Occurrence Of Ventricular Tachycardia Research Articles

Ventricular Tachycardia and Hospital Readmission in Patients Discharged From the Hospital After an Acute Myocardial Infarction

BackgroundAlthough ventricular tachycardia (VT) occurring during hospitalization for an acute myocardial infarction (AMI) increases mortality risk, its relationship with 30-day postdischarge rehospitalization has not been examined. MethodsUsing data from the Worcester Heart Attack Study, we examined the association between early (during the first 48 hours of admission) and late (after 48 hours from admission) VT with 30-day postdischarge all-cause and cardiovascular disease (CVD)-related rehospitalization while analytically controlling for several demographic and clinical factors. ResultsThe study population consisted of 3534 patients who were hospitalized with an AMI between 2005 and 2015 (average age, 67.2 years; 40.7% women); VT occurred in 452 patients (13.7%), with the majority of instances (81.2%) occurring within 48 hours of admission. The 30-day all-cause rehospitalization rate was 17.3%, with 70.9% of the hospitalizations related to CVD. The odds of rehospitalization were 1.63 times (95% confidence interval [CI] = 0.99-2.69) and 1.12 times (95% CI = 0.83-1.51) higher for patients with AMI who developed late VT and early VT, respectively, compared to patients who did not develop VT. The risk of rehospitalization among patients with late VT was higher (odds ratio = 2.22 (95% CI = 0.79-6.26) in those with ST-segment-elevation AMI, compared to those with non-ST-segment-elevation AMI (odds ratio = 1.45 (95% CI = 0.81-2.57); early VT was not associated with rehospitalization in patients with either AMI subtype. No significant association was present between the occurrence of VT and CVD-related rehospitalization. ConclusionsPatients who develop late VT may experience a higher risk of 30-day rehospitalization following hospital discharge for AMI, especially among those with ST-segment-elevation AMI. Larger studies are needed to confirm our findings.

Abstract 16061: Correlation Between Obesity and Ventricular Tachycardia in Individuals With HFrEF: Analysis From the DERIVATE Cohort

Background: Ventricular arrhythmias (VA) are a significant cause of morbidity and mortality in heart failure. Obesity has been proposed as a potential risk factor for increased VA incidence, but previous studies with limited sample sizes and single-center enrollment have yielded conflicting results. To address this, we utilized data from the international multicenter DERIVATE study, which includes individuals with heart failure with reduced ejection fraction (HFrEF) as well as baseline cardiac MRI (CMR) assessment of myocardial structure and function. We sought to investigate the association between obesity and sustained ventricular tachycardia (VT) occurrence in this patient population. Methods: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy (DERIVATE) registry who had HFrEF and had simultaneous baseline CMR and echocardiography evaluation. Demographics, comorbidities, and CMR variables were used to evaluate the correlation between obesity and ventricular tachycardia. Obesity was defined as BMI>30 kg/m 2 . A multivariate logistic regression analysis was used to determine the association between clinical, imaging variables and the occurrence of VA. Statistical software SAS 9.4 was used to perform the analysis. Results: Among 2,537 individuals, 505 (19.9%) were obese. Mean age was 60 years and 23.9% were female. Median follow-up was 994 days. Obesity was not associated with VT (OR 0.94, CI 0.60-1.48, P=0.79). The occurrence of VT was associated with the presence of an ischemic cardiomyopathy (OR 1.76, CI 1.37-2.26, p<0.01), and amiodarone use (OR 1.89, CI 1.28-2.80, P<0.01). As expected, left ventricular ejection fraction was inversely associated with VT (OR 0.96, CI 0.94-0.98, P<0.01), while indexed left ventricular end diastolic volume was directly associated with VT (OR 1.01, CI 1.00-1.01, P<0.01). Conclusions: In individuals with HFrEF, there was no association between obesity and the occurrence of sustained VT. The presence of ischemic cardiomyopathy was associated with higher incidence of sustained VT, as well as larger indexed left ventricular end diastolic volume which is an imaging marker of HF chronicity and severity.

