In previous studies, patients undergoing ablation of ganglionated plexi (GPA) for vagally mediated bradyarrhythmias were noted to have shortening of their corrected QT interval (QTc).

To compare the effects of GPA (group 1) to pulmonary vein isolation + GPA (group 2) on QTc.

We enrolled 39 patients, n = 25 in group 1 and n = 14 in group 2. QTc was calculated at baseline, at 24 h after ablation, and at 9-12 months in the follow-up. Recurrent syncope, asystole >2 s, and/or second- or third-degree AVB episodes were carefully documented as the primary outcome in group 1. Any atrial arrhythmia ≥30 seconds documented on 24-h Holter monitoring was defined as the primary outcome in group 2.

The mean follow-up time was 14.9 ± 4 months. Acute success was achieved in all cases. In whole cohort, a significant shortening on QTcBazett, QTcFramingham, QTcFredericia, and QTcHodges was observed [416 vs 398ms (p = .002), 411vs 378 ms (p < .001), 412 vs 379ms (p < .001), and 420 vs 383ms (p < .001), respectively]. In the linear mixed model analysis, the longitudinal reduction tendency in the QTc level was more pronounced in group 1. Event-free survival was detected in 90.7% (59/65) of cases.

Our results demonstrate a significant shortening of QTc in addition to high medium-term success rates after GPA. Pulmonary vein isolation + GPA was associated with lower QTc shortening effect which implies structural disease may change electrophysiological response to ablation. The most likely mechanism is the effect of GPA on the sympathetic system.

Although parasympathetic effects of cardioneuroablation (CNA) in vagally mediated bradyarrhythmias (VMB) were studied, sympathetic effects have not been elucidated, yet. We aimed to investigate the acute and medium-term outcomes of CNA as well as the impact of CNA on ventricular repolarization by using corrected QT interval (QTc) measurements.

Sixty-five patients (58.5% men; age 39.4 ± 14 years) undergoing CNA were included in the study. Patients who underwent CNA due to VMB were divided into two groups: (1) bi-atrial CNA and (2) right-sided CNA. QTc was calculated at 3 time points: before the procedure (time point 1); 24 h post-ablation (time point 2); and at the last follow-up visit (time point 3).

The mean follow-up time was 20.0 ± 20 months. Acute success was achieved in 64 (98.4%) of cases. In the whole cohort, from time point 1 to 2, a significant shortening in QTcFredericia, QTcFramingham, and QTcHodges was observed which remained lower than baseline in time point 3. Although the difference between measurements in time point 1 and 2 was not statistically significant for QTcBazett, a significant shortening was detected between time point 1 and 3. There was significant difference between groups for shortening in QTcFredericia and QTcFramingham (p = 0.01). Event-free survival was detected in 90.7% (59/65) of cases.

Our results demonstrate a significant shortening of QTc in addition to high acute and medium-term success rates after CNA. The most likely mechanism is the effect of CNA on the sympathetic system as well as on the parasympathetic system. Bi-atrial ablation was found related to higher QTc shortening effect.

Medications such as ß-blockers are currently the primary treatment for patients with hereditary arrhythmia syndromes such as long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, these drugs are ineffective in some patients, and the other treatment option, that is implantable cardioverter defibrillator (ICD) implantation, is associated with significant complications in young and active patients. Left cardiac sympathetic denervation (LCSD) may reduce the wide gap between life-long ß-blocker medication and ICD implantation. Although LCSD is highly effective in prevention of cardiac events in patients with LQTS and CPVT, it is rarely used. The recently introduced procedure video-assisted thoracoscopic LCSD is associated with short hospital stays and low morbidity. Thus, LCSD is an important therapeutic option for patients with LQTS and CPVT.

Videoscopic left cardiac sympathetic denervation (LCSD) is an adjunct therapy for reduction of arrhythmia-induced events in patients with long-QT syndrome (LQTS). LCSD reduces LQTS-triggered breakthrough cardiac events. The temporal effects of QTc changes post-LCSD have not been studied.

We utilized continuous QTc monitoring on 72 patients with LQTS. We evaluated acute and long-term QTc changes in comparison to 12-lead ECG-derived QTc values prior to surgery, 24 hours postsurgery, and at follow up ≥3 months.

