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Background@#Genetic studies are clinically recommended in some cases of inherited arrhythmia syndromes. Nextgeneration sequencing (NGS) would be helpful because of its high analytical throughput and relative speed. This study aimed to assess the mutation-detection yield obtained by NGS compared with conventional Sanger sequencing method. @*Methods@#Patients with aborted sudden cardiac death and their families who underwent gene sequencing tests for inherited arrhythmia syndromes were retrospectively and enrolled in this study from 2017 to 2022 at Chonnam National University Hospital. We evaluated NGS study results of 17 patients (NGS group) and Sanger study results of 19 patients (Sanger group). @*Results@#64.7% of NGS and 94.7% of Sanger group were probands. Type 1 Brugada pattern ECG was more frequent in NGS group (64.7% vs. 21.1%; p = 0.007). BrS was the most common disorder in NGS group (76.5%), and idiopathic ventricular fibrillation was the most common one in Sanger group (63.2%). Mutations with uncertain significance were the most common ones in NGS group (89.5%), and pathogenic or likely pathogenic mutations were the most common ones in Sanger group (45.7%). When positive yield was defined as the ratio of pathogenic or likely pathogenic mutations that were detected by sequencing, the yields were 10.5% and 45.7% in NGS and Sanger groups, respectively. The NGS arrhythmia panel did not cover two inherited arrhythmia-related mutations (RYR1, APOA5) that were detected by the Sanger method. The extended NGS arrhythmia panel was able to detect 84.8% of inherited arrhythmia-related mutations that were detected in Sanger group. @*Conclusions@#NGS study has some limitations in obtaining the full genetic data of probands. Well-designed NGS panels are needed to increase the efficiency of the NGS study. With the well-designed panels, large-scale gene sequencing can efficiently and rapidly be applied in real clinical practices, especially in inherited fatal arrhythmia syndromes that have a high detection yield in genetic analyses.
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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 pseudoelectrocardiograms. 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.
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Background@#Chronic right-ventricular (RV) pacing can exacerbate heart failure in patients with a low ejection fraction (EF). There is little information on the effects of diastolic dysfunction (DD) in patients with preserved EF undergoing permanent pacemaker (PPM) placement. We aimed to investigate the clinical outcomes in these patients. @*Methods@#This multicenter, retrospective analysis of PPM use in Chonnam, South Korea, included all patients with preserved EF undergoing transvenous PPM implantation for atrioventricular blockage from 2017 to 2019. Patients were divided into two groups according to DD, which were assessed by including mitral flow velocities (E′ velocity, E/E′ ratio), peak velocity of the tricuspid regurgitant, and left atrial maximum volume index. Composite outcomes were defined as (1) cardiovascular death, and (2) hospitalization by heart failure during the follow-up period. @*Results@#One hundred sixty-seven patients (66 men; overall mean age, 75.3 ± 11.9 years) were divided into two groups: 125 normal versus 42 DD. Compared with normal subjects, the DD group included older patients (mean age, 79.1 ± 9.9 vs. 74.0 ± 12.3; p = 0.016), and had longer paced QTc interval (pQTc, 168.5 ± 20.1 vs. 159.1 ± 16.3 ms; p < 0.001). Fifteen patients were hospitalized and two died. In a Cox proportional regression analysis, DD (hazard ratio [HR], 7.343; 95% confidence interval [CI], 2.035–26.494; p = 0.002) and pQRSd (HR, 1.046; 95% CI, 1.004–1.091; p = 0.033) were independent predictors of composite outcomes. @*Conclusion@#In patients with DD, RV pacing raised the risk of pacing-induced heart failure despite preserved leftventricular function. Thus, patients with DD should be monitored intensively.
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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.
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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.
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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 highdegree 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/m 2 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.
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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.
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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.
Subject(s)
Humans , Atrial Fibrillation , Follow-Up Studies , Hemorrhage , International Normalized Ratio , Prothrombin Time , Risk Reduction Behavior , Stroke , Thromboembolism , WarfarinABSTRACT
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 highdegree 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/m 2 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.
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Ventricular arrhythmias (VA) are a major cause of sudden cardiac death (SCD) in patients with known heart disease. Risk assessment and effective prevention of SCD are key issues in these patients. Implantable cardioverter defibrillator (ICD) insertion effectively treats sustained VA and reduces mortality in patients at high risk of SCD. Appropriate anti-arrhythmic drugs and catheter ablation reduce the VA burden and the occurrence of ICD shocks. In this guideline, authors have described the general examination and medical treatment of patients with VA. Medications and catheter ablation are also used as acute phase therapy for sustained VA.
