History Of Nonsustained Ventricular Tachycardia Research Articles

A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

Utilization and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Hypertrophic Cardiomyopathy.

Background There is uncertainty about the appropriate use of primary prevention implantable cardioverter-defibrillators (ICDs) among older patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy who received a primary prevention ICD between 2010 and 2016 were identified using the National Cardiovascular Data Registry ICD Registry. Trends in ICD utilization and patient characteristics were assessed over time. Using linked Centers for Medicare and Medicaid Service claims data, Cox proportional hazard models assessed factors associated with mortality and postdischarge hospitalization for cardiac arrest/ventricular arrhythmia. Of 5571 patients with hypertrophic cardiomyopathy, 1511 (27.1%) were ≥65 years old. ICD utilization increased over time in all age groups. There were no changes in the prevalence of risk factors for sudden cardiac death over time. The variables most strongly associated with postdischarge mortality were older age (adjusted hazard ratio (aHR) 1.80 [95% CI, 1.47-2.21]), New York Heart Association class (III/IV versus I/II aHR 2.17 [95% CI, 1.57-2.98]), and left ventricular ejection fraction (left ventricular ejection fraction ≤35% versus >50% aHR 2.34 [95% CI, 1.58-3.48]; left ventricular ejection fraction 36%-50% versus >50% aHR 2.98 [95% CI, 2.02-4.40]), while history of nonsustained ventricular tachycardia (aHR 2.38 [95% CI, 1.62-3.51]) and New York Heart Association class (III/IV versus I/II aHR 1.84 [95% CI, 1.22-2.78]) were strongly associated with hospitalization for ventricular arrhythmia/cardiac arrest. Conclusions Primary prevention ICD utilization in patients with hypertrophic cardiomyopathy increased over time, including among those ≥65 years old. Among older patients, the strongest risk factors for hospitalization for ventricular arrhythmia/cardiac arrest following ICD implantation were history of nonsustained ventricular tachycardia and New York Heart Association class.

Age and the Risk of Ventricular Tachyarrhythmia in Patients With an Implantable Cardioverter-Defibrillator

BackgroundThe benefit of implantable cardioverter-defibrillators (ICDs) in elderly patients is controversial. ObjectivesThe aims of this study were to evaluate the risk for ventricular tachyarrhythmia (VTA) and ICD shocks by age groups and to assess the competing risk for VTA and death without prior VTA. MethodsThe study included 5,170 primary prevention ICD recipients enrolled in 5 landmark ICD trials (MADIT [Multicenter Automatic Defibrillator Implantation Trial] II, MADIT-Risk, MADIT-CRT [MADIT Cardiac Resynchronization Therapy], MADIT-RIT [MADIT Reduce Inappropriate Therapy], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator]). Fine and Gray regression analysis was used to evaluate the risk for fast VTA (ventricular tachycardia ≥200 beats/min or ventricular fibrillation) vs death without prior fast VTA in 3 prespecified age groups: <65, 65 to <75, and ≥75 years. ResultsThe cumulative incidence of fast VTA at 3 years was similar for patients <65 years of age and those 65 to <75 years of age (17% vs 15%) and was lowest among patients ≥75 years of age (10%) (P < 0.001). Multivariate Fine and Gray analysis showed a 40% lower risk for fast VTA in patients ≥75 years of age (HR: 0.60; 95% CI: 0.46-0.78; P < 0.001) compared with patients <65 years of age. In patients ≥75 years of age, a risk reversal was observed whereby the risk for death without prior fast VTA exceeded the risk for developing fast VTA. A history of nonsustained ventricular tachycardia, male sex, and the presence of nonischemic cardiomyopathy were identified as predictors of fast VTA in patients ≥75 years of age. ConclusionsPatients ≥75 years of age have a significantly lower risk for VTA and ICD shocks compared with younger patients. Aging is associated with a higher risk for death compared with the risk for fast VTA, the reverse of what is seen in younger patients.

