Duration Of Arrhythmia Research Articles

Women with PSVT are often misdiagnosed, referred later than men, and have more symptoms after ablation

Objectives. Using a patient and gender perspective, this study evaluates the experiences and perspectives of referral for paroxysmal supraventricular tachycardia (PSVT), and symptoms, Health-Related Quality of Life (HRQOL) and functional impairment before and six months after ablation. Design. This prospective study includes 214 (109 women) patients with PSVT who completed questionnaires before and after ablation addressing referral patterns, duration of arrhythmia, socioeconomic status, symptoms, HRQOL, and functional impairment. Result. Women had a longer history of symptomatic arrhythmia before ablation compared to men (16.2 ± 14.6 vs. 9.9 ± 13.1 years, p = .001). From the patient’s perspective, physicians more often incorrectly interpreted women’s symptoms as anxiety, stress, panic attacks, or depression compared to men, delaying referral for ablation. More women than men stated they were not taken seriously when consulting for their tachycardia symptoms (17% vs.7%, p = .03). At baseline, there were minor differences between the sexes in HRQOL and functional impairment, but women had a higher symptom score on Symptoms Checklist Frequency (19 vs. 14, p < .001) and Severity Scale (12 vs. 16, p = .001). At six months, women were more symptomatic and their HRQOL improved less than in men. Both sexes reported improvement in recreation and pastime (p = .001). Conclusion. Women with PSVT are referred for ablation later, and are more symptomatic before and after ablation than men. Symptoms due to PSVT are often incorrectly diagnosed as panic attacks, stress, anxiety, or depression, misdiagnoses that delay referral for ablation, especially for women.

Predictors of Left Atrial Thrombus and Short-Term Recurrence of Arrhythmia in Patients Undergoing Electrical Cardioversion for Atrial Fibrillation, a Single-Centre Experience

Background: Systemic thromboembolism is a serious complication of electrical cardioversion. Even in the absence of such complications there exists a significant rate of arrhythmia recurrence post cardioversion. Aims: The aim of this study was to identify factors that may aid clinicians in identifying those patients at increased risk of atrial thrombus formation and short-term arrhythmia recurrence. Methods: One-hundred and twelve patients were retrospectively identified across a 2.5 year period as having undergone electrical cardioversion at the Gold Coast University Hospital for atrial fibrillation or atrial flutter. Demographic, clinical and echocardiogram data was analysed to identify potential predictors of thrombus, unsuccessful cardioversion and arrhythmia recurrence. Results: Cardioversion was successful in 87.6% of patients. Cardioversion was more successful initially in males (p&lt;0.01) and those with reduced atrial volume (p&lt;0.01) and higher left ventricular ejection fraction (p&lt;0.01). Arrhythmia recurrence within 3 months occurred in 57.7% of patients. Recurrence was more likely in those with congestive heart failure (p&lt;0.05) and a longer pre-cardioversion duration of arrhythmia (p&lt;0.05). Spontaneous echo contrast was observed in 3 (2.6%) of patients, whilst left atrial thrombus was observed in 7 (6.2%) of patients. Potential predictors of thrombus were congestive heart failure (p&lt;0.05) and increased left atrial volume (p&lt;0.01). Conclusions: This retrospective study identified a number of factors that may useful in the clinical setting in predicting cardioversion success, both initially and short-term, in addition to predicting thrombus formation.

Pericardial adipose and aromatase: A new translational target for aging, obesity and arrhythmogenesis?

