Prophylactic Implantable Cardioverter-defibrillator Implantation Research Articles

Right Bundle Branch Block Predicts Appropriate Implantable Cardioverter Defibrillator Therapies in Patients with Non-Ischemic Dilated Cardiomyopathy and a Prophylactic Implantable Cardioverter Defibrillator.

Background: The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of patients at risk for sudden cardiac death remains a major challenge. Aims/Methods: We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing [ATP] and/or shocks) in this cohort of patients. Results: A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, p = 0.006), of younger age (59 years, (53-65) vs. 64 years, (57-70); p = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, p = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, p = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m2, (90-117) vs. 86, (71-110); p = 0.011) and systolic volumes (72 mL/m2, (59-87) vs. 61, (47-81), p = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02-4.98, p = 0.043) was identified as an independent predictor of appropriate ICD therapies. Conclusion: RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial

BackgroundComprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries.MethodsPatients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD.ResultsWe enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116–0.343, p < 0.0001) lower SCD risk.ConclusionsThere was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent.Trial registrationClinicalTrials.gov, NCT02099721.

Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: afocused update.

The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown. DPP6 risk haplotype-positive family members (DPP6cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023. Implantable cardioverter-defibrillator (ICD) indication was divided in primary or secondary prevention. Cumulative survival and event rates were calculated. We included 327 DPP6cases and 315 DPP6 controls. Median follow-up time was 9years (interquartile range: 4-12). Of the DPP6cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at amedian age of 45years (range: 15-97). Median overall survival was 83years and 87years for DPP6cases and DPP6 controls, respectively (p < 0.001). In DPP6cases, median overall survival was shorter for males (74years) than females (85years) (p < 0.001). Of the DPP6cases, 97 (30%) died, at amedian age of 50years. With aprophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10patients experienced atotal of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6cases with asecondary prevention ICD experienced atotal of 231 appropriate ICD shocks. Patients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using arisk stratification approach based on risk haplotype, sex and age, asubstantial proportion of patients with aprimary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy.

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

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

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

The Heart Failure Optimization Study (HF-OPT): rationale and design.

According to the current guidelines, implantable cardioverter-defibrillators (ICD) for primary prevention in patients with heart failure and reduced ejection fraction (HFrEF) should not be considered until optimal guideline-directed medical therapy (GDMT) has been achieved for aminimum of 3months. Optimization of GDMT often needs time beyond 3months after diagnosis. The aim of the Heart Failure Optimization Study (HF-OPT) is to evaluate the recovery of left ventricular function beyond 3months after diagnosis of newly diagnosed HFrEF. The HF-OPT multicenter study is comprised of two non-randomized phases (registry and study). During the first 90days awearable cardioverter-defibrillator (WCD) is prescribed and patients are enrolled in an observational pre-study registry. Registry subjects meeting inclusion criteria for the study portion at day90 have ongoing left ventricular ejection fraction (LVEF) reassessment at 90, 180 and 360 days after the index hospital discharge, regardless of continued WCD use. Approximately 600 subjects will be enrolled in the study portion. Of those, one-third are anticipated to start the study phase at day90 with reduced LVEF. The primary objective of this study is to observe the rate of recovery of LVEF > 35% between90 and 180days, while key secondary endpoints include mortality and WCD recorded arrhythmias and shocks. The HF-OPT study will provide important information on the rate of additional recovery of LVEF > 35%, between90 and 180days, in newly diagnosed HF with reduced LVEF patients being titrated with GDMT. The results of the study may impact indications for primary prophylactic ICD implantation.

Guideline Directed Medical Therapy at Discharge and Further Uptitration Leading to Reduction in Indication for Prophylactic ICD Implantation during Protected Waiting Period.

