Educational status and the risk of adverse outcomes in Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

BACKGROUND: The aim of this study was to evaluate the impact of educational status (ES) on the clinical course of Asian patients with atrial fibrillation (AF). METHODS: We used data from the prospective APHRS-AF Registry. ES was classified as follows: low (primary school), medium (secondary), and high (University). The primary outcome was a composite of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Secondary outcomes were each component of the primary outcome, cardiovascular death, and major bleeding. The one-year risk of primary and secondary outcomes was assessed through Cox-regressions. Adherence to the Atrial fibrillation Better Care (ABC) pathway was assessed. RESULTS: Among 2697 AF patients (69±12 years, 34.8% females), 34.6% had low ES; 37.3% had medium ES; and 28.1% had high ES. Compared to patients with medium-high ES, patients with low ES were older, more often females, with a higher prevalence of cardiovascular risk factors, and a lower ABC pathway adherence (30.4% vs. 40.2%, P<0.001). On multivariable analysis, low ES was associated with a higher risk for the primary outcome (HR 1.52,95%CI 1.11-2.06) and all-cause death (HR 1.76,95%CI 1.10-2.83) than medium-high ES. A significant interaction was found for the risk of composite outcome among the different age strata, with the higher risk in the elderly (P for int=0.008), whereas the beneficial effect of the ABC pathway was irrespective of ES (P for int=0.691). CONCLUSIONS: In Asian AF patients, low ES is associated with high mortality. Efforts to improve education and include ES evaluation in the integrated care approach for AF are necessary to reduce the cardiovascular burden in these patients.

Adverse Events and Clinical Correlates in Asian Patients with Atrial Fibrillation and Diabetes Mellitus: A Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Aims. To evaluate the adverse events (and its clinical correlates) in a large prospective cohort of Asian patients with atrial fibrillation (AF) and diabetes mellitus (DM). Material and Methods. We recruited patients with atrial fibrillation (AF) from the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry and included those for whom the diabetic mellitus (DM) status was known. We used Cox-regression analysis to assess the 1-year risk of all-cause death, thromboembolic events, acute coronary syndrome, heart failure and major bleeding. Results. Of 4058 patients (mean age 68.5 ± 11.8 years; 34.4% females) considered for this analysis, 999 (24.6%) had DM (age 71 ± 11 years, 36.4% females). Patients with DM had higher mean CHA2DS2-VASc (2.3 ± 1.6 vs. 4.0 ± 1.5, p < 0.001) and HAS-BLED (1.3 ± 1.0 vs. 1.7 ± 1.1, p < 0.001) risk scores and were less treated with rhythm control strategies compared to patients without DM (18.7% vs. 22.0%). After 1-year of follow-up, patients with DM had higher incidence of all-cause death (4.9% vs. 2.3%, p < 0.001), cardiovascular death (1.3% vs. 0.4%, p = 0.003), and major bleeding (1.8% vs. 0.9%, p = 0.002) compared to those without DM. On Cox regression analysis, adjusted for age, sex, heart failure, coronary and peripheral artery diseases and previous thromboembolic event, DM was independently associated with a higher risk of all-cause death (HR 1.48, 95% CI 1.00-2.19), cardiovascular death (HR 2.33, 95% CI 1.01-5.40), and major bleeding (HR 1.91, 95% 1.01-3.60). On interaction analysis, the impact of DM in determining the risk of all-cause death was greater in young than in older patients (p int = 0.010). Conclusions. Given the high rates of adverse outcomes in these Asian AF patients with DM, efforts to optimize the management approach of these high-risk patients in a holistic or integrated care approach are needed.

Risk of Death and Cardiovascular Events in Asian Patients With Atrial Fibrillation and Chronic Obstructive Pulmonary Disease: A Report From the Prospective APHRS Registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations. METHODS AND RESULTS: Prospective observational study conducted on patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox-regression models were used to assess the 1-year risk of a primary composite outcome of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all-cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P<0.001), all-cause death (14.9% versus 2.6%, P<0.001), cardiovascular death (2.0% versus 0.6%, P<0.001), and heart failure (8.3% versus 6.0%, P<0.001). On multiple Cox-regression analysis, COPD was associated with a higher risk of the primary composite outcome (hazard ratio [HR], 3.17 [95% CI, 2.05-4.90]), all-cause death (HR, 3.59 [95% CI, 2.04-6.30]), and heart failure (HR, 3.32 [95% CI, 1.56-7.03]); no statistically significant differences were found for other outcomes. The association between COPD and mortality was significantly modified by the use of beta blockers (Pint=0.018). CONCLUSIONS: In Asian patients with AF, COPD is associated with worse prognosis. In patients with AF and COPD, the use of beta blockers was associated with a lower mortality. REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT04807049.

