Predictors Of Appropriate Therapy Research Articles

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes β-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Right ventricular systolic pressure is an independent risk factor of all-cause death and inappropriate therapies in patients with implanted CRT-D

Abstract Introduction Cardiac resynchronization therapy-defibrillators (CRT-D) are implanted mostly in patients with low left ventricular ejection fraction (LVEF) and wide QRS. In such subjects, there is often a concomitant right ventricular (RV) dysfunction, which has been associated with higher long-term mortality. However, data on the association between RV dysfunction and arrhythmic outcomes in patients with CRT-D are scarce. Purpose To define whether there is any association between right ventricular dysfunction and antiarrhythmic therapies or all-cause mortality in patients with HF and CRT-D. Methods The clinical and demographic data of patients enrolled in this study were obtained from the single-centre COMMIT-HF registry. The parameters regarding right ventricular function, such as right ventricle dimension (RVD), tricuspid annular systolic plane systolic excursion (TAPSE) and right ventricular systolic pressure (RVSP) were obtained from electronic patients’ records. The data on the long-term hard endpoints were obtained from the national healthcare provider, while the data on the risk of arrhythmic events, CRT-D shocks and antitachycardia pacing (ATP) were obtained from investigator-initiated and -adjudicated single-centre remote monitoring database updated annually. Multivariable stepwise logistic regression was used to determine independent predictors of the study outcomes, being all-cause death, and the occurrence of appropriate and inappropriate CRT-D therapies. Results During the period between July, 2009 and November, 2019, 335 patients were enrolled at the RM programme after implantation of CRT-D. Of them, during the median (Q1-Q3) follow-up period of 5.3 (2.8-6.6) years, (113 (33.7%) died, 111 (33.1%) received appropriate and 37 (11%) inappropriate therapies. In the multivariable analysis, the independent predictors of all-cause death were reduction in LVEF and increase in RVSP. Lower age and increased LVEDD were independent predictors of appropriate therapies, while lower age and increased RVSP were independent predictors of inappropriate therapies. No association between TAPSE and RVD and outcomes was found. Conclusions Among right ventricular dysfunction parameters, RVSP is an independent predictor of inappropriate therapies and all-cause death, but not of appropriate therapies in patients with HF and CRT-D.

Implantable cardioverter defibrillators for primary prevention in cardiomyopathies

BackgroundImplantable cardioverter defibrillators (ICD) are often used as primary prevention strategy for sudden cardiac death (SCD) in young individuals. This study analyzed appropriate therapies, complications and inappropriate shocks in the real-world Indian population. MethodsAll patients in the cardiomyopathy cohort under follow up who had ICD implanted as a primary prevention strategy were studied. The objective was to assess the incidence of appropriate ICD therapies, inappropriate therapies and complications. ICD was interrogated and stored electrograms analyzed. Underlying arrhythmia or conditions resulting in appropriate or inappropriate ICD therapy were studied. Correlation and regression studies was done to assess for the predictors of appropriate therapy. ResultsFifty patients were followed up for a mean follow-up duration of 4.4 ± 3.1 years with total follow up of 220.2 patient years. Appropriate ICD therapy was delivered in 16 out of 50 (32%) patients, with 65 appropriate therapies (median 2 per patient, range: 0–20). Inappropriate therapy delivered in 7 of the 50 (14%) patients, with 44 inappropriate therapies (median 5 per patient, range: 0–20). Complications occurred in 8 of the 50 (16%) patients. Overall, the rate of appropriate therapy was 29.5 per 100 patient years, that of inappropriate therapy was 19.9 per 100 patient years and the rate of complications was 3.6 per 100 patient years. ConclusionsWhen implanted for primary prevention in patients with cardiomyopathies over a mean period of 4.4 ± 3.1 years, appropriate ICD therapy was delivered in 32% patients. However, inappropriate therapy (14% patients) and complications (16% patients) were also common.