Heart failure with reduced ejection fraction (LV-EF < 35%) is diagnosed in app. 11,000,000 patients worldwide. For the treatment of these patients, guideline directed medical therapy has proven to reduce mortality and rehospitalization regardless of the disease’s etiology. It is implemented to treat clinical symptoms by improving the left ventricular ejection fraction. Patients with a transient risk of ventricular tachycardia and sudden cardiac death can be protected by a defibrillator vest. The defibrillator vest is capable to detect and terminate ventricular arrhythmias during Guideline Directed Medical Therapy (GDMT). It is based on the recommendations of the European society of cardiology for 3 months. Afterwards, the WCD wear time could be prolonged, or, in case of persistent low ejection fraction (LV-EF ≤ 35%), an implantable cardioverter defibrillator (ICD) should be implanted, as shown in the WEARIT-II-registry. Our goal was to evaluate the effects of GDMT on LV-recovery and reduction of ICD implantations under protection with a defibrillator vest—depending on the uptitration of GDMT. Methods: 339 consecutive patients between August 2017 and September 2020 with newly diagnosed cardiomyopathy and an EF ≤ 35% were analyzed retrospectively by chart review. All patients were protected by a wearable cardioverter defibrillator (WCD). GDMT as recommended by the ESC started at discharge from hospital. The left ventricular ejection fraction (LV-EF) was determined by transthoracic echocardiography at week 4, 8 and at week 12 (in case of prolonged WCD wear time). Uptitration was performed after 4 and 8 weeks during patient visits. We focused on baseline medication as per GDMT and the dosage increase at week 4, 8 and 12. The aim was the uptitration to the maximum dosage tolerated by the patient. We also compared the LV-EF improvement in the group with and without uptitration of medication dosage. Results: The patient age was, on average, 63.2 years (SD ± 11.9 years). A total of 129 pts (38%) had ICM, 196 (58%) had NICM (incl 66 pts (19%) with DCM and 51 pts (15%) with Myocarditis, 79 pts (24%) with unknown origin) and 14 pts (4%) had other entities (e.g., Tachycardiomyopathy). In total, 21 pts (6%) had an LV-EF of less than 16%, 130 pts (38%) between 16–25% and 183 pts (54%) between 26–35%. GDMT started at discharge from the hospital included treatment with beta blocker for 327 pts (96.5%), ACE-inhibitors/Angiotensin/ARNI for 283 pts (83.5%) and Mineralcorticoid receptor antagonists (MRA) for 334 pts (88.4%). Uptitration was performed in all groups at a rate of 82.3%, 91.1% and 81.0% after 4 weeks and 64.7%, 50.3% and 66.3% after 8 weeks, respectively. After 4 weeks, 25 pts (7.4%) and, after 8 weeks, 171 pts (50.4%) had an EF increase of 5% or more (mean 14.2%). After 4 weeks, 81 patients had an LV-EF more than 35%. A total of 169 pts had a wear time of 12 weeks and an improvement of LVEF of more than 35%. Interestingly, in our study we did not find a significant difference in LV-EF improvement between the group with no uptitration and the group with uptitration. Conclusions: Guideline-directed medical therapy under protection with a WCD from ventricular arrhythmia can reduce the need for implantation of an ICD and can lead to an improvement of ejection fraction. Interestingly, the LV-EF improvement depends on the GDMT at discharge. Current guidelines recommend an initiation of all therapy columns of GDMT (sacubitril/valsartan, ACE-inhibitor/AT1-blocker, mineralcorticoidreceptorblocker, beta blocker) at once and further uptitration to the maximal dosage (ESC Guidelines 2021). A further uptitration of all drugs of GDMT should lead to improvement of LV-EF and consequently to a reduction in ICD implantations.

