Previous Ventricular Arrhythmias Research Articles

High-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias

ObjectiveTo investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). MethodsA referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events. ResultsOf 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60). ConclusionIn a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.

663 OCCURRENCE OF VENTRICULAR AND SUPRAVENTRICULAR ARRHYTHMIAS IN BRUGADA SYNDROME: RESULTS OF A TERTIARY REFERRAL CENTER EXPERIENCE

Abstract Brugada Syndrome (BrS) is one of the most common channelopathies and is related to an increased risk of ventricular arrhythmias. Current guidelines recommend the implantation of a Cardiac Defibrillator (ICD) in those patients that have a diagnostic ECG pattern and a history of aborted cardiac arrest. Nevertheless, management of asymptomatic patients, who are the majority, remains controversial as their risk stratification is often based on the results of an inductive Electrophysiologic Study (EPS) the predictive accuracy of which is debated. Furthermore, BrS has also been associated to an increased risk of supraventricular tachy- and bradyarrhythmias. Aim to describe the occurrence of ventricular and supraventricular arrhythmias in BrS patients that receive an implantable cardiac monitoring device following an EPS study Methods we retrospectively identified all BrS patients followed at our tertiary referral centre that were candidate to an EPS. Patient were candidate to EPS if: (1) they had a spontaneous diagnostic Brugada pattern at ECG and (2) they had no history of previous ventricular arrhythmias or high-risk syncope. Those patients that tested positive for induction of a sustained ventricular arrhythmia at EPS received an ICD; those that tested negative received an ILR. During the follow-up visits, implantable devices were interrogated for the occurrence of ventricular and supraventricular arrhythmias. Results We identified 87 patients matching the inclusion criteria. Of these, 31 (35.7%) received an ICD for a positive EPS while the remaining 56 (64.3%) received an ILR. Over a mean follow-up period of 34 months (IQR 5-45, 249 patient-year), only one patient in the EPS positive group experienced a ventricular arrhythmia effectively treated by the ICD (0.3 events per patient-year) compared to zero patients in the EPS negative group (100% NPV, 3.2% PPV). Notably, implanted devices allowed for the detection of supraventricular arrhythmias in 12 out of the 87 patients (14%): 5 were cases of symptomatic sinus bradycardia, with an indication to permanent pacing in two of them, and 7 were cases of atrial tachycardia/fibrillation. Discussion in our registry, consistently with previous literature, ventricular arrhythmias in BrS patients are rare and a negative EPS identifies with high accuracy those that are at low risk for this event. Conversely, a positive EPS may overestimate the risk of these patients resulting, according to current practice, in frequent implantations of ICD that will never be required for defibrillation. Although the patient-year observation period of the presented cohort is sizeable, our results should be furtherly validated on multi-center cohorts with even longer follow-up periods. Nonetheless, our results support the idea that risk stratification tools other than EPS are probably needed to properly identify the minority of BrS patients that will experience a ventricular arrhythmia throughout their life. In addition, we report a considerable number of supraventricular arrhythmias recorded by the implanted cardiac monitoring devices in our population. This is consistent with the knowledge of BrS patients being at increased risk of sinoatrial node dysfunction and atrial fibrillation and may elicit a more widespread and methodical screening for these events.

Ventricular arrhythmias following coronary artery bypass grafting for ischemic cardiomyopathy: When to insert an implanted cardioverter defibrillator?

ObjectivesThe study objectives were to determine the incidence, predictors, and clinical impact of ventricular arrhythmias after coronary artery bypass grafting and to evaluate the impact of implantable cardioverter defibrillators on the survival of patients with ventricular arrhythmias. MethodsWe enrolled 498 patients with a left ventricular ejection fraction of 40% or less who underwent coronary artery bypass grafting between 1993 and 2015. Clinical follow-up was completed in 94.0% of patients, with a median follow-up of 58.4 months. ResultsOverall, 212 patients (43%) died, mainly of heart failure (n = 54, 10.8%) or sudden cardiac death (n = 40, 8.0%). The sudden cardiac death rate was highest during the first 6 months, with a monthly rate of 0.37%. Overall, 99 patients (20%) developed postoperative ventricular arrhythmias, and implantable cardioverter defibrillator was implanted in 55 patients. Previous ventricular arrhythmias (hazard ratio, 3.22; 95% confidence interval, 1.98-5.24; P < .001), left ventricular end-systolic dimension (hazard ratio, 1.07; 95% confidence interval, 1.04-1.10; P < .001), and myocardial infarction in the left anterior descending artery territory (hazard ratio, 1.73; 95% confidence interval, 1.10-2.73; P = .02) were independent predictors of postoperative ventricular arrhythmias. Notably, the 5-year survival of patients with ventricular arrhythmias who received an implantable cardioverter defibrillator was significantly higher than that of patients with ventricular arrhythmias who did not receive it (76.1% vs 22.7%, P < .001) and was comparable to that of patients without ventricular arrhythmias (76.1% vs 73.6%, P = .98). ConclusionsSudden cardiac death affects a significant proportion of patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, most frequently within 6 months postoperatively. To prevent sudden cardiac death, earlier implantable cardioverter defibrillator implantation should be indicated for high-risk patients with scars in the left anterior descending artery territory and excessive left ventricular remodeling.

