Effect of implantable cardioverter-defibrillator in non-ischemic heart failure according to background medical therapy: Extended follow-up of the DANISH trial.

BACKGROUND: The Heart Failure Collaboratory (HFC) score integrates types and doses of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to modified HFC (mHFC) score in 1,116 patients with non-ischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic HF on Mortality (DANISH). METHODS AND RESULTS: Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (0: no use; 1: <50% of maximum dose; 2: ≥50% of maximum dose). The maximum score was 6, corresponding to ≥50% of maximum dose for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with mHFC score=3-4, mHFC score=1-2 was associated with a higher rate of all-cause death (mHFC=1-2: adjusted HR 1.67 [95%CI,1.23-2.28]; mHFC=3-4, reference; mHFC=5-6: adjusted HR 1.07 [95%CI,0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95%CI,0.74-1.08]) regardless of mHFC score (mHFC=1-2: HR 0.98 [95%CI,0.56-1.71]; mHFC=3-4: HR 0.89 [95%CI,0.66-1.20]; mHFC=5-6: HR 0.85 [95%CI,0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95%CI,0.70-1.09]) regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). CONCLUSIONS: Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with non-ischemic HFrEF regardless of mHFC score.

New York Heart Association functional class and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: Extended follow-up of the DANISH trial.

AIMS: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of ≤35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. METHODS AND RESULTS: The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; pinteraction = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; pinteraction = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; pinteraction = 0.39). CONCLUSIONS: In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00542945.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

BACKGROUND: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. RESULTS: A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. CONCLUSIONS: In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

Estimated Glomerular Filtration Rate and Implantable Cardioverter-Defibrillator in Nonischemic Systolic Heart Failure: Extended Follow-Up of DANISH.

BACKGROUND: Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter-defibrillators (ICDs). We examined the long-term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). METHODS AND RESULTS: In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m2) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all-cause mortality (no CKD, HR, 0.82 [95% CI, 0.64-1.04]; CKD, HR, 1.02 [95% CI, 0.75-1.38]; Pinteraction=0.31) or cardiovascular death (no CKD, HR, 0.77 [95% CI, 0.58-1.03]; CKD, HR, 1.05 [95% CI, 0.73-1.51]; Pinteraction=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 [95% CI, 0.32-1.00]; CKD, HR, 0.65 [95% CI, 0.34-1.24]; Pinteraction=0.70). CONCLUSIONS: ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

Association between QRS shortening and mortality after cardiac resynchronization therapy: Results from the DANISH study.

BACKGROUND: Changes in QRS duration (∆QRS) are often used in the clinical setting to evaluate the effect of cardiac resynchronization therapy (CRT), although an association between ∆QRS and outcomes is not firmly established. We aimed to assess the association between mortality and ∆QRS after CRT in patients from the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) study. METHODS: We included all patients from DANISH who received a CRT device and had available QRS duration data before and after implantation. Cox proportional hazards models were used to assess associations between ∆QRS (post-CRT QRS minus pre-CRT QRS) and mortality. RESULTS: Complete data were available in 572 patients. Median baseline QRS duration was 160 ms (IQR [146;180]). Post-CRT QRS was recorded a median of 48 days (IQR [33;86]) after implantation, and the median ∆QRS was -14 ms (IQR [-38;-3]). During a median follow-up of 4.1 years (IQR [2.5;5.8]), 106 patients died. In crude Cox regression, all-cause mortality was reduced by 6% per 10 ms shortening of QRS (HR 0.94; CI: 0.88-1.00, p = 0.04). The effect did not remain significant after multivariable adjustment (HR 1.01, CI: 0.93-1.10, p = 0.77). Further, no association was found between ∆QRS and improvement of New York Heart Association functional class at 6 months (OR 1.03, CI: 0.96-1.10, p = 0.42). CONCLUSION: In a large cohort of patients with non-ischemic cardiomyopathy, reduction of QRS duration after CRT was not associated with changes in mortality during long-term follow-up.

Ten-year trends in incidence and prevalence of atrial fibrillation and flutter in Denmark according to demographics, ethnicity, educational level, and area of residence (2009-2018).