Diabetes may modify the efficacy of primary prevention implantable cardioverter-defibrillators in non-ischemic systolic heart failure: an extended follow-up of the DANISH trial

Abstract Background Since patients with both diabetes and heart failure (HF) have a substantially worse prognosis than those with each of these alone, the efficacy of implantable cardioverter defibrillator (ICD) implantation in patients with systolic HF may be modified by diabetes status. Purpose In this extended follow-up analysis of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary prophylactic ICD implantation, compared with usual clinical care, in patients with non-ischemic systolic HF according to diabetes status. Methods In DANISH, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual clinical care (N=550). Outcomes were analyzed according to diabetes status at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results Of the 1,116 patients randomized in DANISH, 211 (18.9%) had diabetes at baseline (median age 64 year-old, 159 males, median left ventricular ejection fraction 25%). There was a statistically significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death. There was a trend toward a reduction in both outcomes with ICD implantation, compared with usual clinical care; in patients without diabetes (death from any cause, HR 0.81 [95% CI, 0.65–1.01]; cardiovascular death, HR 0.77 [0.59–1.01]), but not in those with diabetes (death from any cause, HR 1.19 [0.81–1.74]; cardiovascular death, HR 1.20 [0.79–1.82]) (P for interaction = 0.04 and 0.04 for death from any cause and cardiovascular death, respectively). Although there was no statistically significant interaction between diabetes and the effect of ICD implantation on sudden cardiovascular death, ICD implantation significantly reduced the rate of sudden cardiovascular death in patients without diabetes (HR 0.51 [0.31–0.85]), but not in those with diabetes (HR 0.91 [0.41–1.99]) (P for interaction = 0.15). Conclusions In patients with non-ischemic systolic HF, there was a significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death, suggesting that individuals without diabetes may derive greater benefit from ICD implantation. Funding Acknowledgement Type of funding sources: None.

Long-term clinical course and prognostic factors of heart failure with reduced ejection fraction (HFrEF) patients underwent primary prophylactic implantable cardioverter defibrillator (ICD)

Abstract Background For decades, ICD is a well-established therapy for improving prognosis of structural heart disease with severe cardiac dysfunction, and ICD for primary prophylaxis against sudden cardiac death were routinely provided. However, long-term prognosis and clinical course are different in each individual patient with an ICD, and it is moreover unclear what kind of factors might have influences on their clinical outcomes. Purpose The aim of this study is to clarify long-term prognosis and predictors of future major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis in Japanese population. Methods We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2006 to 2020 at our institute and met the criteria of ICD recommendation of the latest Japanese guideline. Its requirements are receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). Additionally, prior NSVT is considered Class I ICD recommendation. In the case of ischemic cardiomyopathy (ICM), ICD implantation was done at least 40 days after myocardial infarction and at least 90 days after revascularization. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. Results A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). One hundred twenty patients (81%) were programmed with a shock-only zone over 200 beats per minute. The median follow-up duration was 58.5 months. Among those 148 patients, MACEs were occurred to 60 patients (41%). As a result of dividing all patients into two groups by the occurrence of MACE, LVEF and LVDd were worse in MACE(+) group, whereas, MACE(−) had greater number of co morbidities. The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03–1.12, p&amp;lt;0.001), AF (HR: 2.88, 95% CI: 1.56–5.31, p&amp;lt;0.001) and ICM (HR: 1.78, 95% CI: 1.00–3.16, p=0.049) were the independent predictors of MACEs (Table). However, initial ICD programming was not related to the occurrence of MACE. Conclusions The incidence of MACEs in patients with an ICD and severe HFrEF was substantially high in this Japanese population. Etiology of ICM, left ventricle size, and AF were the potential risk factors for future MACEs. Funding Acknowledgement Type of funding sources: None.

Predictors of late arrhythmic events after generator replacement in Brugada syndrome treated with prophylactic ICD.

