Risk Of Ventricular Tachyarrhythmias Research Articles

Digoxin and Risk of Ventricular Tachyarrhythmia and Death in ICD Recipients

BackgroundSome studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD). ObjectivesThis study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials. MethodsThe study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death. ResultsAt baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001). ConclusionsOur findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.

Whether to implant a defibrillator or not? The Possibility of Using the MADIT-ICD Benefit Score Calculator in Real Practice

To study the predictive capabilities of the MADIT-ICD Benefit Score calculator in assessing the benefit of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). This study included 388 patients with NYHA II-IV functional class chronic heart failure (CHF) with a left ventricular ejection fraction (LVEF) ≤35 % who underwent ICD placement for the primary prevention of SCD. Patients were followed up for two years to record the endpoints of first-time paroxysmal sustained ventricular tachyarrhythmia (VT) or non-arrhythmic death. According to the results of calculation with the MADIT-ICD Benefit Score calculator, 276 (71 %) patients had a high risk of VT (score ≥7) and 150 (39 %) had a high risk of non-arrhythmic death (score ≥3). 336 (94%) patients would benefit from an ICD: 148 (38 %) with a high level of probability and 218 (56 %) with a medium level of probability. According to the incidence of endpoints, VT episodes predominated in the low-ICD benefit group (36%), while the high-ICD benefit group had a relatively high incidence of non-arrhythmic death (12%). The results obtained for a cohort of Russian patients with CHF and reduced LVEF indicated that the use of the MADIT-ICD Benefit Score in routine clinical practice does not improve the stratification of SCD risk compared to the traditional approach to selecting patients with CHF for ICD based on the LVEF value.

Effect of sodium glucose cotransporter 2 inhibitors on atrial tachy-arrhythmia burden in patients with cardiac implantable electronic devices.

Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy-arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs). All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy-arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed. During a total follow-up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70-0.87]; p < .001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71-0.85]; p < .001); and with a 35% reduction in the risk of all-cause mortality (HR = 0.65 [95% CI = 0.45-0.92]; p = .015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80-1.06]; p = .26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58-0.80, p < .001 vs. Diabetes: HR = 0.95, 95% CI = 0.86-1.05, p = .29; p < .001 for interaction between SGLT2i indication and ATA burden). Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all-cause mortality when compared with those not on SGLT2i.

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

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

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.

Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies—External validation of the LMNA-risk ventricular tachyarrhythmia calculator

LMNA genotype-positive patients have high risk of experiencing life-threatening ventricular tachyarrhythmias (VTAs). The LMNA-risk VTA calculator published in 2019 has not been externally validated. The purpose of this study was to validate the LMNA-risk VTA calculator. We included LMNA genotype-positive patients without previous VTAs from 2 large Scandinavian centers. Patients underwent electrocardiography, 24-hour Holter monitoring, and echocardiographic examinations at baseline and repeatedly during follow-up. Validation of the LMNA-risk VTA calculator was performed using Harrell's C-statistic derived from multivariable Cox regression analysis. We included 118 patients (age 37 years [IQR 27-49 years]; 39 [33%] probands; 65 [55%] women; 100 [85%] with non-missense LMNA variants). Twenty-three patients (19%) experienced VTA during 6.1 years (interquartile range 3.0-9.1 years) follow-up, resulting in 3.0% (95% confidence interval 2.0%-4.5%) yearly incidence rate. Atrioventricular block and reduced left ventricular ejection fraction were independent predictors of VTAs, while nonsustained ventricular tachycardia, male sex, and non-missense LMNA variants were not. The LMNA-risk VTA calculator showed 83% sensitivity and 26% specificity for identifying patients with VTAs during the coming 5 years, and a Harrell's C-statistic of 0.85, when applying ≥7% predicted 5-year VTA risk as threshold. The sensitivity increased to 100% when reevaluating risk at the time of last consultation before VTA. The calculator overestimated arrhythmic risk in patients with mild and moderate phenotype, particularly in men. Validation of the LMNA-risk VTA calculator showed high sensitivity for subsequent VTAs, but overestimated arrhythmic risk when using ≥7% predicted 5-year risk as threshold. Frequent reevaluation of risk was necessary to maintain the sensitivity of the model.

