Upper turnover portion of the reentry circuit for typical and reverse typical atrial flutter.

BACKGROUND: The posteromedial right atrium (PMRA) forms a block line during typical atrial flutter (AFL). However, whether upper turnover portion exists at the anterior or posterior superior vena cava (SVC) has not been determined. METHODS: We performed right atrial mapping during AFL in 20 patients (typical AFL, n = 17; reverse typical AFL, n = 3) using an electroanatomical mapping system. RESULTS: Mean AFL cycle length was 224 +/- 20 ms and mean number of mapping points was 140 +/- 27. PMRA formed a block line during both typical and reverse AFL in all patients. However, in 16 of 17 patients mapped with typical AFL, PMRA did not extend superiorly to the orifice of the SVC and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. In the remaining patient mapped with typical AFL, a double potential was recorded along the PMRA continuously between the orifices of the inferior vena cava (IVC) and SVC. In the three patients mapped with reverse typical AFL, a posterior barrier was detected from IVC to the upper limit of the PMRA and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. Mean length from IVC to upper limit of the PMRA was 81 +/- 8% of the length from IVC to SVC. CONCLUSIONS: PMRA forms a functional block line during both typical and reverse typical AFL. The upper turnover portion of reentry circuit for AFL was observed between the upper limit of the PMRA and the posterior SVC in the majority of isthmus-dependent AFL patients.

Endocardial substrate mapping for monomorphic ventricular tachycardia ablation in ischemic and non-ischemic cardiomyopathy.

We investigated the differences in the endocardial substrates between ischemic cardiomyopathy (ICM) and non-ICM (NICM) by using electro-anatomical mapping and pace-mapping. We studied 18 patients (ICM and NICM, 9 each) with monomorphic ventricular tachycardia (VT) documented by 12-leads ECG. Low voltage area was defined by signal amplitude <1.5 mV. A pace-map QRS morphology that matched VT in >10 of the 12-leads ECG was regarded as a pace-map match. And conduction delay during pace-mapping was defined as the stimulus to QRS interval >or=40 ms. Low voltage area was 53.8 +/- 21.5 and 20.8 +/- 16.7 cm2 in ICM and NICM patients, respectively (P = 0.002). Pace-mapping was assessed in 6 ICM and 9 NICM. Pace-map match with conduction delay were obtained in all the 6 ICM patients. But in NICM patients, pace-map match with conduction delay was obtained in 3 patients. Pace-map match sites where conduction delay was not observed were obtained in 5 patients. Pace-map match could not be obtained in 1 patient. We attempted ablation in 6 ICM and 7 NICM patients. Subsequently, VT recurrence was not observed in ICM but it was observed in 6 of 7 NICM patients (log-rank P = 0.0016). In NICM patients, the arrhythmogenic substrate that represented the abnormal electrogram and conduction delay was observed less within the endocardial surface when compared with that observed in ICM. VT recurrence rate subsequent to endocardial ablation was higher in NICM than in ICM patients.

Acute effects of angiotensin II receptor blocker on ventricular repolarization alternans in chronic heart failure.

Repolarization alternans, which can be detected clinically as microvolt-level T-wave alternans (TWA), is considered an important mechanism underlying the initiation of ventricular tachycardia/ventricular fibrillation (VT/VF) linked to sudden cardiac death (SCD). Recently, the rennin-angiotensin system (RAS) inhibitors have been suggested to have potential benefits in reducing SCD as well as heart failure death with chronic heart failure (CHF). In this study, we tested the acute effects of an angiotensin II receptor blocker (ARB), valsartan, on the development of TWA and the heart rate at which TWA appeared (onset heart rate; OHR). Fifty consecutive patients with CHF underwent TWA measurement. Patients with positive TWA were administered valsartan (80 mg/day) orally for 3 days. Alternans voltage in the vector magnitude lead (Valt) and the OHR were compared before and after the drug exposure. TWA was positive in 19 patients (38%), negative in 16 (32%), and indeterminate in 15 (30%). Nineteen patients with positive TWA received valsartan. However, 3 patients were withdrawn due to adverse drug reactions. In all the remaining 16 patients, markedly reduced Valt (6.1 +/- 3.8 microV to 2.5 +/- 1.9 microV; P = 0.002) and increased OHR (94 +/- 9 beats/min to 102 +/- 9 beats/min; p = 0.002) were observed. In particular, 3 patients became TWA negative. These results suggest that the RAS inhibitors prevent SCD by the improvement of repolarization abnormality.

Correlation of connexin43 expression and late ventricular potentials in nonischemic dilated cardiomyopathy.

