Search

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.

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.

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

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., Graphical Abstract

Background Data comparing outcomes in heart failure ( HF ) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN ‐HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction ( EF ; Methods and Results The ASIAN ‐ HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced r EF ). The primary outcome was 1‐year all‐cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One‐year, crude, all‐cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One‐year, all‐cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region‐specific risk factors and gaps in guideline‐directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01633398.

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.

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.

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 I to 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.

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.

Background and Objectives It is widely known that angiotensin-II receptor blockers (ARBs) have reverse remodeling effects in atrium. Although atrial fibrillation is frequent in ischemic heart failure clinically, experiments to demonstrate ARB's effects on atrial remodeling in a heart failure model are rare. Materials and Methods A heart failure model and a sham-operated group were formed in 25 Sprague-Dawley male rats of roughly 260 g in weight. Ischemic heart failure models were obtained via ligation of the left anterior descending coronary artery. In the ARB group, 30 mg/kg of losartan was administrated over a day for 4 weeks. Echocardiography was performed to measure left ventricle ejection fraction and left atrial diameter (LAD) at the baseline and 4 weeks after the operation. 4 weeks later, histologic and immunohistochemical evaluation were performed. Results Groups were divided into the sham group, heart failure group, and heart failure-ARB group. We maintained 5 rats in each group for 4 weeks after operation. The decrease of left ventricular ejection fraction in the heart failure-ARB group was less than that in the heart failure group (p=0.023). The increase of LAD in the heart failure-ARB group was less than that in the heart failure group (p=0.025). Masson's trichrome stain revealed less fibrosis in the heart failure-ARB group. Immunohistochemical stain and western blot for connexin 43 showed less expression in the heart failure-ARB group. Conclusion In the ischemic heart failure model of rats, structurally and histologically, the ARB, losartan, has atrial reverse-remodeling effects. However, electrically, its role as an electrical stabilizer should be studied further.

Up to best our knowledge, for patients with Brugada syndrome, the best treatment is implantation of implantable cardioverter defibrillator. Pharmacologically, there are continuous efforts to find new agents that can treat the Brugada syndrome fundamentally. One of mechanism of Brugada syndrome is

The remodeling of gap junctions may affect their conduction properties and contribute to the maintenance of atrial fibrillation. The significance of the role of angiotensin-II receptor blockers (ARBs) in upstream therapy is not clear. This study was performed to investigate the effects of ARBs on atrial remodeling in a heart failure model. A model of heart failure was established or sham surgery performed in 24 Sprague-Dawley male rats. The rats were divided into sham, heart failure and heart failure-ARB groups. In the ARB group, 30 mg/kg of losartan was administered each day for 4 weeks. Echocardiography was performed at the baseline and 4 weeks following the surgery. An atrial fibrillation induction study and histological and immunohistochemical evaluation were performed 4 weeks after surgery. The increase in the left atrial diameter of the heart failure-ARB group was smaller than that of the heart failure group (P=0.028). The atrial fibrillation inducibility and duration of induced atrial fibrillation were not different between the heart failure and heart failure-ARB groups. Masson's trichrome staining revealed less fibrosis in the heart failure-ARB group compared with the heart failure group. Immunohistochemical staining and western blot analysis for connexin 43 showed a lower expression level in the heart failure-ARB group compared with that in the heart failure group. In a rat model of ischemic heart failure the ARB losartan had structural and histological atrial reverse-remodeling effects. However, its role as an electrical stabilizer requires further study.

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.

Background: Total left atrial volume (LAV) is one of important predictors in ablation success of atrial fibrillation (AF). As left atrial remodeling advances, atrial volume distribution may be changed. Sometimes left anterior, sometimes left posterior volume increases. Methods: We evaluated consecutive 40 patients. LAV was measured with Aquarius workstation. Anterior and posterior atriums were separated by plane made of pulmonary vein ostiums. Results: Paroxysmal (n=18) and non-paroxysmal (n=22) AF patients were enrolled. 19 patients had been treated with amiodarone. Left atrial diameter (LAD) was 39.0±4.5 mm. 23 patients were treated with antral isolation. 17 patients were treated with antral isolation and additional linear ablation. LAV was 129.6±23.6 cc. Posterior LAV was 32.3±7.0 cc (12.6±13.3%). Total and posterior LAV were not different between short term success (n=15) and fail (n=25) patients. However, ratio of posterior LAV and total LAV was significantly higher in short term success patients (21.8±13.1% vs. 8.4±11.4%, p=0.013). This ratio was independent of AF duration, hs-CRP, LAD and total LAV to predict short term success (p=0.032). When posterior LAV ratio is greater than 24.9%, prediction specificity was 93.7% and sensitivity was 66.7%. Conclusion: Posterior left atrial volume estimated by multi-detector computed tomography may be useful to identify patients in whom short term success can be achieved in AF ablation. This volume distribution difference seems to be valuable to study the relation with left atrial remodeling.

Background and Objectives:It has been known that various vasoactive agents are involved in the regulation of cardiac function through the modification of the K + channel activities, including the ATP-sensitive K + channel (KATP). We examined the effects of several vasoactive agents on the cardiac KATP currents in isolated cardiac myocytes. Materials and Methods:Ventricular myocytes were isolated from the hearts of ICR mice by enzymatic digestion. The channel currents were recorded by the excised inside-out and cell-attached patch clamp configurations. Results:In the excised inside-out patches, bradykinin (BRK; 1-10 μM) and prostaglandin I2 (PGI; 10-50 μM) did not affect the channel activities, whereas the vasodilators increased the attenuated channel activities in the presence of 100 μM ATP. BRK and PGI in parallel shifted the dose-response curves of ATP (1-1,000 μM), and this inhibited the KATP currents to the right. Endothelin (ET-1; 0.1-1 nM) and leukotriene D4 (LTD; 3-10 μM) decreased the channel activities immediately after making the inside-out patches. However, the vasocons- trictors did not affect the attenuated channel activities by ATP. In the cell-attached patches, both BRK and PGI increased the channel activities and these effects were markedly attenuated by glibenclamide (50 μM). ET-1 and LTD did not affect the baseline channel activities in the cell-attached patches, but they markedly attenuated the dinitrophenol-induced activities. Conclusion:It was inferred that certain vasoactive substances are involved in the regulation of cardiac KATP channel activities, and that bradykinin and PGI2 enhance the channel activities, and ET-1 and LTD4 inhibit the channel activities. (Korean Circulation J 2006;36:516-525)

Atrial fibrillation has been known for a predictor of poor prognosis in myocardial infarction. We assessed the impact of the CHADS2 and CHA2DS2-VASc score on prognosis in patients with atrial fibrillation combined with acute myocardial infarction (AMI) treated invasively. We analyzed 10,482