Occurrence Of Sustained Ventricular Arrhythmia Research Articles

Regional cardiac denervation predicts sustained ventricular arrhythmias in non-ischemic cardiomyopathy patients without LGE on CMR imaging

Abstract Background In patients with non-ischemic cardiomyopathy (NICM) and no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in NICM is unknown. Purpose To assess the risk prediction of sympathetic denervation for the occurrence of VA in NICM patients without LGE. Methods Consecutive patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent programmed electrical stimulation, LGE-CMR and 123I- MIBG imaging between 2011-2018 were included. The presence of LGE and global and regional sympathetic denervation on 123I- MIBG was evaluated and patients were followed for occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score and the weighted denervation size. Results Of 75 included patients (63 years [52-68], 79% male, LVEF 36% [27-44], 37% inducible for VA) 35 had no LGE. During 4.5±1.6 years follow-up, VA occurred in 8/35 (23%) patients without LGE and in 18/40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (number of DS 8 [8-10] vs. 2 [1-5], P=0.004; ratio of DS 0.5 [0.5-0.7] vs. 0.2 [0.1-0.4], P=0.007; defect score 36 [31-41] vs. 18 [14-24], P=0.01; weighted denervation size 47 [39-53] vs. 22 [16-30], P=0.01). In univariable analysis the number of DS (HR 1.25, 95% CI 1.06–1.46, P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥ 7 segments identified patients without LGE at risk for VA (AUC: 0.83, sensitivity: 88%; specificity: 89%). Among patients with LGE, innervation state was not associated with VA during follow-up. Conclusions In NICM patients without LGE the extent of regional denervation may contribute to risk stratification for VA.Graphical Abstract

Incremental Prognostic Value of Cardiac MRI Feature Tracking and T1 Mapping in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To explore the role of cardiac MRI feature tracking (FT) and T1 mapping in predicting sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to investigate their possible incremental value beyond ARVC risk score. Materials and Methods The retrospective study analyzed 91 patients with ARVC (median age, 36 years [IQR, 27-50 years]; 60 male, 31 female) who underwent cardiac MRI examinations between November 2010 and March 2022. The primary end point was the first occurrence of sustained VA after cardiac MRI to first VA, with censoring of patients who were alive without VA at last follow-up. Cox regression analysis was performed to assess the association between variables and time to sustained VA. Time-dependent receiver operating characteristic (ROC) analysis was performed to determine the incremental value of cardiac MRI FT and T1 mapping. Results During a median follow-up of 55.0 months (IQR, 37.0-76.0 months), 36 of 91 (40%) patients experienced sustained VA. A 1% worsening in left ventricular global longitudinal peak strain (GLS), 1% worsening in right ventricular GLS, and a 1% increase in extracellular volume fraction (ECV) were associated with increased risk of sustained VA, with hazard ratios of 1.14 (95% CI: 1.06, 1.23; P = .001), 1.09 (95% CI: 1.02, 1.16; P = .02), and 1.13 (95% CI: 1.08, 1.18; P < .001), respectively, after adjustment for ARVC risk score. Adding both biventricular GLS and ECV to ARVC risk score showed significant incremental value for predicting sustained VA (area under the ROC curve: 0.73 vs 0.65; P < .001). Conclusion Cardiac MRI-derived biventricular GLS and ECV provided independent and incremental value for predicting sustained VA beyond ARVC risk score alone in patients with ARVC. Keywords: Cardiovascular MRI, Feature Tracking, T1 Mapping, Arrhythmogenic Right Ventricular Cardiomyopathy, Sustained Ventricular Arrhythmias Supplemental material is available for this article Published under a CC BY 4.0 license.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial

BackgroundStereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75–85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation.ObjectiveA single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk.MethodsPatients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D.DiscussionDEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure.Trial registrationNCT05594368.

Survival, ventricular arrhythmia, and implantable cardioverter-defibrillator usefulness in toxic cardiomyopathy due to substance abuse.