Long-term mortality benefit of CRT-D vs. CRT-P upgrade procedures from conventional devices without prior ventricular arrhythmias

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the ÚNKP-20-3-I New National Excellence Program if the Ministry for Innovation and Technology in Hungary, the National Research, Development, and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program), and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University. This work was also supported by the Artificial Intelligence Research Filed Excellence Program of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary (TKP/ITM/NKFIH). The research was also financed by the Thematic Excellence Program (Tématerületi Kiválósági Program, 2020-4.1.1-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging thematic program of the Semmelweis University. Background Cardiac Resynchronization Therapy (CRT) upgrade can reverse pacing-induced cardiomyopathy (PiCMP) and related major ventricular arrhythmias (MVA). However, there is a lack of data comparing mortality benefit of adding an ICD to CRT during upgrade procedures in those without prior malignant ventricular arrhythmias (VAs). Purpose We aimed to compare the all-cause mortality, echocardiographic response, MVA occurrence and the rate of complications of patients with prior pacemakers (PM) upgraded to CRT-P or CRT-D devices. Methods Between 2000-2018 patients who underwent a successful CRT upgrade procedure from conventional pacemaker without a prior MVAs were collected. From 270 patients 83 (30.7%) upgraded to CRT-D, 187 (69.3%) to CRT-P device. The primary endpoint was all-cause mortality, secondary endpoints were echocardiographic response defined as left ventricular ejection fraction (LVEF) increase ≥5%, the occurrence of subsequent MVAs and the rate of periprocedural complications. Results CRT-D upgrade patients were more likely to be males, have a favourable renal function and lower LVEF compared to CRT-P group. During the median follow-up time of 3.7 years, 25 (30%) CRT-D and 131 (70%) CRT-P upgrade patients reached the primary endpoint. By univariate analysis, CRT-D upgrade patients showed 45% (HR 0.55; 95%CI 0.38-0.78; p &amp;lt; 0.01) lower all-cause mortality risk than CRT-P group. By multivariate analysis CRT-D (HR 0.39; 95%CI 0.23-0.66; p &amp;lt; 0.01), male sex (HR 1.60; 95%CI 1.03-2.47; p = 0.04), LVEF (HR 0.97; 95%CI 0.94-0.99; p &amp;lt; 0.01) have confirmed as independent predictors of all-cause mortality. Assessing secondary endpoints, LVEF response (66% vs 63%; p = 0.72), MVA occurrence (3.4% vs 0.8%; p &amp;lt; 0.01) and the rate of periprocedural complications were comparable in the two groups (14.8% vs 7%; p = 0.87), despite the higher number of lead explantations during CRT-D procedures than CRT-P upgrade (13% vs 1%; p &amp;lt; 0.001). Conclusions Adding an ICD during CRT upgrade procedures showed 45% lower all-cause mortality risk than CRT-P alone in patients with a pacemaker and no previous ventricular arrhythmias. This beneficial effect was independent of the echocardiographic response, safety or subsequent ventricular arrhythmias. Abstract Figure.