CE-522-03 LONGITUDINAL PREDICTION OF VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator (https://www.arvcrisk.com) stratifies risk for ventricular arrhythmia (VA) at the time of ARVC diagnosis. However, the risk factors included in the ARVC calculator change with time, and how well it performs at follow up evaluations is unknown. To identify the temporal trends of VA risk factors and test the longitudinal performance of the ARVC calculator. This was a retrospective analysis of ARVC patients without prior VA (sustained ventricular tachycardia (VT), appropriate ICD therapy, sudden cardiac death/arrest) enrolled in the Johns Hopkins Hospital ARVC registry and Netherlands ACM registry. Risk factors for VA (age, sex, history of cardiac syncope, burden of PVC on 24-hour heart monitor, history of non-sustained VT, number of T-wave inversions on ECG, and right ventricular ejection fraction) were assessed at the time of ARVC diagnosis and upon repeat evaluations. The 5-year risk of VA was predicted longitudinally using 1) the ARVC calculator (baseline risk factors), 2) the ARVC calculator (updated risk factors), 3) time varying Cox regression. 408 patients (37±15 years old, 40% male) were followed for a median of 5.2 [2.8, 9.6] years, during which time 132 experienced a first VA (4.0% events/year). Comparison of risk factors at baseline versus at >5 years of follow up revealed decreases in 24-hour PVC Burden (3,560 vs 2,510) and prevalence of non-sustained VT on the most recent Holter (53% vs 27%), and an increase in number of T-wave inversions (3.4 vs 3.9 leads). Prevalence of right ventricular dysfunction was unchanged. When calculated using baseline risk factors, the ARVC calculator’s ability to predict 5-year VA risk worsened after 3 years of follow up (from ROC-AUC 0.82 at baseline to 0.69 by 5 years). When calculated using updated risk factors, the ARVC calculator (ROC-AUC 0.77) performed as well as time varying Cox regression (ROC-AUC 0.77) after 5 years of follow up (Figure). Risk factors for VA in ARVC change over time. Up-to-date assessment of these risk factors is warranted for VA risk stratification at evaluations beyond 3 years from the time of initial ARVC diagnosis.

Magnetic resonance imaging in the evaluation of idiopathic frequent premature ventricular complexes with normal ventricular function

Abstract Background The role of cardiac magnetic resonance (CMR) imaging in the diagnostic evaluation of patients with frequent premature ventricular complexes (PVCs) and normal left ventricular ejection fraction (LVEF) remains unclear. Existing data has been predominantly derived from highly selected populations, that may overestimate the true prevalence of abnormal findings on CMR in this patient population. Purpose The aim of this study was 2-fold: 1) to establish the prevalence of CMR imaging abnormalities in a cohort with normal LVEF and high PVC burden; 2) to identify predictors of CMR imaging abnormalities in patients with frequent PVCs and normal LVEF. Methods In this cohort study, 211 patients (age 53.2±19 years; 41% male) with frequent PVCs (≥5%/24 h), of normal LVEF (≥50% by echocardiography) and no known underlying structural heart disease were prospectively enrolled from 2016–2020. Of these, 166 (79%) patients were symptomatic from their PVCs in the form of palpitations, fatigue, chest pain, dizziness, and/or dyspnea. Patients underwent CMR imaging (1.5 Tesla) with a late gadolinium enhancement (LGE) protocol at the time of enrollment for the detection of scarring and/or fibrosis. Results Patients had a median baseline echocardiographic LVEF of 60% (± 5%) with 195 (92%) of patients having a normal native QRS morphology. Median PVC burden of the study cohort was 16% (± 14%). CMR LGE abnormalities were found in 19 (9%) patients including 17 scans with non-ischemic LGE and 2 with ischemic LGE. Age &amp;gt;60 (odds ratio [OR]: 3.20, 95% confidence interval [CI]: 1.20–8.51, p=0.020), male sex (OR: 4.67, 95% CI: 1.61–13.50, p=0.004), history of hypertension (OR: 3.43, 95% CI: 1.31–8.97, p=0.012), native QRS duration (OR: 1.03, 95% CI: 1.00–1.05, p=0.031), and history of non-sustained ventricular tachycardia (OR: 2.81, 95% CI: 1.03–7.68, p=0.044) were significantly associated with the presence of imaging abnormalities on CMR. Dominant PVC origin from the left ventricle had a positive trend (OR: 2.60, 95% CI: 0.99–7.66, p=0.083) to association with CMR imaging abnormalities. On multivariate analysis, male sex (OR: 4.10, 95% CI: 1.40–12.04, p=0.010) and history of hypertension (OR: 2.89, 95% CI: 1.08–7.75, p=0.035) remained significantly associated with the presence of CMR abnormalities. There was no association between CMR imaging abnormalities and the burden of PVCs or the number of PVC morphologies. Conclusion In this cohort, only 9% of patients with apparently idiopathic frequent PVCs and normal LVEF had concealed myocardial abnormalities on CMR imaging. Male sex and history of hypertension were associated with a higher rate of CMR abnormalities. Funding Acknowledgement Type of funding sources: None.