Toxic dilated cardiomyopathy (T-DCM) due to substance abuse is now recognized as a potential cause of severe left ventricular dysfunction. The burden of ventricular arrhythmias (VA) and the role of a prophylactic implantable cardioverter-defibrillator (ICD) are not well documented in this population. We aim to assess the usefulness of ICD implantation in a T-DCM cohort. Patients younger than 65 years with a left ventricular ejection fraction (LVEF)<35% followed at a tertiary center heart failure (HF) clinic between January 2003 and August 2019 were screened for inclusion. The diagnosis of T-DCM was confirmed after excluding other etiologies, and substance abuse was established according to the DSM-5 criteria. The composite primary endpoints were arrhythmic syncope, sudden cardiac death (SCD), or death of unknown cause. The secondary endpoints were the occurrence of sustained VA and/or appropriate therapies in ICD carriers. Thirty-eight patients were identified, and an ICD was implanted in 19 (50%) of these patients, only one for secondary prevention. The primary outcome was similar between the two groups (ICD vs. non-ICD; p=1.00). After a mean follow-up of 33±36 months, only two VA episodes were reported in the ICD group. Three patients received inappropriate ICD therapies. One ICD implantation was complicated with cardiac tamponade. Twenty-three patients (61%) had an LVEF ≥35% at 12 months. VA are infrequent in the T-DCM population. The prophylactic ICD benefit was not observed in our cohort. The ideal timing for potential prophylactic ICD implantation in this population needs further studies.

Ringlike late gadolinium enhancement provides incremental prognostic value in non-classical arrhythmogenic cardiomyopathy

BackgroundThe 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. MethodsIn this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. ResultsA total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13–56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89–54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). ConclusionRinglike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

EP News: Pediatric and Congenital Electrophysiology.

Jorda et al (Eur Heart J 2022;43:3041, PMID 35766180) validated the ARVCrisk.com prediction model in an observational, retrospective, longitudinal study in an external multicenter cohort and compared its performance to current guideline recommendations for implantable cardioverter-defibrillator (ICD) use on the basis of decision curve analysis. (The ARVCrisk.com calculator is an online algorithm published in 2019 that intends to predict the occurrence of sustained ventricular arrhythmias [including sudden cardiac death or arrest] within 5 years of arrhythmogenic right ventricular cardiomyopathy diagnosis in patients aged 14 years.) The validation cohort included 429 patients (mean age 43 years), of whom 103 (24%) experienced sustained ventricular tachycardia during a median follow-up of 5 years.

SURVIVAL, VENTRICULAR ARRHYTHMIA, AND IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR USEFULNESS IN A COHORT OF PATIENTS WITH TOXIC DILATED CARDIOMYOPATHY

SURVIVAL, VENTRICULAR ARRHYTHMIA, AND IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR USEFULNESS IN A COHORT OF PATIENTS WITH TOXIC DILATED CARDIOMYOPATHY

Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD

ObjectivesThis study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). BackgroundImproved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. MethodsSeventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [15O]H2O and [11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. ResultsIn total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. ConclusionsIn patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.

Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy

BackgroundPresence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. MethodsConsecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. ResultsFifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). ConclusionsThe presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up.

Seasonal trend of ventricular arrhythmias in a nationwide remote monitoring database of implantable defibrillators and cardiac resynchronization devices