Risk of subsequent ventricular arrhythmia is higher in primary prevention patients with implantable cardioverter defibrillator than in secondary prevention patients

BackgroundBecause of previous ventricular arrhythmia (VA) episodes, patients with implantable cardioverter-defibrillator (ICD) for secondary prevention (SP) are generally considered to have a higher burden of VAs than primary prevention (PP) patients. However, when PP patients experienced VA, the difference in the prognosis of these two patient groups was unknown.MethodsThe clinical characteristics and follow-up data of 835 ICD patients (364 SP patients and 471 PP patients) with home monitoring feature were retrospectively analysed. The incidence rate and risk of subsequent VA and all-cause mortality were compared between PP patients after the first appropriate ICD therapy and SP patients.ResultsDuring a mean follow-up of 44.72 ± 20.87 months, 210 (44.59%) PP patients underwent appropriate ICD therapy. In the Kaplan-Meier survival analysis, the PP patients after appropriate ICD therapy were more prone to VA recurrence and all-cause mortality than SP patients (P<0.001 for both endpoints). The rate of appropriate ICD therapy and all-cause mortality in PP patients after the first appropriate ICD therapy was significantly higher than that in SP patients (for device therapy, 59.46 vs 20.64 patients per 100 patient-years; incidence rate ratio [IRR] 2.880, 95% confidence interval [CI]: 2.305–3.599; P<0.001; for all-cause mortality, 14.08 vs 5.40 deaths per 100 patient-years; IRR 2.607, 95% CI: 1.884–3.606; P<0.001). After propensity score matching for baseline characteristics, the risk of VA recurrence in PP patients with appropriate ICD therapy was still higher than that in SP patients (41.80 vs 19.10 patients per 100 patient-years; IRR 2.491, 95% CI: 1.889–3.287; P<0.001), but all-cause mortality rates were similar between the two groups (12.61 vs 9.33 deaths per 100 patient-years; IRR 1.352, 95% CI: 0.927–1.972; P = 0.117).ConclusionsOnce PP patients undergo appropriate ICD therapy, they will be more prone to VA recurrence and death than SP patients.

P5023A mutation specific prediction model for ventricular arrhythmias in the phospholamban (PLN) p.Arg14del cardiomyopathy

Abstract Background/Introduction The founder mutation p.Arg14del in the gene encoding phospholamban (PLN) is a known cause of arrhythmogenic cardiomyopathy (ACM) with distinct clinical features, such as microvoltages on the ECG and right or left ventricular dysfunction or both. At present, risk stratification for ICD implantation in carriers of this mutation is based on left ventricular ejection fraction and previous ventricular arrhythmia's, which are not specific risk factors for the PLN p.Arg14del cardiomyopathy. Purpose Our goal is to develop a mutation specific prediction model for incident malignant ventricular arrhythmia to guide ICD implantation. Methods Data were collected from p.Arg14del carriers with no history of malignant VA at baseline, identified between September 2009 and June 2018 in three Dutch university hospitals. Genetic analysis of PLN was performed in a clinical setting in index patients with clinical signs of DCM/ACM, or in family members of p.Arg14del carriers. We collected clinical data from the first cardiac evaluation and follow-ups. Malignant VAs were defined as sustained VA, appropriate ICD intervention or (aborted) sudden cardiac death. A prediction model was developed using Cox Proportional Hazard regression. Candidate baseline predictors were pre specified based on literature and clinical expertise. Age, sex, proband status, sudden cardiac death (SCD) in 1st degree relative, repolarization abnormalities, microvoltages, premature ventricular complexes (PVC) burden on 24hrs Holter monitoring, LVEF and non-sustained ventricular arrhythmias (NSVT) were considered. The multivariable model was fitted using stepwise backward selection based on Akaike's Information Criterion. Results We included 440 p.Arg14del carriers with a mean age of 41±18 years and 41% males. During a median follow-up of 4.7 years (IQR 1.7–7.3), 44 incident malignant VA occurred, 20 sustained VAs and 24 appropriate ICD therapies. The multivariable HR's of selected predictors were: 2.2 for minor and 4.5 for major repolarization abnormalities vs no abnormalities (p value respectively 0.06 and 0.01), 2.2 for LVEF &lt;45% (p value 0,1) and 7.7 for &gt;500PVC/24hrs (p value 0.003). Carriers with and without events could be accurately distinguished with this model, with an optimism corrected C-statistic of 0.81. The model calibrated well, with agreement of observed and predicted 5 year malignant VA risk. Risk groups were split into quintiles of predicted risk, figure 1 shows the Kaplan Meier curve of incident malignant VA per risk group. The 5 year risk of incident malignant VA in the lowest 3 quintiles was 0%, 9% in the 4th quintile and 25.2% in the highest quintile. Conclusion We created a PLN p.Arg14del mutation specific prediction model to estimate risk of incident malignant VA. With this model a clear distinction between high risk and low risk patients can be made and can be used to guide ICD implantation for primary prevention.

