Novel Pharmaceutical Concepts in Cardiac Remodeling

By the term Cardiac Remodeling (REM) is defined as a process leading to left ventricular dilation and heart failure in response to various harmful stimulai, mainly an acute myocardial infarction (AMI).It has been estimated 30% of anterior and a lower percentage of inferior infarcts develop REM despite timely primary coronary intervention. The more widely used definition is a >20% increase in left ventricular end-diastolic (LVEDV), of end-systolic volume (LVESD). There is evidence that regression of REM, i.e reverse REM can occur. It is defined as a ≥10% decrease in left ventricular end-systolic volume (LVESV).

Therapeutically many medications are used acutely during primary intervention (cardioprotection) and chronically (cardiopreservation). Few have concrete benefits. The only drugs currently used in clinical practice are converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs), β-blockers, aldosterone inhibitors and statins. Erythropoietin has disappointed. Thyroid supplementation in small doses is effective in our studies. We have also used the neuroprotective drug rasagiline with good results. A main consideration is that experimentally used drugs are administered to healthy young animals with only one artery included.

Revascularization, volume reducing surgery and where applicable resynchronization can be of benefit. SERCA-2a transfer has disappointed in the CUPID 2 trial; stem cell administration is being tried, with variable although in the majority favorable results. Their exact mode of action remains undetermined. Thus REM remains a therapeutic problem in search of solution.