B-PO03-169 MYOCARDIAL SCAR BURDEN QUANTIFIED BY CARDIAC MAGNETIC RESONANCE IMAGING IS PREDICTIVE OF VENTRICULAR TACHYCARDIA IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Patients with hypertrophic cardiomyopathy (HCM) are at a higher risk of developing ventricular tachycardia (VT) and sudden cardiac death (SCD). Previous studies have demonstrated a correlation between late gadolinium enhancement (LGE) measured by cardiac magnetic resonance imaging (MRI) quantified as % of myocardial mass and VT; however, the predictive value of a more practical and routinely performed semi-quantitative assessment of LGE remains unknown. To determine whether a semi-quantitative assessment of myocardial fibrosis by cardiac MRI (number of myocardial segments with LGE) is predictive of VT in patients with HCM. We identified 65 patients (mean age 47±17, 34% female) with a clinical diagnosis of HCM who had a cardiac MRI prior to an implantable cardioverter defibrillator (ICD) implantation for primary prevention of SCD. VT was defined as appropriate anti-tachycardia pacing or shocks for sustained ventricular arrhythmias. The MRI was analyzed by an experienced radiologist blinded to the clinical data. LGE was assessed by both quantitative (% of total myocardial mass) and semi-quantitative (number of myocardial segments involved) methods. During the follow-up period (median 33 months), seven patients experienced VT. Patients with > 6 myocardial segments with LGE were at higher risk to develop VT (OR: 5.7, p=0.03) which remained significant after adjusting for age, maximum left ventricular wall thickness, left atrial size, maximum left ventricular outflow gradient, history of nonsustained VT, unexplained syncope, and family history of SCD (p=0.03). Similarly, patients with a higher fibrosis burden (LGE >10% myocardial mass) were more likely to develop VT (OR: 8.6, p=0.01) even after adjusting for the abovementioned traditional risk factors (p=0.04). The extent of LGE, assessed by both quantitative and semi-quantitative measures, is strongly associated with ventricular arrhythmias requiring ICD therapy in patients with HCM even after accounting for traditional risk factors. Fibrosis burden as detected by cardiac MRI may serve as an imaging biomarker to improve risk stratification and patient selection for primary prevention ICD implantation in patients with HCM.

