Catheter-induced mechanical trauma to fast and slow pathways during radiofrequency ablation of atrioventricular nodal reentry tachycardia: incidence, predictors, and clinical implications.

BACKGROUND: Data on the incidence and significance of catheter-induced trauma to fast and slow pathways are scarce. OBJECTIVES: To evaluate the incidence, predictors, and clinical implications of inadvertent catheter-induced mechanical trauma to fast and slow pathways during radiofrequency ablation (RFA) of atrioventricular nodal reentry tachycardia (AVNRT). METHODS: A total of 901 consecutive patients (aged 9-92 years old) with inducible sustained AVNRT underwent RFA of the slow pathway. All procedures were closely monitored for appearance of catheter-induced mechanical block of fast or slow pathways. RESULTS: Catheter-induced mechanical trauma to fast and/or slow pathways was observed in 121 (13.4%) patients: 86 (71%) patients had trauma of the fast pathway, three (2.4%) had trauma of the slow pathway, and 32 (26.4%) had trauma of both pathways. Mechanical trauma lasted <1 minute in 87 (72%) patients, 1-30 minutes in 23 (19%) and >30 minutes in 11 (9%). A significantly increased procedure discontinuation rate was observed in patients with mechanical trauma as compared to those with no trauma (P < 0.0001). Young patient age (<35) was a strong predictor for the occurrence of mechanical trauma to AV nodal pathways. No significant difference between the trauma and non-trauma groups was found in respect to the number of catheters used during the procedure, the incidence of AV block, and the need for permanent pacemaker implantation. CONCLUSIONS: Mechanical trauma to fast and slow pathways during ablation of AVNRT is more common than previously recognized, occurring especially in patients aged <35 years.

The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias.

OBJECTIVES: The purpose of this study was to define the electrocardiographic (ECG) predictors of torsade de pointes (TdP) during acquired bradyarrhythmias. BACKGROUND: Complete atrioventricular block (CAVB) might lead to downregulation of potassium channels, QT interval prolongation, and TdP. Because potassium-channel malfunction causes characteristic T-wave abnormalities in the congenital long QT syndrome (LQTS), we reasoned that T-wave abnormalities like those described in the congenital LQTS would identify patients at risk for TdP during acquired bradyarrhythmias. METHODS: In a case-control study, we compared 30 cases of bradyarrhythmias complicated by TdP with 113 cases of uncomplicated bradyarrhythmias. On the basis of the criteria used for the congenital LQTS, T waves were defined as LQT1-like (long QT interval with broad T waves), LQT2-like (notched T waves), and LQT3-like (small and late) T waves. RESULTS: Neither the ventricular rate nor the QRS width at the time of worst bradyarrhythmia predicted the risk of TdP. However, the QT, corrected QT (QTc), and T(peak)-T(end) intervals correlated with the risk of TdP. The best single discriminator was a T(peak)-T(end) of 117 ms. LQT1-like and LQT3-like morphologies were rare during bradyarrhythmias. In contrast, LQT2-like "notched T waves" were observed in 55% of patients with TdP but in only 3% of patients with uncomplicated bradyarrhythmias (p < 0.001). A 2-step model based on QT duration and the presence of LQT2-like T waves identified patients at risk for TdP with a positive predictive value of 84%. CONCLUSIONS: Prolonged QT interval, QTc interval, and T(peak)-T(end) correlate with increased risk for TdP during acquired bradyarrhythmias, particularly when accompanied by LQT2-like notched T waves.

Radiofrequency ablation of atrioventricular nodal reentry tachycardia: a 14 year experience with 901 patients at the Tel Aviv Sourasky Medical Center.