Predictors of Appropriate Therapies and Death in Patients with Implantable Cardioverter-Defibrillator and Chronic Chagas Heart Disease.

There are few retrospective and prospective studies on implantable cardioverter-defibrillators (ICD) in primary and secondary prevention of sudden death in chronic Chagas heart disease (CCHD). To describe the long-term evolution of patients with CCHD and ICD and to identify and analyze predictors of mortality and appropriate device therapy in this population. This was a historical prospective study with 117 patients with ICD and CCHD. Devices were implanted from January 2003 to December 2021. Predictors of appropriate therapies and long-term mortality were identified and analyzed. The level of statistical significance was p < 0.05. Patients (n = 117) had a median follow-up of 61 months (25 to 121 months); they were predominantly male (74%), with a median age of 55 years (48 to 64 years). There were 43.6% appropriate shocks, 26.5% antitachycardia pacing (ATP), and 51% appropriate therapies. During follow-up, 46 patients (39.7%) died. Mortality was 6.2% person-years (95% confidence interval [CI]: 4.6 to 8.3), with 2 sudden deaths during follow-up. Secondary prevention (hazard ratio [HR] 2.1; 95% CI: 1.1 to 4.3; p = 0.029) and ejection fraction less than 30% (HR 1.8; 95% CI: 1.1 to 3.1; p < 0.05) were predictors of appropriate therapies. Intermediate Rassi score showed a strong association with the occurrence of ATP alone (p = 0.015). Functional class IV (p = 0.007), left ventricular ejection fraction < 30 (p = 0.010), and age above 75 years (p = 0.042) were predictors of total mortality. ICDs in CCHD showed a high incidence of appropriate activation, especially in patients with secondary prevention, low left ventricular ejection fraction, and intermediate Rassi score. Patients with congestive heart failure, elevated functional class, and age over 75 years showed elevated mortality. Survival function of patients with implantable cardioverter-defibrillators and chronic Chagas heart disease. A - According to New York Heart Association functional class; B - According to left ventricular ejection fraction; C - According to Rassi score. D - According to age. CCHD: chronic Chagas heart disease; HR: hazard ratio; ICD: implantable cardioverter-defibrillator.

Predicting Malignant Ventricular Arrhythmias Using Real-Time Remote Monitoring

BackgroundAlthough implantable cardioverter-defibrillator (ICD) therapies are associated with increased morbidity and mortality, the prediction of malignant ventricular arrhythmias has remained elusive. ObjectivesThe purpose of this study was to evaluate whether daily remote-monitoring data may predict appropriate ICD therapies for ventricular tachycardia or ventricular fibrillation. MethodsThis was a post hoc analysis of IMPACT (Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices), a multicenter, randomized, controlled trial of 2,718 patients evaluating atrial tachyarrhythmias and anticoagulation for patients with heart failure and ICD or cardiac resynchronization therapy with defibrillator devices. All device therapies were adjudicated as either appropriate (to treat ventricular tachycardia or ventricular fibrillation) or inappropriate (all others). Remote monitoring data in the 30 days before device therapy were utilized to develop separate multivariable logistic regression and neural network models to predict appropriate device therapies. ResultsA total of 59,807 device transmissions were available for 2,413 patients (age 64 ± 11 years, 26% women, 64% ICD). Appropriate device therapies (141 shocks, 10 antitachycardia pacing) were delivered to 151 patients. Logistic regression identified shock lead impedance and ventricular ectopy as significantly associated with increased risk of appropriate device therapy (sensitivity 39%, specificity 91%, AUC: 0.72). Neural network modeling yielded significantly better (P < 0.01 for comparison) predictive performance (sensitivity 54%, specificity 96%, AUC: 0.90), and also identified patterns of change in atrial lead impedance, mean heart rate, and patient activity as predictors of appropriate therapies. ConclusionsDaily remote monitoring data may be utilized to predict malignant ventricular arrhythmias in the 30 days before device therapies. Neural networks complement and enhance conventional approaches to risk stratification.

