Case Report: Comprehensive evaluation of ECG phenotypes and genotypes in a family with Brugada syndrome carrying SCN5A-R376H.

Background: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly. Case: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation. The patient did not have underlying diseases. The routine laboratory results, imaging study, coronary angiogram, and echocardiogram (ECG) were normal. A type 1 BrS pattern was identified in one resting ECG. Furthermore, prominent J wave accentuation with PR interval prolongation was identified during therapeutic hypothermia. Therefore, we were easily able to diagnose BrS. For secondary prevention, the patient underwent implantable cardioverter defibrillator implantation. Before discharge, a genetic study was performed using next-generation sequencing. Genotyping was performed in the first-degree relatives, and ECG evaluations of almost all maternal and paternal family members were conducted. The proband and his mother showed SCN5A-R376H and RyR2-D4038Y variants. However, his mother did not show the BrS phenotype on an ECG. One maternal aunt and uncle showed BrS phenotypes. Conclusion: Genetics alone cannotdiagnose BrS. However, genetics could supply evidence or direction for evaluating ECG phenotypes in family groups. This case report shows how family evaluation using ECGs along with a genetic study can be used in BrS diagnosis.

Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (Ito) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. METHODS: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 µM), calcium channel blocker verapamil (1 µM), and Ito agonist NS5806 (6-10 µM) were used. Artemisinin (100-150 µM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. RESULTS: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. CONCLUSIONS: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation.

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.

Clinical outcomes in patients with atrioventricular block undergoing pacemaker: 3-year follow-up.

PURPOSE: Left ventricular function can be affected by chronic ventricular pacing. Different right ventricular (RV) pacing sites have shown heterogeneous clinical outcomes. We investigated these factors in patients receiving permanent pacemaker (PPM) implants. METHODS: This multicenter, retrospective analysis of PPM use in South Korea, included all patients undergoing de novo transvenous PPM implantation for atrioventricular block from 2017 to 2019. Clinical characteristics, 12-lead electrocardiograms, echocardiography, and laboratory parameters were evaluated. Composite outcomes are defined by two coprimary endpoints: (1) hospitalizations and (2) cardiac death by heart failure during follow-up period. RESULTS: There were 167 patients (66 males; overall mean age 75.3 ± 11.9 years), divided into two groups according to the pacing site: 83 apical RV (RVA) vs. 84 septal RV (RVS). There were no significant baseline differences. Paced QRS duration (pQRSd) increased with RVA (168.5 ± 20.1 vs. 159.1 ± 16.3 ms; p < 0.001). Over a median 31-month follow-up, there were 15 hospitalizations and 2 deaths. More patients with RVA were hospitalized or died (16% vs. 5%, respectively; p = 0.049). In Cox proportional regression analysis, pQRSd (hazard ratio [HR] 1.046; 95% confidence interval [CI] 1.004-1.091; p = 0.033), and diastolic dysfunction (HR 7.343; 95% CI 2.035-26.494; p = 0.002) were independent predictors of composite clinical outcomes. CONCLUSIONS: RVS placement shortened the pQRSd and improved clinical outcomes. However, the determinants of these were pQRSd and diastolic dysfunction. Therefore, clinicians should try to shorten the pQRSd when implanting a PPM, and patients with diastolic dysfunction should be monitored intensively.

Post-operative Atrial Fibrillation Impacts on Outcomes in Transcatheter and Surgical Aortic Valve Replacement.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) has poor outcomes after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively). We compared the incidence of AF after aortic valve replacement (AVR) according to the treatment method and the impact of AF on outcomes. Methods: We investigated the incidence of AF and clinical outcomes of AVR according to whether AF occurred after TAVR and SAVR after propensity score (PS)-matching for 1 year follow-up. Clinical outcomes were defined as death, stroke, and admission due to heart failure. The composite outcome comprised death, stroke, and admission due to heart failure. Results: A total of 221 patients with severe AS were enrolled consecutively, 100 of whom underwent TAVR and 121 underwent SAVR. The incidence of newly detected AF was significantly higher in the SAVR group before PS-matching (6.0 vs. 40.5%, P < 0.001) and after PS-matching (7.5 vs. 35.6%, P = 0.001). TAVR and SAVR showed no significant differences in outcomes except in terms of stroke. In the TAVR group, AF history did not affect the outcomes; however, in the SAVR group, AF history affected death (log rank P = 0.038). Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.049) and composite outcomes in the SAVR group. Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.008) and composite outcome in the TAVR group. Conclusion: Post-AVR AF could be considered as a predictor of the outcomes of AVR. TAVR might be a favorable treatment option for patients with severe symptomatic AS who are at high-risk for AF development or who have a history of AF because the occurrence of AF was more frequent in the SAVR group.

