Primary Prophylactic Implantable Cardioverter Defibrillator Research Articles

A comparison of symptoms of anxiety and depression in patients with a primary and secondary prophylactic indication for an implantable cardioverter defibrillator. [Data from the ACQUIRE-ICD RCT

Abstract Introduction Indication for the implantable cardioverter defibrillator (ICD) is either primary or secondary prophylactic. Symptoms of anxiety and depression are known to be evident in patients with an ICD. However, research has not shown agreement in whether there is a difference in the degree of symptoms in these two indication groups. Purpose We investigated the association between anxiety and depression and indication for ICD from implantation and up to 24 months of follow-up. Methods Data was derived from a national randomized controlled trial the "Web-based healthcare innovation to advance the quality of life and care of patients with an implantable cardioverter defibrillator [ACQUIRE-ICD]" to perform a secondary analysis. A total of 478 patients with a first-time ICD were included and completed the Generalized Anxiety Disorder Assessment (GAD-7) and the Patient Health Questionnaire (PHQ-9) after ICD implantation and at 6, 12 and 24 months. Mixed effects regression models and estimated marginal means were used to analyze longitudinal data. Results Anxiety mean scores did not differ statistically between patients with a primary prophylactic ICD as compared to patients with a secondary prophylactic ICD. Most patients showed limited symptoms of anxiety. However, 9% reported values above the cut-off for clinical relevant anxiety. Depression mean scores were significantly higher at 24 months in patients with primary prophylactic ICD as compared to patients with a secondary prophylactic ICD (mean 4.15 vs. 3.05; p=0.014) but not statistically significant at other time points. Most patients showed limited levels of depression. However, 13.2% reported values above the cut-off for clinical relevant depression. Both anxiety and depression scores decreased over time from baseline in both groups. Conclusion Patients with a primary prophylactic ICD did not differ in symptoms of anxiety and had mostly the same level of depression as compared to patients with a secondary prophylactic ICD. However, at 24 months patients with a primary prophylactic ICD reported more symptoms of depression as compared to patients with a secondary prophylactic ICD.Table 1

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 μV and <60 μV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 μV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

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.

Long-term prognosis and prognostic factors after primary prophylactic implantable cardioverter-defibrillator therapy

BackgroundLittle is known regarding which patients with ischemic cardiomyopathy (ICM) should be considered for prophylactic therapies, such as an implantable cardioverter-defibrillator (ICD), in the primary percutaneous intervention era. The aim of this study was to investigate the influence of non-sustained ventricular tachycardia (NSVT) on major adverse cardiac events (MACE) in heart failure with reduced ejection fraction (HFrEF) patients. MethodsWe retrospectively analyzed patients of ICM and non-ICM who underwent ICD implantation at our institute from October 2006 to August 2020. MACE were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. ResultsA total of 167 patients were enrolled [male, 138 (83 %); age, 62.1 ± 11.7 years; left ventricular ejection fraction, 23.5 ± 6.1 %; left ventricular diastolic diameter, 67.4 ± 9.0 mm; atrial fibrillation, 47 (28 %); NSVT, 124 (74 %); use of class III antiarrhythmic drugs, 55 (33 %); ischemic cardiomyopathy, 56 (34 %); cardiac resynchronization therapy, 73 (44 %)]. The median follow-up duration was 61 months. MACE occurred with 71 patients (43 %). When comparing baseline characteristics of the patients, left ventricular ejection fraction (p = 0.02) and atrial fibrillation (p = 0.04) were significantly associated with MACE. The multivariable Cox analysis for the target variable MACE identified atrial fibrillation (hazard ratio 2.00; 95 % confidence index 1.18–3.37; p = 0.01) as an independent predictor for MACE. ConclusionsPrior NSVT before ICD implantation was not an independent predictor of future MACE in patients with HFrEF with primary prophylactic ICD. In contrast, atrial fibrillation was associated with worse prognosis. To predict the prognosis of patients with primary prophylactic ICD, these factors should be assessed as comprehensive risk stratification factors for MACE.