Nonischemic dilated cardiomyopathy (DCM) is associated with a high risk of sudden cardiac death. Signal-averaged electrocardiography (SAECG) is a useful clinical tool for detecting late ventricular potentials (LP). Gap junction alterations have recently been shown to be involved in the pathogenesis of ventricular arrhythmias in DCM; however, the possible relationship between gap junctional connexin43 (C x 43) expression and SAECG has not yet been evaluated. In the present study 16 patients (47+/-13 years) with DCM who had undergone SAECG testing were evaluated. In each patient, the expression of C x 43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy and right ventricular biopsy specimens. The level of expression of C x 43 protein was defined as the proportion of tissue area occupied by C x 43 (percent tissue area) in each test area. The abundance and distribution of the C x 43 signal was assessed in relation to LP. Late ventricular potentials were positive in 5 patients (LP (+) group) and negative in 11 patients (LP (-) group). The incidence of sustained ventricular tachycardia in the LP (+) group was higher than that in the LP (-) group (80% vs 18%, p=0.04). The percent tissue area of C x 43 in the LP (+) group was significantly lower than that in the LP (-) group (p=0.02). Furthermore, C x 43 protein in the LP (+) group was distributed more heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous expression of C x 43 protein may contribute to impaired ventricular conduction, which may be related to the LP detected on SAECG.

Identification of functional block line in atrial flutter using three-dimensional intracardiac echocardiography.

The crista terminalis (CT) is reportedly a critical barrier for maintaining typical atrial flutter (AFL), but recent observations have suggested the presence of posteromedial functional block, as well as crista conduction. Therefore, this study was designed to identify the correlation between the posterior boundary of AFL and anatomical architecture in the human right atrium (RA) using 3-dimensional (D) intracardiac echocardiography (ICE). In 11 patients with AFL (typical 9, reverse typical 2), mapping with a 10-pole (n=5) or 32-pole (n=6) catheter was performed during AFL. ICE was used to determine the catheter's position relative to the intra-atrial structures. In all patients, double potentials were recorded at the posteromedial RA and the catheter positions were recognized as posterior to the CT by 3-D ICE. Double potentials were not recorded on the CT, and the activation sequence revealed a craniocaudal direction in the 9 patients with typical AFL and caudocranial direction in the 2 patients with reverse typical AFL. These findings demonstrate that the posterior boundary of the AFL circuit is in the sinus venosa region posterior to the CT, which may provide an important insight into the mechanism of maintaining AFL.

Comparative usefulness of beat-to-beat QT dispersion and QT interval fluctuations for identifying patients with organic heart disease at risk for ventricular arrhythmias.

The comparative usefulness of 10 min of beat-to-beat 12-lead QT dispersion (QTd) and QT interval variability index (QTVI) analysis for identifying patients with organic heart disease (OHD) at risk for ventricular arrhythmias was assessed in 86 subjects: 54 had OHD without a history of ventricular arrhythmias, 15 had OHD with documented ventricular tachycardia, and there were 17 controls. The following parameters were analyzed among the groups: (1) the average QTd (mean QTd), (2) the difference between the maximum and minimum QTd observed over the recording time (QTd variation), (3) the maximum difference of QTd between consecutive beats (QTd maximum), (4) the QTd standard deviation (QTd variability), and (5) QTVI, calculated in lead I or II according to an established formula: log 10 [(QTv/QTm2) / (HRv/HRm2)]. All the analyzed parameters were significantly increased in the patients with and without ventricular tachycardia when compared with the controls. QTd variation, QTd maximum and QTd variability were the only variables that remained significantly increased in the group of patients with documented ventricular tachycardia, compared with those without arrhythmia. Thus, beat-to-beat fluctuations of both the QT interval and QTd may be markers of temporal electrical instability in patients with OHD.

Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia.

INTRODUCTION: Gap junction alterations recently have been implicated in chronic heart failure, but direct evidence between gap junction manifestation in nonischemic dilated cardiomyopathy (DCM) is lacking. The current study examines whether qualitative changes or altered distribution of gap junctional connexin43 (Cx43) are related to global ventricular function and ventricular arrhythmia in DCM. METHODS AND RESULTS: We investigated 31 DCM patients (52 +/- 15 years) and 5 control subjects (55 +/- 10 years). Expression of Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy in right ventricular biopsy specimens from each patient. The expression level of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. Cx43 immunoreactive signal expressed as percent tissue area was not correlated with the change in left ventricular ejection fraction (P = 0.17). Of 31 DCM patients, 23% subsequently developed sustained ventricular tachycardia (VT), which allowed retrospective division of the samples into two groups: non-VT and VT. Left ventricular ejection fraction was comparable in both groups, but the percent tissue area in the VT groups was significantly decreased compared with that of the non-VT groups (P = 0.03). Furthermore, Cx43 protein was distributed heterogeneously in the VT groups (P < 0.0001). CONCLUSION: Heterogeneous reduction of Cx43 protein may result in development of malignant ventricular arrhythmia in DCM.