Abstract 17896: Implantable Cardioverter Defibrillator in Cardiac Resynchronization Therapy Recipients With Advanced Chronic Kidney Disease

Introduction: The effectiveness of the implantable cardioverter defibrillator (ICD) in preventing sudden cardiac death (SCD) is well-established in heart failure patients with reduced ejection fraction (HFrEF). However, the benefit of the ICD in advanced chronic kidney disease (CKD) patients remains elusive, particularly in those who are cardiac resynchronization therapy (CRT) recipients. Hypothesis: In CRT recipients with CKD, the benefit of the ICD may be attenuated due to the competing risk of mortality before experiencing an arrhythmia. Methods: A total of 1015 patients receiving CRT with defibrillator (CRT-D) for primary prevention of SCD were included from the MADIT-CRT and RAID trials. Patients were categorized into two groups based on kidney disease (KD) stage: Stage 1-3a (S1-S3a) CKD and Stage 3b-5 (S3b-S5) CKD. The primary endpoint was the occurrence of ventricular tachycardia (VT) or ventricular fibrillation (VF). Results: The cumulative incidence of any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p<0.001 [Figure left panel]). Death without VT/VF occurred in 6.6% of patients with (S1-S3a)KD and 21.6% of patients with( S3b-S5)KD (p<0.001 [Figure right panel]). A multivariate competing risk regression model revealed that patients with (S3b-S5)KD had a 43% lower risk of experiencing any VT/VF compared to those with (S1-S3a)KD (HR=0.56, 95% CI [0.33-0.94], p=0.03). Over two years of follow-up, patients with (S3b-S5)KD had nearly a five-fold increased risk of death without VT/VF compared to those with (S1-S3a)KD (HR=4.63, 95% CI [2.46-8.72], p for interaction with time=0.012). Conclusions: The benefit of the ICD may be attenuated in CRT recipients with advanced CKD due to a lower incidence of arrhythmias and a higher risk of non-arrhythmic death. Future prospective trials should investigate whether CRT without a defibrillator is more suitable for these patients.

Arrhythmias and Clinical Outcomes in a Swiss Multicenter Cohort of Patients With Dextro-Transposition of the Great Arteries and Atrial Switch.

Background Data on the incidence of arrhythmias, associated cardiac interventions, and outcome in patients with dextro-transposition of the great arteries and atrial switch are scarce. Methods and Results In this multicenter analysis, we included adult patients with dextro-transposition of the great arteries and atrial switch regularly followed up at 3 Swiss tertiary care hospitals. The primary outcome was a composite of left ventricular assist device, heart transplantation, and death. The secondary outcome was occurrence of ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. We identified 207 patients (34% women; median age at last follow-up, 35 years) with dextro-transposition of the great arteries and atrial switch. Arrhythmias occurred in 97 patients (47%) at a median age of 22 years. A pacemaker or an implantable cardioverter-defibrillator was implanted in 39 (19%) and 13 (6%) patients, respectively, and 33 (16%) patients underwent a total of 51 ablation procedures to target 60 intra-atrial re-entry tachycardias, 4 atrioventricular nodal re-entry tachycardias, and 1 atrial fibrillation. The primary outcome occurred in 21 patients (10%), and the secondary outcome occurred in 18 patients (9%); both were more common in patients with concomitant ventricular septum defect than in those without (hazard ratio [HR], 3.06 [95% CI, 1.29-7.27], P=0.011; and HR, 3.62 [95% CI, 1.43-9.18], P=0.007, respectively). Conclusions In patients with dextro-transposition of the great arteries and atrial switch reaching adulthood, arrhythmias occur in almost half of patients, and associated rhythm interventions are frequent. One-tenth of those patients do not survive until the age of 35 years free from left ventricular assist device or heart transplantation, and the outcome is worse in patients with concomitant ventricular septum defect.

