Preventing Sudden Cardiac Death

European Coordinator:
  • Denis ESCANDE († 13 November 2006)/Jean Jacques SCHOTT, INSERM U533, Nantes (France)
North American Coordinator:
  • Dan RODEN, Vanderbilt University, Nashville (USA)
  • Eduardo MARBAN, Cedars-Sinai Heart Institute, Los Angeles (USA)
  • Robert J. MYERBURG, University of Miami (USA)
  • Peter SPOONER, Johns Hopkins University, Baltimore (USA)
  • Arthur WILDE, University of Amsterdam (The Netherlands)

Sudden cardiac death (SCD) due to coronary disease continues to be the single most important cause of death in the adult population of the industrialized world. We now understand that ventricular fibrillation (VF), a disorganized electrical activity of the heart associated with a failure to pump blood, is a significant underlying cause of SCD. Some patients, particularly those with established disease in the coronary arteries, are known to be at risk for SCD. Medications which can help to control rhythm, and devices that deliver an electric shock in order to convert malignant changes in rhythm, are effective and available therapies for these patients. For a significant proportion of people, however, the first sign of cardiac disease is SCD. The transatlantic network proposed here is organized around the following questions: Is there any way to predict who is at risk for SCD? If in the general population people at risk for SCD can be identified, is there any way to prevent SCD?

It appears that there is a genetic predisposition to SCD. Drs. Roden and Escande hypothesize that the mechanism involves the constitution of the cardiac electrical conduction system. Particularly implicated are the determinants of current across the cell membrane such as the function of the sodium channel SCN5A, and the regulation of intracellular calcium. Variations at this cellular level, which arise as a result of differences in gene expression, may increase the risk for SCD. In particular, in a population at increased risk for SCD, fatal arrhythmias can develop in the setting of various triggers, such as medications, heart failure, or heart attack. The investigators propose to identify the variations in the population at the level of the gene and its function, and to compare function across different high risk groups. The goal is to generate what is essentially a genetic risk profile for SCD, which would allow a calculation of a patient’s risk based on a genetic test.

The Fondation Leducq grant will enable a close collaboration between American and European investigators, with the exchange of personnel, and access to well defined patient populations on both sides of the Atlantic.