BACKGROUND: Atrioventricular nodal reentry tachycardia is the most frequent cause of regular, paroxysmal supraventricular tachycardia. Radiofrequency ablation of the slow pathway has been recommended as first-line therapy for curing AVNRT. OBJECTIVES: To report a 14 year experience of RFA of the slow pathway in patients with AVNRT treated in our laboratory. METHODS: A total of 901 consecutive patients (aged 9-92, mean 50.8 +/- 18.2 years) underwent RFA of the slow pathway. All patients had sustained AVNRT induced with or without intravenous administration of isoproterenol. A standard electrophysiologic method with three diagnostic and one ablation catheter was used in 317 patients (35.2%); in the remaining 584 patients (64.8%), only two electrode catheters (one diagnostic, one ablation) were used ("two-catheter approach"). RESULTS: Catheter ablation of the slow pathway abolished AVNRT induction in 877 patients (97.3%). In 14 patients (1.6%) the procedure was discontinued while in 10 (1.1%) the procedure failed. In 864 patients (95.9%) there were no complications. Transient or permanent AV block occurred during the procedure in 31 patients (3.4%), of whom 8 (0.9%) eventually required pacemaker insertion (n = 7) or upgrade of a previously implanted WI pacemaker (n = 1) during the month following the procedure. The number of catheters used did not significantly affect the rate of results or complications of the ablation procedure. The success and complication rates remained stable over the years, although a significant trend for increased age and associated heart disease was observed during the study period. CONCLUSIONS: The results of this single-center large study, which included patients with a wide age range, showed results similar to those of previous studies. The use of a "two-catheter approach" (one diagnostic and one ablation) was as effective and safe as a multi-catheter approach.

Effects of losartan + L-arginine on nitric oxide production, endothelial cell function, and hemodynamic variables in patients with heart failure secondary to coronary heart disease.

The purpose of the present study was to evaluate the effects of losartan and the combination of losartan and L-arginine on endothelial function and hemodynamic variables in patients with heart failure (HF). Endothelium-dependent vasodilation is impaired in patients with HF. It was hypothesized that the administration of losartan and the combination of losartan and L-arginine might increase nitric oxide production and have a beneficial additive effect on endothelial function and hemodynamic variables in patients with HF. Nine patients with HF (ejection fraction<35%) were given losartan 50 mg orally on 2 consecutive days. On the second day, 1 hour after losartan 50 mg administration, L-arginine 20 g was given by intravenous infusion. Endothelial function in the form of endothelium-dependent brachial artery flow-mediated vasodilation (FMV) was measured by ultrasound. Hemodynamic variables were estimated using Doppler echocardiography at baseline and at 2 and 4 hours after losartan alone and after combination therapy. Urinary levels of nitrite (NO2) or nitrate (NO3) were measured. Four hours after losartan administration, significant reductions in systemic vascular resistance and estimated end-systolic elastase were observed. On the second day, 1 hour after L-arginine infusion, an additive hemodynamic effect was observed, with significant increases in the cardiac index and stroke volume and significant reductions in systemic vascular resistance and calculated left ventricular end-diastolic pressure. A trend toward improved FMV was observed with losartan alone, but without statistical significance. Combination therapy significantly improved postintervention FMV compared with baseline. The increase in urinary nitric oxide excretion after losartan treatment and combination therapy was significantly correlated with improved hemodynamic variables and improved FMV. In conclusion, losartan induces significant afterload reduction, reduced contractility, and increased nitric oxide urinary excretion. The combination of L-arginine and losartan seems to have superior effects on hemodynamic variables and endothelium-dependent vasodilation compared with losartan alone.

Long-term effects of dual-chamber pacing with periodic echocardiographic evaluation of optimal atrioventricular delay in patients with hypertrophic cardiomyopathy >50 years of age.