QRS complex and T wave planarity for the efficacy prediction of automatic implantable defibrillators

ObjectiveTo test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks.MethodsDigital...

Impact of late gadolinium-enhanced cardiac MRI on arrhythmic and mortality outcomes in nonischemic dilated cardiomyopathy: updated systematic review and meta-analysis

Risk stratification based mainly on the impairment of left ventricular ejection fraction has limited performance in patients with nonischemic dilated cardiomyopathy (NIDCM). Evidence is rapidly growing for the impact of myocardial scar identified by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) on cardiovascular events. We aim to assess the prognostic value of LGE on long-term arrhythmic and mortality outcomes in patients with NIDCM. PubMed, Scopus, and Cochrane databases were searched from inception to January 21, 2022. Studies that included disease-specific subpopulations of NIDCM were excluded. Data were independently extracted and combined via random-effects meta-analysis using a generic inverse-variance strategy. Data from 60 studies comprising 15,217 patients were analyzed with a 3-year median follow-up. The presence of LGE was associated with major ventricular arrhythmic events (pooled OR: 3.99; 95% CI 3.08, 5.16), all-cause mortality (pooled OR: 2.14; 95% CI 1.81, 2.52), cardiovascular mortality (pooled OR 2.83; 95% CI 2.23, 3.60), and heart failure hospitalization (pooled OR: 2.53; 95% CI 1.78, 3.59). Real-world evidence suggests that the presence of LGE on CMR was a strong predictor of adverse long-term outcomes in patients with NIDCM. Scar assessment should be incorporated as a primary determinant in the patient selection criteria for primary prophylactic implantable cardioverter-defibrillator placement.

Reduced inferior wall longitudinal strain is associated with malignant arrhythmias in non-ischemic heart failure.

Reduced systolic myocardial function in the inferior region of the left ventricle has been suggested to be associated with malignant arrhythmias. We tested this hypothesis in patients with non-ischemic heart failure. Patients with non-ischemic heart failure (left ventricular ejection fraction [LVEF]<35%) were evaluated by 2D-speckle-tracking echocardiography. The regional longitudinal strain was calculated for each of the six left ventricular walls. The reduced regional function was defined as strain below the median. The outcome was a composite of sudden cardiac death, admission with sustained ventricular arrhythmia, resuscitated cardiac arrest, and appropriate therapy from a primary prophylactic implantable cardioverter defibrillator. Time-to-first-event analysis was performed using a Cox model. From two centers, 401 patients were included (median age: 63 years, 72% male) with a median LVEF of 25% (interquartile range [IQR] 20;30), and a median inferior wall strain of -9.0% (-12.5; -5.4). During a median follow-up of 4.0 years, 52 outcomes occurred. After multivariate adjustment for clinical and electrocardiographic parameters, inferior wall strain was independently associated with the outcome (HR 2.50 [1.35; 4.62], p=.003). No independent association was found between the composite outcome and reduced strain in any of the other left ventricular walls, Global Longitudinal Strain (HR 1.66 [0.93; 2.98], p=.09), or LVEF (HR 1.33 [0.75; 2.33], p=.33). Below median strain in the left ventricular inferior region was independently associated with a 2.5-fold increase in the risk of malignant arrhythmias and sudden cardiac death in patients with non-ischemic heart failure.

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.

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.