Electrical storm - still an extremely poor prognosis. Do these acute states of life-threatening arrhythmias require a multidirectional approach from the start?

Electrical storm (ES) is a state of electrical instability of the heart manifesting as multiple and potentially lethal recurring ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation. This definition is not related to the condition of each patient, who can present from asymptomatic to unconscious and in deep cardiogenic shock. Most patients affected by ES have heart failure (HF) of ischaemic origin. Ischaemia, exacerbation of HF, low ejection fraction, previous ventricular arrhythmias, infection or electrolyte disturbances together with other factors, or a few factors combined, may result in ES. The prognosis of ES survivors is very poor, with 1-year mortality exceeding 40%, which should draw attention to this group of patients as one of extremely high risk. The number of patients with cardioverter-defibrillators is increasing and so is the number of patients suffering from ES. Therefore, each patient should be supported with tailored therapy, and not only restricted to pharmacotherapy or ablation procedures. This paper was written to analyse the most frequent causes of ES and prompt the most appropriate clinical pathways and possibilities, underlining the need for a comprehensive invasive approach to diagnosis, treatment and circulatory stabilization in addition to adequate pharmacotherapy. This approach might help to reduce the mortality rate in this group of patients and improve the prognosis.

Arrhythmic Risk Stratification in Patients With Idiopathic Dilated Cardiomyopathy

Arrhythmic risk stratification in idiopathic dilated cardiomyopathy (IDC) remains a major concern. As the ventricles remodel in time, risk factors for arrhythmic death may change. A cohort of 710 patients with idiopathic dilated cardiomyopathy, without previous ventricular arrhythmias, was retrospectively studied to understand how risks vary in time. The primary end point was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator interventions. The prediction of the arrhythmic outcome was assessed dynamically through landmark analysis. Patients were assessed at baseline, short term (12 months, interquartile range 6 to 18), and long-term (72 months, interquartile range 60 to 84). The strongest risk predictors at each evaluation were combined in 3 multivariate models. During a median follow-up of 102 months, 80 patients (11%) experienced the primary end point. At baseline, QRS duration (p = 0.008), disease duration (p <0.001), and mitral regurgitation (p = 0.010) were significantly associated with the primary end point. The 12 months' landmark model included disease duration (p = 0.049), syncope (p = 0.005), New York Heart Association classes III and IV (p = 0.02), and indexed left ventricular end-diastolic volume (p = 0.001). Finally, the 72 months' landmark model combined the indexed left ventricular end-diastolic volume (p = 0.048), the left ventricular ejection fraction (p = 0.008), and the left atrial area (p = 0.001). All the 3 models provided a satisfactory accuracy (area under the curve ranging from 0.76 to 0.82, p <0.001). With an implantable cardioverter-defibrillator, the natural course of the disease influences the effect of arrhythmic risk factors overtime. Different predictors should be considered for the risk stratification according to the timing of assessment. Impaired left ventricular ejection fraction was significantly associated with major arrhythmias only in the long term.

Analysis of 24-h Rhythm in Ventricular Repolarization Identifies QT Diurnality As a Novel Clinical Parameter Associated with Previous Ventricular Arrhythmias in Heart Failure Patients.

Introduction: Cardiac repolarization abnormalities are among the major causes of ventricular arrhythmias and sudden cardiac death. In humans, cardiac repolarization duration has a 24-h rhythm. Animal studies show that this rhythm is regulated by 24-h rhythms in ion channel function and that disruption of this rhythm leads to ventricular arrhythmias. We hypothesized that 24-h rhythms in QT duration can be used as a predictor for sudden cardiac death and are associated with ventricular arrhythmias. Secondly, we assessed a possible mechanistic explanation by studying the putative role of hERG channel dysfunction.Materials and Methods: In 2 retrospective studies, measures of the 24-h variation in the QT and QTc intervals (QT and QTc diurnality, QTd and QTcd, respectively) have been derived from Holter analyses and compared between groups: 1) 39 post-infarct patients with systolic heart failure (CHF: EF < 35%), of which 14 with, and 25 without a history of ventricular arrhythmias and 2) five patients with proven (LQTS2) and 16 with potential (Sotalol-induced) hERG channel dysfunction vs. 22 controls.Results: QTd was two-fold higher in CHF patients with a history of ventricular arrhythmias (38 ± 15 ms) compared to CHF patients without VT (16 ± 9 ms, p = 0.001). QTd was significantly increased in LQT2 patients (43 ± 24 ms) or those treated with Sotalol (30 ± 10 ms) compared to controls (21 ± 8 ms, p < 0.05 for both).Discussion: QT diurnality presents a novel clinical parameter of repolarization that can be derived from Holter registrations and may be useful for identification of patients at risk for ventricular arrhythmias.