Dysrhythmic profile of inotropic therapy in patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with acute coronary syndrome (ACS) may develop ventricular dysfunction and need to use drugs with a positive inotropic effect, during the acute phase. Despite the hemodynamic benefit of the use of these drugs, positive inotropic drugs may have several side effects, including ventricular tachycardia (VT)and atrial fibrillation (AF). AF can complicate the management of patients with ACS, since these patients need intense antiplatelet therapy, and in the case of AF, it may have to be associated with anticoagulant therapy, thereby increasing the bleeding risk. The clinical significance of AF during an acute event remains to be ascertained. Purpose This study aims to assess the frequency of occurrence of dysrhythmic complications with the use of positive inotropic drugs in patients hospitalized for ACS. Methods We performed a 6-year retrospective, observational, multicenter study. We included patients with ACS who used positive or not inotropic drugs during hospitalization, dividing the sample into two groups respectively (Group 1 and Group 2). Between the two groups we compared the occurrence of ventricular tachycardia and atrial fibrillation. In addition, we performed an analysis for the use of levosimendan. Results We analyzed a sample of 5860 patients. Of these, 70.3% were male. In Group 1 we included 377 patients and in Group 2 5329 patients. The occurrence of VT in Group 1 was higher than in Group 2 (15.5% vs 1.6%; p<0.001; OR: 11.472; 95% CI [8.212;16.027]). The rate of occurrence of AF in Group 1 was higher than in Group 2 (19.3% vs 5.1%; p<0.001; OR:4.413; 95% CI [3.388;5.749]). Regarding the use of levosimendan, 50 patients were analyzed. VT was more frequent with the use of this drug than without it (18.0% vs 2.5%; p<0.001; OR: 8.576 95% CI [4.092;17.976]). Atrial fibrillation was more frequent with levosimendan use than with no use (34.0% vs 6.0%; p>0.001; OR: 8.137; 95% CI [4.487;14.754]). Conclusion Arrhythmic complications were much more frequent in the group that used positive inotropic drugs, namely VT and AF. Levosimendan stands out, related to the increase in the occurrence of AF and the remaining inotropes with an increased risk of VT. These arrhythmic complications pose a challenge in the management of these patients, as in patients with ACS, the use of Levosimendan is associated with more episodes of AF, and might complicate the antithrombotic therapy strategy choice.

Ventricular tachycardia predicts all-cause mortality and non-sudden cardiac death in non-ischaemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The DCM-VT study was partially supported by an investigator-initiated grant (IIS-310) from Biosense Webster (a Johnson & Johnson company). The DANISH study was supported by unrestricted grants from Medtronic, St. Jude Medical, TrygFonden, and the Danish Heart Foundation. Background Endstage heart failure, ventricular tachycardia (VT) and sudden cardiac death (SCD) are sequels of non-ischaemic cardiomyopathies (NICM). Implantable cardioverter defibrillators (ICDs) can terminate VT and prevent SCD but mortality benefit has been limited in recent trials suggesting that VT may also be associated with non-sudden cardiovascular death (NSCVD). Purpose To assess the effect of VT on all-cause mortality and NSCVD in NICM patients with ICDs. Methods Two multicenter cohorts of NICM patients were merged for analysis: (1) patients randomized to ICD in the DANISH trial, which included patients with NICM, LVEF ≤35% and no prior VT and (2) the DCM-VT study cohort, which included consecutive NICM patients with any LVEF referred for ablation of sustained VT. Predictors for the primary composite outcome of all-cause death and heart transplant (death/HTx) and for the secondary outcome of NSCVD were assessed. In addition, propensity score matching was performed using the parameters age, gender, LVEF and eGFR. Finally, survival following VT occurrence was compared between DANISH and DCM-VT patients. Results A total of 828 patients (556 DANISH, 272 DCM-VT) were followed for a median of 3.9 years (2.1 – 5.8). DANISH patients had a median LVEF of 25% (20 – 30) and DCM-VT patients 35% (27 – 43). A total of 148 patients (DANISH 16.4%, DCM-VT 21.0%) experienced death/HTx and NSCVD occurred in 78 patients (7.7%, 12.9%, respectively). In multivariable analysis history of VT at inclusion was a significant predictor of the primary outcome with an adjusted hazard ratio (HRa) of 3.81 (95% CI 2.33 - 6.24) as were age [HRa 1.02 per year (1.01 - 1.04)], LVEF [HRa 0.96 per 1% increase (0.94 - 0.98)] and reduced eGFR [HRa 1.71 (1.15 – 2.53 )]. History of VT predicted NSCVD with an HRa of 7.54 (3.97 - 14.33). After matching, history of VT still predicted death/HTx [HR 4.12 (2.48 - 6.82)] and NSCVD [HR 6.92 (3.30 - 14.52)]. Risk of death/HTx, as well as NSCVD, for DANISH patients was similar to DCM-VT patients after they experienced their first VT event [HRa 0.90 (0.48 - 1.69) and HRa 1.07 (0.56 - 2.06) resp.]. Conclusions VT occurrence appears to be an important predictor of non-sudden CV death as well as all-cause death in NICM patients independent of other markers of heart failure severity. VT may be a marker of progressive disease and remodelling that could be incorporated into risk-stratification to help predict deterioration and need for HTx.