Coronary artery disease is a stronger predictor of mortality than left ventricular ejection fraction among newly diagnosed patients with heart failure

Abstract Background Heart failure (HF) prevalence remains high and prognosis is poor despite improvements in both medical treatment and implantation of primary prophylactic implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices. At present, classification of HF and treatment algorithms are determined by the left ventricular ejection fraction (LVEF). However, in patients with LVEF &amp;lt;50% and newly diagnosed HF, evidence remains sparse as to whether LVEF per se or presence of CAD provide independent prognostic information on mortality. Methods Using the Western Denmark Heart Registry, we identified newly diagnosed patients with HF and LVEF 10–49% undergoing first-time coronary angiography (CAG) from 2003 to 2016 referred due to HF. Patients were stratified by LVEF (10–35% vs. 36–49%, according as to whether primary prophylactic ICD and CRT treatment should be considered) and presence of coronary artery disease (CAD). Maximum follow-up was 10 years. We estimated 10-year cumulative incidence of death and calculated hazard ratios (HR) adjusted for relevant comorbidities and risk factors. Results Of 154,186 Western Danish residents undergoing CAG, 3,620 patients had HF and LVEF 10–49%. Among these, 2,780 (77%) patients had LVEF 10–35% and 840 (23%) patients had LVEF 36–49%. CAD was present in 1,592 (44%) patients. There was a potential association in 10-year mortality when comparing patients with HF and LVEF 36–49% to those with LVEF 10–35% (37.3% vs. 42.1%, HR 1.15; 95% CI 0.99–1.34) (Figure 1A), with point estimates of mortality ranging from being 1% reduced to 24% increased. This result was not strongly influenced by the presence of CAD (HR 1.11; 95% CI 0.91–1.35) or absence of CAD (HR 1.24; 95% CI 0.97–1.57) (Figure 1B). There was no trend between LVEF categorized by 5-percentiles and mortality (p for trend = 0.24) (Table 1). In contrast, CAD was more strongly associated with increased 10-year mortality (55.0% vs. 31.5%, HR 1.43; 95% CI 1.25–1.64) irrespective of LVEF (Figure 1B). Conclusion Among newly diagnosed patients with HF and LVEF 10–49%, presence of CAD impacts mortality substantially more than LVEF per se. These results emphasize that assessment of CAD is pivotal for prognostication of newly diagnosed patients with HF and LVEF 10–49%. Funding Acknowledgement Type of funding sources: None.

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.

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.

Nocturnal respiratory rate predicts ICD benefit: A prospective, controlled, multicentre cohort study

BackgroundImplantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations.MethodsThis prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419).FindingsOf the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376–0.746); p = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669–1.438); p = 0.9202).InterpretationIn the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially.FundingEuropean Community's 7th Framework Programme FP7/2007-2013 (602299)

Prevalence and prognostic association of ventricular arrhythmia in non-ischaemic heart failure patients: results from the DANISH trial.

Improved risk stratification to identify non-ischaemic heart failure patients who will benefit from primary prophylactic implantable cardioverter-defibrillator (ICD) is needed. We examined the potential of ventricular arrhythmia to identify patients who could benefit from an ICD. A total of 850 non-ischaemic systolic heart failure patients with left ventricle ≤35% and elevated N-terminal pro-brain natriuretic peptides had a 24-h Holter monitor recording performed. We examined present non-sustained ventricular tachycardia (NSVT), defined as ≥3 consecutive premature ventricular contractions (PVCs) with a rate of ≥100/min, and number of PVCs per hour stratified into low (<30) and high burden (≥30) groups. Outcome measures were overall mortality, sudden cardiac death (SCD), and cardiovascular death (CVD). In total, 193 patients died, 49 from SCD and 125 from CVD. Non-sustained ventricular tachycardia (365 patients) was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.47; 95% confidence interval (CI) 1.07-2.03; P = 0.02] and to CVD (HR 1.89; CI 1.25-2.87; P = 0.003). High burden PVC (352 patients) was associated with increased all-cause mortality (HR1.38; CI 1.00-1.90; P = 0.046) and with CVD (HR 1.78; CI 1.19-2.66; P = 0.005). There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation. Ventricular arrhythmia in non-ischaemic heart failure patients was associated with a worse prognosis but could not be used to stratify patients to ICD implantation.

