Deleterious left ventricular remodeling routinely occurs after myocardial infarction (MI) and novel strategies to attenuate this phenomenon may prove valuable. Here, we describe the potential role of left ventricular (LV) peri-infarct pacing (delivered via biventricular pacemakers) to reduce post-MI remodeling. Regional wall stress in the infarcted area is predictive of remodeling and therefore represents a potential therapeutic target. Using an intrinsic property of pacing to reduce stress and work at the pacing site, there are animal data to suggest that long-term peri-infarct pacing can have a salutary effect on cardiac structure after MI. This concept was tested in a pilot human study, suggesting attenuation of ventricular dilation in post-MI patients treated with LV pacing compared with control. To further characterize this concept, a 110-patient, multicenter, randomized Prevention of Myocardial Enlargement and Dilatation post-Myocardial Infarction Study (MENDMI) has completed enrollment. Inclusion criteria included anterior MI, QRS < 120 ms, ejection fraction <or= 35%, CPK > 2,000, and wall motion abnormalities in at least five of 16 segments. MENDMI will help to determine whether chronic application of peri-infarct pacing provides structural and clinical benefits and will help in the design of further investigations to modify postinfarction ventricular remodeling.