Various treatment modalities have been introduced to reduce the subaortic pressure gradient in patients with obstructive hypertrophic cardiomyopathy, including pacemaker insertion. Complete ventricular capture during pacing is essential and requires optimization of the atrioventricular interval (AVI). In this study, a protocol using echocardiographic examination assessing the changes in the left ventricular outflow tract (LVOT) gradient in different AVIs, pacing rates, and pacing modes was used for optimal pacemaker programming. Twenty-five patients with obstructive hypertrophic cardiomyopathy were implanted with DDD pacemakers and evaluated prospectively. The LVOT gradient was measured during periodic evaluations every 3 to 6 months. Gradient measurements were done with 5 different AVIs and 3 different rate combinations. After each evaluation, the optimal AVI, pacing rate, and mode were set on the basis of the minimal LVOT gradient not associated with systolic arterial cuff pressure reduction. Follow-up ranged from 18 to 126 months. Peak LVOT gradient immediately decreased in 92% of patients. During follow-up, the optimal AVI was prolonged in most patients. Sixty-four percent of patients showed a clear relation between pacemaker modifications and gradient reduction. In 75% of these patients, optimal gradient reduction required repeated AVI and pacing rate programming on the basis of echocardiographic evaluation. Symptoms decreased in 92% of patients, and New York Heart Association class improved significantly (3.1+/-0.7 vs 1.3+/-0.4, p<0.001) during follow-up. The symptomatic reduction was positively correlated with the LVOT gradient reduction. In conclusion, DDD pacing is effective in reducing the LVOT gradient and improving functional capacity in adult patients with hypertrophic cardiomyopathy. Pacemaker programming with the periodic echocardiographic evaluation of the optimal AVI, pacing rate, and mode is imperative for optimal results.

Frequency of spontaneous and inducible atrioventricular nodal reentry tachycardia in patients with idiopathic outflow tract ventricular arrhythmias.

OBJECTIVES: We sought to assess the frequency of spontaneous or inducible atrioventricular nodal reentry tachycardia (AVNRT) in patients referred for radiofrequency ablation (RFA) of idiopathic outflow tract ventricular arrhythmias. BACKGROUND: In patients with no obvious heart disease, AVNRT and outflow tract ventricular tachycardia (VT) are the most frequently encountered supraventricular and ventricular tachycardias, respectively. An increased coexistence of the two arrhythmias has been recently suggested. METHODS: In 68 consecutive patients referred for RFA of an idiopathic ventricular outflow tract arrhythmia, a stimulation protocol including repeated bursts of rapid atrial pacing, up to triple atrial extrastimuli during sinus rhythm and rapid ventricular pacing was performed before and after isoproterenol infusion following RFA of the ventricular arrhythmia. In patients with inducible AVNRT, RFA of the slow pathway was performed. RESULTS: Of the 68 study patients, 17 (25%) had either spontaneous AVNRT documented prior to RFA of the ventricular arrhythmia (n = 4) or inducible AVNRT at the time of RFA of the ventricular arrhythmia (n = 13). AVNRT was induced by atrial pacing in 15 (88%) of 17 patients: in 3 patients without isoproterenol and in 12 patients during isoproterenol infusion. Uncomplicated RFA of the slow pathway was successfully achieved in all patients with inducible AVNRT. CONCLUSION: Spontaneous or inducible AVNRT is relatively common in patients with idiopathic outflow tract ventricular arrhythmias. Atrial stimulation, especially when performed after isoproterenol infusion plays a major role in AVNRT inducibility. Although we performed RFA of the slow pathway in patients with inducible AVNRT and no prior tachycardia documentation, the question whether this is mandatory remains unsettled.

Idiopathic left ventricular tachycardia with a right bundle branch block morphology and left axis deviation ("Belhassen type"): results of radiofrequency ablation in 18 patients.