Outcomes after transvenous defibrillator implantation in cardiac sarcoidosis: A systematic review.

IntroductionSarcoidosis is a systemic inflammatory disorder associated with ventricular arrhythmias (VAs) and sudden death in the context of cardiac involvement. Guidelines advocate implantable cardioverter‐defibrillator (ICD) implantation in specific subcohorts, but there is a paucity of data on outcomes.Methods and ResultsA systematic review was performed to assess outcomes in patients with definite or probable cardiac sarcoidosis (CS) treated with ICD. Observational studies were identified from multiple databases from inception to 21st May 2021. Outcomes of interest included appropriate and inappropriate ICD therapies in addition to all‐cause mortality. Study quality was assessed individually using the Newcastle Ottawa Scale (NOS).Eight studies were identified comprising 530 patients, with follow‐up period of 24–66 months (weighted average 40 months). Mean age was 53.9 years with ejection fraction of 41.3%. Overall incidence of appropriate therapy was 38.1% during follow‐up. Left ventricular systolic dysfunction (LVSD) with ejection fraction <40% was a predictor of appropriate therapy in the majority of studies, as were sustained VAs during electrophysiological testing (EP) in one study. There was no interaction with device indication (i.e. primary or secondary). Where documented, inappropriate therapy was primarily driven by atrial arrhythmias. All‐cause mortality was 6.0% over a median follow‐up period of 42 months. Only three studies achieved good quality in the comparability domain of NOS.ConclusionsAppropriate ICD therapy in patients with CS is commonly associated with LVSD, which can act as a surrogate for scar burden. The utility of EP testing in this setting remains unclear.

Predictors of appropriate implantable cardiac defibrillator therapy in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is associated with an increased risk for sudden cardiac death. An implantable cardiac defibrillator (ICD) is recommended in a subgroup of CS patients. However, the recommendations for primary prevention differ between guidelines. The purpose of the study was to evaluate the efficacy and safety of ICDs in CS and to identify predictors of appropriate therapy. A retrospective cohort study was performed in CS patients with an ICD implantation between 2010 and 2019. Primary outcome was appropriate ICD therapy. Independent predictors were calculated using Cox proportional hazard analysis. 105 patients were included. An ICD was implanted for primary prevention in 79%. During a median follow-up of 2.8 years, 34 patients (32.4%) received appropriate ICD therapy of whom 24 (22.9%) received an appropriate shock. Three patients (2.9%) received an inappropriate shock due to atrial fibrillation. Independent predictors of appropriate therapy included prior ventricular arrhythmias (hazard ratio [HR]: 10.5 [95% confidence interval (CI): 5.0-21.9]) and right ventricular late gadolinium enhancement (LGE) (HR: 3.6 [95% CI: 1.7-7.6]). Within the primary prevention group, right ventricular LGE (HR: 5.7 [95% CI: 1.6-20.7]) was the only independent predictor of appropriate therapy. Left ventricular ejection fraction did not differ between patients with and without appropriate therapy (44.4% vs. 45.6%, p = .70). In CS patients with an ICD, a high rate of appropriate therapy was observed and a low rate of inappropriate shocks. Prior ventricular arrhythmias and right ventricular LGE were independent predictors of appropriate therapy.

