The interplay between chronic kidney disease, sudden cardiac death, and ventricular arrhythmias

Chronic kidney disease patients face an increased risk of cardiovascular disease mortality, and the risk of sudden cardiac death increases as kidney function declines. Risk factors for sudden cardiac death are poorly understood and understudied among chronic kidney disease patients. In the general population, coronary heart disease-associated risk factors are the most important determinants of sudden cardiac death risk, but among chronic kidney disease patients, there is evidence that these factors play a much smaller role. Complex relationships between chronic kidney disease-specific risk factors, structural heart disease, and arrhythmic triggers contribute to the high risk of sudden cardiac death and ventricular arrhythmias, and modulate the effectiveness of available therapies. This review examines recent data on the epidemiology, pathophysiology, and mechanisms of sudden cardiac death among patients with chronic kidney disease and examines current evidence regarding the use of pharmacologic and device-based therapies for management of sudden cardiac death risk. those who are maintained on hemodialysis, are exposed to a wide array of potential arrhythmic triggers. The finding that SCD occurs most frequently on hemodialysis days, especially on the first hemodialysis day after the long dialysis-free weekend for patients on a thrice-weekly treatment schedule, suggests that factors related to the hemodialysis procedure trigger fatal arrhythmias. (25, 43) Observational studies have identified both hyperkalemia and hypokalemia (44), exposure to low potassium and calcium dialysate (12, 44), and rapid ultrafiltration rate (45-47) with an increased risk of cardiovascular mortality and SCD. Over the course of a dialysis treatment, electrocardiogram (ECG) measures related to ventricular repolarization such as QT interval dispersion and QT interval prolongation worsen. (48) These ECG changes have been shown to be influenced by exposure to low calcium and potassium during hemodialysis, and have been independently associated with cardiovascular mortality in dialysis patients, although they are yet to be specifically linked to a SCD risk. (49) These findings suggest that perturbations in potassium and calcium are critical risk factors for SCD in dialysis patients; among patients with moderate stage 3-4 CKD, no study to date has examined the role of serum electrolyte levels in SCD risk. (25) If similar relationships are seen among moderate level throughout treatment to reduce large potassium shifts, has been shown to reduce the incidence of premature ventricular contractions during dialysis. (78) Avoidance of low calcium dialysate and reduction in the serum-dialysate calcium gradient has also been associated with a significant reduction in the risk of SCD. (79) Making efforts to reduce interdialytic weight gain and ultrafiltration rates is supported by consistent associations between higher ultrafiltration rates and cardiac events. (47) Evolving data also supports the reduction of dialysate to serum sodium gradient as a means to reduce weight gain and large ultrafiltration targets. (80) There is renewed interest in dialysate cooling as a means to reduce intradialytic hypotension and repetitive ischemic myocardial injury. A recent study suggests that reducing dialysate temperature to two degrees Celsius below body temperature reduces the occurrence of dialysis induced myocardial wall motion abnormalities, which have been associated with an increased risk of cardiac death. (81) Reductions in left ventricular mass that were observed in clinical trials of frequent and long slow hemodialysis are cause for optimism that these modalities may