Short‐Term Variability of the QT Interval Can be Used for the Prediction of Imminent Ventricular Arrhythmias in Patients With Primary Prophylactic Implantable Cardioverter Defibrillators

BackgroundShort‐term variability of the QT interval (STVQT) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STVQT can predict imminent ventricular arrhythmias in patients.Methods and ResultsIn 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24‐hour ECG Holter recordings were obtained as part of the EU‐CERT‐ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study. ECG Holter recordings showing ventricular arrhythmias of >4 consecutive complexes were selected for the arrhythmic groups (n=170), whereas a control group was randomly selected from the remaining Holter recordings (n=37). STVQT was determined from 31 beats with fiducial segment averaging and calculated as ∑Dn+1‐Dn/30×2, where Dn represents the QT interval. STVQT was determined before the ventricular arrhythmia or 8:00 am in the control group and between 1:30 and 4:30 am as baseline. STVQT at baseline was 0.84±0.47 ms and increased to 1.18±0.74 ms (P<0.05) before the ventricular arrhythmia, whereas the STVQT in the control group remained unchanged. The arrhythmic patients were divided into three groups based on the severity of the arrhythmia: (1) nonsustained ventricular arrhythmia (n=32), (2) nonsustained ventricular tachycardia (n=134), (3) sustained ventricular tachycardia (n=4). STVQT increased before nonsustained ventricular arrhythmia, nonsustained ventricular tachycardia, and sustained ventricular tachycardia from 0.80±0.43 ms to 1.18±0.78 ms (P<0.05), from 0.90±0.49 ms to 1.14±0.70 ms (P<0.05), and from 1.05±0.22 ms to 2.33±1.25 ms (P<0.05). This rise in STVQT was significantly higher in sustained ventricular tachycardia compared with nonsustained ventricular arrhythmia (+1.28±1.05 ms versus +0.24±0.57 ms [P<0.05]) and compared with nonsustained ventricular arrhythmia (+0.34±0.87 ms [P<0.05]).ConclusionsSTVQT increases before imminent ventricular arrhythmias in patients, and the extent of the increase is associated with the severity of the ventricular arrhythmia.

Mortality after implantable cardioverter defibrillators in dialysis patients: a nationwide study

Abstract Background Although randomized clinical trials have shown that implantable cardioverter defibrillators (ICDs) reduce mortality in selected patients, patients on dialysis are excluded from these trials. Thus, data on mortality risk after ICD implantation in these patients are sparse. Purpose To examine all-cause mortality in patients receiving an ICD according to dialysis status and to identify factors associated with all-cause mortality in patients on dialysis. Methods Using Danish nationwide registries from 2000–2017, all patients ≥18 years old undergoing first-time ICD implantation were included. Patients on dialysis were identified prior to ICD implantation and followed for up to five years. The cumulative incidence of all-cause mortality according to dialysis status was assessed. Factors associated with all-cause mortality after ICD implantation in dialysis patients were examined using multivariable Cox proportional hazard regression. Results A total of 14,681 ICD patients were identified, of which 218 (1.5%) were on dialysis prior to ICD implantation. Compared with ICD patients not on dialysis, those on dialysis were younger (median age 64 years [IQR: 58–70] vs. 66 years [IQR: 57–72], p=0.02), more likely to receive an ICD for secondary prophylaxis (69.7% vs 53.7%), and had more comorbidities including ischaemic heart disease (60.6% vs. 46.3%), diabetes (28.4% vs. 20.4%), and peripheral vascular disease (10.1% vs. 5.6%) (p for all &amp;lt;0.05). The median time to death among ICD patients on dialysis and not on dialysis were 1.3 years (IQR: 0.4–2.8 years] and 2.2 years [IQR: 1.0–3.5 years], respectively. One-year mortality among ICD patients on dialysis (13.0%) was significantly higher compared with ICD patients not on dialysis (4.7%), p&amp;lt;0.001 (Figure). Five-year mortality was significantly higher in ICD patients on dialysis than those not on dialysis (42.2% vs 23.6%), p&amp;lt;0.001 (Figure). Factors associated with increased risk of all-cause mortality among ICD patients on dialysis were age ≥65 years at time of implantation (reference: age &amp;lt;65 years) (HR 1.90 [95% CI: 1.13–3.19]), primary prophylactic ICD (HR 1.81 [95% CI 1.08–3.05]), and diabetes (HR 1.87 [95% CI 1.14–3.07]). Sex, ischaemic heart disease, heart failure, stroke, chronic obstructive pulmonary disease, and malignancy were not associated with the risk of mortality (p&amp;gt;0.05 for all). Cardiovascular causes of death were common both in patients with- and without dialysis, 69.6% and 60.0%, respectively. Conclusion Five-year mortality in ICD patients on dialysis was 42% and twice as high compared with ICD patients not on dialysis. Age ≥65 years, primary prophylactic indication, and diabetes were factors associated with increased mortality. Careful evaluation of the potential benefit from an ICD implantation in dialysis patients is important considering the overall high mortality rates. Funding Acknowledgement Type of funding source: None