Seventy-two patients underwent LCSD at our institution (46% male, mean age at LCSD was 14 ± 10 years). The mean baseline, pre-LCSD QTc was 505 ± 56 ms, which had decreased significantly at ≥3 months post-LCSD to 491 ± 40 ms (P = 0.001). QTc monitoring revealed that the majority of the cohort (53/72; 74%) had a transient increase >30 ms in QTc from baseline, with an average maximum increase of 72 ± 30 ms. Resolution within 10 ms of baseline or less occurred in 57% (30/53) at 24 hours post-LCSD.

Although LQTS patients may have a paradoxically increased QTc post-LCSD, the effects are transient in most patients. Importantly, no patients experienced any arrhythmias in the postoperative setting related to this transient rise in QTc.

Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA.

One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-α, and interleukins (IL-1α, IL-1β, IL-6, IL-10). QTc was calculated using the Bazett (QTBAZ = QT ÷ √RR) and Framingham Heart Study (QTFHS = QT + 0.154 × [1 - RR]) heart rate correction formulas.

Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were positively correlated with QTBAZ (Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with QTBAZ (β = 0.202, p = 0.023) and QTFHS (β = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QTBAZ (β = 0.278, p = 0.001), but not QTFHS.

To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro- and antiinflammatory cytokines on QTc interval.

Long QT syndrome is a congenital disorder accompanied by a high incidence of sudden cardiac death. β-adrenergic blockade is the therapy of choice, and it is successful in 75-80% of patients. However, for those in whom refractory arrhythmia or cardiac events are not prevented by medication, the literature suggests that left cardiac sympathetic denervation may be useful. Here we present a girl 20 months of age with refractory ventricular tachycardia due to long QT syndrome successfully treated by left cardiac sympathetic denervation. There was no significant complication.

An 18-year-old woman with catecholaminergic polymorphic ventricular tachycardia (CPVT) underwent pulmonary vein isolation (PVI) because of frequent and inappropriate shocks from an implantable cardioverter defibrillator (ICD) associated with atrial fibrillation (AF) with a rapid ventricular response. While the PVI did not completely suppress the AF induced by an isoproterenol infusion, the Holter monitor recordings demonstrated a major decrease in the clinical episodes of AF and ventricular tachyarrhythmias in association with a reduced high-frequency (HF) component and ratio of the low-frequency (LF) component power to the HF component (LF/HF) after the PVI. The PVI can decrease the substrates that trigger and maintain the AF when it involves a pulmonary vein origin, and may exert an additional effect on the sympathetic nerve input to the heart. The PVI may be an adjunctive therapy for CPVT cases with drug refractory AF causing inappropriate ICD discharges.

Long QT syndrome (LQTS) is a congenital or drug-induced change in electrical activity of the heart that can lead to fatal arrhythmias. Mutations in 12 genes encoding ion channels and associated proteins are linked with congenital LQTS. With a computational systems biology approach, we found that gene products involved in LQTS formed a distinct functional neighborhood within the human interactome. Other diseases form similarly selective neighborhoods, and comparison of the LQTS neighborhood with other disease-centered neighborhoods suggested a molecular basis for associations between seemingly unrelated diseases that have increased risk of cardiac complications. By combining the LQTS neighborhood with published genome-wide association study data, we identified previously unknown single-nucleotide polymorphisms likely to affect the QT interval. We found that targets of U.S. Food and Drug Administration (FDA)-approved drugs that cause LQTS as an adverse event were enriched in the LQTS neighborhood. With the LQTS neighborhood as a classifier, we predicted drugs likely to have risks for QT effects and we validated these predictions with the FDA's Adverse Events Reporting System, illustrating how network analysis can enhance the detection of adverse drug effects associated with drugs in clinical use. Thus, the identification of disease-selective neighborhoods within the human interactome can be useful for predicting new gene variants involved in disease, explaining the complexity underlying adverse drug side effects, and predicting adverse event susceptibility for new drugs.

The purpose of this study was to assess the feasibility and long-term effect of video-assisted thoracoscopic left cardiac sympathetic denervation for congenital long-QT syndrome.

From December 2002 to May 2007, 11 patients who could not tolerate or who were refractory to beta-blocker therapy received video-assisted thoracoscopic left cardiac sympathetic denervation. Under general anesthesia, the pleural cavity was entered through three 1.5-cm incisions in the left subaxillary area. The left thoracic sympathetic chain was identified, and the lower one third of the left stellate ganglion, together with T(2) to T(5) sympathetic chain, was resected.

