Antiarrhythmic Pharmacotherapy Research Articles

Totally thoracoscopic atrial fibrillation surgery following massive small bowel resection due to superior mesenteric artery embolization: report of two cases

BackgroundThromboembolic occlusion of the superior mesenteric artery (SMA) is a grave complication in individuals diagnosed with atrial fibrillation (AF). This condition often necessitates extensive bowel resection, culminating in short bowel syndrome, which presents challenges for anticoagulant administration and/or antiarrhythmic therapy.Case presentationPresented here are findings of two patients, aged 78 and 72 years, respectively, who underwent comprehensive thoracoscopic AF surgery subsequent to extensive small bowel resection following SMA embolization. In each, onset of AF precipitated an embolic event, while the concurrent presence of short bowel syndrome complicated anticoagulation management. Total thoracoscopic AF surgery, comprised stapler-closure of the left atrial appendage (LAA) and bilateral epicardial clamp-isolation of the pulmonary veins, an operative modality aimed at addressing AF rhythm control and mitigating embolic events such as cerebral infarction, led to favorable outcomes in both cases. Additionally, computed tomography (CT) conducted one month post-surgery revealed the absence of residual tissue in the LAA, with the left atrium demonstrating a well-rounded, spherical shape. At the time of writing, the patients have remained asymptomatic following surgery regarding thromboembolic and arrhythmic manifestations for 29 and 10 months, respectively, notwithstanding the absence of anticoagulant or antiarrhythmic pharmacotherapy. Additionally, electrocardiographic surveillance has revealed persistent sinus rhythm.ConclusionsThe present findings underscore the feasibility and efficacy of a total thoracoscopic AF surgery procedure for patients presented with short bowel syndrome complicating SMA embolization, thus warranting consideration for its broader clinical application.

CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2.

Ventricular arrhythmia and sudden cardiac death are the most common lethal complications after myocardial infarction. Antiarrhythmic pharmacotherapy remains a clinical challenge and novel concepts are highly desired. Here, we focus on the cardioprotective CNP (C-type natriuretic peptide) as a novel antiarrhythmic principle. We hypothesize that antiarrhythmic effects of CNP are mediated by PDE2 (phosphodiesterase 2), which has the unique property to be stimulated by cGMP to primarily hydrolyze cAMP. Thus, CNP might promote beneficial effects of PDE2-mediated negative crosstalk between cAMP and cGMP signaling pathways. To determine antiarrhythmic effects of cGMP-mediated PDE2 stimulation by CNP, we analyzed arrhythmic events and intracellular trigger mechanisms in mice in vivo, at organ level and in isolated cardiomyocytes as well as in human-induced pluripotent stem cell-derived cardiomyocytes. In ex vivo perfused mouse hearts, CNP abrogated arrhythmia after ischemia/reperfusion injury. Upon high-dose catecholamine injections in mice, PDE2 inhibition prevented the antiarrhythmic effect of CNP. In mouse ventricular cardiomyocytes, CNP blunted the catecholamine-mediated increase in arrhythmogenic events as well as in ICaL, INaL, and Ca2+ spark frequency. Mechanistically, this was driven by reduced cellular cAMP levels and decreased phosphorylation of Ca2+ handling proteins. Key experiments were confirmed in human iPSC-derived cardiomyocytes. Accordingly, the protective CNP effects were reversed by either specific pharmacological PDE2 inhibition or cardiomyocyte-specific PDE2 deletion. CNP shows strong PDE2-dependent antiarrhythmic effects. Consequently, the CNP-PDE2 axis represents a novel and attractive target for future antiarrhythmic strategies.