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia and a major global health burden. Updated trends in the epidemiology of atrial fibrillation or flutter (AF) are needed. METHODS: Using the Danish Heart Statistics, we investigated nationwide trends 2009-2018 in incidence rate and prevalence of AF according to age as well as age-standardized incidence rate (ASIR) and prevalence (ASP) of AF according to sex, ethnicity, educational level, and area of residence. Comparing year 2018 to 2009, we calculated stratum-specific ASIR ratios (ASIRR) and changes in ASP. RESULTS: During 2009-2015 the ASIR for AF increased for both men and women, followed by a decline from 2015-2018. Overall, this resulted in a 9% increase among men (ASIRR: 1.09, 95% CI: 1.06-1.12), but no change among women (ASIRR: 1.00, 95% CI: 0.97-1.04). The ASP increased by 29% among men and 26% among women. An increase in ASIR was observed in all ethnic groups except men of Far Eastern ethnicity. Lower educational level was associated with greater increases in both ASIR and ASP. ASIR and ASP differed slightly between the Danish regions but increased in all of them. CONCLUSIONS: During 2009-2018 the incidence and prevalence of AF in Denmark increased although the increase in incidence was transient among women. Factors associated with higher incidence were male sex, higher age, Danish and Western ethnicity as well as Middle Eastern/North African ethnicity among women, and lower educational level. Within Denmark, we observed only minor regional differences in AF incidence and prevalence.

A web-based intervention for patients with an implantable cardioverter defibrillator - A qualitative study of nurses' experiences (Data from the ACQUIRE-ICD study).

Objective: The aim of this study was to explore cardiac nurses' experiences with a comprehensive web-based intervention for patients with an implantable cardioverter defibrillator. Methods: We conducted an explorative qualitative study based on individual semi-structured interviews with 9 cardiac nurses from 5 Danish university hospitals. Results: We found one overall theme: "Between traditional nursing and modern eHealth". This theme was derived from the following six categories: (1) comprehensive content in the intervention, (2) patient-related differences in engagement, (3) following the protocol is a balancing act, (4) online communication challenges patient contact, (5) professional collaboration varies, and (6) an intervention with potential. Cardiac nurses were positive towards the web-based intervention and believe it holds a large potential. However, they felt challenged by not having in-person and face-to-face contact with patients, which they found valuable for assessing patients' wellbeing and psychological distress. Conclusion: Specific training in eHealth communication seems necessary as web-based care entails a shift in the nursing role and requires a different way of communication.InnovationFocusing on the user experience in web-based care from the perspective of cardiac nurses is innovative, and by applying implementation science this leads to new knowledge to consider when developing and implementing web-based care.

Conduction System Pacing Versus Conventional Cardiac Resynchronization Therapy in Congenital Heart Disease.

BACKGROUND: Dyssynchrony-associated left ventricular systolic dysfunction is a major contributor to heart failure in congenital heart disease (CHD). Although conventional cardiac resynchronization therapy (CRT) has shown benefit, the comparative efficacy of cardiac conduction system pacing (CSP) is unknown. OBJECTIVES: The purpose of this study was compare the clinical outcomes of CSP vs conventional CRT in CHD with biventricular, systemic left ventricular anatomy. METHODS: Retrospective CSP data from 7 centers were compared with propensity score-matched conventional CRT control subjects. Outcomes were lead performance, change in left ventricular ejection fraction (LVEF), and QRS duration at 12 months. RESULTS: A total of 65 CSP cases were identified (mean age 37 ± 21 years, 46% men). The most common CHDs were tetralogy of Fallot (n = 12 [19%]) and ventricular septal defect (n = 12 [19%]). CSP was achieved after a mean of 2.5 ± 1.6 attempts per procedure (38 patients with left bundle branch pacing, 17 with HBP, 10 with left ventricular septal myocardial). Left bundle branch area pacing [LBBAP] vs HBP was associated with a smaller increase in pacing threshold (Δ pacing threshold 0.2 V vs 0.8 V; P = 0.05) and similar sensing parameters at follow-up. For 25 CSP cases and control subjects with baseline left ventricular systolic dysfunction, improvement in LVEF was non-inferior (Δ LVEF 9.0% vs 6.0%; P = 0.30; 95% confidence limits: -2.9% to 10.0%) and narrowing of QRS duration was more pronounced for CSP (Δ QRS duration 35 ms vs 14 ms; P = 0.04). Complications were similar (3 [12%] CSP, 4 [16%] conventional CRT; P = 1.00). CONCLUSIONS: CSP can be reliably achieved in biventricular, systemic left ventricular CHD patients with similar improvement in LVEF and greater QRS narrowing for CSP vs conventional CRT at 1 year. Among CSP patients, pacing electrical parameters were superior for LBBAP vs HBP.

Antithrombotic treatment beyond 1 year after percutaneous coronary intervention in patients with atrial fibrillation.

