The Knot That Binds Mitral Valve Prolapse and Sudden Cardiac Death.

S olving the puzzle that ties mitral valve prolapse (MVP) to sudden cardiac death necessarily means overcoming 2 central challenges: establishing a mechanistic association between a very common disorder (MVP) and a rare outcome (sudden cardiac death) and discerning the cause and effect of an increasing array of associated structural, electrocardio-graphic, and now pathological findings. In this issue of Circulation, Basso et al 1 demonstrate an important and possibly critical piece of this association: magnetic resonance imaging (MRI) evidence of an underlying arrhythmogenic substrate. Studying 2 distinct and complementary populations (young patients who died suddenly with MVP as the sole structural cardiac abnormality and a group of patients with MVP and complex ventricular arrhythmia) and suitable control groups, they report pathological and MRI findings that strongly suggest pathology in the region of the mitral valve apparatus that may explain a hitherto missing link between MVP and sudden cardiac death. A tenable assumption, given the widespread prevalence of MVP, is that, when sudden death occurs, the typically innocent valvular abnormality is a bystander with no pathogenic significance. However, researchers in this field have cyclically readdressed a putative link with a series of anecdotes and retrospective analyses. This would appear as futile an endeavor as trying to link gray hair to the risk of developing atypical atrial flutter! Except for the fact that the population of interest , as is the one studied by Basso et al, 1 is young and otherwise healthy and should not be dying suddenly. Given that MVP is so common, it seems likely that patients who develop malignant arrhythmia have a second, unrelated proarrhythmic factor that (although by itself may be relatively benign) creates a potentially fatal admixture of trigger and substrate. In a recent report, benign outflow tract ectopy was associated with malignant MVP syndrome. 2 Both entities (outflow tract ectopy and MVP) are common and independently benign but, with the potential for relative entrance block and nonsup-pressibility as a result of heterogeneous tissue at the semilunar valve and papillary muscle region, may have been the mutual second hit needed for malignant arrhythmia generation. Several other potential pathogenic risk factors with MVP have been explored in trying to explain why only a minority of patients have major arrhythmia. Bileaflet MVP was found in 70% of affected patients in the present study and was nearly universal in a prior report. 2 Complex ectopy, including nonsustained arrhythmia and …