A correlation exists between the extent of pericardial adipose and atrial fibrillation (AF) risk, though the underlying mechanisms remain unclear. Selected adipose depots express high levels of aromatase, capable of converting androgens to estrogens – no studies have investigated aromatase occurrence/expression regulation in pericardial adipose. The Women's Health Initiative reported that estrogen-only therapy in women elevated AF incidence, indicating augmented estrogenic influence may exacerbate cardiac vulnerability. The aim of this study was to identify the occurrence of pericardial adipose aromatase, evaluate the age- and sex-dependency of local cardiac steroid synthesis capacity and seek preliminary experimental evidence of a link between pericardial adipose aromatase capacity and arrhythmogenic vulnerability. Both human atrial appendage and epicardial adipose exhibited immunoblot aromatase expression. In rodents, myocardium and pericardial adipose aromatase expression increased >20-fold relative to young controls. Comparing young, aged and aged-high fat diet animals, a significant positive correlation was determined between the total aromatase content of pericardial adipose and the occurrence/duration of triggered atrial arrhythmias. Incidence and duration of arrhythmias were increased in hearts perfused with 17β-estradiol. This study provides novel report of pericardial adipose aromatase expression. We show that aromatase expression is remarkably upregulated with aging, and aromatase estrogen conversion capacity significantly elevated with obesity-related cardiac adiposity. Our studies suggest an association between adiposity, aromatase estrogenic capacity and atrial arrhythmogenicity – additional investigation is required to establish causality. The potential impact of these findings may be considerable, and suggests that focus on local cardiac steroid conversion (rather than systemic levels) may yield translational outcomes.

P4599Atrial arrhythmia detection by Implantable Loop Recorder in patients with and without previous stroke; impact of arrhythmia duration and time to diagnosis

P4599Atrial arrhythmia detection by Implantable Loop Recorder in patients with and without previous stroke; impact of arrhythmia duration and time to diagnosis

Intra-Atrial Conduction Delay Revealed by Multisite Incremental Atrial Pacing is an Independent Marker of Remodeling in Human Atrial Fibrillation.

ObjectivesThis study sought to characterize direction-dependent and coupling interval–dependent changes in left atrial conduction and electrogram morphology in uniformly classified patients with paroxysmal atrial fibrillation (AF) and normal bipolar voltage mapping.BackgroundAlthough AF classifications are based on arrhythmia duration, the clinical course, and treatment response vary between patients within these groups. Electrophysiological mechanisms responsible for this variability are incompletely described.MethodsIntracardiac contact mapping during incremental atrial pacing was used to characterize atrial conduction, activation dispersion, and electrogram morphology in 15 consecutive paroxysmal AF patients undergoing first-time pulmonary vein isolation. Outcome measures were vulnerability to AF induction at electrophysiology study and 2-year follow-up for arrhythmia recurrence.ResultsConduction delay showed a bimodal distribution, occurring at either long (high right atrium pacing: 326 ± 13 ms; coronary sinus pacing: 319 ± 16 ms) or short (high right atrium pacing: 275 ± 11 ms; coronary sinus pacing: 271 ± 11 ms) extrastimulus coupling intervals. Arrhythmia recurrence was found only in patients with conduction delay at long extrastimulus coupling intervals, and patients with inducible AF were characterized by increased activation dispersion (activation dispersion time: 168 ± 29 ms vs. 136 ± 11 ms). Electrogram voltage and duration varied throughout the left atrium, between patients, and with pacing site but were not correlated with AF vulnerability or arrhythmia recurrence.ConclusionsWithin the single clinical entity of paroxysmal AF, incremental atrial pacing identified a spectrum of activation patterns correlating with AF vulnerability and arrhythmia recurrence. In contrast, electrogram morphology (characterized by electrogram voltage and duration) was highly variable and not associated with AF vulnerability or recurrence. An improved understanding of the electrical phenotype in AF could lead to improved mechanistic classifications.

Effects of phosphodiestrase type 5 inhibitors in epinephrine-induced arrhythmia in rats: Involvement of lactate dehydrogenase and creatine kinase downregulation and adiponectin expression.

Cardiac arrhythmia is a common cause of mortality, and its progression may be due to abnormal sympathetic nerve activity and catecholamine release. Besides, lactate dehydrogenase (LDH) and creatine kinase (CK) downregulation and adiponectin expression play important roles in promoting coronary artery disease. The study aimed to examine the possible cardioprotective effect of members of phosphodiesterase type 5 (PDE-5) inhibitors in epinephrine-induced arrhythmia in rats. Arrhythmia was induced by cumulative boluses of epinephrine (4, 8, 16, 32, 64, and 128 mg/kg) given at 10-min intervals. Rats were randomly allocated into five groups. Group I: Normal control group received only saline. Group II: Rats injected with epinephrine and served as arrhythmia group. Groups III, IV, and V: Rats received daily oral sildenafil (0.5 mg/kg), vardenafil (3 mg/kg), and tadalafil (10 mg/kg), respectively, for 30 days prior to epinephrine injections. Injection of epinephrine to rats decreased heart rate and QTc interval but increased RR interval and duration of arrhythmia. Epinephrine group had lower serum reduced glutathione (GSH) and adiponectin levels and higher serum malondialdehyde (MDA), nitric oxide (NO), heart LDH, and CK contents. Histopathological investigations of epinephrine group provoked necrotic changes with strong positive immunoreactivity for caspases-3. While pretreatment of rats with PDE-5 inhibitors improved GSH and adiponectin contents, ameliorated serum MDA and NO levels and heart LDH and CK contents and corrected epinephrine-induced histopathological changes. PDE-5 inhibitors may delay epinephrine-induced arrhythmia through expression of adiponectin and downregulation of heart LDH and CK.

IMPACT OF ARRHYTHMIA DURATION AND INDEX LEFT VENTRICULAR EJECTION FRACTION ON RECOVERY OF LEFT VENTRICULAR FUNCTION IN PATIENTS WITH ARRHYTHMIA-INDUCED CARDIOMYOPATHY

Background: Improvement in left ventricular ejection fraction (LVEF) can occur with prompt treatment of the culprit arrhythmia in patients with arrhythmia-induced cardiomyopathy (AIC). Predictors of recovery, however, are not well understood. We assessed the impact of arrhythmia duration and index

Predictors of Left Atrial Thrombus and Short-Term Recurrence of Arrhythmia in Patients Undergoing Electrical Cardioversion for Atrial Fibrillation, a Single-Centre Experience

Background: Systemic thromboembolism is a serious complication of electrical cardioversion. Even in the absence of such complications there exists a significant rate of arrhythmia recurrence post cardioversion. Aims: The aim of this study was to identify factors that may aid clinicians in identifying those patients at increased risk of atrial thrombus formation and short-term arrhythmia recurrence. Methods: One-hundred and twelve patients were retrospectively identified across a 2.5 year period as having undergone electrical cardioversion at the Gold Coast University Hospital for atrial fibrillation or atrial flutter. Demographic, clinical and echocardiogram data was analysed to identify potential predictors of thrombus, unsuccessful cardioversion and arrhythmia recurrence. Results: Cardioversion was successful in 87.6% of patients. Cardioversion was more successful initially in males (p&lt;0.01) and those with reduced atrial volume (p&lt;0.01) and higher left ventricular ejection fraction (p&lt;0.01). Arrhythmia recurrence within 3 months occurred in 57.7% of patients. Recurrence was more likely in those with congestive heart failure (p&lt;0.05) and a longer pre-cardioversion duration of arrhythmia (p&lt;0.05). Spontaneous echo contrast was observed in 3 (2.6%) of patients, whilst left atrial thrombus was observed in 7 (6.2%) of patients. Potential predictors of thrombus were congestive heart failure (p&lt;0.05) and increased left atrial volume (p&lt;0.01). Conclusions: This retrospective study identified a number of factors that may useful in the clinical setting in predicting cardioversion success, both initially and short-term, in addition to predicting thrombus formation.

The E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium channel increases susceptibility to ventricular arrhythmia in response to ischemia in rats

BackgroundThe E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel has been implicated in cardiac remodeling. However, the effects of E23K variant on ventricular electrophysiology and arrhythmogenesis remain unclear. MethodsTransgenic rats were generated to express human E23K-variant genomic DNA in the heart under the α-myosin heavy chain promoter. Electrophysiological parameters including electrocardiograph, ventricular action potential duration (APD), effective refractory period (ERP), electrical alternans and ventricle arrhythmia threshold were examined in wild type (WT) and transgenic rats. The KATP current in cardiomyocytes was recorded using whole-cell patch clamp techniques. ResultsNo differences in the electrophysiological parameters between the two groups were found at baseline. However, after acute ischemic stress, shortened QT intervals were further aggravated in the E23K-variant rats. Additionally, the E23K variant exacerbated the decrease of APD70, APD90 and ERP. The ventricular arrhythmia and alternans thresholds were significantly attenuated, and the duration of ventricular arrhythmia induced by electrical stimulation was significantly prolonged in the E23K-variant rats. More importantly, the KATP current in cardiomyocytes was significantly increased in the E23K-variant rats after ischemia. ConclusionThe E23K variant of the KATP channel increased the susceptibility to ventricular arrhythmia under acute ischemia stress.

Acute Oestradiol Increases the Propensity for Atrial Arrhythmias in the Isolated Mouse Heart

Atrial fibrillation (AF) is the most common sustained arrhythmia, significantly contributing to cardiovascular morbidity/mortality. Epidemiological studies have reported sex differences in AF incidence and outcomes. The influence of sex steroids on AF vulnerability is poorly understood, though clinical trial findings (ie WHI) have indicated that hormone supplementation using oestrogen-only therapy significantly increased AF risk. Experimental data addressing oestrogenic influence on atrial arrhythmias are lacking. We have previously shown that oestrogen influences ventricular electromechanical properties and arrhythmia vulnerability. The aim of this study was to assess the influence of acute oestradiol treatment on atrial arrhythmias in isolated mouse hearts. Bipolar electrograms were recorded from hearts subjected to programmed pulse stimulations in the presence/absence of 10 nM estradiol (vs vehicle control). Oestradiol significantly increased the incidence of atrial arrhythmias (# episodes; 2.8 ± 0.5 vs 0.9 ± 0.3), with the mean duration of each arrhythmic episode exhibiting similar trend. The total duration of atrial arrhythmias throughout the pulse stimulation protocol was significantly increased in the presence of oestradiol (s; 6.9 ± 3.2 vs 1.0 ± 0.4). Augmented atrial arrhythmia vulnerability was likely not due to oestrogenic action on sinus node automaticity, as no effect was observed on sinus node recovery time (ms; 424 ± 46 vs 397 ± 47). These data show for the first time in an experimental setting that acute oestrogen exposure increases cardiac vulnerability to atrial arrhythmia. This finding demonstrates potential cardiac vulnerability to local increase in oestrogen of endogenous and exogenous origin. Further studies are required to identify and target the cellular mechanisms by which oestrogen exerts this arrhythmogenic influence.

Augmented Capacity of Pericardial Adipose to Synthesise Oestrogen Linked with Greater Vulnerability to Atrial Arrhythmias

A link exists between atrial fibrillation (AF) risk and the extent of pericardial adipose (epicardial/paracardial). The underlying mechanisms remain poorly understood. We recently reported that aromatase is expressed in human epicardial adipose–thus providing capacity for local cardiac oestrogen synthesis. Earlier clinical trial findings (WHI) indicated that oestrogen-only therapy was associated with significantly increased AF risk. The extent to which endogenous oestrogen, produced locally, might contribute to AF substrate is unknown. The aim of this study was to determine the relationship between pericardial adipose accumulation, local oestrogen synthesis capability and atrial arrhythmia vulnerability in mouse models of adiposity: aged (50wks) and aged high-fat diet (HFD) fed. Pericardial adipose expression was measured by Western immunoblot. Atrial arrhythmias were assessed using bipolar electrograms recorded from isolated hearts subjected to programmed pulse stimulation. Compared with young controls (age 12wks), pericardial adipose weight was significantly increased in HFD and aged mice (mg; 260 ± 36 vs 114 ± 15 vs 22 ± 9, HFD vs aged vs young). Total aromatase content was similarly elevated (arb. units; 10.2 ± 1.7 vs 4.6 ± 0.9 vs 0.1 ± 0.0). The hearts from these mice exhibited a greater incidence of atrial arrhythmias (# episodes; 3.6 ± 1.3 vs 2.8 ± 1.0 vs 0.4 ± 0.1). A significant positive correlation was determined between the total aromatase content of pericardial adipose and the incidence (p = 0.0015) and duration (p = 0.0136) of triggered arrhythmias. This study provides the first evidence linking atrial arrhythmia with augmented local oestrogen biosynthetic capacity in pericardial adipose. These findings provide new leads for the targeting of anti-arrhythmic therapies in aged/obese populations exposed to AF risk.

Water-soluble acacetin prodrug confers significant cardioprotection against ischemia/reperfusion injury.

The morbidity and mortality of patients with ischemic cardiomyopathy resulted from ischemia/reperfusion injury are very high. The present study investigates whether our previously synthesized water-soluble phosphate prodrug of acacetin was cardioprotective against ischemia/reperfusion injury in an in vivo rat model. We found that intravenous administration of acacetin prodrug (10 mg/kg) decreased the ventricular arrhythmia score and duration, reduced ventricular fibrillation and infarct size, and improved the impaired heart function induced by myocardial ischemia/reperfusion injury in anesthetized rats. The cardioprotective effects were further confirmed with the parent compound acacetin in an ex vivo rat regional ischemia/reperfusion heart model. Molecular mechanism analysis revealed that acacetin prevented the ischemia/reperfusion-induced reduction of the anti-oxidative proteins SOD-2 and thioredoxin, suppressed the release of inflammation cytokines TLR4, IL-6 and TNFα, and decreased myocyte apoptosis induced by ischemia/reperfusion. Our results demonstrate the novel evidence that acacetin prodrug confer significant in vivo cardioprotective effect against ischemia/reperfusion injury by preventing the reduction of endogenous anti-oxidants and the release of inflammatory cytokines, thereby inhibiting cardiomyocytes apoptosis, which suggests that the water-soluble acacetin prodrug is likely useful in the future as a new drug candidate for treating patients with acute coronary syndrome.

Surgery for supraventricular tachycardia and congenital heart defects: long-term efficacy of the combined approach in adult patients

Supraventricular arrhythmias are a major cause of morbidity and mortality in adult patients with congenital heart disease (CHD). Intraoperative ablation offers an alternative for patients who failed ablation procedures or are requiring concomitant surgical intervention. We present our long-term results with the surgical treatment of arrhythmias in adults with CHD (ACHD) undergoing elective cardiac surgery and the clinical predictors for arrhythmia recurrence. Between 2002 and 2013, 80 consecutive patients with CHD, mean age of 39 years, underwent intraoperative ablation with monopolar irrigated radiofrequency during cardiac surgery procedures. Significant clinical predictors of arrhythmia recurrence were determined by univariate analysis. We performed 47 right-sided Maze procedures, and 33 Cox-Maze III procedures. In 75 survivors, the ablation was effective immediately. Over an average follow-up period of 72 months (12-155 months), arrhythmias recurred in nine (20%) patients after right-sided Maze, and in six (19%) patients after Cox-Maze III. Eleven patients were controlled with medical therapy, three underwent catheter ablation of the arrhythmia, and one required a permanent pacemaker. Preoperative arrhythmia length ≥3 years (P ≤ 0.001), tetralogy of Fallot (P ≤ 0.006), and preoperative atrial fibrillation (P ≤ 0.016) were associated with recurrence arrhythmia. Conversely, NYHA class <3 (P ≤ 0.047) was associated with a lower risk of recurrence. Surgical treatment of unresponsive supraventricular arrhythmia during concomitant cardiac surgery in ACHD is a safe and effective procedure. Freedom from arrhythmias recurrence is 75% after 6 years of follow-up. Long-term recurrence of arrhythmia in these patients seems to be strongly correlated to preoperative arrhythmia duration.

Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes (n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

16-24: Identification of Heterogeneous Intra-Atrial Conduction Delay in Paroxysmal AF Patients by Dynamic Electrophysiological Characterization

Purpose of the Study: Although atrial fibrillation (AF) is classified by arrhythmia duration, the presentation, clinical course and response to treatment vary widely within paroxysmal AF (PAF) patients. We hypothesized that variable electrical remodeling exists between PAF patients, resulting in intra-atrial conduction delay which could be identified using a novel programmed stimulation technique. Methods Used: In 15 PAF patients undergoing index PVI, high density LA contact mapping using a 20 pole Pentaray catheter was performed during pacing from two atrial sites (BCL 470ms, S1S2 350ms to atrial ERP in -2% steps). Regional atrial conduction delay (S1S2delay), activation dispersion, and AF vulnerability were measured. Computer modeling was used to interrogate the mechanism of conduction delay. Summary of Results: Conduction delay showed a bimodal distribution (peaks for HRA / CS pacing 275 ± 11 / 271 ± 11ms and 326 ± 13 / 319 ± 16ms) and patients with inducible AF were characterized by increased activation dispersion (ΔLAT 672 ± 41ms vs 542 ± 17ms, P = 0.0446, Fig). Action potential remodeling across the population could explain observed variation in conduction delay, but resulted in insufficient conduction velocity restitution variation (3.7 ± 0.5ms-1/s vs 2.3 ± 0.5 ms-1/s, P = 0.1926) to explain the activation dispersion seen in AF-inducible patients.

Association of Soluble CD40 Ligand WithDuration of Atrial Fibrillation andWith Intensity of Spontaneous Echocardiographic Contrast.

The authors tested the hypothesis that the inflammatory response of nonvalvular atrial fibrillation (NVAF) is associated with elevated soluble CD40 ligand (sCD40L). NVAF is generally believed to be an inflammatory disease process. sCD40L represents a sensitive invivo indicator of platelet activation and may serve as an "inflammatory and thrombotic thermometer." Plasma sCD40L was measured using enzyme-linked immunoadsorbent assay in 109 NVAF cases (60.9 ± 15 years of age; 26% women) and 48normal sinus rhythm (NSR) controls (62.3 ± 15 years of age; 44% women). Patients were separated by arrhythmia duration of<1 month (n= 21), 1 to 12 months (n= 18), and >12 months (n= 70). Median sCD40L level was significantly higher in NVAF cases than in NSR controls (321 pg/ml vs. 238 pg/ml, respectively; p= 0.029). This difference was driven by higher levels in patients with NVAF duration for<1 month (552pg/ml) and 1 to 12 months (328 pg/ml). NVAF patients with arrhythmia duration for over 1 year had sCD40L levels not significantly different from those of NSR controls. An sCD40L concentration of 552 pg/ml distinguished NVAF patients with dysrhythmia duration of<1 month (area under the curve [AUC] of 0.72; p= 0.0010) or duration for ≤12months (AUC: 0.69; p= 0.0003) from NSR controls. Circulating sCD40L levels were also significantly higher among patients with mild spontaneous echocardiogram contrast (SEC) (p= 0.0378) and those with moderate SEC (p= 0.007) compared with NSR controls. sCD40L levels are significantly higher in NVAF patients than in NSR controls but only for up to 1 year after development of dysrhythmia. An sCD40L concentration of 552 pg/ml can help to assess development or recurrence of asymptomatic NVAF.

0291 : Mitochondrial permeability transition pore opening might contribute to ventricular arrhythmia maintenance

Calcium leak from the sarcoplasmic reticulum (SR) favors cardiac sudden death through a calcium overload mechanism. Here we investigate the crosstalk between the calcium overload SR-mediated and the mitochondrial permeability transition pore (mPTP) opening during a ventricular arrhythmic episode. a burst pacing protocol was developed to induce ventricular arrhythmia in the perfused rat heart. Surface electrocardiogram, left ventricular pressure, and oxygen consumption were monitored. Epicardial fluorescence was recorded from either a mitochondrial membrane potential dye or an intracellular calcium dye. ECG signals were used to assess both arrhythmia complexity and duration. Hearts were perfused with tacrolimus (FK506) alone or in combination with cyclosporin A (CsA) to promote SR calcium leak or inhibit mPTP, respectively. Prior to arrhythmia induction, FK506 promoted mitochondrial depolarization and intracellular calcium overload in a CsA-sensitive manner. More than 90% of hearts developed complex ventricular arrhythmias in the FK506 group and this was accompanied by a strong mitochondrial membrane depolarization. In contrast, in the FK506 + CsA group, 100% of the hearts spontaneously defibrillate after a few seconds of arrhythmias. In this group, following arrhythmia induction, mitochondrial depolarization amplitude, intracellular calcium overload and heart efficiency depression was decreased in comparison to the FK506 group. Here we suggest that the FK506-induced calcium overload promotes mitochondrial calcium accumulation and leads to mPTP opening. We propose that mPTP opening should be considered as an arrhythmogenic substrate. The author hereby declares no conflict of interest

Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia.

We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7-/- mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff-perfused Alk7-/- hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito carrying channel), was markedly decreased in Alk7-/- hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia.

Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients

BackgroundLimited data are available about direct current cardioversion (DCCV) in Fontan patients. MethodsRetrospective review of adult Fontan patients that underwent DCCV for atrial arrhythmias at Mayo Clinic, 1994–2014. Study endpoints were to determine procedural success, safety, and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. Results86 patients underwent 152 DCCV; age 27±8years; male 49 (57%); atriopulmonary Fontan, 64 (74%); atrial flutter/interatrial reentry tachycardia 125 (82%). Freedom from recurrence was 84% and 47% at 12 and 36months; freedom from repeat DCCV was 91% and 64% at 12 and 36months. Procedural failure occurred in 41 (27%); predictors of procedural failure were older age (HR 1.91, CI 1.16–2.73 per decade) and prior DCCV (HR 2.71, CI 1.22–3.21). Concomitant oral class I or III antiarrhythmic medication was associated with an increased likelihood of success (HR 0.64, CI 0.41–0.87). Predictors of recurrence were older age (HR 3.26, CI 1.19–6.55 per decade); duration of arrhythmia (HR 1.87, CI 1.14–2.56 per decade); and presence of atriopulmonary Fontan (HR 1.54, CI 1.27–1.85). Procedural complications were symptomatic bradycardia in 2 cases (1%). No thromboembolic complications or deaths occurred. ConclusionDCCV in Fontan patients is safe but is associated with significant procedural failure and recurrence rates. Ideally, antiarrhythmic medication should be instituted prior to DCCV in stable patients and DCCV alone should be considered as a temporizing measure to maintain sinus rhythm.

The Effect of PM 10 on Ischemia- Reperfusion Induced Arrhythmias in Rats

Epidemiological studies show that particulate matter (PM) is the principal instigator of some adverse clinical symptoms involving cardiovascular diseases. PM exposure can increase experimental infarct size and potentiate myocardial ischemia and arrhythmias in experimental MI models such as ischemia-reperfusion (I/R) injury.The present study was aimed to evaluate the effects of particulate matter (PM10) on ischemia- reperfusion induced arrhythmias with emphasis on the protective role of VA as an antioxidant on them. Male Wistar rats were divided into 8 groups (n=10): Control, VAc, Sham, VA, PM1 (0.5 mg/kg), PM2 (2.5 mg/kg), PM3 group (5 mg/kg), PM3 + VA group. Within 48 hours, PM10 was instilled into trachea in two stages. Then the hearts were isolated, transferred to a Langendorff apparatus, and subjected to global ischemia (30 minutes) followed by reperfusion (60 minutes). The ischemia- reperfusion induced ventricular arrhythmias were assessed according to the Lambeth conventions.In the present study,the number, incidence and duration of arrhythmiasduring30 minutes ischemia were demonstrated to be more than those in the reperfusion stage. PM exposure increased significantly the number, incidence and duration of arrhythmias in the ischemia and reperfusion duration. Vanillic acid reduced significantly the number, incidence and duration of arrhythmias during the ischemia and reperfusion period.In summary, the results of this study demonstrated that the protective and dysrhythmic effects of VA in the PM exposure rats in I/R model are probably related to its antioxidant properties.