Echocardiographic Predictors of Ventricular Tachyarrhythmias in Patients With Cardioverter-Defibrillator Implanted for Primary Prevention of Sudden Cardiac Death. Results From a two-Year Prospective Follow-up Study

Aim To compare variables of transthoracic EchoCG for determining echocardiographic predictors and their prognostic role in the development of persistent paroxysmal ventricular tachyarrhythmias (VT) in patients with ischemic CHF who had been implanted with a cardioverter defibrillator (CD) for primary prevention of sudden cardiac death.Material and methods This single-site prospective study included 176 patients with CHF of ischemic origin aged 58.7±7.4 years with a left ventricular ejection fraction (LV EF) of 30 % [25; 34] % who had been implanted with CD. The follow-up duration was 24 months. The primary endpoint was a newly developed persistent paroxysm of VT (duration ≥30 sec) detected in the "monitored" VT area or a VT paroxysm that required electric treatment. The echocardiographic picture was evaluated by 28 variables. Statistical analysis was performed with the c2, Fisher's, and Mann-Whitney tests, and the one-factor logistic regression (LR). Prognostic models were developed with a multifactorial LR. The model accuracy was evaluated by 4 metrics: area under the ROC (AUC), sensitivity, specificity, and diagnostic efficacy.Results The primary endpoint was observed in 60 (34 %) patients. Mean time to a persistent VT episode was 19.2±0.8 months (95 % confident interval (CI): 17.5-20.8). Superior-inferior dimensions of the right and left atria (RA and LA, respectively) and the left atrial volume (LAv) were independent predictors for VT. The odds of VT development in patients of the study cohort increased with RAl ≥4.5 cm (odds ratio (OR), 1.6; 95 % CI: 1.4-1.9; р=0.03), LAl ≥5.5 cm (OR, 2.5; 95 % CI: 1.01-6.1; р=0.04), LAv ≥95 ml (OR, 3.2; 95 % CI: 1.3-17.5; р=0.01). A comprehensive analysis of echocardiographic variables proved the prognostic potential of LAv that was linearly associated with the development of VT. The metrics of the best prognostic model were AUC 0.7±0.07 with 95 % CI: 0.54-0.83; specificity, 20.9 %; sensitivity, 95.7 %; and diagnostic efficacy, 47 %.Conclusion This study allowed evaluation of capabilities of transthoracic EchoCG for predicting the probability of VT in patients with CHF of ischemic origin and reduced LV EF. It was shown that linear and volumetric atrial dimensions could be used for stratification of risk of VT and for determining the tactics for primary prevention of sudden cardiac death in this patient category.

History of betablocker treatment breaks and risk of ventricular tachyarrhythmias among patients with heart failure and implantable cardioverter defibrillator: a nationwide cohort study

Abstract Background Beta-blockers have in randomized clinical trials been shown to reduce the risk of life-threatening arrhythmias and sudden cardiac death (SCD) in patients with heart failure (HF), and treatment is a class 1A recommendation in current guidelines. Thus, beta-blocker treatment breaks (i.e. planned break, beta-blocker related side-effects, or poor adherence) may increase risk of life-threatening arrhythmias and SCD. Whether patients with HF and a history of beta-blocker treatment breaks before implantable cardioverter defibrillator (ICD) is associated with increased risk of device related therapy and mortality is largely unknown. Aims In patients with HF and an ICD alone or combined with cardiac resynchronization therapy (CRT-D), we examined the association between a history of a beta-blocker treatment breaks prior to device implantation and the risk of appropriate and inappropriate device related therapy (i.e., anti-tachycardia pacing [ATP] or DC shock [DC]), and all-cause mortality. Methods Using the Danish Pacemaker and ICD Registry, we identified all patients with HF receiving a first-time ICD (2000–2018). Beta-blocker treatment breaks &amp;gt;60 consecutive days up to 3 years prior to device implantation were identified using the National Prescription Registry. Patients were able to switch between beta-blockers and were required to be in treatment at the time of implantation. We used multivariable Cox regressions to compare the 1-year risks of device-related therapy and all-cause mortality between patients with and without a history of a beta-blocker treatment break. Results We identified 9,239 patients with HF and an ICD (82.6% male; median age 67 years). A total of 82.5% had ischemic heart disease, 33.9% atrial fibrillation, and 33.1% of ICDs were secondary prophylaxis. During one-year follow-up, 5.7% of all patients died and appropriate DC and appropriate ATP was identified for 3.9% and 6.7% of patients, respectively. Overall, 14.6% of all HF patients had one or more beta-blocker treatment break &amp;gt;60 days. Compared with HF patients with no history of treatment breaks, a history of treatment breaks &amp;gt;60 days were associated with increased risk of appropriate DC (hazard ratio (HR)=1.33; 95% confidence interval [CI], 1.02–1.73) and appropriate ATP (HR 1.30; CI, 1.06–1.59), but also inappropriate DC and ATP therapy (Figure 1). There was no difference between groups with respect to all-cause mortality (HR=0.96; CI: 0.76–1.22). Treatment breaks of &amp;gt;30 or &amp;gt;90 days were also evaluated and yielded similar results as the main analysis. Conclusion Patients with heart failure who had a history of treatment breaks with beta-blockers prior to ICD implantation was associated with a higher 1-year risk of appropriate and inappropriate shocks and anti-tachycardia pacing, but not all-cause mortality. Funding Acknowledgement Type of funding sources: None.