IntroductionPredictors of late life-threatening arrhythmic events in Brugada syndrome (BrS) patients who received a prophylactic ICD implantation remain to be evaluated. The aim of the present long-term multicenter study was to assess the incidence and clinical-electrocardiographic predictors of late life-threatening arrhythmic events in BrS patients with a prophylactic implantable cardioverter defibrillator (ICD) and undergoing generator replacement (GR).MethodsThe study population included 105 patients (75% males; mean age 45 ± 14years) who received a prophylactic ICD and had no arrhythmic event up to first GR.ResultsThe median period from first ICD implantation to last follow-up was 155 (128–181) months and from first ICD Implantation to the GR was 84 (61–102) months. During a median follow-up of 57 (38–102) months after GR, 10 patients (9%) received successful appropriate ICD intervention (1.6%/year). ICD interventions included shock on ventricular fibrillation (n = 8 patients), shock on ventricular tachycardia (n = 1 patient), and antitachycardia pacing on ventricular tachycardia (n = 1 patient). At survival analysis, history of atrial fibrillation (log-rank test; P = 0.02), conduction disturbances (log-rank test; P < 0.01), S wave in lead I (log-rank test; P = 0.01) and first-degree atrioventricular block (log-rank test; P = 0.04) were significantly associated with the occurrence of late appropriate ICD intervention. At Cox-regression multivariate analysis, S-wave in lead I was the only independent predictor of late appropriate ICD intervention (HR: 9.17; 95%CI: 1.15–73.07; P = 0.03).ConclusionsThe present study indicates that BrS patient receiving a prophylactic ICD may experience late appropriate intervention after GR in a clinically relevant proportion of cases. S-wave in lead I at the time of first clinical evaluation was the only independent predictor of persistent risk of life-threatening arrhythmic events. These findings support the need for GR at the end of service regardless of previous appropriate intervention, mostly in BrS patients with conduction abnormalities.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still needan implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

Programmed ventricular stimulation for risk stratification in patients with myocardial scarring and an ejection fraction above or equal to 40%

Abstract Funding Acknowledgements Type of funding sources: None. Background Sudden cardiac death (SCD) is one of the leading causes of death, particularly among patients with myocardial scars. Implantable cardioverter defibrillators (ICD) are recommended in patients with a left ventricular ejection fraction (LVEF) ≤ 35%. Another recognised indication is the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during programmed ventricular stimulation (PVS) in post-myocardial infarction patients with non-sustained VT and a LVEF between 35% and 40%. However, no recommendation exists to guide the use of prophylactic ICD implantation in patients with less altered LVEF, even though they represent the majority of SCDs. Purpose We aimed to evaluate the prognostic value of PVS in patients with myocardial scars and a relatively preserved LVEF (≥ 40%). Methods Patients with evidence of a chronic myocardial scar and a LVEF ≥ 40%, who underwent PVS at two hospital centers were considered for inclusion. Ischemic and non-ischemic myocardial scars were included. The primary endpoint was the occurrence of a Major Arrhythmic Event (MAE), namely SCD, clinical VT/ventricular fibrillation, or appropriate ICD therapy. Results 134 patients were included (mean age 62.4 ± 12.5 years, LVEF 54.7 ± 8.6 %). Indication for PVS was mostly non-sustained VT and/or syncope (84%). Post-myocardial infarction patients represented about half of the cases (53%). Inducibility during PVS was observed in 17 patients (13%). There was a nonsignificant trend towards higher inducibility rates in ischemic versus nonischemic scars (17% and 8%, respectively; p-value = 0.1). Of these patients, 15 received an ICD (88%). Over a mean follow-up of 49 (±42) months, a MAE occurred in 7 patients (41.2%) with positive PVS, versus 4 patients (3.4%) with negative PVS. MAE-free survival at 10 years was 91% and 43% in PVS-negative and PVS-positive patients, respectively (p-value &amp;lt; 0.001). One SCD occurred in a PVS-positive patient who denied prophylactic ICD implantation. Inducibility during PVS provided a 64% sensitivity and a 97% negative predictive value (PV) to predict the occurrence of MAE (specificity 92%, positive PV 41%). Conclusion PVS is a useful tool to discriminate patients with myocardial scars and LVEF ≥ 40% at increased arrhythmic risk. Effective utilisation of ICD may be anticipated in case of positive PVS, while non-inducible patients are at lower MAE risk.

