2002 and 2017 we assessed 150 HT patients for s-Mg levels. In accordance with the median value of all s-Mg levels recorded during the first 3 months post-HT, patients were divided into high (n=68) and low (n=82) s-Mg groups. Endpoints included survival, freedom from cardiac allograft vasculopathy (CAV), freedom from any-treated rejection (ATR) and non-fatal major adverse cardiac events (NF-MACE). Results Mean s-Mg was 2.0±0.3mg/dL vs 1.6±0.1 mg/dL for the high and low s-Mg groups, respectively (p<0.001). Baseline patient and donor clinical and demographic characteristics were similar for the two groups. Kaplan-Meier survival analysis showed that at 15 years after HT survival was higher in the high s-Mg group than in the low s-Mg group (82 vs 38%, log-rank p=0.013, Figure). Similarly, 15-year freedom from CAV was significantly higher in the high vs low s-Mg group (82 vs 42%, log-rank p<0.001, Figure). There were no significant differences in freedom from NF-MACE or ATR between the two groups. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant >3-fold increased risk of mortality and >4-fold increased risk of CAV (95% CI 1.3-11.8, p=0.02; 95% CI 1.6-15.1, p=0.01 respectively). Conclusion Low post-HT s-Mg is independently associated with increased mortality and CAV in HT patients. Larger prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation. Hypomagnesemia is commonly observed in heart transplant (HT) recipients treated with calcineurin inhibitors. Low serum magnesium (s-Mg) is associated with inflammation and disturbances in the regulation of vascular tone and endothelial function and has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, atrial and ventricular arrhythmias and sudden cardiac death. We therefore investigated the association between s-Mg and HT outcomes. Between 2002 and 2017 we assessed 150 HT patients for s-Mg levels. In accordance with the median value of all s-Mg levels recorded during the first 3 months post-HT, patients were divided into high (n=68) and low (n=82) s-Mg groups. Endpoints included survival, freedom from cardiac allograft vasculopathy (CAV), freedom from any-treated rejection (ATR) and non-fatal major adverse cardiac events (NF-MACE). Mean s-Mg was 2.0±0.3mg/dL vs 1.6±0.1 mg/dL for the high and low s-Mg groups, respectively (p<0.001). Baseline patient and donor clinical and demographic characteristics were similar for the two groups. Kaplan-Meier survival analysis showed that at 15 years after HT survival was higher in the high s-Mg group than in the low s-Mg group (82 vs 38%, log-rank p=0.013, Figure). Similarly, 15-year freedom from CAV was significantly higher in the high vs low s-Mg group (82 vs 42%, log-rank p<0.001, Figure). There were no significant differences in freedom from NF-MACE or ATR between the two groups. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant >3-fold increased risk of mortality and >4-fold increased risk of CAV (95% CI 1.3-11.8, p=0.02; 95% CI 1.6-15.1, p=0.01 respectively). Low post-HT s-Mg is independently associated with increased mortality and CAV in HT patients. Larger prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.