Ventricular tachycardia substrates in young patients with repaired tetralogy of fallot

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research lnitiative: An initiative with support of the Dutch Heart Foundation and Hartekind. Background Patients with repaired tetralogy of Fallot (rTOF) have a time-dependent increase in risk of ventricular tachycardia (VT) after the age of 30 years (Y), with slow conducting anatomical isthmus (SCAI) 3, located between the pulmonary annulus and the ventricular septal defect (VSD) patch, as dominant VT substrate (1-4). However, SCAI may be already present before 30Y. Purpose To assess (1) the prevalence of SCAI, (2) the associated factors in SCAI development, and (3) the occurrence of clinical VT, in rTOF patients <30Y. Methods From a database of 146 patients with rTOF or related lesions who underwent electroanatomical mapping (EAM) and programmed electrical stimulation (PES) between 2007 and 2022 for treatment of ventricular arrhythmias (VA), risk stratification or before pulmonary valve replacement (PVR), those aged <30Y at time of procedure were selected and analysed. Results Of 146 rTOF patients, 55 (38%) were <30Y (median 16Y [IQR 14-22]); 33/55 (60%) had TOF, 9/55 (16%) TOF with double outlet right ventricle (DORV), and 13/55 (24%) complex TOF variants, including 8 patients with pulmonary atresia with VSD, 2 patients with absent pulmonary valve, and 3 with other variations. Initial intracardiac surgical repair (median age 0.8Y [IQR 0.4-1.4]) was performed via a ventriculotomy in 10/55 (18%) after palliative shunts in 16/55 (29%). An RV to pulmonary artery (RV-PA) conduit was inserted during initial or early after (<1Y) initial repair in 12/55 (22%). In 14/55 (25%) pulmonary valve replacement (PVR) was performed later in life (median age 10.1Y [IQR 2.7-14.3]). Five of 55 (9%) underwent EAM/PES after a spontaneous VA, 40/55 (73%) before PVR, and 10/55 (18%) for risk stratification. Monomorphic VT was inducible in 8/55 (15%), including 4/5 patients with spontaneous VT, and was proven related to a SCAI 3 in 7/8 (88%). In 16/55 (29%) SCAI 3 could be identified; no other SCAI (1,2,4) was present. Of note, 9/16 (56%) of patients with SCAI 3 had initial RV-PA conduit repair/early PVR, in comparison with only 3/39 (8%) of patients without SCAI. In univariable analysis complex TOF (OR 6.8 [95% CI 1.8-26.4]), ventriculotomy (OR 5.3 [95% CI 1.2-22.3]), any prior PVR (OR 4.8 [95% CI 1.4-16.7]), and initial RV-PA conduit/early PVR (OR 15.4 [95% CI 3.3-71.8]) were significantly associated with SCAI 3. In multivariable analysis initial RV-PA conduit/early PVR remained the only independent predictor of SCAI 3 (OR 13.0 [95% CI 1.2-142.4]). Conclusions A SCAI 3 is present in 29% of rTOF patients <30Y referred for EAM/PES and the dominant VT substrate for spontaneous and inducible VTs. RV-PA conduit placement during initial repair or early PVR (<1Y after repair) is associated with SCAI 3 in young rTOF. Whether the early conduit/valve placement causes scarring at the infundibulum with consecutive slow conduction and/or whether the complex variants contribute to SCAI requires additional studies.

Syncope in patients with diagnosed with hypertrophic cardiomyopathy: risk of ventricular tachycardia, cardiac arrest and death

