Skeletal Myoblast Transplantation in Ischemic Heart Failure

Abstract

Background-Skeletal myoblast (SM) transplantation (Tx) in a post-myocardial infarction (MI) scar experimentally improves left ventricular (LV) ejection fraction (EF). Short-term follow-up (FU) studies have suggested that a similar benefit could clinically occur despite an increased risk of LV arrhythmias. Methods and Results-We report the long-term FU of the first worldwide cohort of grafted patients (n ϭ9, 61.8Ϯ11.6 years, previous MI, EF Յ35%) operated on (autologous SM Tx and bypass surgery) in 2000 to 2001 and evaluated before Tx, at 1 month (M1) and at a median FU of 52 (18 to 58) months after Tx (37 patient-years). NYHA class improved from 2.5Ϯ0.5 to 1.8Ϯ0.4 at M1 (Pϭ0.004 versus baseline) and 1.7Ϯ0.5 at FU (Pϭnot significant versus M1; Pϭ0.0007 versus baseline). EF increased from 24.3Ϯ4% to 31Ϯ4.1% at M1 (ϩ28%, Pϭ0.001 versus baseline) and remained stable thereafter (28.7Ϯ8.1%, ϩ18% versus baseline). There were 5 hospitalizations for heart failure in 3 patients at 28.6Ϯ9.9 months, allowing implant in 2 patients with a resynchronization pacemaker. An automatic cardiac defibrillator (ACD) was implanted in 5 patients for nonsustained (n ϭ1) or sustained (n ϭ4) ventricular tachycardia at 12.2Ϯ18.6 (1 to 45) months. Despite a beta-blocker/amiodarone combination therapy, there were 14 appropriate shocks for 3 arrhythmic storms in 3 patients at 6, 7, and 18 months after ACD implantation. Conclusions-In this cohort of severe heart failure patients both clinical status and EF stably improve over time with a strikingly low incidence of hospitalizations for heart failure (0.13/patient-years) and the arrhythmic risk can be controlled by medical therapy and/or on-request ACD implantation.

Cell transplantation for cardiac regeneration: where do we stand?

“…[41][42][43][44][45][46][47] The first phase II, multicentre, double-blind, placebo-controlled, doseranging, randomised study using myoblast transplantation as an adjunct to CABG, the MAGIC trial, was recently stopped because of lack of efficacy. Preliminary results from this trial suggest a modest increase in ejection fraction, as assessed by nuclear imaging and a reduction in left ventricular volumes.…”

“…48 The final results of this trial have not yet been reported. Four of the phase I studies involved myoblast transplantation as an adjunct to CABG, 41,42,44,45 one involved endoventricular injections of myoblasts 46 and one study used a coronary sinus approach. 47 Generally, patients had signs of congestive heart failure class 2-3 (NYHA), with two-to three-vessel coronary disease and an ejection fraction ranging between 20 and 40%.…”

“…Although, in the first study by Menasche, five of nine patients 41 developed ventricular tachycardias (VT) after the procedure, the first results of the MAGIC trial did not show a higher incidence of adverse events in the treated group. 48 In most study protocols, implantable cardioverter defibrillators (ICDs) are now prophylactically implanted.…”

Curiosity Killed the Cat and Found New Myocytes

“…Researchers tried to force myocytes to divide using molecular maneuvers, 7,8 force neonatal myocytes to engraft into mature hearts, 9 and even force chimeric marriage between skeletal muscle and the heart in attempts to restore contractile function. 10,11 A lot of hearts were broken, but we were not doing a very good job of fixing them.…”

A Caveat Emptor for myocardial regeneration: Mechanical without electrical recovery will not suffice

“…Both in vitro studies [7] and human trials [8] have shown the propensity of SKMBs to induce arrhythmias while exerting mechanical benefit. Further, preliminary in vivo studies in animals and humans have shown that MSCs also can be mechanically beneficial [9][10][11].…”