Sex-related differences in presentation, treatment, and outcomes of Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

We aimed to investigate the sex-related differences in the clinical course of patients with Atrial Fibrillation (AF) enrolled in the Asia-Pacific-Heart-Rhythm-Society Registry. Logistic regression was utilized to investigate the relationship between sex and oral anticoagulant, rhythm control strategies and the 1-year chance to maintain sinus rhythm. Cox-regression was utilized to assess the 1-year risk of all-cause, and cardiovascular death, thromboembolic events, acute coronary syndrome, heart failure, and major bleeding. In the whole cohort (4121 patients, 69 ± 12 years,34.3% female), females had different cardiovascular risk factors, clinical manifestations, and disease perceptions than men, with more advanced age (72 ± 11 vs 67 ± 12 years, p < 0.001) and dyslipidemia (36.7% vs 41.7%, p = 0.002). Coronary artery disease was more prevalent in males (21.1% vs 16.1%, p < 0.001) as well as the use of antiplatelet drugs. Females had a higher use of oral anticoagulant (84.9% vs 81.3%, p = 0.004) but this difference was non-significant after adjustment for confounders. On multivariable analyses, females were less often treated with rhythm control strategies (Odds Ratio [OR] 0.44,95% Confidence Interval [CI] 0.38-0.51) and were less likely to maintain sinus rhythm (OR 0.27, 95% CI 0.22-0.34) compared to males. Cox-regressions analysis showed no sex-related differences for the risk of death, cardiovascular, and bleeding. The clinical management of Asian AF patients should consider several sex-related differences.

Integrated Care for Atrial Fibrillation Using the ABC Pathway in the Prospective APHRS-AF Registry.

Background: The Atrial Fibrillation Better Care (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF), based on 3 pillars: "A" Avoid stroke with Anticoagulation; "B" Better symptoms control; "C" Cardiovascular risk-factor and comorbidities management. Objectives: This study sought to investigate the association with outcomes of ABC adherence in the prospective multinational Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. Method: Cox-regression analyses adjusted for age, sex, CHA2DS2-VASc score, paroxysmal AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia were performed to investigate the association with outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures, and advancing heart failure. Results: Of the 4,013 included patients with AF (mean age 68 ± 12 years; 34.4% female); 38.6% were adherent to all 3 main ABC pillars. After 1 year of follow-up, adherence to the ABC pathway was associated with a low incidence of composite outcome (4.0% vs 8.5%, P < 0.001), all-cause and cardiovascular death, and advancing heart failure. On Cox regression analysis, ABC adherence was associated with a lower risk of primary outcome (HR: 0.72; 95% CI: 0.53-0.97), with risk reduction progressively higher with a higher number of ABC criteria attained. No significant interaction in the association was seen according to the different geographic areas (Pint = 0.217). Conclusions: In a large contemporary cohort of Asian patients with AF, adherence to ABC pathway was associated with a reduction of the risk for adverse outcomes. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia (AF-Registry; NCT04807049).

Clinical utility and prognostic implications of the 4S-AF scheme: Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