Abstract Funding Acknowledgements Type of funding sources: None. Background Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder; however, detection rates remain low. While most patients are only mildly symptomatic, some develop serious complications such as heart failure (HF), atrial fibrillation (AF), and sudden cardiac death (SCD). Given the possibility of severe outcome, a large focus is put on early detection and prevention of possible HCM related complications. Syncope has long been one of these factors associated with increased risk of SCD, however little concrete data on the impact and consequences of prior syncope in a large HCM population exist. Objectives To determine the risk of ventricular tachycardia (VT), cardiac arrest (CA) and death in patients with HCM and prior history of syncope compared to HCM patients without syncope. Methods All patients aged ≥16 years diagnosed with HCM from 2005 - 2018 were identified in the Danish National Registers and included at first time diagnosis. All admissions or prior presentation of syncope were registered and analyzed for the outcome of a combined endpoint comprising occurrence of VT, CA or death. The association between HCM, syncope and the combined endpoint were investigated using multivariable cox proportional-hazard analysis adjusted for gender, age, and comorbidities. Cumulative incidence of the combined endpoint was calculated using the Aalen-Johansen estimator. Results In this study 3,856 HCM patients were included (median age 68 years [IQR 56-78]) with near equal gender distribution (males 53%, females 47%). Overall 361 (9%) of patients had a registered contact for syncope prior to HCM diagnosis. A total of 1356 patients (35%) reached the combined endpoint. Of those patients with prior syncope 163 patients (45%) reached the endpoint, compared to 1193 patients (34%) who had no registered syncope prior to HCM diagnosis. Univariate analysis showed a significantly increased risk (HR 1.5 (CI 1.3-1.8) p = <0.001) of patients in the syncope group of VT, CA and death, however in multivariate analysis adjusted for gender, age and comorbidities this difference did not prove significant (HR 1.1 (CI 0.9-1.3) p = 0.35) (Figure 1). Subgroup analysis revealed a striking disparity between male and female HCM patients with prior syncope in their risk of reaching the combined endpoint. Adjusted for age and comorbidities, males were at a significantly increased risk of ventricular tachycardia, cardiac arrest and death (HR 1.6 (CI 1.1-2.2) p = 0.008) (Figure 2). Conclusion Although there was a significant increased rate of HCM patients with prior syncope reaching the combined endpoint of ventricular tachycardia, cardiac arrest and death, multivariate analysis showed this association to be mainly driven by comorbidity and age. In this cohort males with prior syncope were at a significantly higher risk of reaching the combined endpoint. More research will be needed to explore this disparity.

Catheter ablation of ventricular tachycardia-Update2023

The management of ventricular tachycardias (VT), which are often associated with severe cardiac disease, is achallenging clinical task. The structural damage to the myocardium associated with cardiomyopathy is crucial to the occurrence of VT and plays afundamental role in arrhythmia mechanisms. The goal of catheter ablation is to develop an accurate understanding of the patient-specific arrhythmia mechanism as a first procedural step. As a second step, the ventricular areas that maintain the arrhythmia mechanism can be ablated and thereby electrically inactivated. Catheter ablation thereby enables causal therapy of VT by modifying the areas of the affected myocardium in such away that VT can no longer be triggered. The procedure is an effective treatment option for affected patients.

PO-05-079 SMOKING AND THE RISK OF VENTRICULAR TACHYARRHYTHMIAS AMONG IMPLANTABLE CARDIOVERTER DEFIBRILLATOR RECIPIENTS FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

Smoking has been linked to increased morbidity and mortality in patients with cardiovascular disease. However, limited data exist regarding the arrhythmic effects of smoking in patients at risk for sudden cardiac death (SCD). We aimed to evaluate the relationship between smoking and the risk of ventricular tachyarrhythmias and SCD. The study population comprised 5,015 patients implanted with an implantable cardioverter defibrillator (ICD) from five landmark randomized ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID trials). Patients were categorized into three groups based on smoking status at the time of ICD implantation: non-smokers, past smokers, and current smokers. The primary endpoint was the first occurrence of ventricular tachycardia ≥170 bpm or fibrillation (VT/VF). Secondary endpoints included the composite endpoint of VT/VF or SCD and inappropriate ICD shocks. A competing risk analysis was carried out using the Fine and Gray method to generate cumulative incidence function (CIF) curves and regression models for the defined endpoints. The 5-year cumulative incidence of a first episode of VT/VF was higher in current smokers (32%) than in past- (29%) and non-smokers (25%) (p=0.009, [Figure, left panel]). Consistent results were obtained for the endpoint of inappropriate ICD shocks (10%, 9%, 6%%, respectively; p=0.007, [Figure, right panel]). Multivariate current smoking vs. non-smoking was associated with a significant 25% increased risk of VT/VF (HR=1.25, p=0.034); with a corresponding 28% increased risk of the composite endpoint of VT/VF or SCD (HR=1.28, p=0.014); and with a 49% increased risk of inappropriate ICD shocks (HR=1.49, p=0.03). Conversely, the risk of the aforementioned endpoints was not significantly difference between past-smokers and never-smokers. Patients who smoke at the time of ICD implantation experience a significantly increased risk of VT/VF and inappropriate ICD shocks.