A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk)

BackgroundNon-ischemic dilated cardiomyopathy (DCM) can be complicated by sustained ventricular arrhythmias (SVA) and sudden cardiac death (SCD). By now, left-ventricular ejection fraction (LV-EF) is the main guideline criterion for primary prophylactic ICD implantation, potentially leading either to overtreatment or failed detection of patients at risk without severely impaired LV-EF. The aim of the European multi-center study DETECTIN-HF was to establish a clinical risk calculator for individualized risk stratification of DCM patients. Methods1393 patients (68% male, mean age 50.7 ± 14.3y) from four European countries were included. The outcome was occurrence of first potentially life-threatening ventricular arrhythmia. The model was developed using Cox proportional hazards, and internally validated using cross validation. The model included seven independent and easily accessible clinical parameters sex, history of non-sustained ventricular tachycardia, history of syncope, family history of cardiomyopathy, QRS duration, LV-EF, and history of atrial fibrillation. The model was also expanded to account for presence of LGE as the eight8h parameter for cases with available cMRI and scar information. ResultsDuring a mean follow-up period of 57.0 months, 193 (13.8%) patients experienced an arrhythmic event. The calibration slope of the developed model was 00.97 (95% CI 0.90–1.03) and the C-index was 0.72 (95% CI 0.71–0.73). Compared to current guidelines, the model was able to protect the same number of patients (5-year risk ≥8.5%) with 15% fewer ICD implantations. ConclusionsThis DCM-SVA risk model could improve decision making in primary prevention of SCD in non-ischemic DCM using easily accessible clinical information and will likely reduce overtreatment.

Three-Dimensional Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Predicts Inducibility of Ventricular Tachycardia in Adults With Repaired Tetralogy of Fallot.

Adults with repaired tetralogy of Fallot die prematurely from ventricular tachycardia (VT) and sudden cardiac death. Inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement (LGE) cardiovascular magnetic resonance but whether this relates to inducible VT is unknown. Sixty-nine consecutive repaired tetralogy of Fallot patients (43 male, mean 40±15 years) clinically scheduled for invasive programmed VT-stimulation were prospectively recruited for prior 3-dimensional LGE cardiovascular magnetic resonance. Ventricular LGE was segmented and merged with reconstructed cardiac chambers and LGE volume measured. VT was induced in 22 (31%) patients. Univariable predictors of inducible VT included increased RV LGE (odds ratio [OR], 1.15; P=0.001 per cm3), increased nonapical vent LV LGE (OR, 1.09; P=0.008 per cm3), older age (OR, 1.6; P=0.01 per decile), QRS duration ≥180 ms (OR, 3.5; P=0.02), history of nonsustained VT (OR, 3.5; P=0.02), and previous clinical sustained VT (OR, 12.8; P=0.003); only prior sustained VT (OR, 8.02; P=0.02) remained independent in bivariable analyses after controlling for RV LGE volume (OR, 1.14; P=0.003). An RV LGE volume of 25 cm3 had 72% sensitivity and 81% specificity for predicting inducible VT (area under the curve, 0.81; P<0.001). At the extreme cutoffs for ruling-out and ruling-in inducible VT, RV LGE >10 cm3 was 100% sensitive and >36 cm3 was 100% specific for predicting inducible VT. Three-dimensional LGE cardiovascular magnetic resonance-defined scar burden is independently associated with inducible VT and may help refine patient selection for programmed VT-stimulation when applied to an at least intermediate clinical risk cohort.

Relation of Late Gadolinium Enhancement and Extracellular Volume Fraction to Ventricular Arrhythmias in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) represents a major cause of sudden cardiac death in young adults. Late gadolinium enhancement (LGE) and extracellular volume (ECV) by T1 mapping are cardiac magnetic resonance (CMR) techniques to quantify fibrosis in HC. The relationships of LGE and ECV with ventricular arrhythmia, left ventricular (LV) diastolic function, and risk factors for sudden cardiac death (SCD) in HC are unclear. We studied 103 HC patients (mean age 51 ± 14, 42% women) who underwent CMR from 2012 to 2014. Global LGE and mean ECV were evaluated in relation to history of nonsustained ventricular tachycardia (NSVT), diastolic function by echocardiography, and SCD risk factors. LGE was present in 71 (69%) subjects. Wide variation was demonstrated in LGE (0.5% to 45.9%) and mean ECV (17.6% to 47.4%). Prevalence of NSVT increased continuously with LGE and was greater in subjects with ECV above the study population mean (27%). Increased LGE was associated with LV diastolic dysfunction and LV wall thickness. In conclusion, while ECV appears to have a threshold (27%) above which it is associated with NSVT, LGE demonstrates a more robust relationship with NSVT and measures of diastolic dysfunction.

