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1.
JAMA Netw Open ; 7(5): e2410288, 2024 May 01.
Article En | MEDLINE | ID: mdl-38717772

Importance: Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). Objective: To evaluate the risk of late VT and VF after primary PCI for STEMI. Design, Setting, and Participants: This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Main Outcomes and Measures: Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. Results: A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). Conclusions and Relevance: In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.


Hospital Mortality , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Tachycardia, Ventricular , Ventricular Fibrillation , Humans , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/statistics & numerical data , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/complications , Male , Female , Middle Aged , Aged , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/mortality , Tachycardia, Ventricular/etiology , Ventricular Fibrillation/therapy , Ventricular Fibrillation/mortality , Cohort Studies , Registries , Risk Factors
2.
Radiol Technol ; 95(5): 321-326, 2024 May.
Article En | MEDLINE | ID: mdl-38719553

BACKGROUND: This case details a 44-year-old man with end-stage ischemic cardiomyopathy with refractory ventricular tachycardia (VT). The patient has a single-chamber implantable cardioverter-defibrillator, has had 2 VT ablations, and uses medication to manage his VT. Despite these interventions, he continued to have episodes of VT. The patient underwent stereotactic body radiation therapy (SBRT) to help reduce the burden of his VT. The patient received a dose of 25 Gy to his right inferior lateral region of the heart and a dose of 15 Gy to the inferior portion of the heart closer to the stomach. The patient followed up 1 month later and reported that his energy levels improved and that no arrhythmias had occurred since his SBRT treatment. DISCUSSION: The options for treating end-stage VT are limited. However, a treatment option using SBRT has been introduced to reduce the VT burden in patients. Cardiac SBRT is a noninvasive outpatient procedure that, while still awaiting U.S. Food and Drug Administration approval, reduces arrhythmia episodes and offers favorable short-term benefits for patients who have not responded to traditional treatment modalities. CONCLUSION: Cardiac SBRT is a novel treatment for VT in patients where standard treatments have failed. This case study demonstrates that SBRT effectively reduced arrhythmias in a patient with VT. The long-term clinical outcomes are not known, but the opportunity SBRT offers for treatment-refractory patients is favorable and should be considered.


Radiosurgery , Tachycardia, Ventricular , Humans , Male , Tachycardia, Ventricular/surgery , Adult , Radiosurgery/methods , Defibrillators, Implantable , Catheter Ablation/methods
3.
J Med Case Rep ; 18(1): 238, 2024 May 06.
Article En | MEDLINE | ID: mdl-38705996

BACKGROUND: Takotsubo cardiomyopathy is a novel form of rapidly reversible heart failure occurring secondary to a stressor that mimics an acute coronary event. The underlying etiology of the stressor is highly variable and can include medical procedures. Pacemaker insertion is an infrequent cause of Takotsubo cardiomyopathy. CASE PRESENTATION: An 86-year-old Caucasian woman underwent an uncomplicated pacemaker insertion for symptomatic complete heart block in the background of slow atrial fibrillation. A transient episode of polymorphic ventricular tachycardia was noted on day 1 following the procedure; however, her pacemaker was checked and, as she remained stable, she was discharged home. She presented again 5 days later with symptomatic heart failure. Chest X-ray confirmed pulmonary edema. Echocardiography confirmed new onset severe left ventricle dysfunction. Pacemaker checks were normal and lead placement was confirmed. Though her troponin I was elevated, her coronary angiogram was normal. Contrast enhanced echocardiography suggested apical ballooning favoring Takotsubo cardiomyopathy. She was treated for heart failure and made a good recovery. Her follow-up echocardiography a month later showed significant improvement in left ventricle function. CONCLUSIONS: Takotsubo cardiomyopathy is mediated by a neuro-cardiogenic mechanism due to hypothalamic-pituitary-adrenal axis activation. It generally has a good prognosis. Complications though uncommon, can occur and include arrhythmias. Pacemaker insertion as a precipitant stressor is an infrequent cause of Takotsubo cardiomyopathy. As pacemaker insertions are more frequent in the elderly age group, this phenomenon should be recognized as a potential complication.