Right ventricular function as a predictor of appropriate therapy of implantable cardioverter defibrillator

Abstract Funding Acknowledgements Type of funding sources: None. Aim The purpose of this study was to evaluate the association of RV function and appropriate therapy of ICD.Methods: This study was a single-center retrospective cohort study. Consecutive patients who underwent ICD implantation for any diseases were enrolled except for non-dilated phase hypertrophic cardiomyopathy and channelopathy. Transthoracic echocardiographic parameters including left ventricular ejection fraction (LVEF), RV basal diameter, RV end-diastolic area, and right ventricular fractional area change (RVFAC) were evaluated. RV systolic dysfunction was defined as RVFAC &amp;lt;35%. Cox regression analysis was used to analyze the effects of those parameters on appropriate ICD therapy after the implantation. Results In total, 151 patients (60.9 ± 13.6 years, 117 males) consisting of 67 old myocardial infarction, 34 dilated cardiomyopathy, 19 cardiac sarcoidosis, and 31 others were enrolled. Eighty patients received an ICD as a secondary prophylaxis. Mean LVEF and RVFAC were 37.8 ± 13.9% and 33.2 ± 10.8%, respectively. RV systolic dysfunction was present in 86 (57.0%) patients, which was significantly associated with ICD therapy (odds ratio 2.313; 95% confidence interval 1.067-5.014; P = 0.034) according to a univariate analysis. There was no correlation between RVFAC and LVEF (correlation coefficient =0.064). Regarding the subjects LVEF &amp;gt; 35%, RV systolic dysfunction was an independent predictor of ICD therapy in a multivariate analysis. Conclusion RV systolic dysfunction was independently associated with increased ICD therapy despite of relatively preserved LVEF.

Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention

Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P < .001), border zone mass (26.4 ± 12.5 g vs 16.0 ± 9.5 g; P < .001), core mass (9.9 ± 8.6 g vs 5.5 ± 5.7 g; P < .001), and CC mass (3.0 ± 2.6 g vs 1.6 ± 2.3 g; P < .001) were associated with appropriate therapies. Scar mass > 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population.

Usefulness of late gadolinium enhancement cardiac magnetic resonance to predict appropriate therapies in implantable cardioverter defibrillator patients in primary prevention

Abstract Background The scar and the amount of border zone measured by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) has been proposed as an independent predictor of ventricular arrhythmias in patients with ischemic and non-ischemic cardiomyopathy. However, at the present time, the guidelines are based only on the ejection fraction to recommend an implantable cardioverter defibrillator (ICD) in primary prevention, and only a minority of these patients receive appropriate therapies. So, prevention needs to be improved. Purpose To identify predictors of appropriate therapies in patients with a primary prevention ICD using cardiac magnetic resonance imaging and a dedicated software (ADAS-3D) to characterize the scar. Methods Patients who underwent a LGE-MR prior to ICD implantation in primary prevention were retrospectively included. Clinical and cardiac imaging characteristics were collected. The myocardium was segmented with ADAS-3D software in 10 layers (from endocardium to epicardium). The scar, border zone, core and conducting channels were automatically measured in grams by the software. Results Since 2008 to 2017, 206 patients were included. Mean age was 67±28 years, 80% men, mean ejection fraction 26%±9, 52% with ischemic cardiomyopathy and 48% non-ischemic. The primary endpoint was appropriate therapies and/or sudden cardiac death (SCD). Median follow-up was 46.33 months. 46 patients (22%) reached the primary endpoint. Greater scar mass (36.05 grams vs 21.5 grams; HR 1.04; 95% CI (1.03–1-05), p&amp;lt;0.001), core mass (9.8 grams vs 5.6 grams; HR 1.06; 95% CI (1.04–1-09), p&amp;lt;0.001), border zone mass (26.2 grams vs 15.9 grams; HR 1.05; 95% CI (1.04–1-09), p&amp;lt;0.001) and channel mass (3.0 grams vs 1.6 grams; HR 1.15 95% CI (1.06–1.25), p&amp;lt;0.001) were associated with appropriate therapies and SCD. A border zone mass &amp;gt;5.3 grams was independently associated with the primary endpoint (HR: 4.77; 95% CI (1.15–19.73), p=0.03). Conclusions The amount of border zone, core and channel mass measured by LGE-MR and ADAS software are independent predictors of appropriate therapies and SCD in patients with ICD in primary prevention. Scar characterization Funding Acknowledgement Type of funding source: None

Primary prevention implantable cardioverter-defibrillators in hypertrophic cardiomyopathy—Are there predictors of appropriate therapy?