Quality indicators of the atrial fibrillation management from the European (EORP) and Asia-Pacific (APHRS) registries

Abstract Background The 2020 ESC guideline for atrial fibrillation (AF) recommends universal quality indicators to identify areas for improvement in clinical practice. It also recommends using clinical registries to monitor clinical practice and identify areas for improvement. We have analysed two large comprehensive prospective clinical registries of patients with AF, the EURObservational Research Programme (EORP) and the Asia Pacific Heart Rhythm Society (APHRS), to compare the achievement of the ESC quality indicators in two major world populations. Methods The EORP and APHRS registries used the same electronic case report forms to collect data. T-test and Chi-squared test were used to compare registries. Logistic regression was used to identify pharmacological rate control therapy predictors in permanent AF. The model was adjusted for age, oral anticoagulation (OAC), EHRA and CHA2DS2-VASc scores, heart rate on the latest ECG and the region of recruitment (Europe or Asia) (STATA Corp, version 13). Results All 11096 EORP patients (59.3% males, age 69±11 years) and 5460 APHRS patients (66.3% males, age 68±12 years) had CHA2DS2-VASc and HAS-BLED scores documented at enrolment. The EORP register included a higher proportion of patients with CHA2DS2VASc ≥2 (81% vs 70%, p<0.001). These patients had similar OAC use (87%) in both registries, but NOAC use was higher in the APHRS (67% vs 34%, p<0.001), while dual antithrombotic use was more common in the EORP (14% vs 8%, p<0.001). The Table lists paraments that may impact OAC prescription. In patients with permanent AF, heart rate (82±20 vs 78±20, p<0.001) and antiarrhythmic pharmacotherapy (9% vs 5%) was higher in the EORP registry. On logistic regression, independent predictors of rate control with antiarrhythmic pharmacotherapy were higher EHRA 3 score (adjusted odds ratio (aOR) 1.8; 95% confidence interval (CI) 1.3–2.5, p<0.001); faster heart rate (aOR 1.01; 95% CI 1.00–1.02, p<0.001); younger age (aOR 0.97; 95% CI 0.96–0.98, p<0.001) and being recruited to the APHRS (aOR 0.56; 95% CI 0.40–0.79, p=0.001). APHRS vs EORP patients with non-permanent AF were less symptomatic (EHRA score I in 56% vs 38%) with less frequent use of antiarrhythmics (25% vs 37%), rhythm-management interventions (32% vs 46%), but higher use of catheter ablation (p<0.001 for all). Conclusion There are significant regional variations in achievement of the ESC quality indicator for AF. The variations may be due to differences in healthcare systems, but they may also reflect the population characteristics. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported theprogramme: Abbott Vascular Int. (2011-2014), Amgen Cardiovascular(2009-2018), AstraZeneca (2014-2017), Bayer AG (2009-2018),Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), TheBristol Myers Squibb and Pfizer Alliance (2011-2016), The Alliance DaiichiSankyo Europe GmbH and Eli Lilly and Company (2011-2017), Edwards(2016-2019), Gedeon Richter Plc. (2014-2017), Menarini Int. Op. (2009-2012), MSD-Merck & Co. (2011-2014), Novartis Pharma AG (2014-2017), ResMed (2014-2016), Sanofi (2009-2011), and SERVIER (2009-2018).The Atrial Fibrillation NETwork (AFNET), conducting the registryin Germany, received support from The Bristol Myers Squibb/PfizerAlliance (2014-2018) and the German Centre for CardiovascularResearch (DZHK).