Impact of synchronized left ventricular pacing rate on risk for ventricular tachyarrhythmias after cardiac resynchronization therapy in patients with heart failure.

The adaptive cardiac resynchronization therapy (aCRT) algorithm automatically produces synchronized left ventricular pacing (sLVP) with intrinsic atrioventricular conduction to improve clinical outcomes. However, relationship between sLVP percentage and risk for ventricular tachyarrhythmia (VT/VF) remains unclear. This study aimed to evaluate the clinical impact of sLVP rate on VT/VF occurrence. In total, 1,419 device interrogation data from 42 consecutive patients who underwent new aCRT device implantation were retrospectively analyzed. The primary endpoint was the first time VT/VF episode after aCRT device implantation. During a median follow-up of 34months, 15 patients had VT/VF episodes. Patients were divided into a high sLVP (the average sLVP percentage of ≥ 51.5%, n = 27) or low sLVP group (< 51.5%, n = 15). The high sLVP group had a significantly lower VT/VF incidence (22% vs. 60%; p = 0.014) and an independent predictor for VT/VF occurrence on multivariate analysis (hazard ratio 0.21; p = 0.007). LV ejection fraction improvements after 6months (12.3 ± 8.7% vs. 2.8 ± 10.3%; p = 0.004) and 12months (13.8 ± 9.3% vs. 6.2 ± 11.1%; p = 0.030) were significantly greater in the high sLVP group than in the low sLVP group. Age, PR interval, and left atrial diameter were significantly associated with the sLVP rate after aCRT. Patients with high sLVP percentage after aCRT had lower long-term risk of VT/VF incidence with a favorable response to CRT. A synchronized pacing algorithm using intrinsic conduction may prevent malignant arrhythmias, as well as recover cardiac functions.

Predictive potential of blood biomarkers for subsequent ventricular tachyarrhythmias in patients with chronic heart failure and reduced left ventricular ejection fraction: review

The current single-factor prognostic scale for the risk of ventricular tachyarrhythmia in patients with chronic heart failure and reduced left ventricle ejection fraction is considered by most experts to be inconsistent with modern medicine and should be modified. This position directs the efforts of researchers to search for additional prognostic factors, such as serum biomarkers. The last may reflect the state of cardiomyocytes and extracellular cardiac matrix, as well as endogenous and exogenous impacts to these structures. Such information may be important in determining the probability of the presence of myocardial pro-arrhythmic substrate and the electrophysiological conditions necessary to realize its potential. The data presented in this review suggest that concentrations of serum biomarkers may provide additional information for the estimation of personalized arrhythmic risk, which should help to avoid the clinical underestimation of the risk of sudden cardiac death and be a determining factor in the decision to implant a cardioverter-defibrillator.

Sex Differences in the Risk of First and Recurrent Ventricular Tachyarrhythmias Among Patients Receiving an Implantable Cardioverter-Defibrillator for Primary Prevention