Negative prognostic implications of non-sustained ventricular tachycardias in patients after prophylactic defibrillator implantation

Abstract Funding Acknowledgements Type of funding sources: None. Background Non-sustained ventricular tachycardia (NSVT) is frequent phenomenon in severe heart failure with reduced ejection fraction (HFrEF) patients, and causes any negative impacts on such patients. In the Japanese Circulation Society (JCS) and Japanese Heart Rhythm Society (JHRS) guidelines, NSVT is regarded as a major component of indication for implantable cardioverter defibrillator (ICD) implantation. However, the long-term prognostic significance of NSVT in severe HFrEF is incompletely resolved. Purpose The aim of this study is to investigate the relation between prior NSVT episodes and major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis. Methods We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2007 to 2018 following ICD recommendation of JCS and JHRS guidelines. Patients met the criteria of receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). In the case of ischemic cardiomyopathy (ICM), implantation of ICD was done at least 40 days after myocardial infarction and at least 90 days after revascularization. Incidence of NSVT episodes were identified through daily electrocardiogram (ECG), Holter ECG or monitor ECG in the hospital. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. Results A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). The median follow-up duration was 58.5 months. As a result of comparison of the Kaplan-Meier curve between NSVT group (n=113) and non-NSVT group (n=35), cardiovascular death, heart failure hospitalization, and appropriate ICD therapy were not statistically different (Figures). Of those, MACEs were occurred to 60 patients (41%). The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03-1.12, p&amp;lt;0.001), AF (HR: 2.88, 95% CI: 1.56-5.31, p&amp;lt;0.001) and ICM (HR: 1.78, 95% CI: 1.00-3.16, p=0.049) were the independent predictors of MACEs, however NSVT was not (Table). Conclusions In this Japanese population, the long-term prognosis of severe HFrEF patients is considered to be comparable regardless of prior NSVT episodes. However, the incidence of MACEs in patients with severe HFrEF after ICD implantation was substantially high. ICM, left ventricle size, and atrial fibrillation were the potential risk factors for MACEs as the previous reports showed.

Periodic Repolarization Dynamics Identifies ICD Responders in Nonischemic Cardiomyopathy: A DANISH Substudy.

Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation. We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg2 as an exploratory cut-off value for ICD implantation. A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group (P=0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09-1.50] per SD increase; P=0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25-1.81]; P<0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83-1.54]; P=0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality (P=0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg2 (HR, 0.54 [95% CI, 0.34-0.84]; P=0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg2 (HR, 1.17 [95% CI, 0.77-1.78]; P=0.46; P for interaction=0.01). Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.

Depressive symptoms in patients after primary and secondary prophylactic ICD implantation.

Implantable cardioverter defibrillators (ICD) are successfully used to treat life-threatening arrhythmias and prevent sudden cardiac death. However, they are also known to have a major psychological impact leading to higher prevalence of depression and anxiety in a substantial proportion of patients. The aim of this study was to assess the prevalence of depressive symptoms in a large cohort of ICD carriers with a different clinical background and to compare prevalence and risk factors between patients with primary and secondary prophylactic indication for ICD implantation. 315 out of 622 patients (50.6%), who regularly attended ICD assessments at the University Hospital Zurich completed the Beck Depression Inventory (BDI I-II) to estimate current depressive symptoms. Overall, depressive symptoms were common in ICD patients, with 20.3% of the patients showing clinically relevant depression (12.4% mild depressive symptoms, 6.0% moderate, 1.9% severe). Moderate to severe depressive symptoms seem to be more likely in patients with secondary prophylactic indication of the ICD as compared to a group of patients with primary prophylactic implantation. Patients that received more than 5 ICD shocks since implantation reveal more depressive symptoms than those with less events. Mean BDI Score in total (n = 315) was at 8.44 ± 7.56 without a statistically significant difference between the primary (M = 8.04 ± 7.10, n = 153) and secondary (M = 8.81 ± 7.98, n = 162) preventive group (p value = 0.362), even after adjustment for various clinical characteristics. ICD patients should therefore be well supported and advised concerning the psychological impact of their device and particular aspects of daily life concerns (e.g. physical activity), with a special focus on patients, who have received multiple shocks.

