Left Ventricular Remodelling: A Problem in Search of Solutions

Abstract

Cardiac remodelling (REM) is a generally unfavourable process that leads to left ventricular dilation in response to cardiac injury, predominantly acute myocardial infarction (AMI). REM occurs in around 30 % of anterior infarcts despite timely primary coronary intervention and the use of drugs, i.e. angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs), beta-blockers, aldosterone inhibitors and statins. In order to diagnose REM, many imaging modalities (echocardiography, cardiac magnetic resonance, scintigraphy) are employed together with an increasing number of serum biomarkers including microRNAs. The most widely used definition of REM is a >20 % increase in left ventricular end-diastolic volume (LVEDV). There is also evidence that regression of REM can occur, i.e. reverse REM. The latter is defined as a ≥10 % decrease in left ventricular end-systolic volume (LVESV) and confers a more favourable outcome. Many therapeutic agents may be used during primary intervention and over the long term; however, few have demonstrated significant benefits. Revascularisation, anti-REM surgery and, where indicated, cardiac resynchronisation therapy can be of benefit. Gene therapy by sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA-2a) transfer has been investigated but data from the Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2) trial were disappointing. Progenitor cell therapy shows promise. In conclusion, therapy for REM remains inadequate.

Keywords: Acute myocardial infarction; left ventricular function; myocardial remodelling; myocyte biology.