Association between Lifelong Physical Activity and Disease Characteristics in HCM.

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

Clinicalparameters to optimize patient selection for subcutaneous and transvenous implantable defibrillator therapy.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) lacks the antitachycardia pacing (ATP) capability of tranvenous ICDs (TV-ICD). S-ICD patient selection can be challenging as some patients may benefit from ATP. We aim to identify clinical predictors of ATP benefit, in order to improve patient selection for S-ICD or TV-ICD therapy. De novo single- and dual-chamber TV-ICD patients implanted between March 2011 and December 2015 were included. Ventricular arrhythmias terminated by ATP and not followed by a shock were considered successful ATP therapy. Cox proportional hazard analysis was performed to assess the adjusted effect of multiple predictors for appropriate ATP and shock therapy. Note that 431 patients were included with a median follow-up of 26 months. Ninety-nine patients (23%) received appropriate ATP therapy, which terminated the arrhythmia in 67%. A history of nonsustained ventricular tachycardia (NSVT) or monomorphic VT (MVT) was the only predictor of appropriate ATP therapy in the multivariable model (hazard ratio [HR] 2.73, P<0.001). Sixty-five of 221 patients with a history of NS (VT) received appropriate ATP (29%) versus 24 patients (11%) without a history NS (VT) (P<0.001). A secondary prevention indication was the only predictor in the multivariate model for appropriate shock therapy (HR 1.82, P=0.05). A history of NSVT or MVT is a significant predictor for appropriate and successful ATP therapy. One in three patients with NSVT or MVT received appropriate ATP versus one in 10 patients without a history of NSVT or MVT over a 2-year period of follow-up.

Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGEext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

Trends and determinant factors in the use of cardiac resynchronization therapy devices in Japan: Analysis of the Japan cardiac device treatment registry database

BackgroundThe choice of cardiac resynchronization therapy device, with (CRT-D) or without (CRT-P) a defibrillator, in patients with heart failure largely depends on the physician׳s discretion, because it has not been established which subjects benefit most from a defibrillator. MethodsWe examined the annual trend of CRT device implantations between 2006 and 2014, and evaluated the factors related to the device selection (CRT-D or CRT-P) for primary prevention of sudden cardiac death in patients with heart failure by analyzing the Japan Cardiac Device Treatment Registry (JCDTR) database from January 2011 and August 2015 (CRT-D, n=2714; CRT-P, n=555). ResultsThe proportion of CRT-D implantations for primary prevention among all the CRT-D recipients was more than 70% during the study period. The number of CRT-D implantations for primary prevention reached a maximum in 2011 and decreased gradually between 2011 and 2014, whereas CRT-P implantations increased year by year until 2011 and remained unchanged in recent years. Multivariate analysis identified age (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.90–0.95, P<0.0001), male sex (OR 1.99, 95% CI 1.28–3.11, P<0.005), reduced left ventricular ejection fraction (LVEF) (OR 0.96, 95% CI 0.94–0.98, P<0.0001), and non-sustained ventricular tachycardia (NSVT) (OR 2.85, 95% CI 1.87–4.35, P<0.0001) as independent factors favoring the choice of CRT-D. ConclusionsYounger age, male sex, reduced LVEF, and a history of NSVT were independently associated with the choice of CRT-D for primary prevention of sudden cardiac death in patients with heart failure in Japan.