Mortality among ischemic and nonischemic heart failure patients with a primary implantable cardioverter-defibrillator.

BackgroundThe efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention is controversial in patients with nonischemic heart failure (HF). We evaluated the mortality and predictors of mortality in patients with prophylactic ICD implantation for ischemic and nonischemic HF.MethodsFrom 2008 to 2017, 1097 patients (667, nonischemic HF and 430, ischemic HF) who underwent prophylactic ICD implantation, were identified from the Korean National Health Insurance Service database. We used propensity score overlap weighting to correct the differences between two groups.ResultsThose with ischemic HF were older (67.0 ± 10.1 vs 61.8 ± 14.2 years), more often male (71.4% vs 63.7%), and had more comorbidities than patients with nonischemic HF. During a median follow‐up of 37.3 months (interquartile range [IQR], 14.2‐53.8 months), all‐cause mortality was higher in unweighted patients with ischemic HF than in those with nonischemic HF (10.9 vs 6.4 per 100 person‐years; hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.38‐2.20; P < .001). However, after weighting, the annual all‐cause mortality rate was similar in both groups (9.5 vs 8.8 per 100 person‐years), with no significant difference in the risk of all‐cause mortality (HR, 1.08; 95% CI, 0.68‐1.71; P = .755). Older age and chronic kidney disease were independent predictors of all‐cause mortality in both groups. There was no significant difference in cardiac and noncardiac mortality between the weighted nonischemic and ischemic HF groups.ConclusionsThe all‐cause, cardiac, and noncardiac mortality rates were similar between patients with nonischemic and ischemic HF who underwent prophylactic ICD implantation.

Right bundle branch block and male sex may help predict appropriate ICD therapies in patients with non-ischemic dilated cardiomyopathy and a prophylactic implantable cardioverter defibrillator

Abstract Background Previous studies have shown that prophylactic implantable cardioverter-defibrillators (ICD) in patients with symptomatic severe systolic dysfunction reduce all-cause mortality. However, their benefit in patients with severe systolic dysfunction of non-ischemic origin is not so clear, and is currently under debate. Methods/Aim We retrospectively reviewed all consecutive patients with nonischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify predictors of appropriate ICD therapies (ATP and/or shocks) in this cohort of patients. Results A total of 224 patients were included, median age 62.7 years, 73.7% men. During a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD intervention, 7 patients (3.1%) presented inappropriate shocks and 11 (4.9%) had device infection. Patients that received appropriate ICD therapies, as compared to those who did not, were more frequently men (86.9% vs 68.7%, p=0.006) and were significantly younger (median age 58.7 years, IQR 53.0–64.8 vs 63.7, IQR 57.0–69.8; p=0.02). Left ventricular end diastolic volume (LV-EDV) and left ventricular end systolic volume (LV-ESV) were both significantly higher in this subgroup of patients (median LVEDV 100 ml/m2 vs 86, p=0.0106; median LVESV 72.2 ml/m2 vs 60.9, p=0.0467). A trend towards lower LVEF was also noted, but it did not reach statistical significance (26% vs 29%, p=0.077). Regarding ECG previous to implant, patients that required ICD intervention presented more frequently complete right bundle branch block (RBBB) (14.8% vs 4.3%, p=0.007). On the other hand, left bundle branch block (LBBB) was more frequent in those patients who did not receive ICD intervention during follow-up (47.2% vs 26.2%, p=0.005). Table 1 summarizes baseline characteristics and results. In a multivariate Cox regression analysis, RBBB (HR 3.9, CI 95% 1.9–8.0, p&amp;lt;0.001) and male sex (HR 2.38, CI 95% 1.07–5.28, p=0.034) were identified as independent predictors of appropriate ICD therapies (Figure 2). Conclusion RBBB and male sex may help identify patients with NICM at high-risk of ventricular arrhythmias requiring ICD intervention. Funding Acknowledgement Type of funding sources: None. Baseline characteristics and resultsKaplan-Meier curves