Subject(s)
Humans , Arrhythmias, Cardiac , Catheter Ablation , Catheters , Death, Sudden, Cardiac , Defibrillators , Heart Diseases , Mortality , Risk Assessment , ShockABSTRACT
The recommendations outlined constitute the first clinical practice guidelines of the Korean Heart Rhythm Society regarding catheter ablation of ventricular arrhythmias (VA). This is a guideline PART 2, which includes VA in the structurally normal heart, inherited primary arrhythmia syndromes, VA related to congenital heart disease, as well as VA and sudden cardiac death observed in specific populations. In the structurally normal heart, treatment is guided by the occurrence of symptoms or the frequency of arrhythmias that cause ventricular dysfunction over time. Catheter ablation can be recommended in patients in whom anti-arrhythmic medications are ineffective. The sites of origin of arrhythmic activity are known to be the outflow tract, fascicles, papillary muscle, or the annulus. Specific cardiac channelopathies include congenital long QT and Brugada syndrome. This guideline discusses the diagnostic criteria, risk stratification, and treatment of these syndromes. We have included recommendations for adult congenital heart disease. Moreover, we have discussed the management of VA occurring in specific populations such as in patients with psychiatric and neurological disorders, pregnant patients, those with obstructive sleep apnea or drug-related pro-arrhythmias, athletes, and elderly patients.
Subject(s)
Adult , Aged , Humans , Arrhythmias, Cardiac , Athletes , Brugada Syndrome , Catheter Ablation , Catheters , Channelopathies , Death, Sudden, Cardiac , Heart , Heart Defects, Congenital , Nervous System Diseases , Papillary Muscles , Sleep Apnea, Obstructive , Ventricular DysfunctionABSTRACT
Treatment of ventricular arrhythmias (VA) usually involves managing the underlying cardiac conditions that cause the arrhythmia. However, managing the underlying disease is often challenging, and catheter ablation, or treatment targeting the VA itself might be required in a few patients. In this article, we explored evidence and recommendations regarding the treatment of VA in patients with structural heart disease focusing on the utilization of catheter ablation in these patients. The administration of optimal medical therapy, insertion of an implantable cardioverter-defibrillator, or resynchronization therapy improves survival in patients with left ventricular dysfunction. The role of catheter ablation in preventing sudden cardiac death remains uncertain in this population. In patients with coronary artery disease, reversing myocardial ischemia via revascularization is important in managing VA. Catheter ablation is recommended in patients with recurrent ventricular tachycardia in a setting of ischemic heart disease. In patients with non-ischemic cardiomyopathies such as dilated cardiomyopathy or hypertrophic cardiomyopathy, catheter ablation may be considered for those presenting with drug-refractory ventricular tachycardia.
Subject(s)
Humans , Arrhythmias, Cardiac , Cardiomyopathies , Cardiomyopathy, Dilated , Cardiomyopathy, Hypertrophic , Catheter Ablation , Catheters , Coronary Artery Disease , Death, Sudden, Cardiac , Defibrillators, Implantable , Heart Diseases , Myocardial Ischemia , Tachycardia, Ventricular , Ventricular Dysfunction, LeftABSTRACT
The results of trials using novel or non-vitamin K-dependent new oral anticoagulants (NOACs) in the treatment of venous thromboembolism (VTE) reveal that these agents are non-inferior (in terms of efficacy) and possibly safer (particularly in terms of major bleeding) than the standard heparin/vitamin K antagonist (VKA) regimen. High TTR values were achieved under VKA treatment in all trials; however, it should be noted that the study populations comprised relatively young patients, very few of whom had cancer. At present, NOACs can be viewed as an alternative to standard treatment. Currently, experience with NOACs is limited, but continues to be accumulated. Practical recommendations for the use of NOACs in different clinical scenarios and the management of their bleeding complications are needed. The results of the trials using NOACs in the extended treatment of VTE are in line with those of the studies that tested these agents for acute-phase treatment and standard duration of anticoagulation after pulmonary embolism (PE) or VTE. They indicate that NOACs are both, effective (in terms of prevention of symptomatic or fatal recurrence of VTE) and safe (particularly in terms of major bleeding), probably safer than standard VKA regimens.
Subject(s)
Humans , Anticoagulants , Hemorrhage , Pulmonary Embolism , Recurrence , Venous ThromboembolismABSTRACT
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.
Subject(s)
Child , Humans , Infant, Newborn , Bronchopulmonary Dysplasia , Diagnosis , Echocardiography , Education , Hypertension , Infant, Premature , Linear Models , Prognosis , Pulmonary Artery , Tricuspid Valve Insufficiency , Ventricular Function, RightABSTRACT
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.