P1463Regional variation in survival rates among primary prevention implantable cardioverter-defibrillator recipients in Eastern and Northern Europe POLKARD Polish ICD Registry perspective

Abstract Funding Acknowledgements None. OnBehalf POLKARD Polish ICD Registry Objective The findings of Danish Study to assess the efficiency of ICD in patients with non ischemic heart failure has recently raised questions about the current strategy of ICD implantation for the primary prevention of sudden cardiac death. POLKARD - Polish ICD Registry is a prospective, non-randomised, central registry of patients who are referred for an implantation of an ICD in Poland. The Registry contains prospectively collected follow-up data including mortality. Purpose To compare survival rates between Polish and Danish ‘real-world’ non-ischemic primary prevention cohorts. Methods Retrospective analysis of clinical characteristics and long-term follow-up of patients referred for primary prophylactic implantable cardioverter defibrillator (ICD) implantation in Poland between April 2008 and November 2014 was performed. The primary outcome of the trial was all-cause mortality. Results: The polish study cohort was large (964) as compared to Danish population randomized to receive ICD therapy (556). The median follow-up time in DANISH Study and Polish ICD Registry was 67,6 and 77 months, respectively. Compared with patients enrolled in the DANISH Study, patients in the Polish ICD Registry were age-similar. However, the polish study population was male-dominated. What is more, male gender was identified as a risk factor for long-term mortality in polish study population (p = 0.005). In the matched cohorts, there was difference in survival between DANISH Study and Polish ICD Registry patients (all-cause mortality rates: 21,6% - 44 events per 1000 person-years and 39,3% - 72 events per 1000 person-years, respectively). Conclusions Our findings imply that survival among patients who receive a primary prevention ICD for non-ischemic cardiomyopathy in clinical practice in Central Europe is different from Northern Europe.

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study.

AimsThe EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy.Methods and resultsWe recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class <III, and chronic obstructive pulmonary disease. Adjusted mortality associated with ICD vs. control was 27% lower (HR 0.731, 95% CI 0.569–0.938, P = 0.0140). Subgroup analyses indicated no ICD benefit in diabetics (adjusted HR = 0.945, P = 0.7797, P for interaction = 0.0887) or those aged ≥75 years (adjusted HR 1.063, P = 0.8206, P for interaction = 0.0902).ConclusionIn contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics.