Ten-year follow-up of implantable cardioverter-defibrillator device implantation in non-ischaemic cardiomyopathy – an insight from real world practice in a large district general hospital

Abstract Introduction The benefits of implantable cardioverter-defibrillators (ICDs) in ischaemic cardiomyopathy are well established. The DANISH study, a large randomized controlled trial of prophylactic ICD implantation, found no benefit in preventing all-cause mortality in patients with non-ischaemic cardiomyopathy (NICM). However, ESC guidelines recommend ICDs for patients with NICM and LVEF ≤35% who receive optimal medical therapy (IB recommendation). The 2014 NICE guidelines have similar endorsements but prior to that ICDs were not routinely recommended in NICM in the UK. Purpose We evaluated clinical outcomes of patients who had ICDs implanted prior to 2014 in a NICM population at a large district general hospital. Methods An ICD database of 454 patients at our district general hospital was retrospectively reviewed. We identified 70 patients who had ICD insertion for non-ischaemic cardiomyopathy between 2006 and 2014. Mean follow up time was 9 years 9 months (SD 23 months). 39 patients had an ICD inserted for primary prevention and 31 for secondary prevention. Data was collected from patients' electronic notes and analysed with relation to baseline demographics, mortality, complications and both appropriate and inappropriate therapy in these two subgroups. Results The baseline patient characteristics are presented in Table 1 and show similar characteristics between the primary and secondary prevention groups, except for a higher level of CRT-D implantation in the primary prevention group (p=0.006). Table 2 shows therapy that the device delivered and complication rates. Overall, 16% of patients with an ICD for non-ischaemic cardiomyopathy received a shock for VF. 41% of patients received appropriate therapy (Shocks or Anti-Tachycardia Pacing (ATP)) from their ICD with median time to first therapy of 30 months (IQR 12–66). Shocks for VF were similar in each group (15% vs. 16%, p=0.919). Six patients (8.6%) had inappropriate shocks and two inappropriate ATP (2.9%). 9 (13%) of patients had a complication either at implant or during follow-up; two had pericardial effusions following implant of which one required pericardiocentesis, three required lead replacement due to lead failure, two developed device infections, one was anticoagulated for a lead thrombus and one patient's device failed to treat VF. Conclusion 16% of non-ischaemic cardiomyopathy patients received a shock for VF and 41% received ICD therapy for VT or VF over a mean follow-up period of almost 10 years. This was seen in both primary and secondary prevention. Inappropriate shocks and life-threatening complications were uncommon. Funding Acknowledgement Type of funding sources: None. Table 1. Patient characteristicsTable 2. ICD therapy and complications

Idiopathic HFrEF. Is there room left for defibrillators?