Clinical features and predictors of lethal ventricular tachyarrhythmias after cardiac resynchronization therapy for primary prevention of sudden cardiac death

BackgroundCardiac resynchronization therapy (CRT) reduces the mortality rate among patients with advanced heart failure (HF) and a wide QRS complex. Despite such clinical improvement, the clinical features of ventricular tachyarrhythmias (VA) and the risk of sudden cardiac death (SCD) among these patients still remain to be elucidated. MethodsIn total, 128 consecutive patients with advanced HF (mean age, 68±10 years; 90 men; mean left ventricular ejection fraction [LVEF], 27±7%) who underwent CRT with a cardioverter-defibrillator (CRT-D) as the primary prevention for SCD were examined. Twenty-nine patients had ischemic cardiomyopathy (ICM), whereas the other 99 patients had nonischemic cardiomyopathy (NICM). At each follow-up examination, patient- and device-related data were collected. All detected VA episodes were analyzed. ResultsDuring a mean period of 1009±566 days, 30 patients (23%) experienced appropriate cardioverter-defibrillator treatment for sustained VA. Twenty-six had NICM and the other 4 had ICM. The first VA episodes mostly involved monomorphic ventricular tachycardia (VT) at 187±30beats/min (28 patients, 93%). The mode of successful therapy was antitachycardia pacing (ATP) in 60% of patients. Multiple linear regression analysis revealed that among clinically plausible predictors (age; gender; LVEF; underlying rhythms; QRS duration; QT interval; ischemic cause of HF; history of nonsustained VT; and the uses of amiodarone, β-blockers, and renin-angiotensin inhibitors), only the history of nonsustained VT (P<0.0001) was a significant predictor of appropriate cardioverter-defibrillator therapy. ConclusionsAfter implantation of a CRT-D device for primary prevention, VAs were more prone to occur in patients with nonischemic HF than in those with ischemic HF. Moreover, the first VA episodes were mostly monomorphic VT, and most episodes were terminated by ATP. In addition, nonsustained VT was a potent predictor of VA after CRT.

Electrocardiographic left ventricular hypertrophy predicts arrhythmia and mortality in patients with ischemic cardiomyopathy

The relatively low incidence of device-treated ventricular arrhythmias in patients with ischemic cardiomyopathy (ICM) who receive implantable cardioverter defibrillators (ICDs) for primary prevention makes improved risk stratification of ICM patients a priority. Although Cornell product (CP) ECG left ventricular hypertrophy (LVH) has been associated with increased mortality in hypertensive patients and population-based studies, whether CP LVH can improve risk stratification of high-risk ICM patients is unclear. The aim of this study is to examine if electrocardiographic LVH predicts mortality and incident ventricular arrhythmia in patients with ICM. All-cause mortality was examined in 317 patients with ICM and a history of non-sustained ventricular tachycardia (VT) who underwent electrophysiology testing. Incident VT and ventricular fibrillation (VF) were assessed in ICD recipients (n = 186). ECG LVH was defined by CP criteria: [(R (aVL) + S (V3)) + 6 mm in women] × QRS duration >2,440 mm ms. During 3 years of follow-up, mortality was 20% (64 of 317) and death or incident VT or VF occurred in 35% of ICD recipients. CP LVH was associated with significantly greater 3-year mortality (28% vs 15%, p = 0.015) and 3-year mortality or incident VT/VF in ICD patients (48% vs 35%, p = 0.011). In Cox multivariate models, CP LVH was an independent predictor of mortality in all patients (hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.11-2.97, p = 0.020) and of the composite endpoint of mortality or incident ventricular arrhythmia in ICD patients (HR 1.82, 95% CI 1.12-3.00, p = 0.016). ECG LVH using CP criteria may enhance risk stratification in high-risk patients with ICM.

Angina Pectoris with Troponin Increase in Arrhythmogenic Right Ventricle Dysplasia: Case Article and Review of the Literature

A 16-year-old Hispanic girl with arrhythmogenic right-ventricle dysplasia (ARVD) presented with angina pectoris and troponin increase on three occasions. There was a family history of sudden cardiac death in a cousin. Her mother was diagnosed with ARVD. The patient herself had a history of nonsustained ventricular tachycardia but did not meet diagnostic criteria for ARVD. Cardiac workup, including serial transthoracic echocardiograms and a coronary angiogram, showed a structurally normal heart without coronary artery stenosis. Results of cardiac magnetic resonance imaging were questionable, but endomyocardial biopsy did not show evidence of viral myocarditis by polymerase chain reaction. Genetic testing confirmed ARVD.