The mean operative time was 40.9 +/- 7.7 minutes. Blood loss was minimal. The mean postoperative stay was 6 +/- 1.4 days. There were no major perioperative complications apart from mild ptosis of the left upper eyelid in 1 patient who subsequently recovered shortly after the procedure. The mean follow-up time was 37.0 +/- 26.3 months. Seven of the patients are totally free of cardiac events and report good quality of life. One patient experienced decreased syncopal events from 5 or 6 times per year to 2 or 3 times per year. One patient still experiences syncopal events 3 to 4 times a year, but with shortened duration to several seconds. One patient reports syncope 10 times per year. Only 1 patient died, early in the second year after surgery. In conclusion, the overall efficacy rate (that is, reduction in syncopal episodes) is 81.8% (9 of 11) and the mortality rate, 9.1% (1 of 11).

Video-assisted thoracoscopic left cardiac sympathetic denervation is a simple and minimally invasive technique that results in good long-term benefits in patients with congenital long-QT syndromes.

The implantable cardioverter defibrillator (ICD) may be responsible for psychological disorders especially among patients experiencing multiple shocks. An associated hyperadrenergic state (e.g., anger, anxiety) may trigger malignant ventricular arrhythmias repeatedly treated by ICD shocks, entertaining a "vicious circle" often difficult to interrupt. Despite aggressive cardiac and psychological therapeutic efforts, this condition may be refractory, finally leading to heart transplantation, as described in this case report.

The objective of this study was to investigate the protective effect of U50,488H, a selective kappa-opioid receptor agonist, in the ischemia/reperfusion (I/R) rat and to delineate the underlying mechanism. Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 45 min and restoring perfusion for 120 min. U50,488H or vehicle was intravenously injected before ischemia. Electrocardiogram, heart rate (HR), arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dp/dtmax), and diastolic function (-dp/dtmax) were monitored in the course of the experiment. Myocardial infarction size was evaluated. Plasma concentrations of cardiac troponin T (cTnT), creatine kinase (CK), and lactate dehydrogenase (LDH) were measured. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The potassium currents (IK) of isolated ventricular myocytes were recorded with the whole-cell configuration of the patch-clamp technique. Compared with the sham control group, no significant change was found in HR, while ABP, LVP and +/-dp/dtmax were significantly reduced in the I/R group. Administration of U50,488H significantly lowered HR in both control and I/R groups. Compared with the vehicle-treated I/R group, administration of U50,488H had no significant effect on I/R-induced reduction in ABP, LVP, and +/-dp/dtmax. However, this treatment significantly reduced the myocardial infarction size, and markedly decreased the contents of plasma cTnT, CK and LDH. During ischemia and reperfusion, the incidence of ventricular arrhythmia in U50,488H-treated rats was significantly reduced. These effects were independent of the bradycardia induced by U50,488H, as the reducing infarct size and antiarrhythmic effect of U50,488H were still observed in animals in which heart rate was kept constant by electrical pacing. U50,488H and BRL-52537 still produced an antiarrhythmic effect when the rat heart was subjected to a shorter ischemic period of 10 min occlusion of coronary artery, which produced no infarction. IK of the myocytes were inhibited by U50,488H in a dose-dependent manner in normal and hypoxic rat ventricular myocytes. However, the effects of U50,488H on IK did not show any significant difference in normal and hypoxic myocytes. The above-described effects of U50,488H were totally blocked by nor-Binaltorphimine, a selective kappa-opioid receptor antagonist. The results suggest that kappa-opioid agonist U50,488H exerts its direct cardioprotective and antiarrhythmic effects against I/R via kappa-opioid receptor, which participates in the regulation of potassium channels in normal and hypoxic ventricular myocytes.

The long QT syndrome (LQTS) is characterized by electrocardiographic abnormalities and a high incidence of syncope and sudden cardiac death (SCD). The diagnosis is suggested when ventricular repolarization abnormalities result in prolongation of the corrected QT interval. When LQTS is suspected, genetic screening may identify a specific long QT subtype and provide guidance for appropriate therapy. Treatment depends on the relative risk of SCD, which is increased with longer QT durations, prior cardiac events, and a family history of SCD. beta Blockers are considered the initial treatment of choice, with implantable cardioverter-defibrillator (ICD) therapy warranted in high-risk patients. In patients with frequent ICD shocks or in those at high risk for SCD where ICD placement cannot be performed, cardiac pacing and/or left cardiac sympathetic denervation may be indicated.