BACKGROUND: The 4S-AF classification scheme comprises of four domains (stroke risk [St], symptoms [Sy], severity of atrial fibrillation (AF) burden [Sb] and substrate [Su]), which has been recommended in the 2020 ESC guidelines to characterize and evaluate patients with AF. OBJECTIVES: We aimed to determine whether the 4S-AF scheme would be useful for AF characterization and provides prognostic information in a large contemporary prospective Asian registry conducted by the Asia Pacific Heart Rhythm Society (APHRS). METHODS: Among 4666 patients enrolled in APHRS registry, 3586 of them whose data about left atrial (LA) dimension and European Heart Rhythm Association (EHRA) symptom score were available have constituted as the study population. The 4S-AF score was calculated as the sum of each domain with a maximum score of 9. The clinical endpoint was defined as the 1-year composite risk of any thromboembolic event, ischaemic stroke, heart failure, acute coronary syndrome, significant coronary artery disease requiring coronary intervention and all-cause mortality. RESULTS: Based on the 4S-AF domains, 86.7% were 'non-low risk' for stroke; 94.3% had EHRA Class I-II, 48.5% were newly diagnosed or paroxysmal AF; and only 8.4% had no cardiovascular risk factors or LA enlargement. The risk of clinical events was higher in patients who were 'non-low risk' for stroke (aOR 2.175, 95% CI 1.060-4.461), with permanent AF (aOR 1.579, 95% CI 1.106-2.225) and increasing points for substrate (aORs 2.376-4.968 from score 2 to 4). When compared to the first tertile of 4S-AF score (0-3 points), patients in the second tertile (4-5 points) had approximately 2.5-fold increase in adverse events (OR 2.478, 95% CI 1.678-3.661, p < .001), while those in the third tertile (6-9 points), had a 3.5-fold increase (OR 3.484, 95% CI 2.322-5.226, p < .001), both without significant differences between the 5 participating countries (p for interaction > .05). If all 4S-AF domains were appropriately treated, this was associated with a lower risk of composite clinical outcomes (aOR 0.384, p < .001; p for interaction for different countries = .234). CONCLUSIONS: Categorization according to the 4S-AF scheme can be related to the risk of the composite adverse event rate in Asian AF patients, and appropriate treatments based on the 4S-AF scheme resulted in better clinical outcomes. These observations support the characterization and management according to the 4S-AF scheme in Asian patients.

XaMINA: A Real-World, Prospective, Observational Study of Treatment-Naïve Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Asia.

INTRODUCTION: The efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism have been demonstrated in Asian and non-Asian patients with non-valvular atrial fibrillation (NVAF) in multiple studies. However, limited published data exist on its use specifically in treatment-naïve patients from the Asia region. Patients in South Korea and Taiwan can now receive rivaroxaban as first-line therapy, allowing for data generation in this patient group. METHODS: XaMINA was a prospective, real-world, multicenter, single-arm, observational cohort study of patients with NVAF in South Korea and Taiwan naïve to anticoagulation and initiating rivaroxaban. The primary outcome was major bleeding; secondary outcomes included all-cause mortality, symptomatic thromboembolic events, and treatment persistence. RESULTS: In total, 1094 patients were included and the follow-up was 1 year. The baseline mean CHADS2 score was 1.63 ± 0.98, mean CHA2DS2-VASc score was 2.92 ± 1.42, and mean HAS-BLED score was 1.00 ± 0.75. The primary outcome occurred in 20 (1.8%) patients [incidence rate 2.1 events per 100 patient-years (95% CI 1.35-3.25)]. Thromboembolic events occurred in 9 (0.8%) patients, of whom 5 (0.5%) had stroke, 3 (0.3%) myocardial infarction, and 1 (0.1%) a transient ischemic attack. There were no cases of non-central nervous system systemic embolism, and 735 (67.2%) patients persisted with rivaroxaban treatment for 1 year. CONCLUSION: XaMINA demonstrated low incidence rates of major bleeding events and thromboembolic events in patients with NVAF newly initiating rivaroxaban in South Korea and Taiwan, consistent with previous real-world studies reconfirming the results of the ROCKET AF study. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (identifier NCT03284762) on 15 September 2017.

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

AIMS: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions. METHODS AND RESULTS: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality. CONCLUSION: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.

Comparative occurrence of ischemic stroke with the rhythm versus rate control strategy in a national prospective cohort of atrial fibrillation.

BACKGROUND/AIMS: Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. METHODS: The CODE-AF registry prospectively enrolled 6,280 consecutive patients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. RESULTS: Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA2DS2-VASC score compared to those treated with the rate control strategy. The rate of oral anticoagulation, all bleeding, and hospitalization were also similarly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). CONCLUSION: The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.

A prospective, observational study of rivaroxaban for stroke prevention in atrial fibrillation: the XANAP Korea.

BACKGROUND/AIMS: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. METHODS: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. RESULTS: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. CONCLUSION: This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Status of international normalized ratio control and treatment patterns in patients with nonvalvular atrial fibrillation taking vitamin K antagonist with or without antiplatelet therapy: Results from KORAFII registry.

BACKGROUND: Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. METHODS: Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. RESULTS: A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow-up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. CONCLUSIONS: The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Benefit of statin therapy in patients with coronary spasm-induced acute myocardial infarction.