Current guidelines for primary implantable cardioverter-defibrillator (ICD) therapy do not account for sex differences in arrhythmic risk in ICD candidates. To evaluate the association between sex and risk of ventricular tachyarrhythmia (VTA) and mortality. This cohort study compared differences in the risk of VTA and mortality between 4506 men and women enrolled in the 4 Multicenter Automatic Defibrillator Implantation Trials (MADIT) between July 1, 1997, and December 31, 2011. Data from prospective randomized controlled multicenter studies were analyzed retrospectively. Men and women with an ICD or cardiac resynchronization therapy defibrillator who were enrolled in all MADIT studies were included. Data were analyzed between January 10 and June 10, 2021. ICD implant. The primary end point was sustained VTA, defined as ICD-recorded, treated or monitored VTA at least 170/min or ventricular fibrillation. Secondary VTA end points included VTA at least 200/min, appropriate ICD shocks, and appropriate antitachycardia pacing. All end points were included in a first and recurrent event analysis. Of the 4506 study participants, 3431 were men (76%). Mean (SD) age of the cohort was 64 (12) years. For women vs men, the mean (SD) age (64 [12] years vs 64 [11] years) and left ventricular ejection fraction (24% vs 25%) were similar, but women exhibited a higher frequency of nonischemic cardiomyopathy (454 of 1075 women [42%] vs 2535 of 3431 men [74%]). Women had significantly lower 3-year cumulative probability of sustained VTA (16% vs 26%), fast VTA (9% vs 17%), and appropriate ICD shocks (7% vs 15%) compared with men (P < .001 for all). Multivariable analysis showed that female sex was independently associated with at least 40% lower risk of all first and recurrent VTA end points (P < .001 for all), including the primary end point (first event, HR = 60 [95% CI, 50-73], P < .001; recurrent event, HR = 49 [95% CI, 43-55], P < .001), after accounting for the competing risk of all-cause mortality and nonarrhythmic mortality. The lower VTA risk associated with female sex was consistent in risk subsets but was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio, 0.73 [95% CI, 0.56-0.95], P = .02; nonischemic group: hazard ratio, 0.50 [95% CI, 0.38-0.66], P < .001; P = .03 for interaction between female sex and cardiomyopathy). Findings suggest that women display a significantly lower risk of first and recurrent life-threatening VTA events than men, and that it is more pronounced in patients with nonischemic cardiomyopathy, suggesting a need for sex-specific risk assessment for primary prevention ICD therapy.

Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAIDTrial.

The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age≥65 years, New York Heart Association functional class≥III, QRS complex (≥130ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95%CI: 0.55-0.84; P< 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95%CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95%CI: 0.47-0.86; P< 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95%CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Comparison of Frequency of Ventricular Tachyarrhythmia in Men-Versus-Women in Patients with Implantable Cardioverter-Defibrillator for Primary Prevention

Current guidelines do not account for possible sex differences in the risk of ventricular tachyarrhythmia (VTA). We sought to identify specific factors associated with increased risk for VTA in women implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Our study cohort consisted of 4,506 patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in the 4 landmark MADIT studies - MADIT-II, MADIT-RISK, MADIT-CRT and MADIT-RIT (1,075 women [24%]). Fine and Gray regression models were used to identify female-specific risk factors for the primary end point of VTA, defined as ICD-recorded, treated, or monitored, sustained ventricular tachycardia ≥170 beats per minute or ventricular fibrillation. At 3.5 years of follow-up, the cumulative incidence of VTA was significantly lower in women than men (17% vs 26%, respectively; p <0.001 for the entire follow-up). Use of amiodarone at enrollment, Black race, and history of previous myocardial infarction without previous revascularization was found to be independent risk factors of VTA in women. Of these factors, only Black race was associated with a statistically significant risk increase in men. At 3.5 years, the cumulative incidence of VTA in women with one or more of these risk factors was 27% compared with 14% in women with none of the risk factors (hazard ratio [confidence interval]=2.08 [1.49 to 2.91]). In conclusion, our study, comprising 4 landmark ICD clinical trials, shows that sex and race have the potential to be used for improved risk stratification of patients who are candidates for primary prevention ICD.

Delayed detection programming significantly reduces inappropriate ICD therapies in patients with left-ventricular assist devices

