IV. NEW FRONTIERS
A ray of hope has been generated by the work of Dr. M. H. Yacoub, who describes a novel strategy: a com¬bination of surgery and physiologic hypertrophy. The surgical process involves implantation of a left ventricular assist device and medical therapy with a drug, clenbuterol, a beta-2-agonist which induces reverse remodeling of the left ventricular myocardium and subsequent physiologic myocardial hypertrophy. This strategy improves left ven¬tricular contractility and ejection fraction sufficiently to allow explantation of the assist device (the Harefield protocol).
The small study of 19 patients resulted in 4 deaths. Among the 15 patients, 11 had sufficient recovery from
heart failure and had the left ventricular assist device explanted. Ten patients are alive at two and a half years follow up and showed excellent exercise capacity with remarkable improvement in ejection fraction and lead a relatively normal life.
Clenbuterol changes phenotype, genotype, and gene expression in myocytes; in animal studies the agent has been shown to improve pressure volume relationships, increase myocyte size, and enhance organization of myofibrils. Dr. Yacoub indicates that not all hypertrophy is maladaptive. The strategy is to rest the heart and make it as small as possible, then activate the genes associated with the fetal heart and make it mature again. Once the heart is atrophied it is appropriate to enhance physiologic hypertrophy with clenbuterol or similar agents, which leads to improved left ventricle function.