BACKGROUND: Coronary artery spasm is associated with vascular smooth muscle hyper-reactivity. Statins suppress coronary spasm by inhibiting the vascular smooth muscle contraction. However, it is unclear whether statin therapy benefits patients with coronary spasm-induced acute myocardial infarction (AMI). METHODS AND RESULTS: We analyzed 501 (median age 57 years; male/female, 346/155) patients with coronary spasm-induced AMI with nonobstructive coronary arteries (stenosis severity <50%) from the Korea AMI Registry between November 2005 and October 2013. They were divided into two groups according to statin prescription at discharge (statin group n=292; nonstatin group n=209). The primary endpoint was the composite of 12-month major adverse cardiac events, including all causes of death, non-fatal myocardial infarction, and target vessel revascularization. The primary endpoint occurred in 17 patients during 12 months of follow-up. Statin therapy significantly reduced the risk of the composite primary endpoint [adjusted hazard ratio (HR): 0.30; 95% confidence interval (CI): 0.09-0.97; p=0.045]. Statin therapy reduced the risk of myocardial infarction (HR: 0.19; 95% CI: 0.04-0.93; p=0.040). However, we found no significant difference in the risk of the composite of all-cause death. CONCLUSION: Statin therapy in patients with coronary spasm-induced AMI with nonobstructive coronary arteries was associated with improved clinical outcome, which was predominantly accounted for by reducing the incidence of myocardial infarction.

Benefit of implantable cardioverter-defibrillator therapy after generator replacement in patients with Brugada syndrome.

BACKGROUND: An implantable cardioverter-defibrillator (ICD) is the only proven effective therapeutic strategy for patients with Brugada syndrome (BS). However, it is controversial whether the device should be replaced even in patients who had never experienced appropriate ICD therapy until the time of generator replacement. METHODS AND RESULTS: This was a nationwide, multicenter retrospective study that enrolled patients who were diagnosed with BS and had an ICD implantation between January 1998 and April 2014. Appropriate ICD therapies administered for ventricular tachyarrhythmia were evaluated during follow-up. A total of 117 patients (age 43 ± 12 years, male 115 [98.3%]) were enrolled, and the mean follow-up duration was 6.0 ± 4.1 years. Thirty-seven (31.6%) patients had experienced appropriate ICD therapy during follow-up. Of all patients, 46 underwent replacement of the device. After the first generator replacement, the incidence of appropriate ICD therapy remained as high as 65.2% in patients who previously experienced appropriate ICD therapy before generator replacement. In 30 patients who did not experience any cardiac events until the first generator change, two (8.7%) had an episode of appropriate ICD therapy afterwards. CONCLUSIONS: No episode of ICD therapy before generator replacement could not guarantee a safe clinical course. ICD generator replacement should be considered even in patients without ICD therapy before.

Dosimetric comparison of three different treatment modalities for total scalp irradiation: the conventional lateral photon-electron technique, helical tomotherapy, and volumetric-modulated arc therapy.

The aim of this study was to compare lateral photon-electron (LPE), helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT) plans for total scalp irradiation. We selected a single adult model case and compared the dosimetric results for the three plans. All plans mainly used 6-MV photon beams, and the prescription dose was 60 Gy in 30 fractions. First, we compared the LPE, HT and VMAT plans, with all plans including a 1-cm bolus. We also compared HT plans with and without the bolus. The conformity indices for LPE, HT and VMAT were 1.73, 1.35 and 1.49, respectively. The HT plan showed the best conformity and the LPE plan showed the worst. However, the plans had similar homogeneity indexes. The dose to the hippocampus was the highest in the VMAT plan, with a mean of 6.7 Gy, compared with 3.5 Gy in the LPE plan and 4.8 Gy in the HT plan. The doses to the optical structures were all within the clinically acceptable range. The beam-on time and monitor units were highest in the HT plan. The HT plans with and without a bolus showed similar target coverage and organ-at-risk (OAR) sparing. The HT plan showed the best target coverage and conformity, with low doses to the brain and hippocampus. This plan also had the advantage of not necessarily requiring a bolus. Although the VMAT plan showed better conformity than the LPE plan and acceptable OAR sparing, the dose to the hippocampus should be considered when high doses are prescribed.

Hypokalemia promotes late phase 3 early afterdepolarization and recurrent ventricular fibrillation during isoproterenol infusion in Langendorff perfused rabbit ventricles.