Radiofrequency ablation impact on the morpho-functional state of the heart in patients with atrial fibrillation and chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Heart failure with preserved left ventricular ejection fraction (HFpLVEF) has become the dominant form of heart failure worldwide, along with an aging population and an increasing prevalence of obesity, diabetes and hypertension. Drug rhythm control has limited efficacy in HFpLVEF and a fairly high risk of side effects. The aim of the study was to evaluate the radiofrequency ablation impact on the morpho-functional state of the heart in patients with atrial fibrillation and HFpLVEF based on 2-year follow-up. Materials and methods The study included 194 patients with an average age of 59.3±8.5 years with atrial fibrillation and concomitant HFpLVEF of I-III functional class of New York Heart Association. Patients were divided into 2 groups: 136 patients who underwent radiofrequency catheter ablation and 58 patients in the control group who did not undergo intervention and continued antiarrhythmic pharmacotherapy. Patients were comparable in terms of basic clinical and demographic indicators. In order to assess the morpho-functional state of the heart, transthoracic echocardiography was performed at the stage of inclusion in the study and 2 years after. Results and discussion. According to the results of the analysis in the radiofrequency catheter ablation group 2 years after the intervention revealed: a statistically significant decrease in the mean end-systolic diameter of the left ventricle (3.3±0.48 cm versus 3.2±0.41cm, p<0.001); decreased size of the left atrium (4.3±0.71 cm versus 4.2±0.30 cm, p<0.001); LVEF increased significantly (61.9±7.14% versus 63.9±5.65%, p<0.001); the E/e’ ratio decreased statistically significantly (11.9±1.65 versus 9.4±1.48; p<0.001) and the left ventricular myocardial mass index (118.3±25.04 g/m2 versus 116.4±18.04 g/m2; p=0.045). In the pharmacotherapy group there were: a statistically significant increase in the average end-systolic size of the left ventricle (3.61±0.45 cm versus 3.63±0.41, p=0.007); statistically significant increased left atrium (4.3±0.61 cm versus 4.4±0.36; p <0.001) and the right atrium (4.1±0.52 cm versus 4.2±0.26; p<0.001); decreased left ventricular ejection fraction (58.1±6.12% versus 56.6±6.11; p<0.001); increased values of the ratio E/e’ (12.1±1.63 versus 12.7±1.27; p=0.002) and decreased level of the left ventricular myocardial mass index (120.5±24.05 g/m2 versus 118.3±20.13 g/m2; p=0.044). Conclusion Radiofrequency ablation of atrial fibrillation in patients with HFpLVEF to control sinus rhythm is associated with improved morpho-functional state of the heart at the 2-year follow-up compared with antiarrhythmic pharmacotherapy strategy: the left ventricular ejection fraction increases, the left ventricular diastolic function improves according to the E/e’ value, the size of the left atrium decreases.

Peculiarities of pharmacotherapy of chronic heart failure with retained left ventricular efficiency and associated atrial fibrilation depending on the method of heart rhythm control

Introduction. Only small studies in selected centers have examined the effect of rhythm control strategy, including catheter ablation, on major cardiovascular events, mortality in patients with long-term atrial fibrillation and concomitant chronic heart failure with preserved left ventricular ejection fraction and features of pharmacotherapy. The aim. To study the peculiarities of pharmacotherapy in patients with heart failure with preserved left ventricular ejection fraction and concomitant atrial fibrillation over a long period of observation, depending on the implementation of a rhythm control strategy: radiofrequency ablation or pharmacotherapy and their impact on endpoints. Materials and Methods. The study included 194 patients with a mean age of 59.3 ± 8.5 years with atrial fibrillation and concomitant heart failure with preserved left ventricular ejection fraction I–III of the NYHA functional class. Patients were divided into 2 groups: 136 patients who underwent radiofrequency ablation, and 58 patients in the control group who did not undergo intervention and continued antiarrhythmic pharmacotherapy. The patients were compared according to the main clinical and demographic indicators. An assessment was made of the characteristics of pharmacotherapy and different stages of observation by group and its impact on endpoints. Results. In the control group, the use of antiarrhythmic drugs other than amiodarone and oral anticoagulants at the baseline of the study was associated with the primary endpoint. The chance of its occurrence was 3.9 times higher among patients taking other antiarrhythmic drugs (odds ratio–3.949, 95 % confidence interval 1.198–13.013) and 1.8 times lower among patients taking anticoagulants (odds ratio - 0.556, 95 % confidence interval 0.399–0.965). In the ablation group, the chance of a primary endpoint event occurring was 3.1 times higher among patients taking diuretics at 2-year follow-up (odds ratio –3.130, 95 % confidence interval 1.111–8.824), and beta-blockers were associated with 3.4 times lower chance of these events (odds ratio – 0.296, 95 % confidence interval 0.128–0.688). In the ablation group, there was a statistically significant decrease in the percentage of patients requiring diuretics 2 years after inclusion in the study compared with the 3-month stage (p < 0.001) and the inclusion stage (p < 0.001). Conclusions. Long-term use of beta-blockers after intervention is associated with a reduced risk of primary endpoint events in the ablation group. Taking diuretics, beta-adrenergic receptors, and renin-angiotensin-aldosterone system inhibitors during the first 3 months after the intervention reduces the risk of atrial fibrillation recurrence in the long-term follow-up period in the ablation group.