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantation of a left ventricular assist device (LVAD) is an established therapy for end-stage heart failure, either as bridge to transplantation or as destination therapy. Virtually all LVAD patients carry an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention. The risk of ventricular tachyarrhythmias is significant in LVAD patients, but so is the burden of supraventricular tachycardia and the ensuing risk of inappropriate ICD therapies. The present retrospective study sought to quantify the impact of standard ICD programming vs. a ICD programming with long detection delays on the occurrence of inappropriate ICD therapies. Methods and results We retrospectively identified 337 consecutive patients (292 male, mean age 54.2 ± 12.3 years) who received a continuous-flow LVAD at our institution. Median follow-up duration was 2.3 (IQR 1.3, 3.7) years. Heart failure etiology was ischemic cardiomyopathy in 155 patients (46.0 %) and non-ischemic dilated cardiomyopathy in 150 (44.5 %). Other etiologies accounted for 32 patients (9.4 %). ICDs implanted at the time of LVAD implantation were single chamber devices in 176 patients (52.2 %), dual chamber devices in 45 patients (13.4 %), and CRT-D in 116 patients (34.4 %) A total of 2228 ICD-treated arrhythmia episodes occurred in 153 patients. 2066 (92.6 %) episodes were appropriate interventions for ventricular arrhythmias. 162 (7.3 %) treatments were inappropriate due to supraventricular tachyarrhythmias (n=115; 71.4 %), sinus tachycardia (n=15; 9.3 %) or oversensing (n=21; 12.9%). We retrospectively compared a standard programming (number of intervals for detection [NID] in the slowest therapy zone ≤ 40) and a long delay programming (NID &amp;gt; 40) and investigated the time to the first inappropriate therapy. A total of 285 patients were programmed to NID ≤ 40 at the first ICD interrogation after LVAD implant, 47 were programmed to NID &amp;gt; 40. Therapies were inactive in the remaining 5 patients. Median NID was 30 (IQR 23, 35) in the standard programming group and 60 (IQR 50, 76) in the long delay group, with similar rates for detection (median cycle lengths 340 [IQR 330, 350] ms and 330 [IQR 322, 340] ms for standard and long delay, respectively). Long delay programming was associated with significantly higher freedom from inappropriate therapies during follow-up (Hazard ratio 0.14, p [log rank] 0.027). No significant difference was observed between groups with regard to time to first appropriate therapy. Conclusion A number of intervals for detection greater than 40 in the slowest therapy zone was associated with a significantly increased freedom from inappropriate therapies in this large retrospective single-center cohort of LVAD patients with an ICD and should be considered as the default ICD programming strategy in this population.

PO-628-03 ASSOCIATION OF MINERALOCORTICOID RECEPTOR ANTAGONIST USE WITH MORTALITY AND VENTRICULAR ARRHYTHMIA RISK IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Heart failure (HF) patients with implantable devices have improved outcomes on optimal Guideline-Directed Medical Therapy (GDMT), yet few studies have evaluated the impact of mineralocorticoid receptor antagonists (MRA) on mortality and arrythmia risk in patients who may be unable to tolerate optimal GDMT. To assess the impact of MRA use on the risk of all-cause mortality and ventricular tachyarrhythmia (VTA) in HF patients with an ICD or CRT-D who were not concomitantly treated with both beta blockers (BB) and ACE-inhibitors/angiotensin receptor blockers (ACE/ARB) in 4 MADIT (Multicenter Automatic Defibrillator Implantation Trial; MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK) and Ranolazine in High-Risk Patients with ICD (RAID) clinical trials. We included 5504 patients enrolled in 5 landmark ICD clinical trials. Patients were categorized by MRA use in addition to baseline BB and/or ACE/ARB use into subgroups of those who were prescribed both BB and ACE/ARB (2-drug GDMT) and those who were prescribed only one of the two drugs (1-drug GDMT) at enrollment. Cox proportional hazards regression models and Fine and Gray regression models, stratified by studies, were performed to assess the association between time-dependent MRA use and risks of all-cause mortality and VTA. VTA was defined as any treated or monitored sustained ventricular tachycardia (≥170 bpm) or ventricular fibrillation. Among 5504 study patients, 4392 (80%) were prescribed 2-drug GDMT and 1016 (18%) were prescribed 1-drug GDMT. MRA was prescribed to 1656 (30%) patients. Multivariate analysis demonstrated that MRA use was associated with a 52% reduction in mortality risk when prescribed in patients on 1-drug GDMT (HR=0.48 [95% CI: 0.27-0.86], p=0.014). The mortality benefit of MRA therapy was attenuated among patients on 2-drug GDMT (HR=1.05 [95% CI: 0.82-1.34], p=0.7) (Figure 1). Further, MRA use was associated with a 36% reduction in VTA risk in patients on 1-drug GDMT (HR=0.64 [95% CI: 0.40-1.01], p = 0.05), while among patients on 2-drug GDMT the association of MRA use with VTA risk was also attenuated (HR=1.09 [95% CI: 0.93-1.29], p=0.28) (Figure 2). In HF patients with an ICD or CRT-D who are unable to tolerate 2-drug GDMT, MRA use is associated with a reduction in the risk of mortality and VTA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Angiotensin Converting Enzyme Inhibitors versus Receptor Blockers in Patients with Ventricular Tachyarrhythmias.