Hypertrophic Cardiomyopathy and Implantable Defibrillators in Sweden: Inappropriate Shocks and Complications Requiring Surgery.

The expanded use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) based on risk stratification in individuals without known previous ventricular arrhythmia is justified by an acceptable risk of device-related adverse events. Such complications, leading to surgical procedures or inappropriate electrical shocks, may impact mortality, morbidity, quality of life, and cost-effectiveness. From the Swedish ICD Registry, implants due to HCM since 1995 until November 2012 in patients aged ≥18 years were identified and medical records reviewed. Inappropriate ICD shock occurred in 14.3% (46 of 321 patients; mean follow-up 5.4 years) with a recurrent episode in 28.2% of them. In multivariable analysis, hazard ratio (HR) for atrial fibrillation was 3.5 (95% confidence interval 1.8-6.8; P < 0.001) but showed no significant association to male sex (HR = 0.77), age (HR = 0.99), secondary indication (HR = 1.02) or device, ICD-DR/CRTD vs. ICD-VR (HR 1.07). Inappropriate shocks were triggered by atrial fibrillation/flutter or ectopic tachycardia (56.5%), sinus tachycardia (14.5%), lead dysfunction (14.5%), and T-wave oversensing (13.0%). A reintervention, besides elective device replacement, occurred in 92 patients (totally 150 procedures). The majority were lead-related (70.0%) procedures, especially of the ICD lead. Reintervention was associated with female sex (HR = 1.6 P = 0.04). Inappropriate ICD shock triggered by atrial arrhythmias, lead dysfunction, or complications requiring surgical interventions, is a concern in HCM patients who will be eligible for long-term prevention of sudden death. Efforts to avoid adverse events and provide balanced risk-benefit information are important, especially in primary prevention.

Syncope in High-Risk Cardiomyopathy Patients With Implantable Defibrillators: Frequency, Risk Factors, Mechanisms, and Association With Mortality

Background— There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter-defibrillators, and it is controversial whether nonarrhythmogenic syncope is associated with increased mortality. Methods and Results— The Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) randomized 1500 patients to 3 different implantable cardioverter-defibrillator programming arms: (1) Conventional programming with therapy for ventricular tachycardia ≥170 bpm; (2) high-rate cutoff with therapy for ventricular tachycardia ≥200 bpm and a monitoring zone at 170 to 199 bpm, and (3) prolonged 60-second delay with a monitoring zone before therapy. Syncope was a prespecified safety end point that was adjudicated independently. Multivariable Cox models were used to identify risk factors associated with syncope and to analyze subsequent risk of mortality. During follow-up, 64 of 1500 patients (4.3%) had syncope. The incidence of syncope was similar across the 3 treatment arms. Prognostic factors for all-cause syncope included the presence of ischemic cardiomyopathy (hazard ratio [HR], 2.48; 95% confidence interval [CI], 1.42–4.34; P =0.002), previous ventricular arrhythmias (HR, 2.99; 95% CI, 1.18–7.59; P =0.021), left ventricular ejection fraction ≤25% (HR, 1.65; 95% CI, 0.98–2.77; P =0.059), and younger age (by 10 years; HR, 1.25; 95% CI, 1.00–1.52; P =0.046). Syncope was associated with increased risk of death regardless of its cause (arrhythmogenic syncope: HR, 4.51; 95% CI, 1.39–14.64, P =0.012; nonarrhythmogenic syncope: HR, 2.97; 95% CI, 1.07–8.28, P =0.038). Conclusions— Innovative programming of implantable cardioverter-defibrillators with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (&lt;200 bpm) is a rare event. The clinical risk factors associated with syncope are related to increased cardiovascular risk profile, and syncope is associated with increased mortality irrespective of the cause. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00947310.

Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. Bridging integrator 1 (BIN1) is a membrane-associated protein important to cardiomyocyte homeostasis and is downregulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing secondary to ARVC. To determine whether plasma BIN1 levels can be used to measure disease severity in patients with ARVC. We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to correlate with cardiac functional status and predict ventricular arrhythmias. Mean plasma BIN1 levels were decreased in patients with ARVC with heart failure (15 ± 7 vs 60 ± 17 in patients without heart failure, P <.05; the plasma BIN1 level was 60 ± 10 in non-ARVC normal controls). BIN1 levels correlated inversely with number of previous ventricular arrhythmia (R = -.47; P <.05), and low BIN1 levels correctly classified patients with advanced heart failure or ventricular arrhythmia (receiver operator curve area under the curve of 0.88 ± 0.07). Low BIN1 levels also predicted future ventricular arrhythmias (receiver operator curve area under the curve of 0.89 ± 0.09). In a stratified analysis, BIN1 levels could predict future arrhythmias in patients without severe heart failure (n = 20) with an accuracy of 82%. In the 7 patients with ARVC with serial blood samples, all of whom had evidence of disease progression during follow-up, plasma BIN1 levels decreased significantly (a decrease of 63%; P <.05). Plasma BIN1 level seems to correlate with cardiac functional status and the presence or absence of sustained ventricular arrhythmias in a small cohort of patients with ARVC and can predict future ventricular arrhythmias.

Continuation of Amiodarone Therapy Despite Type II Amiodarone-Induced Thyrotoxicosis

Amiodarone is a powerful antiarrhythmic drug; however, its use may be complicated by thyrotoxicosis. When this occurs, clinicians must balance the continuation of amiodarone for antiarrhythmic purposes, and the discontinuation of treatment in order to prevent aggravation of the thyrotoxicosis. We studied the consequences of continuation or cessation of amiodarone in patients with type II amiodarone-induced thyrotoxicosis. Consecutive patients who developed type II amiodarone-induced thyrotoxicosis between September 1997 and September 2000 were studied. Amiodarone was continued in patients with previous ventricular arrhythmia or supraventricular arrhythmia associated with severe haemodynamic changes and was withdrawn in the other patients. In patients with persistent, severe symptomatic thyrotoxicosis, corticosteroids were added to therapy. Thirteen patients were studied (nine with previous atrial fibrillation/flutter and four with ventricular tachycardia). Amiodarone treatment was continued in ten patients, including eight patients who received corticosteroids, and was temporarily halted in three patients. All patients recovered, with no difference in the duration of thyrotoxicosis between the two groups. Corticosteroid treatment was well tolerated and seemed to hasten the return to a euthyroid state (mean of 3.7 +/- 0.7 months vs 6.3 +/- 1.7 months). No recurrence of hyperthyroidism occurred during long-term follow-up. In patients who require amiodarone, treatment may be safely continued despite the development of type II amiodarone-induced thyrotoxicosis.

The clinical and cost-effectiveness of implantable cardioverter defibrillators: a systematic review

To consider the clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators (ICDs) for arrhythmias. Electronic databases. Manufacturer submissions. A systematic review of the literature on clinical and cost-effectiveness was undertaken. The quality of selected randomised controlled trials (RCTs) was assessed using the Jadad criteria, and of selected systematic reviews using criteria developed by the NHS Centre for Reviews and Dissemination. Economic evaluations were quality assessed by their internal validity (i.e. the methods used) using a series of relevant questions, and external validity (i.e. generalisability of the economic study to the population of interest) by modified standard criteria. The clinical effectiveness and cost-effectiveness of ICDs for arrhythmias were synthesised through a narrative review with full tabulation of results of all included studies. Eight RCTs, two systematic reviews and a meta-analysis met the inclusion criteria of the review. The RCTs were of variable quality, with most trials having a Jadad quality score of 1/5 or 2/5, owing to the nature of comparing a device with drug therapy and the impossibility of double-blinding. The outcome measure of interest was mortality, which was reported as all-cause mortality in most trials and sudden cardiac death in some trials. Eleven economic evaluations of ICDs for arrhythmias were identified. None were shown to have high internal and external validity. One unpublished study relevant to the UK was identified. The evidence suggests that ICDs reduce mortality in patients with previous ventricular arrest or symptomatic sustained ventricular arrhythmias, in patients who have not had a previous sudden cardiac episode or previous ventricular arrhythmia but have reduced left ventricular function due to coronary artery disease with asymptomatic non-sustained ventricular arrhythmia and sustained tachycardia that could be induced electrophysiologically, and in some patients with severe left ventricular dysfunction (ejection fraction 30%) after myocardial infarction. QoL data are inconsistent but suggest that there is impaired QoL in patients who received numerous shocks from implanted devices. Studies show that ICDs improve survival compared with drug treatment, but with considerably increased cost. Incremental cost per life-year gained ranges from 27,000 US dollars to 213,543 Can dollars and incremental cost per quality-adjusted life-year from 71,700 US dollars to 558,000 US dollars in the published literature. The use of ICDs in the UK is increasing, but the technology is still under-utilised compared with other developed countries. Extending the current indications to patients with prior myocardial infarction and depressed heart function would impact on costs and service provision. Further research is needed on the risk stratification of patients in whom ICDs are most likely to be clinically and cost-effective. An evaluation of shock frequency on QoL is also required.

