Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Fourteen-year-old boy with decreased appetite and pedal swelling.

CLINICAL INTRODUCTION: A 14-year-old boy presented with history of decreased appetite and bilateral swelling of feet for 6 months. He did not give any associated history of orthopnoea or paroxysmal nocturnal dyspnoea. He was born by a normal delivery after a non-consanguineous marriage. He had an unremarkable birth and childhood health history. There was no family history of significant cardiovascular illness or sudden death. Clinical examination showed an average built boy with elevated jugular venous pressure with prominent v wave and bilateral pitting pedal oedema. Cardiovascular examination showed normal first (S1) and second (S2) heart sounds and a short early systolic murmur over tricuspid region. Other systems examination was remarkable for soft tender hepatomegaly.ECG showed sinus rhythm with tall, peaked p waves. Chest X-ray revealed enlargement along the right cardiac border. Transthoracic echocardiographic images are shown in figure 1A (apical four-chamber view) and figure 1B (tricuspid inflow Doppler). There was no colour Doppler evidence of interatrial shunt.heartjnl;105/5/405/F1F1F1Figure 1(A) Transthoracic echocardiographic apical four-chamber view. (B) Tricuspid inflow continuous wave Doppler image. QUESTION: What is the most likely diagnosis of his condition? Endomyocardial fibrosis (EMF)Ebstein's anomalyArrhythmogenic right ventricular dysplasia (ARVD)Idiopathic dilatation of right atriumRestrictive cardiomyopathy.