Abstract Background and aim Prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is class 1 recommendation for heart failure (HF) patients with reduced ejection fraction (HFrEF) even though its proven advantage is weaker among nonischemic aetiology. In fact, in an era where both optimal medical therapy (OMT) and cardiac resynchronization therapy (CRT) significantly reduce sudden cardiac death (SCD), it is questionable whether ICD still have additional value. The aim of this study was to assess the current benefit of ICDs in preventing sudden cardiac death through resuscitated cardiac arrest (RCA), appropriate therapy for sustained ventricular tachycardia (VT) or fibrillation (VF) in a contemporary population of idiopathic HFrEF patients. Methods Single-centre retrospective study of consecutive symptomatic (NYHA class II to IV) idiopathic HFrEF patients with an ICD (either alone or in association with CRT), and remote monitoring with the corresponding software (MerlinTM, LatitudeTM, CarelinkTM, MicroPortTM or BiotronikTM) to assure appropriate event supervising. Idiopathic aetiology was assumed after excluding other probable causes. Coronary angiogram was required to exclude ischemic aetiology. Only those with prophylactic ICD implantation were included. RCA was defined as collapse with clinical signs of cardiac arrest and VF or VT appropriately terminated by ICD. In order to be sustained, VT episode had to have last at least 30 seconds. Results From 781 remote monitoring controlled patients, a total of 187 consecutive symptomatic idiopathic HFrEF patients with an ICD (125 men, mean age 64±18 years) were enrolled. Patients were on optimal medical therapy (ACEi/ARB: n=168, 90%; BB: n=154, 82%; mineralocorticoid antagonists: n=91, 49%; CRT: n=130, 70%; see Table). After a median follow-up of 99 months (IQR 62.2), RCA occurred in 10.7% (n=20) and 36.9% (n=69) had appropriately terminated VT. Both left ventricular ejection fraction (LVEF) improvement and CRT implantation did not independently reduce the incidence of RCA and VT requiring ICD therapy (OR, 1.02; 95% CI, 0.99–1.05; P=0.146 and OR, 0.85; 95% CI, 0.34–2.13; P=0.728; respectively). All cause mortality was 20 (10.7%). Inappropriate therapy was given as shocks to 41 patients (21.9%) and as antitachycardia pacing (ATP) to 30 (16%), opposing with appropriately given therapy to 43 (23%) and 63 (33.7%) patients, respectively (see Figure), contributing to a net clinical benefit (NCB) of 18.8%, favouring ICD implantation. Conclusion In this contemporaneous real-world population of symptomatic idiopathic HFrEF patients, episodes of impending cardiac death were frequent. Prophylactic ICD implantation seems to have added further benefit reducing SCD on top of optimal medical therapy, LVEF improvement and coexisting CRT. Funding Acknowledgement Type of funding source: None

Long-Term Outcome of the Randomized DAPA Trial.

The randomized DAPA trial (Defibrillator After Primary Angioplasty) aimed to evaluate the survival benefit of prophylactic implantable cardioverter defibrillator (ICD) implantation in early selected high-risk patients after primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction. A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk patients with primary percutaneous coronary intervention, based on one of the following factors: left ventricular ejection fraction <30% within 4 days after ST-segment-elevation myocardial infarction, primary ventricular fibrillation, Killip class ≥2 or TIMI (Thrombolysis in Myocardial Infarction) flow <3 after percutaneous coronary intervention. ICD was implanted 30 to 60 days after MI. Primary end point was all-cause mortality at 3 years follow-up. The trial prematurely ended after inclusion of 266 patients (38% of the calculated sample size). Additional survival assessment was performed in February 2019 for the primary end point. A total of 266 patients, 78.2% males, with a mean age of 60.8±11.3 years, were enrolled. One hundred thirty-one patients were randomized to the ICD arm and 135 patients to the control arm. All-cause mortality was significant lower in the ICD group (5% versus 13%, hazard ratio, 0.37 [95% CI, 0.15-0.95]) after 3 years follow-up. Appropriate ICD therapy occurred in 9 patients at 3 years follow-up (5 within the first 8 months after implantation). After a median long-term follow-up of 9 years (interquartile range, 3-11), total mortality (18% versus 38%; hazard ratio, 0.58 [95% CI, 0.37-0.91]), and cardiac mortality (hazard ratio, 0.52 [95% CI, 0.28-0.99]) was significant lower in the ICD group. Noncardiac death was not significantly different between groups. Left ventricular ejection fraction increased ≥10% in 46.5% of the patients during follow-up, and the extent of improvement was similar in both study groups. In this prematurely terminated and thus underpowered randomized trial, early prophylactic ICD implantation demonstrated lower total and cardiac mortality in patients with high-risk ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Registration: URL: https://www.trialregister.nl; Unique identifier: Trial NL74 (NTR105).