A Comparison of the AVID and DAVID Trials of Implantable Defibrillators

We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at 40 beats/min in patients with ICDs reduced the combined end point of death and hospitalization for congestive heart failure compared with DDDR pacing at 70 beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of 506) meeting common inclusion and all exclusion criteria were studied. The major end points were the time to death, and the composite end point of time to death or hospitalization for congestive heart failure. Patients in the AVID and DAVID trials were similar, but more AVID patients had coronary artery disease (p = 0.04), history of myocardial infarction (p = 0.005), and previous ventricular arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary intervention, p = 0.001), and were more often taking beta-blocking drugs at hospital discharge (p <0.001). The backup VVI ICD groups in both studies had similar outcomes (p = 0.4), even when corrected for the previous demographic differences. The time-to- composite end point was similar in AVID patients treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p = 0.6). Despite improved pharmacologic therapy and revascularization, outcomes have not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID trial, benefit from ICDs for patients with serious ventricular arrhythmias could have been missed.

Postoperative ventricular arrhythmias after cardiac surgery: immediate- and long-term significance.

AF is frequent after cardiac surgery. However, ventricular arrhythmias are less known. The purpose of the study was to evaluate the causes and the prognostic significance of severe ventricular arrhythmias occurring after cardiac surgery. For 10 years, among 2,100 cardiac surgeries, 16 (0.8%) patients (13 men, 3 women; age 49-71 years, mean 62 +/- 9 years) without previous ventricular arrhythmias, with preserved left ventricular ejection fraction, and without acute cause of ventricular arrhythmias, developed VF (n = 4) or a sustained VT between 3 days and 3 weeks after cardiac surgery (coronary artery bypass grafting [n = 6], valve replacement [n = 10]). Rapid AF (n = 5) or slow AF (n = 1) were present at the time of VT/VF. Programmed ventricular stimulation occurred after up to three extrastimuli in the basal state and after infusion of 20-30 micrograms of isoproterenol. An echocardiogram, coronary angiography, Holter monitoring with heart rate variability (HRV) study were performed. Ventricular stimulation was negative in six patients (with AF); sustained and clinical VT was induced in 10 patients with a left ventricular ejection fraction > 0.40, except in one patient. Valvular prothesis and coronary bypass graftings were normal. In all patients, HRV was normal before surgery and decreased after cardiac surgery; before versus after surgery, respectively, HR 69 +/- 9 and 89 +/- 30 beats/min (P < 0.01), SDNN 117 +/- 31 and 50 +/- 11 ms (P < 0.001), low frequency (LF) 474 +/- 658 and 51 +/- 40 ms2 (P < 0.05), high frequency (HF) 115 +/- 23 and 33 +/- 32 ms2 (P < 0.05), LF:HF 4 +/- 3 and 1 +/- 0.6 (P < 0.01). Follow-up lasted from 6 months to 10 years (mean 3 +/- 2 years). In patients without induced VT, 1 patient died from asystole, 1 had an ICD but no subsequent events, and the other 4 untreated patients are free of events. Patients with induced VT were treated with amiodarone and beta-blockers except in one patient who died from extracardiac complications. Six of nine patients had no inducible VT with this treatment and are alive; 3 patients had inducible VT, 1 died suddenly before implantation of ICD, and 2 patients are alive with an ICD; recurrent VTs were noted in one patient and received an ICD. In conclusion, recent heart surgery may increase the risk of ventricular arrhythmias. The reduction of indexes reflecting sympathetic and parasympathetic tone could facilitate the occurrence of atrial arrhythmias (and then VT) in patients without ventricular arrhythmogenic substrate or the development of VT/VF in patients with a latent previous ventricular arrhythmogenic substrate. In patients without inducible VT, the prognosis is excellent and an ICD is not recommended in these patients. In those with inducible VT, there is a high incidence of responders to antiarrhythmic drugs with a favorable prognosis.