BackgroundThe occurrence of sustained ventricular arrhythmias (SVA) may be influenced by environmental factors. We aimed to investigate annual periodic trends of SVA from the intracardiac electrograms (IEGMs) stored in the implantable defibrillators (ICDs) or cardiac resynchronization therapy (CRT-D) recipients. MethodsData from the Home Monitoring Expert Alliance project, a pooled repository of remote monitoring transmissions were analyzed. All IEGMs stored were independently adjudicated by three cardiac electrophysiologists. Periodicity of SVA was evaluated with Generalized Estimating Equations (GEE) models, including periodic terms depending on months in a year. ResultsA total of 2936 ICD/CRT-D patients (median age 70 years, 79.6% male) were followed for a median period of 25[13–44] months. Most prevalent structural heart diseases were ischemic (50.8%) and idiopathic dilated (30.6%) cardiomyopathies. Overall, 942 (32.1%) patients experienced a total of 4824 SVA. At GEE analysis, we found a significant periodic component (p = 0.048) when considering both shocked and non-shocked episodes. SVA less frequently occurred in Junes and Julies (3.7 × 1000 patient-month). No evidence of significant periodicity was collected in the subgroup of ischemic patients. ConclusionsIn this RM-based cohort of ICD/CRT-T patients, we observed an annual periodicity of SVA occurrence, with a lower incidence in summer months.

Safety and utility of dobutamine and pressure wire use in the hemodynamic assessment of low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction.

The ACC/AHA guidelines recommend low-dose dobutamine challenge for hemodynamic assessment of the severity of AS in patients with low flow, low gradient aortic stenosis with reduced ejection fraction (EF) (LFLG-AS; stage D2). Inherent pitfalls of echocardiography could result in inaccurate aortic valve areas (AVA), which have downstream prognostic implications. Data on the safety and efficacy of coronary pressure wire and fluid-filled catheter use for low dose dobutamine infusion is sparse. We retrospectively analyzed 39 consecutive patients with EF<50%, AVA<1cm2 and SVI<35ml/m2 on echocardiography who underwent simultaneous right and left heart catheterization. Hemodynamic assessments were performed at baseline and at every increment in the dobutamine infusion rate (The infusion was continued until maximal dose of dobutamine or a mean AV gradient>40mmHg was attained. The occurrence of sustained ventricular arrhythmias, symptomatic hypotension or intolerable symptoms leading to cessation of infusion was recorded. Transient ischemic attacks (TIAs) or clinically apparent strokes periprocedurally or up to 30days after the procedure were recorded. Dobutamine challenge confirmed true AS in 26 patients (67%) and pseudosevere AS in 34%. No sustained arrhythmias, hypotension or cessation of infusion from intolerable symptoms were observed. No clinical strokes or TIAs were observed up to 30days after procedure in any of these patients. Hemodynamic assessment of AS using a pressure wire with dobutamine challenge is a safe and effective tool in identifying truly severe AS in patients with LFLG-AS with reduced EF.

P1117The role of MIBG scintigraphy in anticipating the occurrence of sustained ventricular arrhythmias after CRT in patients with remote monitoring

P1117The role of MIBG scintigraphy in anticipating the occurrence of sustained ventricular arrhythmias after CRT in patients with remote monitoring

0211 : Implications of baselines 2010 task force criterias on ventricular arrhythmias in ARVC

Arrythmogenic right ventricular cardiomyopathy (ARVC) is an autosomic dominant disease with a variable penetrance. Based on 2010 task force criteria, baselines characteristics of patients referred from 3 French centers were analyzed to identified risk factors for ventricular arrhythmias. All patients with a diagnosis of ARVC referred from 3 academic French centers between 2006 and 2014 were included. The diagnosis was based on the 2010 Task Force. Occurrence of sustained ventricular arrhythmias and date of last alive status were collected from each center. The population consisted in 259 patients (171 males, sex ratio 1.9) with a mean age at diagnosis of 40+/-17 years. The VA group is composed of 61 patients (23.5%) who experienced at least 1.9 VT episodes. An ICD was implanted in 59% of them. Mean follow-up was 4.0 years in “no VA group” and 7.5 years in “VA group” (p=0.0003). Occurrence of syncope (OR=2.26, 95%CI [0.99-5.0], p=0.03) or VA (OR=3.1, 95%CI[1.8-5.2], p<0.0001) and sustained or non-sustained VA during exercise testing were associated (OR=4.2, 95%CI [0.90-19.5], p=0.03) with VA during follow-up. We failed to identify any ECG parameter related to the occurrence of VA. Dilated right ventricular (RV) was significantly associated with VA during follow-up (OR = 3.6, 95%CI [1.36;9.65], p=0.005). Severe RV dysfunction was more often identified (10% vs 3%, p=0.06) in the “VA group” in echocardiography. By MRI, RVEF was significantly lower in “VA group” (34.6% vs 42.1%, p=0.03) but RV end diastolic volume and presence of akinesia or dyskinesia were not significantly different between two groups. Genetic screening is on-going for all patients. Genetic screening will be performed using HaloPlex™ Target Enrichment System (Agilent Technologies) which allow the sequencing of 163 genes previously reported as involved in cardiac arrhythmias, conduction defect and cardiomyopathies . Occurrence of syncope and VA at baseline or during exercise test are associated with occurrence of VA during follow-up. RV abnormalities on echocardiography and MRI are significantly associated with VT.

Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication

Implantable cardioverter-defibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis. Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes. A total of 400 patients (19.8% female; n = 79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p = 0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p < 0.001). In a multivariate model, only gender (p = 0.02) and history of AF (p < 0.001) were significantly associated predictors of the occurrence of appropriate ICD therapies during follow-up. Based on the propensity score model, the adjusted hazard ratio for male gender was 2.7 (p = 0.02) and 2.6 (p = 0.0004) for history of AF. Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.

Single-Center Experience with Implantable Cardioverter–Defibrillators in Adults With Complex Congenital Heart Disease

Adults with congenital heart disease are at risk of lethal ventricular arrhythmias and are candidates for implantable cardiac defibrillator (ICD) therapy, yet implant risks, long-term outcomes, and rates of appropriate and inappropriate ICD therapies are not well characterized. We reviewed clinical, implantation, and follow-up data on all transvenous ICDs in adults with congenital heart disease at the Mayo Clinic from 1991 through 2008. Seventy-three adults with congenital heart disease received 85 ICDs. Implantation diagnoses included tetralogy of Fallot (44%) and congenitally corrected transposition of the great arteries (17%). Implantation indication was occurrence of sustained ventricular arrhythmias (secondary prevention) in 36% and prophylactic (primary prevention) in the remainder. There were no major implant-related complications. During follow-up (2.2 ± 2.8 years, range 0 to 15) 11 patients died and 4 patients received heart or heart/lung transplants. An appropriate shock for a ventricular arrhythmia was observed in 19% of patients and an inappropriate shock was observed in 15% of patients. Likelihood of an appropriate shock was associated with increased subpulmonic ventricular pressure. In conclusion, implantation of transvenous ICDs in adults with congenital heart disease is associated with a low risk of implant complications. In this high-risk adult population the rate of inappropriate ICD shocks is low, whereas the likelihood of appropriate therapy for potentially lethal ventricular arrhythmias is high. These data suggest overall benefit of ICD therapy in adults with congenital heart disease.

Late potentials and ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

We studied 38 patients (mean age 32 ± 14 years) with arrhythmogenic right ventricular cardiomyopathy (ARVC) to evaluate the clinical significance of histologic features on endomyocardial biopsy specimens as related to signal-averaged electrocardiography (SAECG), spontaneous ventricular arrhythmias, and hemodynamic features. Fifteen patients presented with ventricular tachycardia or fibrillation (sustained ventricular arrhythmias), 23 with other minor arrhythmias. SAECG variables and right ventricular ejection fraction (RVEF) were statistically correlated with the extent of myocardial fibrosis on biopsy in ARVC. An increased percentage of fibrous tissue (≥30%) was a significant univariate predictor of late potentials (p = 0.004) and reduced RVEF (p = 0.02). The 18 patients with late potentials had an increased percentage of fibrous tissue (p = 0.01), a reduced RVEF (p = 0.0004), and a higher risk for sustained ventricular arrhythmias (p = 0.05) than the 20 patients without late potentials. RVEF was the most powerful predictor of late potentials (p = 0.004) at multivariate analysis. Moreover, RVEF ≤50% was associated with an increased risk for development of sustained ventricular arrhythmias (p = 0.02). A SAECG parameter, namely the root-mean-square voltage of the terminal 40 ms at 25 Hz, was an independent predictive factor for the occurrence of sustained ventricular arrhythmias (p = 0.02). Although fibrous tissue may contribute to delayed myocardial activation in ARVC, a reduced RVEF plays an essential role for spontaneous manifestation of sustained ventricular arrhythmias.

Predicting arrhythmic events after acute myocardial infarction using the signal-averaged electrocardiogram

To determine if the signal-averaged (SA) electrocardiogram (ECG) predicts the occurrence of sustained ventricular arrhythmia and sudden death after acute myocardial infarction, 182 consecutive patients underwent systematic noninvasive testing, Including the SAECG. Seventy-one patients (39%) had an abnormal SAECG. The presence of an abnormal SAECG was not related to underlying left ventricular dysfunction or any other clinical or measured variable. There were 16 end points (sustained ventricular arrhythmia or sudden cardiac death) during 14-month follow-up. The SAECG was a significant predictor of these events (p < 0.02), and an abnormal SAECG conferred a 2.7-fold increase in risk. The risk associated with an abnormal SAECG was independent of both left ventricular function and ventricular arrhythmia on Hotter ECG. The SAECG had excellent negative predictive accuracy (95%), but the positive predictive accuracy was low (15%). When the results of the SAECG were combined with the results of the Holter ECG, a group of very high-risk patients was identified; at 18 months, the presence of abnormal SAECG and Holter ECG was associated with a risk of 26% compared with only 4% if both tests were normal. Furthermore, all published studies with a similar design were pooled for meta-analysis. The meta-analysis revealed a sixfold increase in risk, independent of left ventricular function, and an eightfold increase in risk, independent of Holter results when the SAECG was abnormal. The SAECG is a noninvasive test that can rapidly and easily provide potent prognostic information regarding the risk of sustained ventricular arrhythmias for patients after myocardial infarction.

Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia

The proarrhythmic effects of class IA antiarrhythmic drugs were prospectively evaluated during programmed ventricular stimulation in 24 consecutive patients with frequent ventricular premature beats whose baseline study, performed while no antiarrhythmic drugs were being taken, showed no inducible sustained ventricular arrhythmias. No patient had nonsustained (greater than 5 beats) or sustained ventricular tachycardia by history or baseline 24 hour ambulatory electrocardiographic monitoring. Sequential stimulation studies using up to three extra-stimuli were performed after administration of procainamide, quinidine and disopyramide on different days. Proarrhythmic response was defined as induction of one or more of the following: sustained monomorphic ventricular tachycardia; sustained polymorphic ventricular tachycardia; ventricular fibrillation; reproducibly inducible nonsustained monomorphic ventricular tachycardia. During 55 antiarrhythmic drug trials (24 of procainamide, 21 of quinidine, 10 of disopyramide) in the 24 patients, 6 patients had a proarrhythmic response: sustained monomorphic ventricular tachycardia in 3, ventricular fibrillation in 2, nonsustained monomorphic ventricular tachycardia in 1. Thus, 11% of drug trials resulted in a proarrhythmic response and 25% of patients had a proarrhythmic response to one of the drugs tested. A proarrhythmic response to one drug did not predict a similar response to another drug of the same class. The 6 patients with a proarrhythmic response did not differ significantly from the other 18 patients with regard to underlying heart disease, electrocardiographic or baseline 24 hour ambulatory electrocardiographic characteristics; however, they did have a higher incidence of digoxin usage (p less than 0.02), a shorter baseline right ventricular effective refractory period (p less than 0.01) and a smaller increment in effective refractory period during antiarrhythmic drug testing (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.