Identifying patients with hypertrophic cardiomyopathy (HCM) who warrant a primary prevention implantable cardioverter-defibrillator (ICD) is crucial. ICDs are effective in terminating life-threatening arrhythmias; however, ICDs carry risks of complications. The purpose of this study was to assess the incidence and predictors of appropriate ICD therapies, inappropriate shocks, and device-related complications in patients with HCM and primary prevention ICDs. All patients with HCM who underwent primary prevention ICD implantation at Toronto General Hospital between September 2000 and December 2017 were identified. Therapies (shocks or antitachycardia pacing) for ventricular tachycardia >180 beats/min or ventricular fibrillation were considered appropriate. Three hundred two patients were followed for a mean 6.1 ± 4.3 years (1801 patient-years of follow-up). Thirty-eight patients (12.6%) received at least 1 appropriate ICD therapy (2.3%/y); the 5-year cumulative probability of receiving appropriate ICD therapy was 9.6%. None of the conventional risk factors nor the European Society of Cardiology risk score was associated with appropriate ICD therapy. In multivariable analysis, age < 40 years at implantation and atrial fibrillation were independent predictors of appropriate ICD therapy. In a subgroup of patients who had undergone cardiac magnetic resonance imaging before ICD implantation, severe late gadolinium enhancement was the strongest predictor of appropriate ICD therapies. ICD-related complications or inappropriate shocks occurred in 87 patients (28.8%), with an inappropriate shock rate of 2.1%/y; the 5-year cumulative probability was 10.7%. The incidence of appropriate ICD therapies in patients with HCM and primary prevention ICDs is lower than previously reported; a high proportion of patients suffer from an ICD-related complication. Traditional risk factors have low predictive utility. Severe late gadolinium enhancement, atrial fibrillation, and young age are important predictors of ventricular tachyarrhythmias in HCM.

P575Usefulness of late gadolinium enhancement cardiac magnetic resonance to predict appropriate therapies in implantable cardioverter defibrillator patients in primary prevention

Abstract Funding Acknowledgements No funding acknowledgements OnBehalf VT and sudden cardiac death Background The scar and the amount of border zone measured by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) has been proposed as an independent predictor of ventricular arrhythmias in patients with ischemic and non-ischemic cardiomyopathy. However, at the present time, the guidelines are based only on the ejection fraction to recommend an implantable cardioverter defibrillator (ICD) in primary prevention, and only a minority of these patients receive appropriate therapies. So, prevention needs to be improved. Purpose To identify predictors of appropriate therapies in patients with a primary prevention ICD using cardiac magnetic resonance imaging and a dedicated software (ADAS-3D) to characterize the scar. Methods All consecutive patients who underwent a LGE-MR prior to ICD implantation in primary prevention were prospectively included. Clinical and cardiac imaging characteristics were collected. The myocardium was segmented with ADAS-3D software in 10 layers (from endocardium to epicardium). The scar, border zone, core and conducting channels were automatically measured in grams by the software. Results Since 2008 to 2017, 206 patients were included. Mean age was 67 +/- 28 years, 80% men, mean ejection fraction 26%+/-9, 52% with ischemic cardiomyopathy and 48% non-ischemic. The primary endpoint was appropriate therapies and/or sudden cardiac death (SCD). Median follow-up was 46,33 months. 46 patients (22%) reached the primary endpoint. Greater scar mass (36,05 grams vs 21,5 grams; HR 1.04; 95% CI (1.03-1-05), p &amp;lt;0.001), core mass (9,8 grams vs 5,6 grams; HR 1.06; 95% CI (1.04-1-09), p &amp;lt;0.001), border zone mass (26,2 grams vs 15,9 grams; HR 1.05; 95% CI (1.04-1-09), p &amp;lt;0.001) and channel mass (3,0 grams vs 1,6 grams; HR 1.15 95% CI (1.06-1.25), p &amp;lt;0.001) were associated with appropriate therapies and SCD. A border zone mass &amp;gt;5.3 grams was independently associated with the primary endpoint (HR: 4.77; 95% CI (1.15-19.73), p = 0.03). Conclusions The amount of border zone, core and channel mass measured by LGE-MR and ADAS software are independent predictors of appropriate therapies and SCD in patients with ICD in primary prevention. Abstract Figure. Scar characterization