Severe morbidity after coronary artery surgery: development and validation of a simple predictive clinical score.

To develop a predictive clinical risk score of post-operative morbidity after coronary artery bypass grafting. Data were collected retrospectively from 679 patients undergoing emergency or planned bypass surgery between 1 January and 31 December 1996. The incidence of morbidity was 23%. Multivariate stepwise logistic regression analysis on two-thirds of the patients identified eight independent risk factors for severe morbidity. Six of these were pre-operative: symptomatic right heart failure, previous ventricular arrhythmias, previous coronary bypass surgery, chronic pulmonary disease, ST changes on pre-operative electrocardiogram, body mass index <24 kg. m-2, and two were intra-operative factors: the surgeon who operated, and the cardiopulmonary bypass time. A predictive clinical risk score was developed with the six pre-operative risk factors. The negative predictive value of the model is 87% and the area under the receiver operating characteristic curve is 0.77. When tested on the remaining patients not used for developing the model, the area under the curve is 0.65. This pre-operative risk score provides a simple method of risk stratification for patients undergoing coronary artery surgery. However, as for all predictive models, the performance of the score decreases when applied to a population other than that used to develop it.

Flecainide-Induced Ventricular Tachycardia and Fibrillation in Patients Treated for Atrial Fibrillation

Flecainide acetate has a recognized proarrhythmic effect in patients treated for ventricular tachycardia. Three patients developed severe ventricular arrhythmias while taking flecainide for atrial fibrillation. Patient 1 had normal ventricular function and idiopathic atrial fibrillation. Treadmill exercise tests during digoxin therapy showed no ventricular arrhythmia; however, during flecainide therapy the patient developed ventricular flutter at his peak exercise level that required cardioversion. Patient 2 had normal ventricular function and a prosthetic mitral valve. During therapy with flecainide, 150 mg twice daily, he had an episode of sustained ventricular tachycardia, also at his peak exercise level. Patient 3 had paroxysmal atrial fibrillation and hypertrophic cardiomyopathy but no previous ventricular arrhythmia. She died suddenly within 10 days of starting flecainide therapy. Judged from previous findings none of these patients was considered at high risk for proarrhythmia. These cases suggest a possible relation between vigorous exercise, atrial fibrillation, and the proarrhythmic properties of flecainide and indicate the limitations of classifying patients as "high-risk" or "low-risk" for proarrhythmic complications of anti-arrhythmic therapy.

Endocardial late potentials recorded during sinus rhythm in man: Incidence in different cardiac disease states

In a prospective study, 100 patients with various cardiac diseases not selected on the basis of previous ventricular arrhythmias underwent left ventricular endocardial mapping. With 10 different positions of the quadripolar catheter per patient, 90 of the 100 patients showed late potentials. These findings were documented in 50 of 52 patients with coronary heart disease compared to 26 of 34 patients with dilative cardiomyopathy (p less than 0.025). Late potentials in diastole were the most frequent type of abnormal electrogram, found in 82 patients. Fractionated electrograms were documented in 43 patients. They were seen in 27 (52%) coronary patients more often than in 8 (24%) patients with dilative cardiomyopathy (p less than 0.025). Onset of fractionated electrograms in coronary patients was somewhat later (301 +/- 177 ms after the QRS) than in the cardiomyopathy group (263 +/- 141 ms). The duration was longer (189 +/- 114 ms) in the former group than in the latter (148 +/- 87 ms). Thus, endocardial late potentials are not uncommon in patients with various cardiac diseases. The more frequent occurrence in coronary heart disease and the higher frequency of fractionated electrograms may indicate a more inhomogeneous, patchy type of fibrosis in the ischemically diseased myocardium.