Sudden cardiac death (SCD) is an enormous public health problem with at least 300 000 deaths per year in the USA alone. The current state-of-the-art for treatment of SCD has several significant limitations. Because ventricular fibrillation (VF) quickly becomes irreversible, successful treatment requires immediate care. Even in metropolitan areas with excellent emergency medical services, survival of out-of-hospital cardiac arrest is extremely low. Attempts to prevent SCD with antiarrhythmic agents have had little success (and in some cases increased mortality). The development of implantable cardioverter-defibrillators (ICDs), which detect and treat VF almost instantly, has revolutionised the treatment of SCD. However, to be effective these devices must be implanted before cardiac arrest. This is the source of one of the major dilemmas in current SCD management: How to identify SCD victims before their first episode.

SCD is defined as unexpected, non-traumatic death within minutes of the onset of symptoms. Recordings obtained during spontaneous episodes of SCD (Holter, telemetry, etc) reveal that SCD results from ventricular arrhythmias in approximately 85% of cases (either primary VF or brief ventricular tachycardia (VT) degenerating to VF).¹ Table 1⇓ lists the main causes of SCD.

Rational strategies for prediction, prevention, and treatment of SCD require an understanding of the mechanisms responsible for the initiation and maintenance of ventricular fibrillation. Many risk stratification tests and medical treatment regimens, however, have been predicated on the physiology of ventricular tachycardia. While there is clear overlap between VT and VF physiology, their mechanisms are not identical. The lack of specificity in testing and lack of efficacy in treatment stem in part from their predication on VT rather than VF physiology. There are ample articles detailing clinical studies of prediction, prevention, and treatment of SCD. Rather than recreate an exhaustive review of such …