AIMS: Beyond 1 year after percutaneous coronary intervention (PCI), guidelines recommend anticoagulant monotherapy in patients with atrial fibrillation (AF) rather than dual therapy with an anticoagulant and an antiplatelet drug. The risks and benefits of this strategy, however, remain uncertain. We examined hospitalization for bleeding and ischaemic risk beyond 1 year after PCI in patients with AF treated with monotherapy vs. dual therapy. Furthermore, among patients treated with monotherapy, we compared direct oral anticoagulant (DOAC) therapy and vitamin K antagonist (VKA) therapy. METHODS AND RESULTS: We included all patients with AF undergoing first-time PCI between 2003 and 2017 from the Western Denmark Heart Registry and followed them for up to 4 years. Follow-up started 15 months after PCI to enable assessment of medical treatment after 12 months. Using a Cox regression model, we computed weighted hazard ratios (HRw) of hospitalization for bleeding and major adverse cardiac events (MACEs). Analyses comparing monotherapy vs. dual therapy included 3331 patients, and analyses comparing DOAC vs. VKA monotherapy included 1275 patients. Risks of hospitalization for bleeding [HRw 0.90, 95% confidence interval (CI) 0.75-1.09] and MACE (HRw 1.04, 95% CI 0.90-1.19) were similar with monotherapy and dual therapy. Similarly, risks of hospitalization for bleeding (HRw 1.27, 95% CI 0.84-1.92) and MACE (HRw 1.15, 95% CI 0.87-1.50) were equal with DOAC and VKA monotherapy. CONCLUSION: Our results support long-term OAC monotherapy beyond 1 year after PCI in patients with atrial fibrillation and suggest that DOAC monotherapy is as safe and effective as VKA monotherapy.

Data standards for atrial fibrillation/flutter and catheter ablation: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation. METHODS AND RESULTS: We used the EuroHeart methodology for the development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach a consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data. CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs, and post-marketing surveillance of devices and pharmacotherapies.

Cardiac Resynchronization Therapy for Adult Patients With a Failing Systemic Right Ventricle: A Multicenter Study.

Background The objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality. Methods and Results This retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.9% women) with a mean age of 45±14 (range, 18-77) years at initiation of CRT. Median follow-up time was 4.1 (25th-75th percentile, 1.3-8.3) years. Underlying congenital heart disease consisted of congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries in 63 (78.8%) and 17 (21.3%) patients, respectively. CRT resulted in significant improvement in functional class (before CRT: III, 25th-75th percentile, II-III; after CRT: II, 25th-75th percentile, II-III; P=0.005) and QRS duration (before CRT: 176±27; after CRT: 150±24 milliseconds; P=0.003) in patients with pre-CRT ventricular pacing who underwent an upgrade to a CRT device (n=49). These improvements persisted during long-term follow-up with a marginal but significant increase in SRV function (before CRT; 30%, 25th-75th percentile, 25-35; after CRT: 31%, 25th-75th percentile, 21-38; P=0.049). In contrast, no beneficial change in the above-mentioned variables was observed in patients who underwent de novo CRT (n=31). A quarter of all patients were readmitted for heart failure during follow-up, and mortality at latest follow-up was 21.3%. Conclusions This international experience with CRT in patients with an SRV demonstrated that CRT in selected patients with SRV dysfunction and pacing-induced dyssynchrony yielded consistent improvement in QRS duration and New York Heart Association functional status, with a marginal increase in SRV function.

Efficacy of Implantable Cardioverter Defibrillator in Nonischemic Systolic Heart Failure According to Sex: Extended Follow-Up Study of the DANISH Trial.

BACKGROUND: Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex. METHODS: In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality. RESULTS: Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47-0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46-0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42-0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40-1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69-1.06]; women, HR, 0.98 [95% CI, 0.64-1.50]; Pinteraction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36-0.92]; women, HR, 0.68 [95% CI, 0.26-1.77]; Pinteraction=0.76). CONCLUSIONS: In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00542945.

Anxiety and depression as risk factors for ICD shocks and mortality in patients with an implantable cardioverter defibrillator - A systematic review.

OBJECTIVE: To examine associations between baseline anxiety and depression and occurrence of ICD shocks and risk of mortality in patients with an implantable cardioverter defibrillator (ICD). METHOD: We systematically searched EMBASE, PubMed, PsycINFO, and CINAHL for eligible studies fulfilling the predefined criteria. RESULTS: We included 37 studies based on 25 different cohorts following 35,003 participants for up to seven years. We observed no association between baseline anxiety nor depression and the occurrence of ICD shocks. More than half of the identified studies (respectively 56% and 60%) indicated a significant association between baseline anxiety or depression and increased risk of mortality (anxiety: n = 5, ranging from Hazard ratios (HR):1.02 [Confidence intervals (CI) 95% 1.00-1.03] to HR:3.45 [CI 95% 1.57-7.60]; depression: n = 6, ranging from HR:1.03 [CI 95% 1.00-1.06] to HR:2.10 [CI 95% 1.44-3.05]). We found a significant association between high methodological quality of the primary study and the detection of a significant association (p < 0.01). CONCLUSIONS: Baseline anxiety and depression are associated with increased risk of mortality in patients with an ICD, but not with occurrence of ICD shocks. Inclusion of baseline anxiety and depression in risk stratification of mortality may be warranted.