The Efficacy of Low-Dose Amiodarone to Life-Threatening Arrhythmia

Background: It is well known that amiodarone has an efficacy to prevent life-threatening arrhythmia especially in the case of severe heart failure, however, some adverse effects would be often serious when the dose of administration is higher. The aim of this study is to evaluate the efficacy of low-dose amiodarone to Japanese cases with dilated cardiomyopathy (DCM). Methods: From November 2010 to April 2011, Nine DCM patients with a history of non-sustained ventricular tachycardia (NSVT) were enrolled.(55.9±17.4 years, 6 women, body weight 57.3±17.1kg, BMI 21.1±4.7kg/m2, left ventricular ejection fraction (LVEF) 28.7±14.9%) All patients received ACE-I/ARB, β-blockade or both. In those cases, the dose of amiodarone was reduced to less than 100mg/day. Results: Nobody showed NSVT. Nobody expired. Nobody showed thyroid dysfunction, interstitial pneumonitis or other adverse events after the reduction of amiodarone. %changes of thyroid function between before and after the administration of low-dose amiodarone were as follows: fT3; -31.9±18.9%, fT4; -36.6±40.6%. KL-6 data between before and after the administration of low-dose amiodarone were 425.4±304.5 and 500.7±387.7U/mL. %changes: +6.49±46.5%. The level of amiodarone and desethylamiodarone was 223.3±86.4ng/mL, and 175.5±71.6ng/mL, respectively. LVEF after the administration of amiodarone showed 42.3±16.2%. Conclusion: The low-dose amiodarone can be safely used in Japanese patients. Relatively low blood concentration of amiodarone in the maintenance stage was enough to control life-threatening arrhythmia in DCM patients.

To the Editor—“Specialization” of Microvolt T-wave Alternans and Electrophysiological Study in Predicting Different Ventricular Arrhythmias in Patients with Ischemic Cardiomyopathy To the editor—Microvolt T-wave alternans, electrophysiologic study, and ventricular arrhythmias