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome.

BACKGROUND: The mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS. METHODS: The RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls. RESULTS: Patients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered. CONCLUSION: The patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.

Positive chronotropic effects of theophylline and cilostazol in patients with symptomatic sick sinus syndrome who have declined permanent pacing.

Pacemakers are more commonly recommended than theophylline for sick sinus syndrome (SSS) treatment. The positive effects of cilostazol on bradyarrhythmias also have been reported. However, no comparison of cilostazol and theophylline has been previously reported found. We retrospectively enrolled SSS patients, who refused a pacemaker implantation. Theophylline or cilostazol was administered, and the heart rate (HR) was evaluated in 4-8 weeks using a digital sphygmomanometer and the electrocardiogram (ECG). A 200-400 mg of theophylline or 100-200 mg of cilostazol were administered per day in 50 and 30 patients, respectively. The baseline HR was 54.8 ± 13.5 beats per minute (bpm) on using sphygmomanometry and 51.9 ± 11.8 bpm using the ECG. In the theophylline group, the HR increased by 12.0 ± 16.3 bpm by sphygmomanometry (P < 0.001) and 8.4 ± 12.0 bpm by the ECG (P < 0.001). In the cilostazol group, the HR increased by 16.8 ± 13.9 bpm by sphygmomanometry (P < 0.001) and 12.4 ± 13.4 bpm using the ECG (P < 0.001). In 15 of the 50 theophylline patients, the medication was switched to cilostazol. The HR increased from 61.4 ± 13.8 bpm to 64.0 ± 12.6 bpm (P = 0.338). Symptoms such as dyspnea, chest discomfort, dizziness, and syncope significantly improved after the administration of the medications. There were no significant differences in the improvement in the symptoms except for dizziness between the two agents. Cilostazol was as effective as theophylline for increasing the HR in SSS patients.

Transmural conduction time in an early repolarization syndrome model.

In the pathological aspect of J wave syndrome, delayed depolarization is defined as the difference in local conduction velocity of the ventricular myocardium. If polymorphic ventricular tachycardia is induced without local conduction velocity heterogeneity, this contradicts the delayed depolarization theory. In the present study, the transmural conduction time at was evaluated at several transmural locations in a canine early repolarization model. The transmural pseudo-electrocardiogram and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n=18). The Ito agonist NS5806 (9-10 µM), Ca2+ channel blocker verapamil (2 µM) and acetylcholine (ACh) (2 µM) were used to pharmacologically mimic early repolarization syndrome genotypes. The transmural conduction times were measured at five fixed epicardial unipolar electrodes before and after the perfusion of provocative agents. The transmural conduction time was defined as the time from endocardial stimulation to the maximal negative deflection (dV/dt) of the endocardial electrogram at the unipolar electrode. Polymorphic ventricular tachycardia developed in 14/18 preparations. In the transmembrane action potentials, there was no definite delayed phase 0 upstroke in any induced polymorphic ventricular tachycardia preparations. In all preparations, the transmural conduction time increased significantly after perfusing the Ito agonist NS5806, verapamil and Ach; however, the increase was only 2.6±0.4 msec, and dispersion of the transmural conduction time did not exhibit significant heterogeneity (7.16±0.93 vs. 7.76±1.21 msec; P=0.240). In the early repolarization model, polymorphic ventricular tachycardia was induced without any regional conduction velocity heterogeneity. This finding suggests that local depolarization heterogeneity would not be a major contributor to the generation of ventricular arrhythmia in the early repolarization syndrome wedge preparation model.

Radiofrequency catheter ablation without radiation exposure in a 13th week pregnant woman with Wolff-Parkinson-White syndrome.

A 36-year-old woman with 12-week gestation visited the emergency department, complaining of palpitations. Her electrocardiography (ECG) demonstrated ventricular pre-excitation combined with atrial fibrillation. The polarity of the delta waves in leads V5, V6, I, and aVL were positive and negative in leads V1, III, and aVF, suggesting that the accessory pathway (AP) was located on the right posterior free wall. She did not want to take any medicine to prevent the tachycardia. Moreover, the shortest pre-excited RR interval during the atrial fibrillation was 200 ms, so we decided to ablate the AP without fluoroscopy. An electrophysiology study was performed with guidance of a 3-dimension (3D) navigation system and intracardiac echocardiography (ICE). We ablated the right free wall AP without fluoroscopy. A follow-up ECG no longer exhibited any delta waves. Even in the early period of pregnancy, catheter ablation might be performed safely using ICE and a 3D navigation system without fluoroscopy. Therefore, it could more often be considered as a therapeutic option in pregnant women without concern for radiation exposure.