Improved Outcomes After Pulmonary Valve Replacement in Repaired Tetralogy of Fallot

BackgroundThe impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. ObjectivesThe purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. MethodsA PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. ResultsAmong 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). ConclusionsCompared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

ObjectiveThe transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products. MethodsThe diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products. ResultsTwo new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity. ConclusionCompared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines.Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302–314.

Risk of ventricular tachycardia and its outcomes in patients undergoing continuous renal replacement therapy due to acute kidney injury.

Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables. VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting &lt;30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23-3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04-8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT. Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.

Single beta-blocker or combined amiodarone therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy—defibrillator patients: Insights from the German DEVICE registry

Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing. The purpose of this study was to assess the periprocedural and postprocedural outcomes of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in the "real-life" cohort of ICD recipients of the German DEVICE registry. A total of 4499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE registry were enrolled from March 2007 to February2014. Amiodarone had no significant effect on the success of defibrillation testing. Early implantation-associated complications were similar between the groups. However, 1-year overall mortality was significantly higher in the beta-blocker plus amiodarone cohort (adjusted hazard ratio 2.09; P <.001). Interestingly, among the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges or syncopal events. Furthermore, the occurrence of ventricular tachycardia (VT) storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups, whereas the rate of rehospitalization was lower in the cohort with only beta-blockers. Although amiodarone has no adverse effect on the success of defibrillation testing, our data suggest an increased all-cause mortality under amiodarone therapy, especially in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.

From evidence-based medicine to digital twin technology for predicting ventricular tachycardia in ischaemic cardiomyopathy.

Survivors of myocardial infarction are at risk of life-threatening ventricular tachycardias (VTs) later in their lives. Current guidelines for implantable cardioverter defibrillators (ICDs) implantation to prevent VT-related sudden cardiac death is solely based on symptoms and left ventricular ejection fraction. Catheter ablation of scar-related VTs is performed following ICD therapy, reducing VTs, painful shocks, anxiety, depression and worsening heart failure. We postulate that better prediction of the occurrence and circuit of VT, will improve identification of patients at risk for VT and boost preventive ablation, reducing mortality and morbidity. For this purpose, multiple time-evolving aspects of the underlying pathophysiology, including the anatomical substrate, triggers and modulators, should be part of VT prediction models. We envision digital twins as a solution combining clinical expertise with three prediction approaches: evidence-based medicine (clinical practice), data-driven models (data science) and mechanistic models (biomedical engineering). This paper aims to create a mutual understanding between experts in the different fields by providing a comprehensive description of the clinical problem and the three approaches in an understandable manner, leveraging future collaborations and technological innovations for clinical decision support. Moreover, it defines open challenges and gains for digital twin solutions and discusses the potential of hybrid modelling.

Comparison Between Treadmill and Bicycle Ergometer Exercises in Terms of Safety of Cardiopulmonary Exercise Testing in Patients With Coronary Heart Disease.

BackgroundCardiopulmonary exercise testing (CPET) is used widely in the diagnosis, exercise therapy, and prognosis evaluation of patients with coronary heart disease (CHD). The current guideline for CPET does not provide any specific recommendations for cardiovascular (CV) safety on exercise stimulation mode, including bicycle ergometer, treadmill, and total body workout equipment.ObjectiveThe aim of this study was to explore the effects of different exercise stimulation modes on the occurrence of safety events during CPET in patients with CHD.MethodsA total of 10,538 CPETs, including 5,674 performed using treadmill exercise and 4,864 performed using bicycle ergometer exercise at Peking University Third Hospital, were analyzed retrospectively. The incidences of CV events and serious adverse events during CPET were compared between the two exercise groups.ResultsCardiovascular events in enrolled patients occurred during 355 CPETs (3.4%), including 2 cases of adverse events (0.019%), both in the treadmill group. The incidences of overall events [235 (4.1%) vs. 120 (2.5%), P < 0.001], premature ventricular contractions (PVCs) [121 (2.1%) vs. 63 (1.3%), P = 0.001], angina pectoris [45 (0.8%) vs. 5 (0.1%), P < 0.001], and ventricular tachycardia (VT) [32 (0.6%) vs. 14 (0.3%), P = 0.032] were significantly higher in the treadmill group compared with the bicycle ergometer group. No significant difference was observed in the incidence of bradyarrhythmia and atrial arrhythmia between the two groups. Logistic regression analysis showed that the occurrence of overall CV events (P < 0.001), PVCs (P = 0.007), angina pectoris (P < 0.001), and VT (P = 0.008) was independently associated with the stimulation method of treadmill exercise. In male subjects, the occurrence of overall CV events, PVCs, angina pectoris, and VT were independently associated with treadmill exercise, while only the overall CV events and angina pectoris were independently associated with treadmill exercise in female subjects.ConclusionIn comparison with treadmill exercise, bicycle ergometer exercise appears to be a safer exercise stimulation mode for CPET in patients with CHD.