Data investigating the prognostic value of treatment with angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) usually focusses on patients presenting with heart failure (HF) or acute myocardial infarction (AMI). However, by preventing adverse cardiac remodeling, ACEi/ARB may also decrease the risk of ventricular tachyarrhythmias and sudden cardiac death (SCD). Although ventricular tachyarrhythmias are associated with significant mortality and morbidity, only limited data are available focusing on the prognostic role of ACEi/ARB, when prescribed for secondary prevention of SCD. Therefore, this study comprehensively investigates the role of ACEi versus ARB in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. The primary prognostic outcome was all-cause mortality at three years, secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, ICD therapies and sudden cardiac death) and cardiac rehospitalization. A total of 1236 patients were included (15% treated with ARB and 85% with ACEi) and followed for a median of 4.0 years. At three years, ACEi and ARB were associated with comparable long-term mortality (20% vs. 17%; log rank p = 0.287; HR = 0.965; 95% CI 0.689–1.351; p = 0.835) and comparable risk of the composite arrhythmic endpoint (HR = 1.227; 95% CI 0.841–1.790; p = 0.288). In contrast, ACEi was associated with a decreased risk of cardiac rehospitalization at three years (HR = 0.690; 95% CI 0.490–0.971; p = 0.033). Within the propensity score matched cohort (i.e., 158 patients with ACEi and ARB), ACEi and ARB were associated with comparable long-term outcomes at three years. In conclusion, ACEi and ARB are associated with comparable risk of long-term outcomes in patients presenting with ventricular tachyarrhythmias.

Predictive value of electrophysiological study for risk stratification of ventricular tachyarrhythmias in patients with non-ischemic cardiomyopathy and chronic systolic heart failure

A systematic review and meta-analysis of studies providing information on the use of intracardiac electrophysiological study (EPS) to stratify the risk of ventricular tachyarrhythmia (VT) in patients with non-ischemic chronic heart failure with low left ventricle ejection fraction (HFrEF). Relevant publications were searched until 20.01.2021 by two independent researchers in major search engines, electronic archives of clinical research, and open access preservatives repository. The end point considered was an episode of sudden cardiac death or sustained paroxysm of VT, or an appropriate electrotherapy of an implanted cardiac defibrillator. Ten clinical trials with 608 relevant patients (mean age: 51.5 ± 12 years; mean left ventricle EF: 26.8±8.5%, NYHA class: I - 17.7%; II - 33.7%; III - 35.9%, IV - 12.7%) were selected. The end point was registered in 92 patients (15.1%): in 47 patients (43.9%) with previously induced VT during EPS and in 45 patients (8.9%) without VT. The diagnostic odds ratio was 5.57 (2.27-13.63). The combined sensitivity and specificity of the EPS were 42% (26-61%) and 88% (83-92%) respectively. The results indicate the potential of EPS to stratify the arrhythmic risk in patients with non-ischemic HFrEF.

Abstract 11977: Cardiac Resynchronization Therapy and the Risk of Ventricular Tachyarrhythmia

Introduction: Cardiac Resynchronization Therapy (CRT) was shown to be associated with clinically significant benefit by lowering mortality, heart failure hospitalizations, and improving quality of life in patients with reduced left ventricular function and a wide QRS. However, there are conflicting data on the effect of CRT on the risk of ventricular tachycardia or ventricular fibrillation (VT/VF) in implantable cardioverter defibrillator (ICD) recipients. Methods: The study population comprised 4531 patients enrolled in the 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID) implanted with an ICD. Three patient groups were generated: ICD with a narrow QRS complex (n=2208), ICD alone with a wide QRS (n=1105), and patients with both ICD and a CRT (CRT-D) (n=2198). We compared the cumulative incidence of VT/VF in each group while accounting for the competing risk of non-arrhythmic mortality using the Fine and Gray Method. Results: Recipients of a CRT-D were more likely to be female, to use a beta blocker, and have a higher New York Heart Association Functional Class. The cumulative incidence of VT/VF at 4 years of follow-up in patients with a CRT-D was significantly lower (24%) as compared with patients with an ICD with or without a wide QRS (31% for both; p&lt;0.001 for the overall difference). Findings were consistent for the endpoints of appropriate ICD shocks and fast VT/VF (&gt;200 bpm). Multivariate analysis showed that compared to ICD-only therapy (with wide QRS), treatment with CRT-D was associated with a significant 20% (p=0.006), in the endpoint of VT/VF and 36% reduction in the endpoint of appropriate shock for VT/VF (p&lt;0.001). Conclusion: Our data from 5 landmark clinical trials suggest that cardiac resynchronization therapy exerts important antiarrhythmic properties, leading to a significant reduction in the risk of ventricular tachyarrhythmia and appropriate ICD shocks in patients implanted with an ICD for primary prevention.