Cisplatin-induced Atrioventricular Block Requiring a Pacemaker: Two Case Reports and a Literature Review.

Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and high-degree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Impact of Anticoagulation Intensity in Korean Patients with Atrial Fibrillation: Is It Different from Western Population?

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients. METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death. RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6-2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19-0.85), major bleeding (HR, 0.43; 95% CI, 0.23-0.81), primary (HR, 0.50; 95% CI, 0.29-0.84) and secondary (HR, 0.45; 95% CI, 0.28-0.74) net-clinical outcomes, whereas mean INR 2.0-3.0 did not. Simultaneous satisfaction of mean INR 1.6-2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes. CONCLUSIONS: Mean INR 1.6-2.6 was better than mean INR 2.0-3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6-2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0-3.0 and TTR ≥70% in Korean patients with non-valvular AF.

Experimental verification of the value of the Tpeak -Tend interval in ventricular arrhythmia inducibility in an early repolarization syndrome model.

INTRODUCTION: In patients with early repolarization patterns on ECG, many researchers have studied to find predictors of fatal arrhythmia. However, there are no satisfying clinical predictors. We evaluated the value of the Tpeak -Tend interval on pseudo-ECG in canine myocardial wedge preparation models of early repolarization syndrome. METHODS AND RESULTS: Transmural pseudo-ECG and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n = 34). The Ito agonist NS5806 (8-10 µM), the calcium channel blocker verapamil (3 µM) and acetylcholine (2-3 µM) were used to mimic the disease model. A ventricular arrhythmia induction test was performed. QTpeak , QTend , Tpeak -Tend , and Tpeak -Tend /QTend were measured at 15 to 20 minutes after the provocative agent infusion. Polymorphic ventricular tachycardias (pVT) developed in 23 of the 34 preparations (67%). The maximal values of Tpeak -Tend and Tpeak -Tend /QTend were recorded just before pVT induction. At baseline, without the provocative agents, Tpeak -Tend and Tpeak -Tend /QTend were not different between pVT-induced and pVT-noninduced preparations. The Tpeak -Tend of the pVT-induced preparations was longer than that of non-induced preparations (58 ± 26.8 msec vs 33 ± 6.8 msec, P < .001). The Tpeak -Tend /QTend of pVT- induced preparations was larger than that of noninduced preparations (0.220 ± 0.1017 vs 0.128 ± 0.0312, P < .001). The transmural and epicardial dispersion of repolarization of pVT-induced preparations were larger than those of pVT-noninduced preparations. The transmural dispersion of repolarization showed a positive correlation with Tpeak -Tend . CONCLUSION: Tpeak -Tend predicted malignant ventricular arrhythmias in early repolarization syndrome models. Tpeak -Tend reflects the repolarization heterogeneity of ventricular myocardium.

Epicardial Substrate as a Target for Radiofrequency Ablation in an Experimental Model of Early Repolarization Syndrome.

BACKGROUND: Early repolarization syndrome (ERS) is an inherited cardiac arrhythmia syndrome associated with sudden cardiac death. Approaches to therapy are currently very limited. This study probes the mechanisms underlying the electrocardiographic and arrhythmic manifestation of experimental models of ERS and of the ameliorative effect of radiofrequency ablation. METHODS: Action potentials, bipolar electrograms, and transmural pseudo-ECGs were simultaneously recorded from coronary-perfused canine left ventricular wedge preparations (n=11). The Ito agonist NS5806 (7-10 µmol/L), calcium channel blocker verapamil (3 µmol/L), and acetylcholine (1-3 µmol/L) were used to pharmacologically mimic the effects of genetic defects associated with ERS. RESULTS: The provocative agents induced prominent J waves in the ECG secondary to accentuation of the action potential notch in epicardium but not endocardium. Bipolar recordings displayed low-voltage fractionated potentials in epicardium because of temporal and spatial variability in appearance of the action potential dome. Concealed phase 2 reentry developed when action potential dome was lost at some epicardial sites but not others, appearing in the bipolar electrogram as discrete high-frequency spikes. Successful propagation of the phase 2 reentrant beat precipitated ventricular tachycardia/ventricular fibrillation. Radiofrequency ablation of the epicardium destroyed the cells displaying abnormal repolarization and thus suppressed the J waves and the development of ventricular tachycardia/ventricular fibrillation in 6/6 preparations. CONCLUSIONS: Our findings suggest that low-voltage fractionated electrical activity and high-frequency late potentials recorded from the epicardial surface of the left ventricle can identify regions of abnormal repolarization responsible for ventricular tachycardia/ventricular fibrillation in ERS and that radiofrequency ablation of these regions in left ventricular epicardium can suppress ventricular tachycardia/ventricular fibrillation by destroying regions of ER.

