To study the long-term evolution, determinants, and clinical relevance of the conduction abnormalities after orthotopic heart transplantation, 87 patients, followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to the characteristics of their electrocardiograms compared with their initial electrocardiogram recorded at study entry. The first group consisted of 24 patients whose initial electrocardiogram was normal, and subsequent electrocardiograms remained normal throughout the study. The second group included 27 patients who developed electrocardiographic evidence of progressive conduction system damage. The third group comprised 36 patients whose initial electrocardiogram was abnormal and subsequent electrocardiograms remained unchanged during follow-up. Although the hemodynamic and echocardiographic evaluation of right and left ventricular function were initially similar among the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/- 14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and 3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in group 1 maintained their normal baseline indices. Incidence and progression of coronary artery disease, as well as frequency of rejection episodes, were comparable among the groups. Mortality was higher in the 2 groups with evidence of conduction defects. Sudden death associated with complete heart block (2 patients) or ventricular arrhythmias (3 patients) was exclusively confined to patients with evidence of progressive electrocardiogram abnormalities. We conclude that, following orthotopic heart transplantation, stable or progressive conduction system damage on the electrocardiogram is associated with left ventricular dysfunction and increased mortality. Sudden death is not uncommon among patients demonstrating worsening cardiac conduction and, in some cases, is related to the development of potentially preventable complete heart block.