Pacemaker, Artificial , Tachycardia, Ventricular , Takotsubo Cardiomyopathy , Humans , Takotsubo Cardiomyopathy/therapy , Takotsubo Cardiomyopathy/complications , Takotsubo Cardiomyopathy/etiology , Female , Aged, 80 and over , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/etiology , Echocardiography , Electrocardiography , Heart Failure/therapy , Heart Failure/complications
4.
J Am Heart Assoc ; 13(9): e034516, 2024 May 07.
Article En | MEDLINE | ID: mdl-38700025

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.


Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Hemorrhage , Hospital Mortality , Out-of-Hospital Cardiac Arrest , Tachycardia, Ventricular , Thrombosis , Ventricular Fibrillation , Humans , Male , Female , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/mortality , Middle Aged , Thrombosis/etiology , Thrombosis/epidemiology , Thrombosis/mortality , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/epidemiology , Tachycardia, Ventricular/mortality , Tachycardia, Ventricular/etiology , Cardiopulmonary Resuscitation/adverse effects , Cardiopulmonary Resuscitation/methods , Ventricular Fibrillation/mortality , Ventricular Fibrillation/therapy , Ventricular Fibrillation/epidemiology , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/methods , Risk Factors , Incidence , Retrospective Studies , Aged , Hemorrhage/mortality , Hemorrhage/etiology , Hemorrhage/epidemiology , Treatment Outcome
5.
Adv Emerg Nurs J ; 46(2): 149-157, 2024.
Article En | MEDLINE | ID: mdl-38736099

Nonsustained ventricular tachycardia (NSVT) is a common arrhythmia associated with heart failure, cardiomyopathy, coronary artery disease, electrolyte imbalances, and congenital heart disorders (Foth et al., 2023). NSVT is often asymptomatic depending on its burden percentage. However, typical NSVT presentation in the emergency department (ED) includes palpitations, near-syncope, dizziness, skipped beats, chest pain, and/or dyspnea (Katritsis et al., 2012). In some instances, NSVT can present with elevated or slightly elevated troponin from demand ischemia. A definite diagnosis of NSVT is not of high complexity; nevertheless, it is not always identified on electrocardiogram (ECG) by the time the patient arrives to the ED. Identification of NSVT usually requires prolonged cardiac monitoring, mobile cardiac telemetry (MCT), and in some instances internal loop recorder placement. The purpose of this case is to discuss the typical presentation and pharmacological approach of patients with stable NSVT.


Electrocardiography , Tachycardia, Ventricular , Humans , Tachycardia, Ventricular/drug therapy , Tachycardia, Ventricular/diagnosis , Anti-Arrhythmia Agents/therapeutic use , Emergency Service, Hospital , Male
6.
Resuscitation ; 198: 110200, 2024 May.
Article En | MEDLINE | ID: mdl-38582444

BACKGROUND: Annually 15,200 children suffer an in-hospital cardiac arrest (IHCA) in the US. Ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) is the initial rhythm in 10-15% of these arrests. We sought to evaluate the association of number of shocks and early dose escalation with survival for initial VF/pVT in pediatric IHCA. METHODS: Using 2000-2020 data from the American Heart Association's (AHA) Get with the Guidelines®-Resuscitation (GWTG-R) registry, we identified children >48 hours of life and ≤18 years who had an IHCA from initial VF/pVT and received defibrillation. RESULTS: There were 251 subjects (37.7%) who received a single shock and 415 subjects (62.3%) who received multiple shocks. Baseline and cardiac arrest characteristics did not differ between those who received a single shock versus multiple shocks except for duration of arrest and calendar year. The median first shock dose was consistent with AHA dosing recommendations and not different between those who received a single shock versus multiple shocks. Survival was improved for those who received a single shock compared to multiple shocks. However, no difference in survival was noted between those who received 2, 3, or ≥4 shocks. Of those receiving multiple shocks, no difference was observed with early dose escalation. CONCLUSIONS: In pediatric IHCA, most patients with initial VF/pVT require more than one shock. No distinctions in patient or pre-arrest characteristics were identified between those who received a single shock versus multiple shocks. Subjects who received a single shock were more likely to survive to hospital discharge even after adjusting for duration of resuscitation.