The article by Amit et al 1 Amit G. Rosenbaum D.S. Super D.M. Costantini O. Microvolt T-wave alternans and electrophysiologic testing predict distinct arrhythmia substrates: implications for identifying patients at risk for sudden cardiac death. Heart Rhythm. 2010; 7: 763-768 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar published in Heart Rhythm [June 2010] provides new insight that noninvasive microvolt T-wave alternans (MTWA) technology and invasive electrophysiologic study (EPS) predict distinct types of malignant ventricular arrhythmias in patients with ischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤40.0, and a history of nonsustained ventricular tachycardia. Using data from the 566 patients of the Alternans Before Cardioverter Defibrillator (ABCD) trial, the authors showed that MTWA predicted unstable ventricular tachyarrhythmic events (U-VTE), defined as polymorphic ventricular tachycardia (PVT), ventricular fibrillation (VF), or sudden cardiac death (SCD), whereas EPS did not. On the other hand, EPS predicted stable monomorphic ventricular tachyarrhythmic events (S-VTE), whereas MTWA did not. Stratification of LVEF to ≤0.30 versus 0.31–0.40 did not predict events. MTWA predicted events better than EPS in patients with LVEF ≤0.30, whereas EPS predicted events better than MTWA in patients with LVEF 0.31–0.40. Finally, the combination of MTWA and EPS predicted events better than either modality alone. As we “digest” the novel knowledge provided by this study, the authors could help by responding to and commenting on the following points. (1) The inclusion of patients with only previous nonsustained S-VTE in the ABCD trial, 2 Costantini O. Rosenbaum D.S. Hohnloser S.H. et al. ABCD InvestigatorsThe Alternans Before Cardioverter Defibrillator (ABCD) trial: a noninvasive strategy for primary prevention of sudden cardiac death using T-wave alternans. J Am Coll Cardiol. 2009; 53: 471-479 Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar instead of also including patients with U-VTE (PVT and VF), constitutes a somewhat biased database for the study of subsequent distinct types of ventricular arrhythmic substrates. (2) The authors reported on outcomes occurring during 1-year follow-up. It would be useful to evaluate whether their findings persist at 18- and 24-month follow-up. (3) The distinction between subgroups with LVEF ≤0.30 versus 0.31–0.40 suggests that cardiologists should become more diligent than they are currently in evaluating the LVEF of their patients, perhaps emulating the practice of serial assessment of LVEF using the same modality and the concern shown by oncologists when administering anthracyclines. (4) What was the outcome in terms of arrhythmic events of the 73 or 74 patients who did not receive an implantable cardioverter-defibrillator (ICD) and/or received an ICD following a negative MTWA and EPS? Microvolt T-wave alternans and electrophysiologic testing predict distinct arrhythmia substrates: Implications for identifying patients at risk for sudden cardiac deathHeart RhythmVol. 7Issue 6PreviewBetter risk stratification of patients receiving an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is needed. Although microvolt T-wave alternans (MTWA) and electrophysiologic study (EPS) are independent markers for SCD, the Alternans Before Cardioverter Defibrillator (ABCD) trial found the combination to be more predictive than either test alone. Full-Text PDF ErratumHeart RhythmVol. 9Issue 12PreviewThe reply by Carl R. Reynolds and Michael R. Gold Optimizing right ventricular lead position for defibrillation should have also published in the March 2011 issue of HeartRhythm as a response to Mark Kroll's letter End of the apex era? (2011;8:e9-e10). Full-Text PDF Author Reply–To the Editor: Microvolt T-wave alternans and electrophysiological testing predict distinct arrhythmia substratesHeart RhythmVol. 9Issue 12PreviewWe thank Dr. Madias for his kind comments and the interest in our article,1 and we would like to respond to the points raised. Full-Text PDF

Prediction of Appropriate Defibrillator Therapy in Heart Failure Patients Treated With Cardiac Resynchronization Therapy

The necessity of implantable cardioverter-defibrillator (ICD) implantation in patients with systolic heart failure (HF) who undergo cardiac resynchronization therapy (CRT) may be questioned. The aim of this study was to identify patients at low risk for sustained ventricular arrhythmia. One hundred sixty-nine consecutive patients with HF (mean age 60 +/- 12 years, 125 men, 73% in New York Heart Association class III) referred for CRT and prophylactic, primary prevention ICD implantation underwent baseline clinical and echocardiographic assessment and regular device follow-up. The primary study end point was appropriate ICD therapy. During a mean follow-up period of 654 +/- 394 days, 35 patients (21%) had sustained ventricular arrhythmias requiring appropriate ICD therapy. Of the 3 patients who experienced sudden cardiac death, 2 had been treated with appropriate ICD therapy before sudden cardiac death. In a multivariate model, only history of nonsustained ventricular tachycardia (p = 0.001), a severely (<20%) decreased left ventricular ejection fraction (p = 0.001), and digitalis therapy (p = 0.08) independently predicted appropriate ICD therapy. Patients with 0 (n = 46), 1 (n = 36), 2 (n = 73), and 3 (n = 14) risk factors for appropriate ICD therapy had a 7%, 14%, 27%, and 64% and 0%, 6%, 10%, and 43% incidence of appropriate ICD therapy for ventricular arrhythmias and for rapid ventricular tachycardia or ventricular fibrillation, respectively. In conclusion, apart from commonsense considerations (age and significant co-morbidities), ICD addition seems ineffective in CRT patients without nonsustained ventricular tachycardia, digoxin therapy, and severely reduced left ventricular systolic function.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI)

AimsTo evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death.Methods and resultsThe SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy.ConclusionSEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.