Tpeak-Tend interval during therapeutic hypothermia can predict upcoming ventricular fibrillation in subjects with aborted arrhythmic sudden cardiac death: 3-years follow-up results.

AIMS: Prolonged Tpeak-Tend interval has been shown to be markers of arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of the obstacles to predict fatal ventricular arrhythmia. This study investigated whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated with ventricular fibrillation (VF) inducibility and clinical arrhythmia in subjects with aborted arrhythmic sudden cardiac death (SCD). METHODS AND RESULTS: The study group included 31 patients (24 males, age 39.1 ± 17.6 years) presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude were measured in electrocardiogram (ECG) of the earliest medical contact and during TH; these patients underwent programmed ventricular stimulation. The summation of J-wave amplitude and QTc interval increased during TH. However, it was not associated with VF inducibility. Patients with inducible VF showed a small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 ± 24.7 vs. 94.0 ± 55.6 ms, P = 0.044) and a marked increase of the dispersion during the TH (36.2 ± 51.2 vs. -6.1 ± 45.5 ms, P = 0.039). Twenty-four patients underwent implantable cardioverter defibrillator (ICD) implantation. Among them, the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH developed VF more frequently (QTc, 511.9 ± 53.71 ms vs. 566.5 ± 56.08 ms, P = 0.038; Tpeak-Tend interval, 145.6 ± 38.4 ms vs. 185.7 ± 49.95 ms, P = 0.048; precordial Tpeak-Tend interval, 139.3 ± 35.11 ms vs. 185.7 ± 49.95 ms, P = 0.018). The initial VF inducibility was not related with the VF development in follow-up. CONCLUSION: In patients with aborted arrhythmic SCD, long Tpeak-Tend interval and QTc interval during TH could predict VF development in their follow-up.

Mechanisms Underlying Epicardial Radiofrequency Ablation to Suppress Arrhythmogenesis in Experimental Models of Brugada Syndrome.

OBJECTIVES: This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS. BACKGROUND: Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects. METHODS: Action potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of INa blocker ajmaline (1 to 10 µM) and IK-ATP agonist pinacidil (1 to 5 µM); or combination of Ito agonist NS5806 (4 to 10 µM) and ICa blocker verapamil (0.5 to 2 µM). After stable induction of abnormal electrograms and arrhythmic activity, the preparation was mapped and epicardial RFA was applied. RESULTS: Fractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used. CONCLUSIONS: Our results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.

Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study.

PURPOSE: To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy. PATIENTS AND METHODS: Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings. RESULTS: After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were -9.67±6.50/-12.89±11.78, -10.72±6.19/-13.79±9.41, and -4.93±7.26/-4.55±11.27 mmHg in the CKD-828 2.5/40 mg (P<0.0001/P<0.0001), CKD-828 2.5/80 mg (P<0.0001/P<0.0001), and S-amlodipine 2.5 mg (P<0.0001/P=0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP: P=0.0002/P<0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP: P=0.0001/P<0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg (P<0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP: P=0.0028/P=0.0001 and P<0.0001/P=0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%, P=0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828. CONCLUSION: CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.

Clinical Utility of Echocardiography for the Diagnosis and Prognosis in Children with Bronchopulmonary Dsyplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) may result in chronic pulmonary artery hypertension and right ventricular (RV) dysfunction. Various echocardiographic assessments of RV dysfunction have been used to determine whether echocardiographic measurements of premature infants with BPD could provide sensitive measures of RV function that correlates with BPD severity. METHODS: Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and tissue Doppler imaging (TDI) measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and TDI measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. RESULTS: None of the standard echocardiographic findings was significantly different between the control group and BPD groups. However, mean septal TDI-MPI of the severe BPD group (0.68 ± 0.06) was significantly (p < 0.01) higher than that of the non-BPD (0.58 ± 0.10) or the mild BPD group (0.59 ± 0.12). In addition, mean RV TDI-MPI of the severe BPD group (0.71 ± 0.13) was significantly (p < 0.05) higher than that of the non-BPD group (0.56 ± 0.08) or the mild BPD group (0.60 ± 0.125). Linear regression showed a good correlation between the severity of BPD and RV TDI-MPI (p = 0.01, R = 0.30) or septal TDI-MPI (p = 0.04, R = 0.24). CONCLUSION: Echocardiographic evaluation of RV function based on an assessment of RV TDI-MPI can provide RV dysfunction parameter in premature infants with BPD.