Mapping and ablation of left atrial roof-dependent tachycardias using an ultra-high resolution mapping system.

BACKGROUND: Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system. METHODS: This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems. RESULTS: Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures. CONCLUSIONS: The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.

The P wave morphology in lead V7 on the synthesized 18-lead ECG is a useful parameter for identifying arrhythmias originating from the right inferior pulmonary vein.

Atrial tachyarrhythmias often originate from the superior vena cava (SVC), and right superior (RSPV) and inferior pulmonary veins (RIPV). However, a precise differentiation of those origins is challenging using the standard 12-lead electrocardiogram (ECG) P-wave morphology due to the anatomical proximity. The recently developed synthesized 18-lead ECG provides virtual waveforms of the right-sided chest and back leads. This study evaluated the utility of the synthesized 18-lead ECG to differentiate atrial arrhythmias originating from 3 adjacent structures. Synthesized 18-lead ECGs were obtained during SVC-, RSPV-, and RIPV-pacing in 20 patients with lone paroxysmal atrial fibrillation to develop an algorithm. The P-wave morphologies were classified into 4 patterns: positive, negative, biphasic, and isoelectric. Subsequently, the algorithm's accuracy was validated prospectively in another 40 patients. In retrospective analyses, isoelectric P-waves in synthesized V7 distinguished RIPV-pacing from the others (sensitivity = 81%, specificity = 92%) (first criteria). The P wave morphologies in Leads II (sensitivity = 83%, specificity = 94%) and V1 (sensitivity = 84%, specificity = 80%) distinguished SVC- and RSPV-pacing (second criteria). In a prospective evaluation, the sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and accuracy of the first criteria for identifying RIPV-pacing was 97%, 90%, 78%, 99%, and 92%, respectively. The sensitivity, specificity, RPV, NPV, and accuracy of the second criteria (amplitudes > 1 mV in lead II or biphasic P-waves in lead V1) for discriminating SVC- and RSPV-pacing was 66%, 95%, 98%, 50%, and 74%, respectively. The P wave morphology pattern in lead V7 in synthesized 18-lead ECGs is useful for differentiating RIPV origins from RSPV/SVC origins.

Different effects of calcium channel blockers on matrix metalloproteinase-2 expression in cultured rat cardiac fibroblasts.

The cardiac effects of calcium channel blockers (CCBs) related to cardiac remodeling are inconsistent. Matrix metalloproteinases (MMPs) contribute to tissue remodeling. Cardiac fibroblasts play an important role in the regulation of collagen degradation by MMPs. Using gelatin zymography, Western blotting, Griess reagent, and a calcium kit-fluo 3, we investigated the effects of nifedipine, verapamil, diltiazem, and amlodipine on MMP-2 expression and further elucidate the mechanisms in cultured rat cardiac fibroblasts. Nifedipine increased and amlodipine decreased the expression of MMP-2; however, neither verapamil nor diltiazem altered MMP-2 expression. Nifedipine also increased nitrite production, and this increase was blunted by a nitric oxide (NO) synthases inhibitor (L-NAME). Nifedipine-induced MMP-2 expression was also blunted by L-NAME. An NO donor (sodium nitroprusside) induced MMP-2 expression. Data indicated that nifedipine might increase MMP-2 expression through a possible NO-dependent pathway. Amlodipine had no influence on nitrite production. The amlodipine-induced decrease of MMP-2 expression was abolished by two protein tyrosine kinase inhibitors, genistein and herbimycin A, indicating that amlodipine might decrease MMP-2 expression through a possible protein tyrosine kinase pathway. None of the four CCBs could alter the fluoscence intensity of fluo 3, indicating that the effects of CCBs on MMP-2 expression were independent of the variation in intracellular C2+ concentration. Our findings revealed that different CCBs exerted different effects on MMP-2 expression in cardiac fibroblasts.

Effects of magnesium on matrix metalloproteinase-2 production in cultured rat cardiac fibroblasts.

The precise correlation between magnesium and cardiac disease remains to be established. Matrix metalloproteinases (MMPs) are important in cardiac disease such as heart failure. Cardiac fibroblasts are the most abundant cell type in the heart and play an important role in the regulation of collagen degradation by MMPs. To assess the association between magnesium and MMPs, we examined the effects of different extracellular magnesium concentrations (0-3.0 mmol/L) on MMP-2 production in cultured rat cardiac fibroblasts. Using gelatin zymography and western blotting, we found that magnesium reduced MMP-2 production dose-dependently, and this effect was inhibited by the tyrosine kinase inhibitors, genistein or herbimycin A. The results of this study indicated that the beneficial effect of magnesium supplementation on the cardiac disease may be due, at least in part, to the inhibitory effect of magnesium on production of MMPs in cardiac fibroblasts, which appears to be mediated by a protein tyrosine phosphorylation related signal transduction pathway.