Ozone preconditioning protects rabbit heart against global ischemia-reperfusion injury in vitro by up-regulating HIF-1α.

Myocardial ischemia-reperfusion injury (MIRI) is a major factor that leads to cardiac dysfunction in cardiovascular surgery during extracorporeal circulation. Recent studies have found that ozone (O3) has protective effect on MIRI caused by the anterior descending branch of the ligated left coronary artery. However, whether O3 preconditioning has the same protective effect on global MIRI and the mechanism underlying this clinical treatment remains elusive. Here, we hypothesized that O3 preconditioning (O3P) could protect rabbit heart against global MIRI in vitro by up-regulating HIF-1α. Rabbits were treated intraperitoneally with O2/O3 mixture with different concentrations and then injected with YC-1 (inhibitor of HIF-1α) before the establishment of the global MIRI model using the Langendorff isolated heart perfusion apparatus. We investigated the effects of O3 preconditioning on cardiac systolic function, myocardial infarction, inflammatory response, mitochondrial function, myocardial pathological changes and arrhythmias. We found that the heart with O3 preconditioning significantly increased HR, LVDP and IL-10 expression, and decreased IL-6 expression, CK-MB, cTnT and cTnI concentration, myocardial infarction area, myocardial pathological injury and the occurrence of ventricular tachycardia and ventricular fibrillation. Meanwhile, the level of HIF-1α was significantly increased. However, after treatment of specific inhibitor of HIF-1α, the protective effect of O3 preconditioning was reversed completely. Our data indicates that O3 preconditioning has protective effect on MIRI and this protective effect is positively associated with dosage of O3. Energy metabolism disorder is the initial stage of MIRI and up-regulation of HIF-1α plays an important role in reducing mitochondrial dysfunction.

HF-567-04 VENTRICULAR TACHYCARDIA PRIOR TO CFLVAD IMPLANTATION DOES NOT IMPACT SURVIVAL WHEN STRATIFIED BY VAD TYPE

Historically, the occurrence of ventricular tachycardia (VT) prior to implantation of continuous flow left ventricular assist device (CFLVAD) has been associated with worse long term survival. In the era of more modern CFLVADs, pre-implant VT may no longer significantly impact survival. To evaluate one-year transplant free survival by modern CFLVAD types based on the occurrence of pre-implant sustained VT. We retrospectively studied all patients who underwent both destination therapy and bridge to transplant initial CFLVAD implantation at our institution from 2017-2019. Patients who received a simultaneous RVAD or orthotropic heart transplant within one year after CFLVAD were excluded. We ascertained the occurrence of sustained VT in the year prior to implantation based on clinical documentation and available implantable cardioverter-defibrillator interrogation reports. Using independent sample t-tests with significance set to p<0.05, one-year transplant free survival was compared in those with and without pre-implant VT for CFLVADs including the Abbott Heartmate 3 (HM3), Abbott Heartmate 2 (HM2), and HeartWare HVAD (HW). There were 103 initial CFLVAD implants between 2017-2019, 38 HM3, 37 HM2, and 28 HW. Within the HM3 group, one-year TFS was 69% in those with pre-implant VT and 88% in those without pre-implant VT, p=0.1654. Within the HM2 group, one-year TFS was 68% in those with pre-implant VT and 61% in those without pre-implant VT, p=0.6526. Within the HW group, one-year TFS was 80% in those with pre-implant VT and 72% in those without pre-implant VT, p=0.6632. For all CFLVADs, one-year TFS was 71% in those with pre-implant VT and 75% in those without pre-implant VT, p=0.6555. Contrary to prior reports, sustained VT in the year prior to CFLVAD implantation did not reduce one-year transplant free survival in this cohort regardless of the type of CFLVAD implanted. In the modern era of CFLVAD implantation, pre-implant sustained VT may not necessarily be a contraindication. Further studies assessing sustained VT in the CFLVAD population are warranted.