Cardiopulmonary Resuscitation , Electric Countershock , Heart Arrest , Registries , Tachycardia, Ventricular , Ventricular Fibrillation , Humans , Male , Female , Child , Electric Countershock/methods , Electric Countershock/statistics & numerical data , Heart Arrest/therapy , Heart Arrest/mortality , Heart Arrest/complications , Child, Preschool , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/mortality , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/epidemiology , Adolescent , Ventricular Fibrillation/complications , Ventricular Fibrillation/therapy , Ventricular Fibrillation/mortality , Cardiopulmonary Resuscitation/methods , Cardiopulmonary Resuscitation/statistics & numerical data , Infant , United States/epidemiology
7.
Europace ; 26(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38657209

AIMS: Primary prevention patients with ischaemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. The trial was designed to evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. METHODS AND RESULTS: The PREVENTIVE VT study was a prospective, multicentre, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented ventricular arrhythmias (VAs), and evidence of scar related to the coronary CTO. Patients were randomly assigned 1:1 to a preventive substrate ablation before ICD implantation or standard therapy with ICD implantation only. The primary outcome was a composite of appropriate ICD therapy or unplanned hospitalization for VAs. Secondary outcomes included the primary outcome's components, the incidence of appropriate ICD therapies, cardiac hospitalization, electrical storm, and cardiovascular (CV) mortality. Sixty patients were included in the study. During the mean follow-up of 44.7 ± 20.7 months, the primary outcome occurred in 5 (16.7%) patients undergoing preventive substrate ablation and in 13 (43.3%) patients receiving only ICD [hazard ratio (HR): 0.33; 95% confidence interval (CI): 0.12-0.94; P = 0.037]. Patients in the preventive ablation group also had fewer appropriate ICD therapies (P = 0.039) and the electrical storms (Log-rank: P = 0.01). While preventive ablation also reduced cardiac hospitalizations (P = 0.006), it had no significant impact on CV mortality (P = 0.151). CONCLUSION: Preventive ablation of the coronary CTO-related substrate in patients undergoing primary ICD implantation is associated with the reduced risk of appropriate ICD therapy or unplanned hospitalization due to VAs.


Catheter Ablation , Coronary Occlusion , Defibrillators, Implantable , Myocardial Ischemia , Primary Prevention , Humans , Male , Female , Middle Aged , Aged , Coronary Occlusion/mortality , Coronary Occlusion/therapy , Coronary Occlusion/prevention & control , Coronary Occlusion/complications , Treatment Outcome , Prospective Studies , Myocardial Ischemia/complications , Myocardial Ischemia/mortality , Tachycardia, Ventricular/prevention & control , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/mortality , Cardiomyopathies/mortality , Cardiomyopathies/complications , Cardiomyopathies/therapy , Death, Sudden, Cardiac/prevention & control , Death, Sudden, Cardiac/etiology , Risk Factors , Electric Countershock/instrumentation , Electric Countershock/adverse effects , Electric Countershock/mortality , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Myocardial Infarction/complications , Chronic Disease , Time Factors
8.
Europace ; 26(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38666444

Stereotactic arrhythmia radioablation (STAR) is a treatment option for recurrent ventricular tachycardia/fibrillation (VT/VF) in patients with structural heart disease (SHD). The current and future role of STAR as viewed by cardiologists is unknown. The study aimed to assess the current role, barriers to application, and expected future role of STAR. An online survey consisting of 20 questions on baseline demographics, awareness/access, current use, and the future role of STAR was conducted. A total of 129 international participants completed the survey [mean age 43 ± 11 years, 25 (16.4%) female]. Ninety-one (59.9%) participants were electrophysiologists. Nine participants (7%) were unaware of STAR as a therapeutic option. Sixty-four (49.6%) had access to STAR, while 62 (48.1%) had treated/referred a patient for treatment. Common primary indications for STAR were recurrent VT/VF in SHD (45%), recurrent VT/VF without SHD (7.8%), or premature ventricular contraction (3.9%). Reported main advantages of STAR were efficacy in the treatment of arrhythmias not amenable to conventional treatment (49%) and non-invasive treatment approach with overall low expected acute and short-term procedural risk (23%). Most respondents have foreseen a future clinical role of STAR in the treatment of VT/VF with or without underlying SHD (72% and 75%, respectively), although only a minority expected a first-line indication for it (7% and 5%, respectively). Stereotactic arrhythmia radioablation as a novel treatment option of recurrent VT appears to gain acceptance within the cardiology community. Further trials are critical to further define efficacy, patient populations, as well as the appropriate clinical use for the treatment of VT.