Electrocardiographic predictors of appropriate implantable cardioverter defibrillator therapies in patients with tetralogy of Fallot

The electrocardiogram (ECG) is widely available and may contribute to a better risk stratification for sudden cardiac death in tetralogy of Fallot. To identify ECG predictors of appropriate therapies in patients with tetralogy of Fallot and implantable cardioverter defibrillator (ICD). The DAI-T4F study is an ongoing national French registry including all patients with tetralogy of Fallot and ICD ( NCT03837574 ). Information have been collected prospectively since 2010. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies. A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. During a median (IQR) follow-up of 6.1 (2.7–10.2) years, 59 (44.0%) patients received at least one appropriate ICD therapy, giving annual incidence of 5.5% and 7.1% in primary and secondary prevention, respectively ( P = 0.058). Overall, QRSd ≥ 180ms ( P = 0.073), QRS fragmentation ( P = 0.052), and QRS vector magnitude (vm, P = 0.327) were not significantly associated with appropriate ICD therapies, whereas the association of QRSd ≥ 180ms and QRS fragmentation (HR = 1.9, 95% CI: 1.1–3.4, P = 0.036) were associated with an increased risk of appropriates ICD therapies. In patients with ICD for primary prevention (47 patients, 35.1%), while non-sustained ventricular tachycardia (NSVT) considered isolated was not associated with events during follow-up ( P = 0.069), combinations with QRSd ≥ 180 ms (HR = 7.2, 95% CI: 1.6–32.7, P = 0.011), QRS fragmentation (HR = 3.8, 95% CI: 1.2–12.4, P = 0.025), or decreased QRS vm (HR = 3.6, 95% CI: 1.1–12.1, P = 0.042) were all associated with a higher incidence of appropriate ICD therapies. Our findings highlight that cumulative risk score derived from ECG may contribute to improve risk stratification in patients with tetralogy of Fallot, in particular QRS fragmentation and QRS vm in association with QRS duration and other traditional risk factors.

Incidence of appropriate implantable cardioverter-defibrillator therapy and mortality after implantable cardioverter-defibrillator generator replacement: results from a real-world nationwide cohort.

The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement. We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13-1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57-6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy. A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events.

Reduced occurrence of appropriate therapy for ventricular arrhythmias after beta-blocker uptitration following implant of a primary prevention CRT-defibrillator

Background: Absence of beta-blocker use independently predicts appropriate therapy. Following cardiac resynchronisation therapy (CRT) implant, reverse remodelling and protection against bradycardia allows for beta-blocker dose uptitration. The differential dosing effects on the occurrence of a first episode of appropriate therapy in primary prevention CRT-defibrillator (CRT-D) patients remains unstudied.Methods and Results: Changes in beta-blocker dose following CRT-D in consecutive primary prevention patients implanted between 2008 and 2015 were retrospectively studied. Beta-blocker dose was expressed as percent of target dose. Uptitration of beta-blocker dose following implant was calculated as the change in percent of target dose between implant and 6-months follow-up. Results from a prospectively maintained database of all device analysis were used to determine the occurrence of appropriate therapy. A total of 162 patients (68 ± 8 years) were studied. One hundred and ten (68%) patients underwent uptitration (mean 47 ± 19% in target dose) and 52 (32%) remained on a stable beta-blocker dose. During 37 ± 22 months follow-up, the cumulative percent of appropriate therapy was 31% in patient receiving no-uptitration versus 10% in the uptitrated patients (p < 0.001). After correction for known predictors of appropriate therapy, uptitration was independently associated with an OR = 0.263 (CI = 0.103–0.675; p = 0.001) for the occurrence of appropriate therapy. Every 1%-increase in target dose for beta-blocker associated with a significant lower risk for appropriate therapy, OR = 0.982 (CI = 0.965–0.999; p = 0.042).Conclusion: Following implantation of a primary prevention CRT-D, uptitration of beta-blockers associated with a reduced occurrence of a first episode of appropriate therapy for ventricular arrhythmias. An inverse dose–response effect was seen between beta-blocker dose and appropriate therapy.

Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up

BackgroundImplantable cardioverter-defibrillator (ICD) indications for primary prevention in Brugada syndrome (BrS) are still debated. ObjectivesThe authors investigated the long-term outcome after ICD implantation in a large cohort of BrS patients. MethodsOf a total of 370 patients with BrS in follow-up (age 43 ± 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors analyzed the long-term incidence of shocks and complications. ResultsAn ICD was implanted for secondary prevention in 10 patients (9.6%) and for primary prevention in 94 patients (90.4%). After a follow-up of 9.3 ± 5.1 years, 21 patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2 per 100 person-years). The rate of appropriate shocks was higher in secondary prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%) experienced appropriate ICD therapy, all with a spontaneous type 1 electrocardiogram and inducible ventricular arrhythmias. In the multivariable analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95% confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were significant predictors of appropriate therapy. Nine patients (8.7%) experienced 37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100 person-years). Three patients (2.9%) died (1 electrical storm and 2 noncardiovascular deaths). ConclusionsICD therapy is an effective therapy in high-risk patients with BrS. However, it is also associated with a significant risk of device-related complications. Special care during ICD implantation, adequate device programming, and regular follow-up may allow reducing the number of adverse events.

Substrate-dependent risk stratification for implantable cardioverter defibrillator therapies using cardiac magnetic resonance imaging: The importance of T1 mapping in nonischemic patients.

The role of implantable cardioverter defibrillators (ICDs) in nonischemic cardiomyopathy is unclear and better risk-stratification is required. We sought to determine if T1 mapping predicts appropriate defibrillator therapy in patients with nonischemic cardiomyopathy. We studied a mixed cohort of ischemic and nonischemic patients to determine whether different cardiac magnetic resonance (CMR) applications (T1 mapping, late gadolinium enhancement, and Grayzone) were selectively predictive of therapies for the different arrhythmic substrates. We undertook a prospective longitudinal study of consecutive patients receiving defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CMR scar assessment before device implantation. QRS duration and fragmentation on the surface electrocardiogram were also assessed. The primary endpoint was appropriate defibrillator therapy. One-hundred thirty patients were followed up for a median of 31 months (IQR ± 9 months). In nonischemic patients, T1_native was the sole predictor of the primary endpoint (hazard ratio [HR] 1.12 per 10 millisecond increment in value [95% confidence interval [CI] 1.04-1.21; P ≤ 0.01]). In ischemic patients, Grayzone_2SD-3SD was the strongest predictor of appropriate therapy (HR 1.34 per 1% left ventricular increment in value [95% CI 1.03-1.76; P = 0.03]). QRS fragmentation correlated well with myocardial scar core (receiver operating characteristic area under the curve [ROC AUC] 0.64; P = 0.02) but poorly with T1_native (ROC AUC 0.4) and did not predict appropriate therapy. In the medium-long term, T1_native mapping was the only independent predictor of therapy in nonischemic patients, whereas Grayzone was a better predictor in ischemic patients. These findings suggest a potential role for T1_native mapping in the selection of patients for ICDs in a nonischemic population.

Clinical decision tool for CRT-P vs. CRT-D implantation: Findings from PROSE-ICD.