Ring-like late gadolinium enhancement for predicting ventricular tachyarrhythmias in non-ischaemic dilated cardiomyopathy.

Myocardial fibrosis is associated with clinical ventricular tachyarrhythmia (VTA) events in patients with non-ischaemic dilated cardiomyopathy (DCM). Subepicardial or mid-wall ring-like late gadolinium enhancement (LGE) has received increasing attention in recent years. The aim of this study was to investigate the relationship between ring-like LGE and VTAs in DCM. Patients diagnosed with non-ischaemic DCM who underwent cardiac magnetic resonance with LGE imaging at baseline were investigated. The composite outcome was the occurrence of VTAs defined as sustained ventricular tachycardia, ventricular fibrillation/flutter, aborted sudden cardiac death (SCD), SCD, and appropriate implantable cardioverter-defibrillator intervention. The final cohort comprised 157 patients, including 36 (22.9%) in no LGE group, 48 (30.6%) in focal LGE group, 40 (25.5%) in multi-focal LGE group, and 33 (21%) in ring-like LGE group. Ring-like LGE group patients were younger compared to focal and multi-focal LGE group (P < 0.001) with higher left ventricular ejection fraction (33.0% vs. 24.4% vs. 22.1%, P < 0.001). After a median of 13 ± 7 months follow-up, compared to patients with no LGE, the hazard ratios (HRs) with 95% confidence intervals (CIs) for VTAs were 2.90 (0.56-15.06), 5.55 (1.21-25.44), and 11.75 (2.66-51.92) for patients with focal LGE, multi-focal LGE, and ring-like LGE, respectively. After multivariable adjustment, ring-like LGE group remained associated with increased risk of VTAs (adjusted HR 10.00, 95% CI 1.54-64.98; P = 0.016) independent of the global LGE burden. The ring-like pattern of LGE is independently associated with an increased risk of VTAs in patients with non-ischaemic DCM.

Clinical Predictors of Occurrence of Ventricular Tachyarrhythmias in Patients with Reduced Left Ventricle Ejection Fraction. Results of Single-Center Prospective Study.

Aim To evaluate the diagnostic significance of clinical and demographic parameters for predicting a 2-year probability of ventricular tachyarrhythmias (VT) in patients with chronic heart failure and reduced left ventricular ejection fraction (CHFrLVEF).Material and methods This single-center, prospective cohort study included 175 patients with CHFrLVEF who were implanted with a cardioverter defibrillator (CD). The endpoint was a CD-detected episode of VT. Patients were followed up for 2 years with visits at 3, 12, and 24 months after CD implantation.Results The primary endpoint was observed in 43 (24.4 %) patients at an average of 20.9 months (95 % confidence interval (CI), 20-21.9). The 2-year risk of fatal ventricular arrhythmias increased with detection of unstable VT (one-factor analysis, odds ratio (OR), 4.2; 95 % CI, 1.1-16.5; р=0.041; multifactor analysis, OR, 6.3; 95 % CI, 1.5-26.3; р=0.012) and with ischemic CHFrLVEF origin (one-factor analysis, OR, 2.2; 95 % CI, 1.1-4.5; p=0.021; multifactor analysis, OR, 2.5; 95 % CI, 1.2-5.1; р=0.018). In the presence of any type of atrial fibrillation (AF) in patients with non-ischemic CHFrLVEF, the probability of VT increased threefold (one-factor analysis, OR, 2.97; 95 % CI, 1.02-8.8; р=0.047; multifactor analysis, OR, 3.5; 95 % CI, 1.1-10.9; р=0.032).Conclusion The presence of ischemic heart disease and unstable VT paroxysms can be included in the number of important clinical predictors of VT in patients with CHFrLVEF. In patients with non-ischemic CHF, the presence of AF is associated with a high risk of VT.