Radiosurgery , Tachycardia, Ventricular , Ventricular Fibrillation , Humans , Female , Male , Tachycardia, Ventricular/surgery , Tachycardia, Ventricular/physiopathology , Adult , Middle Aged , Ventricular Fibrillation/surgery , Ventricular Fibrillation/physiopathology , Radiosurgery/trends , Health Care Surveys , Electrophysiologic Techniques, Cardiac , Recurrence , Treatment Outcome , Practice Patterns, Physicians'/trends , Practice Patterns, Physicians'/statistics & numerical data , Cardiologists/trends , Cardiac Electrophysiology/trends
10.
Europace ; 26(4)2024 Mar 30.
Article En | MEDLINE | ID: mdl-38584394

AIMS: Catheter ablation (CA) of ventricular tachycardia (VT) has become an important tool to improve clinical outcomes in patients with appropriate transvenous implantable cardioverter defibrillator (ICD) shocks. The aim of our analysis was to test whether VT ablation (VTA) impacts long-term clinical outcomes even in subcutaneous ICD (S-ICD) carriers. METHODS AND RESULTS: International Subcutaneous Implantable Cardioverter Defibrillator (iSUSI) registry patients who experienced either an ICD shock or a hospitalization for monomorphic VT were included in this analysis. Based on an eventual VTA after the index event, patients were divided into VTA+ vs. VTA- cohorts. Primary outcome of the study was the occurrence of a combination of device-related appropriate shocks, monomorphic VTs, and cardiovascular mortality. Secondary outcomes were addressed individually. Among n = 1661 iSUSI patients, n = 211 were included: n = 177 experiencing ICD shocks and n = 34 hospitalized for VT. No significant differences in baseline characteristics were observed. Both the crude and the yearly event rate of the primary outcome (5/59 and 3.8% yearly event rate VTA+ vs. 41/152 and 16.4% yearly event rate in the VTA-; log-rank: P value = 0.0013) and the cardiovascular mortality (1/59 and 0.7% yearly event rate VTA+ vs. 13/152 and 4.7% yearly event rate VTA-; log-rank P = 0.043) were significantly lower in the VTA + cohort. At multivariate analysis, VTA was the only variable remaining associated with a lower incidence of the primary outcome [adjusted hazard ratio 0.262 (0.100-0.681), P = 0.006]. CONCLUSION: In a real-world registry of S-ICD carriers, the combined study endpoint of arrhythmic events and cardiovascular mortality was lower in the patient cohort undergoing VTA at long-term follow-up. CLINICALTRIALS.GOV IDENTIFIER: NCT0473876.


Catheter Ablation , Defibrillators, Implantable , Tachycardia, Ventricular , Humans , Arrhythmias, Cardiac/etiology , Catheter Ablation/adverse effects , Catheter Ablation/methods , Electric Countershock/adverse effects , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/surgery , Treatment Outcome
11.
Chem Pharm Bull (Tokyo) ; 72(4): 399-407, 2024.
Article En | MEDLINE | ID: mdl-38644198

Ryanodine receptor 2 (RyR2) is a large Ca2+-release channel in the sarcoplasmic reticulum (SR) of cardiac muscle cells. It serves to release Ca2+ from the SR into the cytosol to initiate muscle contraction. RyR2 overactivation is associated with arrhythmogenic cardiac disease, but few specific inhibitors have been reported so far. Here, we identified an RyR2-selective inhibitor 1 from the chemical compound library and synthesized it from glycolic acid. Synthesis of various derivatives to investigate the structure-activity relationship of each substructure afforded another two RyR2-selective inhibitors 6 and 7, among which 6 was the most potent. Notably, compound 6 also inhibited Ca2+ release in cells expressing the RyR2 mutants R2474S, R4497C and K4750Q, which are associated with cardiac arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT). This inhibitor is expected to be a useful tool for research on the structure and dynamics of RyR2, as well as a lead compound for the development of drug candidates to treat RyR2-related cardiac disease.


Calcium Channel Blockers , Ryanodine Receptor Calcium Release Channel , Humans , Calcium/metabolism , Dose-Response Relationship, Drug , Drug Discovery , HEK293 Cells , Molecular Structure , Ryanodine Receptor Calcium Release Channel/drug effects , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism , Structure-Activity Relationship , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/pharmacology , Anti-Arrhythmia Agents/chemistry , Anti-Arrhythmia Agents/pharmacology , Tachycardia, Ventricular/drug therapy , Tachycardia, Ventricular/genetics
13.
Europace ; 26(4)2024 Mar 30.
Article En | MEDLINE | ID: mdl-38582974

AIMS: The ultra-low-temperature cryoablation (ULTC) ablation system using -196°C N2 cryogen has been reported to create lesions with freeze duration-dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). METHODS AND RESULTS: This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1-9) to 0, IQR (0-2). CONCLUSION: In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. CLINICAL TRIAL REGISTRATION: NCT04893317.


Cardiomyopathies , Catheter Ablation , Cryosurgery , Tachycardia, Ventricular , Aged , Humans , Middle Aged , Cardiomyopathies/complications , Cardiomyopathies/diagnosis , Cardiomyopathies/surgery , Catheter Ablation/adverse effects , Cicatrix/complications , Cryosurgery/adverse effects , Prospective Studies , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/surgery , Temperature , Treatment Outcome
14.
Proc Natl Acad Sci U S A ; 121(17): e2218204121, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38621141

Inherited arrhythmia syndromes (IASs) can cause life-threatening arrhythmias and are responsible for a significant proportion of sudden cardiac deaths (SCDs). Despite progress in the development of devices to prevent SCDs, the precise molecular mechanisms that induce detrimental arrhythmias remain to be fully investigated, and more effective therapies are desirable. In the present study, we screened a large-scale randomly mutagenized mouse library by electrocardiography to establish a disease model of IASs and consequently found one pedigree that exhibited spontaneous ventricular arrhythmias (VAs) followed by SCD within 1 y after birth. Genetic analysis successfully revealed a missense mutation (p.I4093V) of the ryanodine receptor 2 gene to be a cause of the arrhythmia. We found an age-related increase in arrhythmia frequency accompanied by cardiomegaly and decreased ventricular contractility in the Ryr2I4093V/+ mice. Ca2+ signaling analysis and a ryanodine binding assay indicated that the mutant ryanodine receptor 2 had a gain-of-function phenotype and enhanced Ca2+ sensitivity. Using this model, we detected the significant suppression of VA following flecainide or dantrolene treatment. Collectively, we established an inherited life-threatening arrhythmia mouse model from an electrocardiogram-based screen of randomly mutagenized mice. The present IAS model may prove feasible for use in investigating the mechanisms of SCD and assessing therapies.


Tachycardia, Ventricular , Mice , Animals , Ryanodine Receptor Calcium Release Channel/metabolism , Arrhythmias, Cardiac/genetics , Flecainide , Mutation, Missense , Death, Sudden, Cardiac , Mutation
17.
PLoS One ; 19(4): e0301970, 2024.
Article En | MEDLINE | ID: mdl-38626004

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.


Heterocyclic Compounds, 2-Ring , Myocardial Infarction , Pyrimidines , Tachycardia, Ventricular , Animals , Rabbits , Ventricular Fibrillation , Calcium/therapeutic use , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Arrhythmias, Cardiac/drug therapy , Anti-Arrhythmia Agents/therapeutic use , Heart Block , Tachycardia, Ventricular/drug therapy
18.
Eur Rev Med Pharmacol Sci ; 28(6): 2199-2206, 2024 Mar.
Article En | MEDLINE | ID: mdl-38567583

OBJECTIVE: Pediatric heart failure is an important cause of morbidity and mortality in childhood. Left ventricular assist devices (L-VAD) are used for bridging to transplantation in patients with indications for heart transplantation. PATIENTS AND METHODS: The children included in the study were patients who underwent implantation of an L-VAD due to advanced heart failure at Ege University Faculty of Medicine Hospital between January 2009 and January 2023. RESULTS: Of the 33 patients who underwent L-VAD implantation, 16 (48.5%) were female and 17 (51.5%) were male. The median age at surgery was 13 years (IQR, 9.5-15). The median weight was 44 kg (IQR, 25.65-52), the median height was 158 cm (IQR, 134.5-168.5), and the median body surface area was 1.37 m2 (IQR, 0.95-1.51). All patients who underwent L-VAD implantation had an echocardiographic diagnosis of dilated cardiomyopathy. The patients underwent a median of 16 (IQR, 9-21) ECGs, and the median number of 24-hour Holter ECGs obtained was 3 (IQR, 2-5). Arrhythmias that occurred after L-VAD implantation were classified as atrial and ventricular. Ventricular arrhythmia included ventricular tachycardia (VT) lasting for more than 30 seconds (sustained VT), VT lasting for less than 30 seconds (nonsustained VT), and ventricular fibrillation. Atrial arrhythmias included atrial flutter, atrial fibrillation, supraventricular tachycardia, and atrial ectopic tachycardia. During the follow-up, atrial or ventricular arrhythmias were observed in 11 (33%) patients. The most common rhythm disturbances before L-VAD implantation were ventricular arrhythmias, while after the surgery, atrial arrhythmias were found to be the most frequent. A total of 5 patients underwent cardioversion (n=2) or defibrillation (n=3) due to arrhythmia. CONCLUSIONS: In patients undergoing L-VAD implantation, rhythm disorders that could normally lead to hemodynamic instability are frequently encountered. In these rhythm disorders, medical therapy should be attempted before resorting to cardioversion or defibrillation, and subsequently, more aggressive treatment methods should be considered.


Atrial Fibrillation , Heart Failure , Heart-Assist Devices , Tachycardia, Supraventricular , Tachycardia, Ventricular , Humans , Male , Female , Child , Adolescent , Heart-Assist Devices/adverse effects , Heart Failure/therapy , Heart Failure/complications
19.
Am J Cardiol ; 210: 100-106, 2024 Jan 01.
Article En | MEDLINE | ID: mdl-38682708

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.


Electrocardiography , Tachycardia, Ventricular , Takotsubo Cardiomyopathy , Humans , Female , Male , Takotsubo Cardiomyopathy/physiopathology , Takotsubo Cardiomyopathy/complications , Takotsubo Cardiomyopathy/diagnosis , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/etiology , Aged , Retrospective Studies , Middle Aged , Echocardiography , Stroke Volume/physiology , Ventricular Function, Left/physiology
20.
Europace ; 26(4)2024 Mar 30.
Article En | MEDLINE | ID: mdl-38584423

Electrical storm (ES) is a state of electrical instability, manifesting as recurrent ventricular arrhythmias (VAs) over a short period of time (three or more episodes of sustained VA within 24 h, separated by at least 5 min, requiring termination by an intervention). The clinical presentation can vary, but ES is usually a cardiac emergency. Electrical storm mainly affects patients with structural or primary electrical heart disease, often with an implantable cardioverter-defibrillator (ICD). Management of ES requires a multi-faceted approach and the involvement of multi-disciplinary teams, but despite advanced treatment and often invasive procedures, it is associated with high morbidity and mortality. With an ageing population, longer survival of heart failure patients, and an increasing number of patients with ICD, the incidence of ES is expected to increase. This European Heart Rhythm Association clinical consensus statement focuses on pathophysiology, clinical presentation, diagnostic evaluation, and acute and long-term management of patients presenting with ES or clustered VA.


Defibrillators, Implantable , Heart Failure , Tachycardia, Ventricular , Humans , Risk Factors , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/therapy , Incidence , Heart Failure/complications , Asia/epidemiology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/complications
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