Implications of “slower” ventricular tachycardia on clinical management and detection and therapy function of implantable cardioverter defibrillators

Sophisticated dual-chamber atrioventricular and rate-responsive pacing therapies, cardiac resynchronization therapy (CRT), detection and therapies for ventricular tachycardia and fibrillation (VT/VF) form some major components of multitask functions of current implantable cardioverter defibrillators (ICDs). Appropriate programming of these devices is necessary for them to perform all such tasks precisely. In this report, we describe a case of a patient with Chagas cardiomyopathy with marked cardiomegaly, scarred ventricles, prior epicardial and endocardial ablations and on antiarrhythmic pharmacotherapy for VT, who presented with symptomatic wide complex tachycardia at a slower rate than definition of VT, and in whom programming for detection and therapy for "slow" VT could not be performed due to default technological limitation of the CRT-D.

Cardiovascular Complications of Interatrial Conduction Block: JACC State-of-the-Art Review.

Interatrial block (IAB) is an electrocardiographic pattern describing the conduction delay between the right and left atria. IAB is classified into 3 degrees of block that correspond to decreasing conduction in the region of Bachmann's bundle. Although initially considered benign in nature, specific subsets of IAB have been associated with atrial arrhythmias, elevated thromboembolic stroke risk, cognitive impairment, and mortality. As the pathophysiologic relationships between IAB and stroke are reinforced, investigation has now turned to the potential benefit of early detection, atrialimaging, cardiovascular risk factor modification, antiarrhythmic pharmacotherapy, and stroke prevention with oralanticoagulation. This review provides a contemporary overview of the epidemiology, pathophysiology, diagnosis, and management of IAB, with a focus on future directions.

Diagnosis and management of arrhythmias in pregnancy.

Arrhythmias are the most common cardiac complications occurring in pregnancy. Although the majority of palpitations in pregnancy may be explained by atrial or ventricular premature complexes, the full spectrum of arrhythmias can occur. In this article, we establish a systematic approach to the evaluation and management of arrhythmias in pregnancy. Haemodynamically unstable arrhythmias warrant urgent cardioversion. For mild cases of benign arrhythmia, treatment is usually not needed. Symptomatic but haemodynamically stable arrhythmic patients should first undergo a thorough evaluation to establish the type of arrhythmia and the presence or absence of structural heart disease. This will ultimately determine the necessity for treatment given the potential risks of anti-arrhythmic pharmacotherapy in pregnancy. We will discuss the main catalogue of anti-arrhythmic medications, which have some established evidence of safety in pregnancy. Based on our appraisal, we provide a treatment algorithm for the tachyarrhythmic pregnant patient.

Вплив радіочастотної абляції на морфофункціональний стан серця у пацієнтів із фібриляцією передсердь та хронічною серцевою недостатністю

The purpose of the study was to evaluate the radiofrequency ablation impact on the morpho-functional state of the heart in patients with atrial fibrillation and chronic heart failure with preserved ejection fraction based on 2-year follow-up. Materials and methods. The study included 194 patients with an average age of 59.3±8.5 years with atrial fibrillation and concomitant heart failure with preserved left ventricular ejection fraction of I-III functional class of New York Heart Association. Patients were divided into 2 groups: 136 patients who underwent radiofrequency catheter ablation and 58 patients in the control group who did not undergo intervention and continued antiarrhythmic pharmacotherapy. Patients were comparable in terms of basic clinical and demographic indicators. In order to assess the morpho-functional state of the heart, transthoracic echocardiography was performed at the stage of inclusion in the study and 2 years after. Results and discussion. According to the results of the analysis in the radiofrequency catheter ablation group 2 years after the intervention revealed: a statistically significant decrease in the mean end-systolic diameter of the left ventricle (3.3±0.48 cm versus 3.2±0.41cm, p <0.001); decreased size of the left atrium (4.3±0.71 cm versus 4.2±0.30 cm, p <0.001); left ventricular ejection fraction increased significantly (61.9±7.14% versus 63.9±5.65%, p <0.001); the E/e' ratio decreased statistically significantly (11.9±1.65 versus 9.4±1.48; p <0.001) and the left ventricular myocardial mass index (118.3±25.04 g/m2 versus 116.4±18.04 g/m2; p=0.045). In the pharmacotherapy group there were: a statistically significant increase in the average end-systolic size of the left ventricle (3.61±0.45 cm versus 3.63±0.41, p=0.007); statistically significant increased left atrium (4.3±0.61 cm versus 4.4±0.36; p <0.001) and the right atrium (4.1±0.52 cm versus 4.2±0.26; p <0.001); decreased left ventricular ejection fraction (58.1±6.12% versus 56.6±6.11; p <0.001); increased values of the ratio E/e' (12.1±1.63 versus 12.7±1.27; p=0.002) and decreased level of the left ventricular myocardial mass index (120.5±24.05 g/m2 versus 118.3±20.13 g/m2; p=0.044). Conclusion. Radiofrequency ablation of atrial fibrillation in patients with heart failure with preserved left ventricular ejection fraction to control sinus rhythm is associated with improved morpho-functional state of the heart at the 2-year follow-up compared with antiarrhythmic pharmacotherapy strategy: the left ventricular ejection fraction increases, the left ventricular diastolic function improves according to the E/e' value, the size of the left atrium decreases

Ethnic-Related Sodium Voltage-Gated Channel α Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Nav1.5.

Nav1.5-derived Na+ current (INa) exerts a pivotal role in the depolarization phase of cardiomyocytes' action potential, and, therefore, changes in INa can contribute to fatal arrhythmias. Nav1.5 displays naturally occurring ethnicity-related polymorphisms, which might alter the functioning and pharmacology of the channel. Some studies have shown how single-nucleotide polymorphism can change the response to antiarrhythmic drugs. Investigations on the role of Nav1.5 in arrhythmogenesis associated with its functional polymorphisms are currently growing as well as the possible variability in the antiarrhythmic pharmacotherapy among ethnic groups. The influence of the ethnicity-related polymorphisms (S524Y, S1103Y, R1193Q, V1951L) on the responsiveness, selectivity, and pharmacological efficacy of the clinically used antiarrhythmic amiodarone (AMIO) is not completely known. Our objectives were to analyze biophysical and pharmacological aspects of four ethnicity-related polymorphisms before and after exposure to AMIO. Polymorphisms caused reduced AMIO potency compared with wild type (WT), which can vary by up to 4× between them. AMIO shifted the voltage dependency for current inactivation without significant effect in voltage-dependent activation to a similar extent in WT and polymorphisms. The recovery from inactivation was altered between the polymorphisms when compared with WT. Finally, the use dependency of AMIO differed between studied groups, especially at a more depolarized cell membrane. Thus, our work may guide future studies focusing on the efficiency of AMIO in treating different arrhythmias and establish more individualized guidelines for its use depending on the Nav1.5 polymorphism after validating our findings using in vivo studies. SIGNIFICANCE STATEMENT: Sodium voltage-gated channel α subunit 5 (SCN5A) gene encodes the α subunit of Nav1.5, the main cardiac voltage-gated Na+ channel. Interestingly, ethnicity-related polymorphisms are found in SCN5A. Amiodarone is used in clinical practice, and some of its effects are attributed to interaction with Nav1.5. Important, amiodarone efficacy is variable among patients. Here we show that ethnicity-related SCN5A polymorphisms lead to altered Nav1.5-amiodarone interaction, which may be the cause for the variable efficacy observed in clinical usage of amiodarone.

Proarrhythmic Manifestations of Neuromuscular Dystrophinopathies.

Muscular dystrophy has been an elusive term ever since it was first described in the 19th century. Introduced in 1891 by Wilhelm Heinrich Erb, muscular dystrophy has been classified as part of a larger group of genetically determined, progressive degenerative neuromuscular disorders termed "dystrophinopathies." Cardiac arrhythmias may occur during the neurologic course of the disease. Although descriptions of the dystrophinopathies have been reported in the literature, few articles address the use of antiarrhythmic pharmacotherapy in patients with muscular dystrophy. We discuss the pathophysiology of the most common dystrophinopathies, their proarrhythmic sequelae, and the therapeutic use of antiarrhythmic agents in the clinical setting.

P3757Profibrogenic biomarkers and severity of left atrial fibrosis in patients with atrial fibrillation and metabolic syndrome: is it possible to predict the effectiveness of therapy?