Cardiac MRI predictors of good long-term outcomes in patients with repaired TOF

Risk stratification in patients with repaired tetralogy of Fallot (rTOF) have focused on poor clinical outcomes while predictors of a benign clinical course have not been characterized. The goal of this study was to Identify cardiac magnetic resonance (CMR) markers of a good clinical course late after TOF repair. Clinical and CMR data from the International Multicenter TOF Registry (INDICATOR) were analyzed. The primary outcome was time to the earliest occurrence of a composite of death, aborted sudden death, and sustained ventricular tachycardia (VT). The secondary outcome was time to the earliest occurrence of atrial arrhythmia, nonsustained VT, and NYHA class >II. Multinomial regression was used to identify predictors of the 3-category outcome: (a) good outcome, defined as freedom from the primary AND secondary outcomes at age 50 years; (b) poor outcome, defined as presence of the primary outcome before age 50 years; and (c) intermediate outcome, defined as not fulfilling criteria for good or poor outcomes. Among 1088 eligible patients, 96 had good outcome, 60 experienced poor outcome, and 932 had intermediate outcome. Patients were age 25.8±10.8 years at the time of the index CMR. Median follow-up was 5.8 years (IQR 3.0, 9.9) after CMR in event-free patients. By univariate analysis, smaller right ventricular (RV) end-systolic and end-diastolic volume index, smaller left ventricular end-systolic volume index, higher right and left ventricular ejection fraction, lower right and left ventricular mass index, and lower left ventricular mass/volume ratio were associated with good outcome. Multivariable modeling identified higher RV ejection fraction (OR 2.38 per 10% increase, P=.002) and lower RV mass index (OR 1.72, per 10 g/m2 decrease, P=.002) as independently associated with good outcome after adjusting for age at CMR. Classification and regression tree analysis identified important thresholds associated with good outcome that were specific to patients age ≥37 years at the time of CMR; these were RV ejection fraction ≥42% and RV mass index <39 g/m2. Adults with rTOF and no more than mild RV dysfunction combined with no significant RV hypertrophy are likely to be free from serious adverse clinical events into their sixth decade of life and may require less frequent cardiac testing.

The absolute and relative changes in high-sensitivity cardiac troponin I are associated with the in-hospital mortality of patients with fulminant myocarditis

BackgroundWe sought to describe the tendency and extent of high-sensitivity cardiac troponin I (hs-cTnI) changes in patients with fulminant myocarditis (FM) after admission and to explore the relationship between the in-hospital mortality of FM and the absolute and relative changes in hs-cTnI within 24 h and 48 h after admission.MethodsIn the retrospective study, the object are patients diagnosed with FM in our single centre. The value of cardiac troponin was recorded after patients admitted to hospital in succession. The absolute and relative changes in hs-cTnI within 24 h and 48 h were described as range distributions. Receiver operating characteristic (ROC) curve and Cox analyses were performed to determine the relationship between in-hospital mortality of FM and hs-cTnI changes.ResultsA total of 83 FM patients admitted to our centre from January 1, 2010 to December 31, 2019 were included; 69 patients survived and 14 patients died. In the survival group, 78% of patients experienced a decline in hs-cTnI within 24 h, while 36% of the mortality group exhibited a declining tendency in hs-cTnI (P = 0.003). Nearly 60% of survival group had a 0–2000 ng/l reduction in troponin from baseline within 24 h of admission. However, troponin levels of 50% of patients in the mortality group were 0–10,000 ng/ L higher than baseline 24 h after admission. Multivariable logistic analysis revealed that the declining tendency of hs-cTnI within 24 h, in addition to time from onset to admittance to hospital, intravenous immunoglobulin treatment and the abnormal level of creatinine, were associated with the in-hospital mortality of FM (for the declining tendency of hs-cTnI within 24 h, OR = 0.10, 95% CI 0.02–0.68, P = 0.018). The ROC curve revealed optimal cut-off values of − 618 ng/l for absolute change within 24 h (AUC = 0.800, P < 0.01), − 4389 ng/l for absolute change within 48 h (area under the curve = 0.711, P < 0.01), − 28.46% for relative change within 24 h (AUC = 0.810, P < 0.01), and − 52.23% for relative change within 48 h (AUC = 0.795, P < 0.01). Absolute changes and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality by Cox regression analysis after adjustment for sex, time from onset to admission, and occurrence of ventricular tachycardia or ventricular fibrillation.ConclusionMost FM patients who survived experienced a decline in hs-cTnI within 24 h. The absolute and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality.