Statement from the Asia Summit: Current state of arrhythmia care in Asia.

On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummit-22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life-threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region due to differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

Identification of Pacemaker Lead Position Using Fluoroscopy to Avoid Significant Tricuspid Regurgitation.

Permanent pacemaker implantation improves survival but can cause tricuspid valve dysfunction in the form of tricuspid regurgitation (TR). The dominant mechanism of pacemaker-mediated TR is lead impingement. This study evaluated the association between the location of the pacemaker leads crossing the tricuspid valve and the incidence of worsening TR and lead impingement using fluoroscopy. Lead positions were evaluated using perpendicular right anterior oblique (RAO) and parallel left anterior oblique (LAO) fluoroscopic angulation views of the tricuspid annulus. A two-dimensional transthoracic echocardiogram (TTE) was performed to evaluate the maximum TR jet area-to-right atrium ratio and define regurgitation severity. A three-dimensional TTE was performed to evaluate lead impingement. A worsening of TR was observed in 23 of 82 subjects. Most leads had an inferior position in the RAO view and a septal position in the LAO view. The mid position in the RAO view and septal position in the LAO view were risk factors for lead impingement. Mid and septal positions were associated with higher risks of significant TR and lead impingement. Lead impingement was associated with a high risk of significant TR. Pacemaker-mediated TR remains a significant problem after lead implantation.

External Counterpulsation Improves Angiogenesis by Preserving Vascular Endothelial Growth Factor-A and Vascular Endothelial Growth Factor Receptor-2 but Not Regulating MicroRNA-92a Expression in Patients With Refractory Angina.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

AH jump duration is associated with elimination of slow pathway during ablation of atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Ablating the slow pathway (SP) is the superior treatment for atrioventricular nodal reentrant tachycardia (AVNRT) with a low complication rate. However, the ablation of the SP could result in either complete elimination or modification of the SP. We aimed to investigate whether the duration of AH jump pre-ablation associated with the outcome of elimination of SP. METHODS: We included 56 patients with typical AVNRT (slow-fast), 20 males and 36 females, aged 44.2 ± 15.1 years. Slow pathway ablation was performed using classical approach. Univariate and multivariate analysis was performed for potential predictors of SP elimination. RESULTS: Typical AVNRT was inducible in all patients. Post-ablation, non-inducibility of AVNRT was obtained in all 56 (100%) patients, with SP elimination in 33 (61%) patients and SP modification in 23 (39%) patients. Patients with SP elimination had significantly longer AH jump than patients with SP modification. Cox regression analysis showed that AH jump duration was the independent predictor of SP elimination, in which every 20 ms increase in AH jump duration was associated with 1.30 higher rate of SP elimination. Furthermore, ROC curve analysis indicated that the AH jump duration of ≥100 ms had 6.14 times higher probability for complete elimination of the SP with a sensitivity of 79%, specificity of 70%, PPV of 79% and NPV of 70%. CONCLUSIONS: AH jump duration pre-ablation is associated with complete elimination of slow pathway during AVNRT ablation.

Left atrial appendage closure device implantation guided with fluoroscopy only: Long-term results.

BACKGROUND: Left atrial appendage (LAA) closure device is an alternative to anticoagulants for stroke prevention in selected atrial fibrillation (AF) patients. The LAA device implantation is safe with short period of learning curve. The standard implantation technique warrants a transesophageal echocardiography (TEE) guided and general anesthesia. In region of Asia Pacific as well as Indonesia, both TEE and general anesthesia are not always available in district hospital. We studied the safety and efficacy of Amplatzer Cardiac Plug (ACP) implantation guided by fluoroscopy only and without general anesthesia. METHODS: Consecutive nonvalvular AF patients with CHA2DS2VASc score of ≥2 and HASBLED score of ≥3 are participated. Patients requiring long-life anticoagulant for any other indication are excluded. The choice of implanted first or second-generation ACP is that with excess size of 2-4 mm of measured landing zone diameter. RESULTS: Twenty-five subjects were implanted ACP by means fluoroscopy only (Group A) and 28 subjects using standard technique group (Group B). The median AF duration was 36 months (6-276 months) and majority of patients (49%) are having permanent AF. The mean CHA2DS2VASc score is 3.9 ± 1.63. Successful implantation of ACPs was 96% in both groups. Nonfatal pericardial effusion occurred in three patients. During 75 weeks of follow-up period, there were no significant differences of stroke event and death between groups. CONCLUSION: ACP implantation guided with fluoroscopy only is feasible and safe.

SCN5A gene mutations and the risk of ventricular fibrillation and syncope in Brugada syndrome patients: A meta-analysis.

Mutations in the gene encoding the main cardiac sodium channel (SCN5A) are the commonest genetic cause of Brugada syndrome (BrS). However, the effect of SCN5A mutations on the outcomes of ventricular fibrillation (VF) and syncope remains uncertain. To clarify this relationship, a meta-analysis was performed. A comprehensive search was conducted to identify all eligible studies from PubMed, MEDLINE, EBSCO, ProQuest, Science Direct, Clinical Key, and Cochrane database for cohort studies of BrS populations that had been systematically tested for SCN5A mutations. We did meta-analysis to see the relationship between SCN5A mutations and the occurrence of VF and/or syncope using RevMan 5.3. Five clinical studies met our criteria and included a total of 665 BrS patients. These studies included 45 patients with VF and 178 patients with syncope. We found that in BrS patients with SCN5A mutations the rate of VF event was 30.7% while in patients without mutations was 28.5% (Risk Ratio [RR] = 1.11, [95% CI: 0.61, 2.00], P = 0.73, I 2 = 0%). The occurrence of syncope events was 35.9% in patients with SCN5A mutations and 34.5% in patients without mutations (RR = 1.12, [95% CI: 0.87, 1.45], P = 0.37, I 2 = 39%). Furthermore, the occurrence of combined VF and syncope events were similar between the 2 groups (RR = 1.12, [95% CI: 0.89, 1.42], P = 0.34, I 2 = 11%). BrS patients with SCN5A mutations exhibit a similar risk of future occurence of VF and/or syncope as compared to those without SCN5A mutations.

Amplatzer Cardiac Plug for Stroke Prevention in Patients with Atrial Fibrillation and Bigger Left Atrial Appendix Size.

Left atrial appendage (LAA) dimensions have been shown as an independent predictor of higher risk for stroke in AF patients. Little data exist on the outcomes after LAA closure in patients with nonvalvular atrial fibrillation (NVAF) who have relatively bigger LAA size. This study aims to evaluate the results associated with LAA closure with the Amplatzer cardiac plug (ACP, AGA, St. Jude Medical, Minneapolis, MN) in bigger LAA size. A total of 25 patients with NVAF underwent LAA closure with the ACP device. All patients received short-term (up to 3 months) dual-antiplatelet therapy (clopidogrel and aspirin) after the procedure and aspirin only thereafter. A transesophageal echocardiography was performed in all patients at the 3- and 6-month follow-ups. No patient was lost to follow-up (≥ 12 months in all patients). The mean age, CHA2DS2-VASc score, and HAS-BLED score were 66.2 ± 8.79 years; 3.2 ± 1.46 and 2.4 ± 1.0, respectively. The average sizes of the LAA landing zone and ostium were 23.08 ± 5.0 and 24.9 ± 4.4 mm, respectively. The procedure was successful in 23 (92%) patients and was canceled in 2 (8%) patients due to huge LAA dimensions. In 56% of the patients "pull and release" technique is needed to appropriately implant the ACP. During a mean follow-up of 12 months, no cases of periprocedural stroke and no mortality were observed. In patients with NVAF at high risk of cardioembolic events and big LAA size, LAA closure using the ACP device is safe and effective.

Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure.

Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

Electromechanical effects of 1,25-dihydroxyvitamin d with antiatrial fibrillation activities.

INTRODUCTION: Treatment with 1,25-dihydroxyvitamin D (1,25[OH]2 D) has several cardiovascular benefits. 1,25[OH]2 D has direct cellular effects, but its effects on the atrium are not clear. We evaluated the effects of 1,25[OH]2 D on the atrial electrophysiology and atrial fibrillation (AF). METHODS: Conventional microelectrodes were used to record action potentials (APs) and contractility in isolated rabbit left atrium (LA) tissue preparations before and after the administration of 0.01, 0.1, and 1 nM 1,25[OH]2 D with and without rapid atrial pacing (RAP) and acetylcholine (5 mM)-induced AF. Surface ECG and intracardiac electrograms were recorded before and after the intravenous administration of 4 units/kg of 1,25[OH]2 D in heart failure (HF) rabbits (4 weeks after coronary artery ligation) with RAP and acetylcholine-induced AF. RESULTS: 1,25[OH]2 D dose-dependently increased the AP duration in the LA, which was abolished by pretreatment with 0.1 µM ryanodine. RAP and 5 mM acetylcholine-induced fewer (64.3% vs 100%, P < 0.05) AF occurrences in the presence (n = 14) of 1,25[OH]2 D than those (n = 14) in the absence of 1,25[OH]2 D. The LA treated with 1,25[OH]2 D (n = 9) had a slower maximal AF rate (10.9 ± 2.4 Hz vs 13.3 ± 2.7 Hz, P < 0.05) than the LA (n = 14) without 1,25[OH]2 D. Moreover, 1,25[OH]2 D caused a lower AF inducible percentage (11.0 ± 1.9% vs 100 ± 0%, P < 0.001) and a shorter duration (4 ± 0.4 seconds vs 309 ± 26 seconds, P < 0.001) with a prolonged LA 90% monophasic AP duration (94.1 ± 0.2 milliseconds vs 98.5 ± 0.1 milliseconds, P < 0.05) in 5 rabbits with HF. 1,25[OH]2 D did not prolong the QT interval or 90% of the AP duration in isolated Purkinje fibers. CONCLUSION: 1,25[OH]2 D has direct electromechanical effects on the LA and can prevent or terminate AF.

Renal dysfunction and the risk of thromboembolic events in patients with atrial fibrillation after catheter ablation--the potential role beyond the CHA2DS2-VASc score.

BACKGROUND: Renal dysfunction is recognized as an important risk factor for thromboembolic (TE) events in patients with atrial fibrillation (AF) under medical treatment. OBJECTIVE: To investigate whether renal dysfunction is a useful predictor of TE events among patients receiving AF ablation. We also aimed to determine whether the diagnostic accuracy of the CHA(2)DS(2)-VASc score in predicting TE events could be improved by adding renal dysfunction into the scoring system. METHODS: We enrolled a total of 547 patients with AF who underwent catheter ablation. Renal dysfunction was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). The clinical end point was the occurrence of TE events (ischemic stroke, transient ischemic attack, or other systemic embolisms) during follow-up after catheter ablation. RESULTS: During a follow-up of 38.9 ± 22.5 months, 16 patients (2.9%) experienced TE events. Both the CHA(2)DS(2)-VASc score and renal dysfunction were independent predictors of TE events in the multivariate analysis. Among patients with a CHA(2)DS(2)-VASc score of 0 or 1, renal dysfunction can further stratify them into 2 groups with different event rates (4.3% vs 0.3%; P = .046). A new scoring system derived by assigning 1 more point representing renal dysfunction to the CHA(2)DS(2)-VASc score could improve its predictive accuracy; the area under the receiver operating characteristic curve increased from 0.84 to 0.88 (P = .043). CONCLUSIONS: Renal dysfunction was a significant risk factor for TE events after catheter ablation of AF and may improve the diagnostic accuracy of the CHA(2)DS(2)-VASc score.