Abstract Background Galectin-3 (Gal-3) and transforming growth factor-beta1 (TGFbeta1) – biomarkers of fibrosis are increased in patients with atrial fibrillation (AFib) and metabolic syndrome (MetS). We propose that both can impact on progression of the arrhythmia. Purpose Objective of the study was to evaluate the role of Gal-3 and TGFbeta1 in predicting the effect of antiarrhythmic pharmacotherapy (APT) and radiofrequency ablation therapy (RAT) in patients with AFib and MetS. Methods 539 AFib patients hospitalized in cardiology department (2015–2016 years) were examined. 204 AFib patients with paroxysmal (n=156) and persistent (n=48) forms 35–60 years old were included in prospective study: 110 had ≥3 components of MetS (IDF, 2005) and 94 without MetS. Serum GAL-3, TGF-beta1 (Enzyme immunoassay) were performed. Antiarrhythmics were applied during 12 months. Antiarrhythmic effect of pharmacotherapy was established if no episodes of AFib were registered during follow-up. 73 patients without effect of APT were treated with RAT with pulmonary veins isolation. Ablation procedure was performed with the system of electroanatomical mapping CARTO3. In the “offline” mode we evaluated areas of low voltage in the amplitude spectrum of 0,2–1,0 mV and divided all patients into groups: I – minimal (<10% of LAarea, n=18), II – mild (10–19% of LAarea,n=26), III – moderate (20–29% of LAarea, n=17) and IV - severe low voltage area (≥30% of LAarea,n=12). After ablation, we analyzed the clinical data and the effectiveness of RAT during 12 months. Results Gal-3 in patients with recurrent paroxysms and without the effect of APT was higher than in patients without recurrent paroxysms (1312,1 [750,2; 2494,3] and 500,2 [410,3; 723,4] pg/ml, p<0,001). TGF-beta1 was also higher in patients without the effect of APT (11521,2 [2950,2; 17642,2] and 2999,5 [1767,4; 5490,2] pg/ml, p<0,001). Patients from IV group had greater low voltage area of LA, than in I group (33,4±2,1 and 6,6±2,4%, p<0,001), but also higher levels of Gal-3 (1201,1 [950,2; 2140,3] and 490,2 [310,3; 523,4] pg/ml, p=0,027) and TGF-beta1 (9497,2 [1257,2; 14672,2] and 3491,5 [1767,4; 8470,2] pg/ml, p=0,04). The multivariate regression analysis demonstrated that Gal-3 is an independent predictor of non-effective antiarrhythmic pharmacotherapy of AFib (OR=2,38, 95% CI: 1,12–5,04, p=0,024). In patients with AFib and MetS who had Gal-3 above 770,5 pg/ml (cut-off point on ROC-curve) the risk of non-effective APT was in 3,6-fold higher during follow-up (RR=3,6, 95% CI: 1,6–7,9, p=0,002). Binomial regression analysis was found that greater % of LA fibrosis corresponds to higher probability of recurrence of AFib after RAT (OR=1,1, 95% CI: 1,03–1,12, p=0,002). Conclusions Galectin-3 and TGF-beta1 in AFib and MetS patients with left atrium severe fibrosis are higher than in patients with minimal fibrosis. We suppose that profibrogenic substances can impact on progression of AFib and non-effectiveness antiarrhythmic pharmacotherapy. Acknowledgement/Funding Governmental grant 17-75-30052

Incidental significant arrhythmia in scleroderma associates with cardiac magnetic resonance measure of fibrosis and hs-TnI and NT-proBNP.