NT-proBNP and ICD in Nonischemic Systolic Heart Failure: Extended Follow-Up of the DANISH Trial.

OBJECTIVES: In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. BACKGROUND: In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation. METHODS: In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause. RESULTS: All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (Pinteraction = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (Pinteraction = 0.20 and 0.08 for CV death and SCD, respectively). CONCLUSIONS: Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945).

Effect of implantable cardioverter-defibrillators in patients with non-ischaemic systolic heart failure and concurrent coronary atherosclerosis.

AIMS: Prophylactic implantable cardioverter-defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non-ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non-ischaemic HF and the effect of ICD implantation in these patients. METHODS AND RESULTS: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N-terminal pro-brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61-73] vs. 61 [IQR 54-68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow-up of 64.3 months (IQR 47-82), 174 (21%) of the patients died. The effect of ICD on all-cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58-1.52; P = 0.79 vs. HR 0.82; 0.56-1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all-cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04-1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76-1.45, P = 0.76). CONCLUSIONS: In patients with non-ischaemic systolic heart failure, ICD implantation did not reduce all-cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors.

Condition Monitoring of Railway Crossing Geometry via Measured and Simulated Track Responses.

This paper presents methods for continuous condition monitoring of railway switches and crossings (S&C, turnout) via sleeper-mounted accelerometers at the crossing transition. The methods are developed from concurrently measured sleeper accelerations and scanned crossing geometries from six in situ crossing panels. These measurements combined with a multi-body simulation (MBS) model with a structural track model and implemented scanned crossing geometries are used to derive the link between the crossing geometry condition and the resulting track excitation. From this analysis, a crossing condition indicator Cλ1-λ2, Î³ is proposed. The indicator is defined as the root mean square (RMS) of a track response signal γ that has been band-passed between frequencies corresponding to track deformation wavelength bounds of λ1 and λ2 for the vehicle passing speed (f = v/ λ). In this way, the indicator ignores the quasi-static track response with wavelengths predominantly above λ1 and targets the dynamic track response caused by the kinematic wheel-crossing interaction governed by the crossing geometry. For the studied crossing panels, the indicator C1-0.2 m, Î³ (λ1=1 and λ2=0.2) was evaluated for γ = u, v, or a as in displacements, velocities, and accelerations, respectively. It is shown that this condition indicator has a strong correlation with vertical wheel-rail contact forces that is sustained for various track conditions. Further, model calibrations were performed to measured sleeper displacements for the six investigated crossing panels. The calibrated models show (1) a good agreement between measured and simulated sleeper displacements for the lower frequency quasi-static track response and (2) improved agreement for the dynamic track response at higher frequencies. The calibration also improved the agreement between measurements and simulation for the crossing condition indicator demonstrating the value of model calibration for condition monitoring purposes.

Long-Term Follow-Up of DANISH (The Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality).

BACKGROUND: DANISH (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators [ICDs] in Patients With Nonischemic Systolic Heart Failure on Mortality) found that primary-prevention ICD implantation was not associated with an overall survival benefit in patients with nonischemic systolic heart failure during a median follow-up of 5.6 years, although there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional 4 years of follow-up data from DANISH. METHODS: In DANISH, 556 patients with nonischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years). RESULTS: During a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (hazard ratio [HR] 0.89, [95% CI, 0.74-1.08]; P = 0.24). In patients ≤70 years (n = 829), all-cause mortality was lower in the ICD group than the control group (117/389 [30%] versus 158/440 [36%]; HR, 0.78 [95% CI, 0.61-0.99]; P = 0.04), whereas in patients >70 years (n = 287), all-cause mortality was not significantly different between the ICD and control group (91/167 [54%] versus 68/120 [57%]; HR, 0.92 [95% CI, 0.67-1.28]; P = 0.75). Cardiovascular death showed similar trends (overall, 147/556 [26%] versus 164/560 [29%]; HR, 0.87 [95% CI, 0.70-1.09]; P = 0.20; ≤70 years, 87/389 [22%] versus 122/440 [28%]; HR, 0.75 [95% CI, 0.57-0.98]; P = 0.04; >70 years, 60/167 [36%] versus 42/120 [35%]; HR, 0.97 [95% CI, 0.65-1.45]; P = 0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 [6%] versus 57/560 [10%]; HR, 0.60 [95% CI, 0.40-0.92]; P = 0.02) and in patients ≤70 years (19/389 [5%] versus 49/440 [11%]; HR, 0.42 [95% CI, 0.24-0.71]; P = 0.0008), but not in patients >70 years (16/167 [10%] versus 8/120 [7%]; HR, 1.34 [95% CI, 0.56-3.19]; P = 0.39). CONCLUSIONS: During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with nonischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.