CRT Efficacy in "Mid-Range" QRS Duration Among Asians Contrasted to Non-Asians, and Influence of Height.

OBJECTIVES: The purpose of this study was to test the hypotheses that cardiac resynchronization therapy (CRT) efficacy differed among Asians compared with non-Asian populations, differed between QRS duration (QRSd) ranges 120-149 and ≥150 ms, and was influenced by height in the multinational ADVANCE CRT trial. BACKGROUND: CRT guidelines, derived from trials among U.S./European patients, assign weaker recommendations to those with midrange QRSd (QRSd <150 ms). Patient height may modulate CRT efficacy. Together, these may affect CRT prescription and efficacy in Asia. METHODS: CRT response was assessed using the Clinical Composite Score 6 months postimplant (n = 934). Heart failure events and cardiac deaths were reported until 12 months. Asian and non-Asian patients were compared overall, by QRSd <150 ms (Asian n = 71 vs non-Asian n = 248), and QRSd ≥150 ms (Asian n = 180 vs non-Asian n = 435) and by height. RESULTS: Asians comprised 27% (251 of 934) of the primary study population. More Asians had QRSd ≥150 ms (72% [180 of 251] vs 64% [435 of 683] in non-Asian patients; P = 0.022). Overall CRT response was better in Asians vs non-Asians (Clinical Composite Score 85% vs 65%; P <0.001), and following QRSd dichotomization (QRSd <150 ms: 80% vs 59%; P <0.001; QRS ≥150 ms: 86% vs 69%; P < 0.001). HF events and cardiac deaths were fewer in Asians irrespective of QRSd (P < 0.001). Stepwise multivariable analysis indicated that in group QRSd <150 ms, nonischemic cardiomyopathy, number of other comorbidities (0-1 vs ≥4), and atrial fibrillation influenced CRT response. The trend favoring Asian race (OR: 1.46; 95% CI: 0.72-2.95) was eliminated (OR: 1.00; 95% CI: 0.47-2.11) when height or QRSd/height were included (QRSd/height P = 0.006; OR: 1.64; 95% CI: 1.15-2.35). In QRSd <150 ms, probability of CRT response diminished as height increased, but increased with QRSd/height, in both Asians and non-Asians. In QRSd ≥150 ms, height or QRSd/height had minimal effect in Asians or non-Asians. CONCLUSIONS: Height modulates CRT efficacy among patients with QRSd <150 ms and contributes to high probability of benefit from CRT among Asians. CRT should be encouraged among Asian patients with midrange QRSd. (Advance Cardiac Resynchronization Therapy [CRT] Registry; NCT01805154).

J Wave Syndrome: Clinical Diagnosis, Risk Stratification and Treatment.

J wave syndrome has emerged from a benign electrocardiographic abnormality to a proarrythmic state and a significant cause of idiopathic ventricular fibrillation responsible for sudden cardiac death. Electrical genesis, genetics and ionic mechanisms of J wave syndromes are active areas of research. Typically two of these viz., Early repolarization syndrome (ER) and Brugada syndrome (BrS) are fairly well characterized enabling correct diagnosis in most patients. In early repolarization syndrome, J waves are seen in inferior (2,3, avF) or lateral leads (V4, V5, V6), while in Brugada syndrome they are best seen in right precordial leads (V1-V3). The first part of repolarization of ventricular myocardium is governed by Ito current i.e., rapid outward potassium current. The proposed mechanism of ventricular fibrillation (VF) and ventricular tachycardia (VT) storms is faster Ito current in the epicardium than in the endocardium resulting in electrical gradient that forms the substrate for phase 2 re-entry. Prevention of Ito current with quinidine supports this mechanism. Morphological features of benign variety of J wave syndrome and malignant/ proarrythmic variety have now been fairly well characterized. J waves are very common in young, athletes and blacks; risk stratification for VF/sudden cardiac death (SCD) is not easy. Association of both ER syndrome and Brugada syndrome with other disease states like coronary artery disease is being reported frequently. Those with ECG abnormality as the only manifestation are difficult to manage. Certain ECG patterns are more proarrythmic. Individuals resuscitated from VF definitely need an implantable cardiac defibrillator (ICD) but in others there is no consensus regarding therapy. Role of electrophysiology study to provoke ventricular tachycardia or fibrillation is not yet well defined. Radiofrequency ablation of epicardial substrate in right ventricle in Brugada syndrome is reported and is also under critical evaluation. In this review we shall discuss some interesting historical features, epidemiology, electrocardiographic features, and ionic mechanisms on pathogenesis, clinical features, risk stratification and treatment issues in J wave syndromes. Brugada syndrome is not discussed in this review.

Early repolarisation and J wave syndromes.

J wave syndrome has emerged as a significant cause of Idiopathic ventricular fibrillation (IVF) responsible for sudden cardiac death. A large body of data is now available on genesis, genetics and ionic mechanisms of J wave syndromes. Two of these viz., Early repolarization syndrome (ER) and Brugada syndrome (BrS) are fairly well characterized enabling correct diagnosis in most patients. The first part of repolarization of ventricular myocardium is governed by Ito current i.e., rapid outward potassium current. The proposed mechanism of ventricular fibrillation (VF) and ventricular tachycardia (VT) storms is the faster Ito current in the epicardium than in the endocardium results in electrical gradient that forms the substrate for phase 2 reentry. Prevention of Ito current with quinidine supports this mechanism. Majority of ER patterns in young patients are benign. The key issue is to identify those at increased risk of sudden cardiac death. Association of both ER syndrome and Brugada syndrome with other disease states like coronary artery disease has also been reported. Individuals resuscitated from VF definitely need an implantable cardiac defibrillator (ICD) but in others there is no consensus regarding therapy. Role of electrophysiology study to provoke ventricular tachycardia or fibrillation is not yet well defined. Radiofrequency ablation of epicardial substrate in right ventricle in Brugada syndrome is also under critical evaluation. In this review we shall discuss historical features, epidemiology, electrocardiographic features, ionic pathogenesis, clinical features and current status of proposed treatment of ER and BrS.

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.