ObjectivesTo screen for significant arrhythmias with an implantable loop recorder (ILR) in patients with SSc and no known cardiovascular disease, and identify associated disease phenotype, blood and cardiovascular magnetic resonance (CMR) biomarkers.MethodsTwenty patients with SSc with no history of primary SSc heart disease, traditional cardiovascular disease, diabetes or maximum one traditional cardiovascular risk factor underwent clinical assessment, contrast-enhanced CMR and ILR insertion.ResultsILR data were available for 19 patients: 63% female, mean (s.d.) age of 53 (12) years, 32% diffuse SSc. Eight patients had significant arrhythmias over 3 years: one complete heart block, two non-sustained ventricular tachycardia [all three dcSSc, two anti-topoisomerase antibodies (Scl70) positive, three interstitial lung disease and two previous digital ulceration] and five atrial arrhythmias of which four were with limited SSc. These required interventions with one permanent pacemaker implantation, four anti-arrhythmic pharmacotherapy, one anticoagulation.Patients with significant arrhythmia had higher baseline high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide [mean difference (95% CI) 117 (−11, 245) and 92 (−30, 215) ng/l, respectively], and CMR-extracellular volume [mean (s.d.) 32 (2) vs 29 (4)%]. Late gadolinium enhancement was observed in five patients, only one with significant arrhythmia.ConclusionThis first ILR study identified potentially life-threatening arrhythmias in asymptomatic SSc patients attributable to a primary SSc heart disease. Disease phenotype, CMR-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening. Future studies can inform a risk model and provide insights into SSc-associated arrhythmia pathogenesis.

Cost Effectiveness of Ventricular Tachycardia Ablation Versus Escalation of Antiarrhythmic Drug Therapy: The VANISH Trial.

This analysis uses the data from the randomized controlled trial to assess the cost effectiveness of catheter ablation (n= 132) versus escalated antiarrhythmic therapy (n= 127). For survivors of myocardial infarction with implantable cardioverter-defibrillator shocks despite antiarrhythmicdrugs, the VANISH (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial demonstrated improved clinical outcomes with catheter ablation compared with more aggressive antiarrhythmic pharmacotherapy. Health care resource use and quality-of-life data were used to determine the cost effectiveness of catheter ablation. Published references were used to estimate costs (in 2015 Canadian dollars). The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities. Ablation resulted in greater quality-adjusted life-years (QALYs) than escalated drug therapy did (1.63 vs. 1.49; difference: 0.14; 95% confidence interval [CI]: -0.20 to 0.46) and higher cost ($65,126 vs. $60,269; difference: $4,857; 95% CI: -$19,757 to $27,106); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $34,057 primarily due to the initial costs of ablation, which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. For patients with amiodarone-refractory ventricular tachycardia, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs. 1.26; difference: 0.22; 95% CI: -0.19 to 0.59) and lower costs ($67,614 vs. $68,383; difference: -$769; 95% CI: -$35,330 to $27,092). For those with sotalol-refractory ventricular tachycardia, ablation resulted in similar QALYs (1.90 vs. 1.90; difference: -0.00; 95% CI: -0.59 to 0.62) andhigher costs ($60,455 vs. $45,033; difference: $15,422; 95% CI: -$10,968 to $48,555). For the total trial population, results are suggestive that ablation is cost effective compared with escalation of drug therapy. This result was only manifest for the subgroup of patients whose qualifying arrhythmia occurred despite amiodarone.

Superiorly directed atrial ectopy from the left inferior pulmonary vein

P wave morphology is often useful in planning and prognosticating invasive electrophysiology testing with an aim at ablation. It is generally believed that atrial ectopy of a pulmonary vein site of origin will be inferiorly directed. We report the case of superiorly directed P waves originating from the left inferior pulmonary vein, likely the result of a prior pulmonary vein isolation procedure. As demonstrated by our case, standard algorithms to identify the site of origin of atrial ectopy should be used with caution in patients with prior ablative procedures.

Drug-induced Brugada ECG Changes Associated With A Novel SCN5A Mutation In A Patient With Atrial Arrhythmias