Electrocardiogram as a predictor of survival without appropriate shocks in primary prophylactic ICD patients: A retrospective multi-center study

BackgroundAbnormal 12-lead electrocardiogram (ECG) can predict cardiovascular events, including sudden cardiac death. We tested the hypothesis that ECG provides useful information on guiding implantable cardioverter defibrillator (ICD) therapy into individuals with impaired left ventricular ejection fraction (LVEF). MethodsRetrospective data of primary prevention ICD implantations from 14 European centers were gathered. The registry included 5111 subjects of whom 1687 patients had an interpretable pre-implantation ECG available (80.0% male, 63.3 ± 11.4 years). Primary outcome was survival without appropriate ICD shocks or heart transplantation. A low-risk ECG was defined as a combination of ECG variables that were associated with the primary outcome. ResultsA total of 1224 (72.6%) patients survived the follow-up (2.9 ± 1.7 years) without an ICD shock, 224 (13.3%) received an appropriate shock and 260 (15.4%) died. Low-risk ECG defined as QRS duration <120 ms, QTc interval <450 ms for men and <470 ms for women, and sinus rhythm, were met by 515 patients (30.5%). Multivariable Cox regression showed that the hazard (HR) for death, heart transplantation or appropriate shock were reduced by 42.5% in the low-risk group (HR 0.575; 95% CI 0.45–0.74; p < 0.001), compared to the high-risk group. The HR for the first appropriate shock was 42.1% lower (HR 0.58; 95% CI 0.41–0.82; p = 0.002) and the HR for death was 48.0% lower (HR 0.52; 95% CI 0.386–0.72; p < 0.001) in the low-risk group. ConclusionSinus rhythm, QRS <120 ms and normal QTc in standard 12-lead ECG provides information about survival without appropriate ICD shocks and might improve patient selection for primary prevention ICD therapy.

P1428 Mortality in non-ischemic cardiomyopathy is low and close to the general population

Abstract Funding Acknowledgements South Eastern Norway regional health authority Background Patients with non-ischemic dilated cardiomyopathy (NDCM) have lower mortality compared to patients with ischemic cardiomyopathy (ICM). Recent reports suggest less benefit of a primary prophylactic implantable cardioverter defibrillator (ICD) in NDCM. Purpose We aimed to investigate mortality rate and appropriate ICD therapy in a consecutive cohort of patients with NDCM and ICM. Methods In this prospective multi-center study, we consecutively included NDCM and ICM patients with left ventricular ejection fraction (LVEF) &amp;lt; 40% from July 2014 to January 2018. ICM or NDCM classification was based on coronary angiography. Echocardiography was performed at inclusion and LVEF and global longitudinal strain (GLS) were assessed. All-cause mortality and primary prevention ICD therapies were recorded during follow-up. Results We included 290 patients (67 ± 13 years old, 74% males), 207 with ICM and 83 with NDCM. At inclusion LVEF was 31 ± 6% and GLS -10.5 ± -3.3%. Patients with ICM were older (68 ± 12 years vs. 63 ± 15 years, p &amp;lt; 0.01), had better LVEF (32 ± 6% vs. 28 ± 7%, p &amp;lt; 0.01), and shorter QRS duration (106 ± 23 ms vs. 122 ± 28 ms, p &amp;lt; 0.01). A primary prevention ICD was implanted in 18 (9%) ICM patients and in 21 (25%) NDCM patients (p &amp;lt; 0.001). During 22 ±12 months follow up, all-cause mortality was 27 (9%) in the entire population. In patients with ICM 1/18 (6%) received appropriate shock from their primary prevention ICD compared to 3/21 (14%) NDCM patients. Mortality was more frequent in ICM; 26/207 (13%) compared to 1/83 (1.2%) in NDCM (Log rank p &amp;lt; 0.01). All-cause mortality or appropriate ICD shock was more frequent in ICM compared to NDCM (27 (13%) vs. 4 (5%) log rank p = 0.02) (Figure). Assuming the arrhythmias treated by the ICD shocks would have been lethal, annual mortality of 2.5% in the NDCM population was only slightly higher compared to the age matched general population (1% annual mortality) (blue line). Conclusion Patients with NDCM had better survival, and in general a lower event rate, compared to patients with ICM. However, subgroups of NDCM patients may benefit from their primary prophylactic ICD and further studies should investigate the need of primary prevention ICD in patients with NDCM. Abstract P1428 Figure.