Cardiac arrhythmias and sudden cardiac death – an increasing health care problem
Cardiac arrhythmias are associated with significant morbidity and mortality and constitute an increasing global health burden. Arrhythmias with fast and/or irregular rhythm originating in the atria, including atrial fibrillation are the most common. Common complications of atrial arrhythmias include heart failure and cerebral infarction (stroke). Ventricular arrhythmias such as ventricular tachycardia may degenerate into ventricular fibrillation, necessitating resuscitation and defibrillation to restore normal rhythm and prevent imminent sudden cardiac death. Unfortunately, ventricular fibrillation occurs out-of-hospital in the vast majority of cases, resulting in a dismal survival rate. Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all natural deaths, and up to 50% of all cardiovascular deaths.
In the overwhelming majority of cases, sudden cardiac death is caused by lethal cardiac arrhythmias in the setting of cardiovascular disease, including acute myocardial infarction and heart failure. However, in younger apparently healthy individuals, sudden cardiac death most often occurs secondary to rare inherited primary electrical diseases caused by mutations in genes encoding cardiac ion channels, such as Brugada syndrome and Long QT syndrome. Arrhythmogenic cardiomyopathy, an inherited condition caused by mutations in desmosomal genes, is also associated with arrhythmias, sudden cardiac death and heart failure in relatively young individuals. Despite decades of research, few anti-arrhythmic therapeutic options exist. It is furthermore difficult to predict which patient is more at risk for arrhythmias and sudden cardiac death, and who will benefit most from which therapy. Hence, development of efficient preventive and therapeutic strategies is essential but is as yet hampered by incomplete knowledge of disease mechanisms.
The Remme Research Group focuses on basic and translational studies into inherited disorders associated with cardiac arrhythmias and sudden cardiac death, including cardiac sodium channelopathies and arrhythmogenic cardiomyopathy, incorporating clinical and genetic findings with functional and mechanistic studies in transgenic models and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our work is furthermore aimed at identifying novel (genetic) determinants and pathways mediating cardiac electrophysiology and arrhythmia risk, as well as novel targets for the prevention and treatment of cardiac arrhythmias and sudden cardiac death.
Methods and techniques used in the Remme Research Group include in vivo (ECG, echocardiography, telemetry) and ex vivo cardiac electrophysiological phenotyping (Langendorff-perfusion, AV/HV-conduction assessment, arrhythmia inducibility, optical mapping), cardiomyocyte isolation, patch clamp analysis (action potential characteristics, ion channel function, macropatch), assessment of intracellular calcium homeostasis, histology, immunohistochemistry, and molecular biology.
Group Leader, PI