BACKGROUND: Hypokalemia and sympathetic activation are commonly associated with electrical storm (ES) in normal and diseased hearts. The mechanisms remain unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that late phase 3 early afterdepolarization (EAD) induced by IKATP activation underlies the mechanisms of ES during isoproterenol infusion and hypokalemia. METHODS: Intracellular calcium (Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused normal rabbit hearts. RESULTS: Repeated episodes of electrically induced ventricular fibrillation (VF) at baseline did not result in spontaneous VF (SVF). During isoproterenol infusion, SVF occurred in 1 of 15 hearts (7%) studied in normal extracellular potassium ([K(+)]o, 4.5 mmol/L), 3 of 8 hearts (38%) in 2.0 mmol/L [K(+)]o, 9 of 10 hearts (90%) in 1.5 mmol/L [K(+)]o, and 7 of 7 hearts (100%) in 1.0 mmol/L [K(+)]o (P <.001). Optical mapping showed that isoproterenol and hypokalemia enhanced Cai transient duration (CaiTD) and heterogeneously shortened action potential duration (APD) after defibrillation, leading to late phase 3 EAD and SVF. IKATP blocker (glibenclamide, 5 µmol/L) reversed the post-defibrillation APD shortening and suppressed recurrent SVF in all hearts studied despite no evidence of ischemia. Nifedipine reliably prevented recurrent VF when given before, but not after, the development of VF. IKr blocker (E-4031) and small-conductance calcium-activated potassium channel blocker (apamin) failed to prevent recurrent SVF. CONCLUSION: Beta-adrenergic stimulation and concomitant hypokalemia could cause nonischemic activation of IKATP, heterogeneous APD shortening, and prolongation of CaiTD to provoke late phase 3 EAD, triggered activity, and recurrent SVF. IKATP inhibition may be useful in managing ES during resistant hypokalemia.

Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion.

BACKGROUND: Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES: To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS: Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS: We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P<.05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 µm(2)/mm(2)) than in group 2 (5321 ± 3164 µm(2)/mm(2); P<.05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4%±2.3%) than in group 2 (4.9% ± 0.7%; P<.05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9% ± 2.8% in group 1 and 86.1% ± 4.4% in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS: Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-positive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.

Catheter ablation of left ventricular tachycardia through internal jugular vein: refining the continuous line.

A retrograde approach to the left ventricle (LV) from the femoral artery is most commonly used for left ventricular tachycardia (VT) ablation. However, as the patient population gets older, the prevalence of peripheral vascular disease and aortic valve disease increases, hampering the retrograde access to the LV, which may result in significant technical difficulties. The transseptal approach from the femoral vein is an alternative access to the LV. This approach has been effective for addressing LV VT originating from the posterior and posteroseptal region. However, the transseptal approach from the femoral vein is impossible if there are any obstacles in the inferior vena cava. There are also significant limitations in approaching the basal-lateral region of the LV from this approach. We demonstrated the safety and feasibility of catheter ablation of LV VT via the transseptal approach from the right internal jugular vein.

Neural control of ventricular rate in ambulatory dogs with pacing-induced sustained atrial fibrillation.

BACKGROUND: We hypothesize that inferior vena cava-inferior atrial ganglionated plexus nerve activity (IVC-IAGPNA) is responsible for ventricular rate (VR) control during atrial fibrillation (AF) in ambulatory dogs. METHODS AND RESULTS: We recorded bilateral cervical vagal nerve activity (VNA) and IVC-IAGPNA during baseline sinus rhythm and during pacing-induced sustained AF in 6 ambulatory dogs. Integrated nerve activities and average VR were measured every 10 seconds over 24 hours. Left VNA was associated with VR reduction during AF in 5 dogs (from 211 bpm [95% CI, 186-233] to 178 bpm [95% CI, 145-210]; P<0.001) and right VNA in 1 dog (from 208 bpm [95% CI, 197-223] to 181 bpm [95% CI, 163-200]; P<0.01). There were good correlations between IVC-IAGPNA and left VNA in the former 5 dogs and between IVC-IAGPNA and right VNA in the last dog. IVC-IAGPNA was associated with VR reduction in all dogs studied. Right VNA was associated with baseline sinus rate reduction from 105 bpm (95% CI, 95-116) to 77 bpm (95% CI, 64-91; P<0.01) in 4 dogs, whereas left VNA was associated with sinus rate reduction from 111 bpm (95% CI, 90-1250) to 81 bpm (95% CI, 67-103; P<0.01) in 2 dogs. CONCLUSIONS: IVC-IAGPNA is invariably associated with VR reduction during AF. In comparison, right or left VNA was associated with VR reduction only when it coactivates with the IVC-IAGPNA. The vagal nerve that controls VR during AF may be different from that which controls sinus rhythm.