BACKGROUND: Idiopathic left ventricular tachycardia with a right bundle branch block configuration and left axis deviation, first described by Belhassen et al., is a rare electrocardiographic-electrophysiologic entity. Radiofrequency catheter ablation has been proposed as a good therapeutic option, but the best criteria for determining the optimal site of ablation are still under debate. OBJECTIVES: To report the clinical features, electrophysiologic characteristics, results of RFA, and long-term outcome in 18 patients with "Belhassen's VT" treated in our laboratory during the last 10 years, stressing the best electrophysiologic criteria for determining the optimal site of ablation. METHODS: Eighteen consecutive patients with this specific VT underwent RFA in our laboratory during the last 10 years. RFA was acutely successful in 17 patients after one or two procedures (15 and 2 patients, respectively) using 4.1 +/- 2.2 RF pulses. The putative ablation sites were defined by good pace-mapping (3 patients), earliest recorded Purkinje spike prior to the QRS onset during VT or sinus rhythm (6 patients), earliest endocardial activation during VT (1 patient), and diastolic potential preceding the Purkinje spike during VT and/or late diastolic potential in sinus rhythm (7 patients). In the patients with a definite successful ablation, the ratio of successful to unsuccessful radiofrequency pulse delivery to the diastolic potential site was compared to that of other methods. The ratio of successful RFA at the diastolic potential site (5:8) was higher than in the other methods (8:31) and the difference was statistically significant (P = 0.05). Successful ablation sites were more basal when the diastolic potential site was chosen. CONCLUSION: The results of the present study confirm the high success rate and safety of RFA using conventional techniques in the management of "Belhassen VT," suggesting that this procedure can be used as a first-line therapy. Ablating at a site demonstrating a late diastolic potential is at least as effective as ablating at a ventricular exit site, although the use of combined electrophysiologic criteria may be the optimal approach.

The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing.

The fat soluble vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)(2)D(3 )is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)(2)D(3) has anti-inflammatory effects in an in vivo Th2-dependent asthma model. In addition, we demonstrate that 1,25(OH)(2)D(3 )down-regulates the cytoskeleton rearrangement required for promoting integrin-mediated adhesion of naive and effector CD4(+) T cells. Finally, 1,25(OH)(2)D(3 )inhibits chemokine-induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)(2)D(3 )regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.

Cutting edge: anti-inflammatory properties of low levels of IFN-gamma.

Activation of naive T and B cells occurs only within the context of organized lymphoid tissue. Thus, the continuous recirculation of mature lymphocytes is crucial for the development of primary immune response to foreign Ags. We have previously shown that low levels of IFN-gamma inhibit homing of B cells to the secondary lymphoid organs. In this study, we demonstrate that similarly low doses of IFN-gamma down-regulate integrin-mediated adhesion and migration of naive T and Th2 cells, and have a profound effect on the in vivo homing of naive T cells to the lymph nodes. Moreover, we show that these low doses of IFN-gamma have anti-inflammatory effects in an in vivo asthma model. Thus, in contrast to the proinflammatory effects of IFN-gamma at relatively high concentrations, low dose IFN-gamma appears to exert global suppressory effects on T cell trafficking and may have clinical application as an anti-inflammatory agent.

Preferential Th1 immune response in invariant chain-deficient mice.

MHC class II molecules associate with the invariant chain (Ii) molecule during biosynthesis. Ii facilitates the folding of class II molecules, interferes with their peptide association, and is involved in MHC class II transport. In this study, we have investigated the in vitro and in vivo immune response of Ii-deficient mice (Ii(-/-)). Our results have demonstrated that CD4(+) T cells from Ii(-/-) mice proliferate normally in vitro after in vivo immunization with protein Ags. However, cytokine secretion profiles of Ag-primed CD4(+) T cells from Ii(-/-) mice differ from CD4(+) T cells from wild-type mice. Whereas cells from wild-type mice secrete IFN-gamma and IL-4, cells from Ii(-/-) mice secrete mostly IFN-gamma. Moreover, Ii(-/-) mice exhibit a normal Th1 response in the delayed-type hypersensitivity and trinitrobenzene sulfonic acid colitis models; however, these mice lack an in vivo Th2 response, as demonstrated in the asthma model. Therefore, we suggest that defective Ag presentation in Ii(-/-) mice leads selectively to a Th1 effector response.