BackgroundCardiac resynchronization therapy (CRT) devices reduce mortality through pacing-induced cardiac resynchronization and implantable cardioverter defibrillator (ICD) therapy for ventricular arrhythmias (VAs). Whether certain factors can predict if patients will benefit more from implantation of CRT pacemakers (CRT-P) or CRT defibrillators (CRT-D) remains unclear.Methods and resultsWe followed 305 primary prevention CRT-D recipients for the two primary outcomes of HF hospitalization and ICD therapy for VAs. Serum biomarkers, electrocardiographic and clinical variables were collected prior to implant. Multivariable analysis using Cox-proportional hazards model was used to fit the final models. Among 282 patients with follow-up outcome data, 75 (26.6%) were hospitalized for HF and 31 (11%) received appropriate ICD therapy. Independent predictors of HF hospitalization were atrial fibrillation (HR = 1.8 (1.1,2.9)), NYHA class III/IV (HR = 2.2 (1.3,3.6)), ejection fraction <20% (HR = 1.7 (1.1,2.7)), HS-IL6 >4.03pg/ml (HR = 1.7 (1.1,2.9)) and hemoglobin (<12g/dl) (HR = 2.2 (1.3,3.6)). Independent predictors of appropriate therapy included BUN >20mg/dL (HR = 3.0 (1.3,7.1)), HS-CRP >9.42mg/L (HR = 2.3 (1.1,4.7)), no beta blocker therapy (HR = 3.2 (1.4,7.1)) and hematocrit ≥38% (HR = 2.7 (1.03,7.0)). Patients with 0–1 risk factors for appropriate therapy (IR 1 per 100 person-years) and ≥3 risk factors for HF hospitalization (IR 23 per 100-person-years) were more likely to die prior to receiving an appropriate ICD therapy.ConclusionsClinical and biomarker data can risk stratify CRT patients for HF progression and VAs. These findings may help characterize subgroups of patients that may benefit more from the use of CRT-P vs. CRT-D systems.Trial registrationClinicalTrials.gov NCT00733590

Persistence of ICD indication at the time of replacement in patients with initial implant for primary prevention indication: Effect on subsequent ICD therapies

BackgroundIndication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR. MethodsWe identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR. ResultsAt the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01–1.96; p = 0.041). ConclusionIn heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null.

Temporal trends and long term follow-up of implantable cardioverter defibrillator therapy for secondary prevention: A 15-year single-centre experience

BackgroundThe aim of this study was to determine overall and aetiology-related incidence of secondary prevention ICD implantation over the last 15years in Canton Ticino and to assess clinical outcome according to time period of implantation. Methods and resultsConsecutive patients treated by implantation of an ICD for secondary prevention from 2000 to 2015 were included in the current study and compared between 5-year cohorts (2000/2004; 2005/2009; 2010/2015). Yearly implantation rate, changing in clinical presentation over years and events during follow-up were evaluated. One-hundred fifty six patients were included. ICD implantation rate increased from 2.1 in 2000–2005 to 5.1 in 2010–2015, respectively (p 0.001). There was an increase in the proportion of non-ischaemic patients and of ventricular tachycardia (VT) as presenting rhythm. No differences in appropriate ICD interventions were observed according to aetiology, presenting arrhythmia or type of device. Reverse remodelling was observed more often in non-ischaemic patients, without any influence on the occurrence of appropriate interventions. Previous myocardial infarction (MI), atrial fibrillation (AF), NYHA class 2–3 and left ventricular ejection fraction (LVEF)<35% were predictors of appropriate therapies during follow-up. ConclusionsRate of implants for secondary prevention indication has almost doubled during the last 15years. Importantly, there has been a progressive increase of non-ischaemic patients receiving an ICD, and of VT as presenting rhythm. Patients had an overall good survival and a relatively low incidence of appropriate therapies. Improvement of ejection fraction did not correlate with risk reduction of ventricular arrhythmias.