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 × 108 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 108 (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.

Nonresponders to clopidogrel therapy among Indian patients undergoing elective/adhoc angioplasty.

BACKGROUND: Clopidogrel has become the standard antiplatelet drug along with aspirin in patients undergoing coronary angioplasty; however, data regarding the nonresponse rate to clopidogrel therapy in Indian patients are limited. METHODS AND RESULTS: Platelet aggregation was measured at baseline and 2 and 24 hours post administration of bolus dose of 300 mg clopidogrel, followed by 75 mg once daily in patients undergoing elective or adhoc coronary angioplasty. Baseline platelet aggregation with 2.5 and 10 micromol/L ADP was 27.91 +/- 20.9% and 53.45 +/- 22.44%. Platelet aggregation at 2 hours and 24 hours with 2.5 micromol/L of ADP was 19.65 +/- 16.9% and 10.44 +/- 11.9%. The corresponding values with 10 micromol of ADP were 48.81 +/- 25.3% and 27.04 +/- 22.4%. Platelet aggregation was maximally inhibited at 24 hours with both 2.5 and 10 micromol/L of ADP. Marked interpatient variability in platelet aggregation in response to clopidogrel administration was observed and varied from -43 to 65%, -32 to 85% with 2.5 micromol/L at 2 hours and 24 hours and -65 to 53%, -35 to 97% with 10 micromol/L ADP at 2 hours and 24 hours. Nonresponse rate 2 hours after clopidogrel administration was 47.7%, and decreased to 29.2% at 24 hours post drug administration. CONCLUSION: Clopidogrel nonresponse is prevalent among Indian patients, and there is wide interpatient variability in platelet inhibition among individual patients. However, the clinical implications of these findings need to be substantiated in larger studies with clinical end points.

Echocardiographic evaluation of ventricular dyssynchrony in patients with left bundle branch block.

OBJECTIVE: To test whether patients with left bundle branch block (LBBB) and low ejection fraction (EF) have greater dyssynchrony than those with LBBB and normal LV systolic function. METHODS: From a group of patients with LBBB, 38 patients with low EF (<50%) and 31 with normal LV systolic function (EF > or = 50%), all comparable in age and sex underwent standard Doppler echo, ECG and tissue Doppler imaging (TDI). The precontraction time (PCTm) was calculated as an index of myocardial systolic activation in 5 different basal myocardial segments (LV anterior, inferior, septal, lateral walls and RV lateral wall). Intraventricular systolic dyssynchrony was analyzed by difference of PCTm in different LV myocardial segments. Interventricular activation delay was calculated by the difference of PCTm between the most delayed LV segment and RV lateral wall. RESULTS: Patients with low LV EF showed increased QRS duration, intraventricular delay (p = 0.03) and interventricular dyssynchrony (p = 0.006). Patients with normal EF also had evidence of some dyssynchrony. The LV basal lateral segment was significantly delayed when compared to all other segments in the low EF group. The PCTm was greater for those with low EF when compared to the normal EF group. CONCLUSIONS: All patients with LBBB on baseline ECG had some degree of cardiac dyssynchrony; those with lower EF had more dyssynchrony. TDI is an effective non-invasive technique for assessing the severity of regional delay in activation of ventricular walls in patients with LBBB.

Utility of N-terminal pro-brain natriuretic peptide for the diagnosis of heart failure.

BACKGROUND: The goal of this study was to evaluate the utility of plasma N-terminal pro-brain natriuretic peptide for the diagnosis of heart failure in patients presenting with shortness of breath. METHODS AND RESULTS: We measured plasma levels of N-terminal pro-brain natriuretic peptide in 119 patients presenting with shortness of breath. The patients were divided into two groups based on the Framingham criteria and echocardiographic results--those with heart failure and those not in heart failure. Plasma levels of N-terminal pro-brain natriuretic peptide were compared in the two groups. The mean N-terminal pro-brain natriuretic peptide concentration in patients with heart failure (n=73) was higher than that in those not in heart failure (389+/-148 fmol/ml v. 142+/-54 fmol/ml, p<0.001). N-terminal pro-brain natriuretic peptide values increased significantly as the functional severity of heart failure increased (p<0.001). The mean N-terminal pro-brain natriuretic peptide levels were 261+/-34 fmol/ml for patients in New York Heart Association functional class I, 300+/-161 fmol/ml for patients in New York Heart Association functional class II, 427+/-103 fmol/ml for patients in New York Heart Association functional class III and 528+/-170 fmol/ml for patients in New York Heart Association functional class IV. Using a cut-off value of 200 fmol/ml, the sensitivity of N-terminal pro-brain natriuretic peptide was 97%, specificity was 89% and accuracy for differentiating heart failure from other causes of shortness of breath was 93%. CONCLUSIONS: Our results suggest that N-terminal pro-brain natriuretic peptide can be reliably used for the diagnosis of heart failure in an outpatient setting, and this will improve the ability of clinicians to differentiate patients with shortness of breath due to heart failure from those with other causes of shortness of breath.