Background: Subclinical mutations in the genes associated with inherited arrhythmias may cause unexpected pharmacologic responses in antiarrhythmic therapies.Methods: The administration of pilsicainide, a class Ic antiarrhythmic agent, caused marked Brugada-type ST-elevation and frequent PVCs in a 66-year-old Japanese male who had presented with paroxysmal atrial fibrillation and type I atrial flutter. The patient has structurally normal heart, with no family history of Sudden Cardiac Death (SCD) or syncope. Genetic screening using PCR/direct sequencing identified a novel SCN5A mutation, V1328M. Biophysical characteristics of WT and V1328M-SCN5A were studied using patch-clamp techniques.Results: The whole-cell sodium current densities were comparable between WT and V1328M. While V1328M did not significantly affect the voltage-dependent activation kinetics, V1328M was found to rightward shift the voltage-dependency of the peak currents by 10 mV and the steady-state inactivation by 7 mV (inactivation Vh: WT, −100.2± 0.8 mV, n = 10; V1328M, −93.1 ± 0.7 mV, n = 10, p<0.01). The pharmacologic responses of WT and V1328M to pilsicainide were studied .Pilsicainide (25 μM) caused similar extent of the tonic block reduction of sodium currents induced by a low frequency pulse protocol (q15s) in WT and V1328M. On the contrary, V1328M significantly enhanced the use-dependent block (2Hz) by pilsicainide (25 μM) compared to the WT (%block: V1328M, 62.0 ± 1.7, n = 6; WT, 42.6 ± 1.0, n = 6, p<0.001). In addition, intracellular pilsicainide (500 μM) did not block both WT and V1328M currents.Conclusion: Our findings suggest that a SCN5A mutation V1328M might predispose certain individuals in the antiarrhythmic pharmacotherapy to drug-induced Brugada ECG changes. Our data,also, suggests that the SCN5A mutation located in the intracellular side can affect the sodium channel blocking from the extracellular side.

Cellular basis for triggered ventricular arrhythmias that occur in the setting of compensated hypertrophy and heart failure: considerations for diagnosis and treatment

Malignant ventricular tachyarrhythmias are common among patients with hypertrophy and heart failure, and these arrhythmias can initiate by triggered activity. Abnormal repolarization and disturbed calcium handling due to remodeling processes are common features of the hypertrophied and failing heart that conspire to facilitate triggering events. These changes have a different cellular origin in compensated hypertrophy as compared with failure, which underscores the complexity of mechanisms that predispose the remodeled heart to arrhythmias. This hampers the identification of the vulnerable patient and adequate antiarrhythmic pharmacotherapy. Beat-to-beat variability of repolarization has been proposed as an early (noninvasive) electrographic detection method of triggered activity. An increase of variability heralds an enhanced risk of arrhythmias, and controlling this repolarization parameter by pharmacological agents is antiarrhythmic. Different drugs (flunarizine, ranolazine, K201, calmodulin kinase blockers) that are able to prevent and/or suppress triggered arrhythmias by specific mechanisms of action will be discussed.

The hERG potassium channel as a therapeutic target

The hERG (human ether-à-go-go-related gene) potassium channel has elicited intense scientific interest due to its counter-intuitive kinetics and its association with arrhythmia and sudden death. hERG blockade is involved in both antiarrhythmic pharmacotherapy and the pathogenesis of familial and acquired long QT syndrome (LQTS). Short QT syndrome (SQTS), muscular atrophy and many forms of cancer have also been associated with hERG as a target. Molecular models of both the channel and its blocker pharmacophores exist, revealing methods to design hERG liability out of potential drug molecules. Future developments will synthesise preclinical data on hERG with other criteria to determine net arrhythmogenic risk. Also, the molecular actions of hERG and its genetics will be elucidated in detail to allow clinical risk reduction.

Use of telemedicine in the diagnosis of paroxysmal atrial fibrillation and to monitor the effect of antiarrhythmic drug therapy

We present the case of a patient with highly symptomatic tachyarrhythmias for 2 years without any arrhythmia documentation despite numerous ECG and Holter registrations. By means of telemedicine, it was possible to document the arrhythmia--in this case atrial fibrillation--within 10 days and to start antiarrhythmic drug treatment with flecainide and metoprolol. This case demonstrates the diagnostic potential of telemedicine in patients with recurrent episodes of tachyarrhythmias in whom episodes are not sufficiently frequent to allow diagnosis by Holter monitoring. Telemedicine may also be advantageous for ECG monitoring during the early phase after cardioversion or initiation of specific antiarrhythmic pharmacotherapy in order to detect potential drug-induced proarrhythmic changes.

Can T-wave alternans on antiarrhythmic pharmacotherapy predict the recurrence of ventricular tachyarrhythmias in patients with cardiomyopathy?

Can T-wave alternans on antiarrhythmic pharmacotherapy predict the recurrence of ventricular tachyarrhythmias in patients with cardiomyopathy?