Effect of Implantable Cardioverter-defibrillators in Nonischemic Heart Failure According to Background Medical Therapy: Extended Follow-up of the DANISH Trial.

BACKGROUND: The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic 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 dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3-4, an mHFC score of 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 nonischemic HFrEF, regardless of mHFC score.

Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.

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.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: Patients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. METHODS AND RESULTS: In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than -20%. The primary end point was all-cause mortality. The median RV-FWS was -18% (quartiles -23% to -14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). CONCLUSIONS: In patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.

Severity of Brugada syndrome disease manifestation and risk of new-onset depression or anxiety: a Danish nationwide study.

AIMS: Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. METHODS AND RESULTS: All Danish patients diagnosed with BrS (2006-2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46-8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42-13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. CONCLUSION: Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.

Long-term cardiovascular outcomes among immigrants and non-immigrants in cardiac resynchronization therapy: a nationwide study.

AIMS: To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. METHODS AND RESULTS: All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000-2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8-1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2-4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). CONCLUSION: No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Atrial fibrillation is a marker of increased mortality risk in nonischemic heart failure-Results from the DANISH trial.

BACKGROUND: Atrial fibrillation (AF) in heart failure (HF) patients has been associated with a worse outcome. Similarly, excessive supraventricular ectopic activity (ESVEA) has been linked to development of AF, stroke, and death. This study aimed to investigate AF and ESVEA's association with outcomes and effect of prophylactic implantable cardioverter defibrillator (ICD) implantation in nonischemic HF patients. METHODS: A total of 850 patients with nonischemic HF, left ventricle ejection fraction ≤35%, and elevated N-terminal pro-brain natriuretic peptides underwent 24 hours Holter recording. The presence of AF (≥30 seconds) and ESVEA (≥30 supraventricular ectopic complexes (SVEC) per hour or run of SVEC ≥20 beats) were registered. Outcomes were all-cause mortality, cardiovascular death (CVD), and sudden cardiac death (SCD). RESULTS: AF was identified in 188 patients (22%) and ESVEA in 84 patients (10%). After 4 years and 11 months of follow-up, a total of 193 patients (23%) had died. AF was associated with all-cause mortality (hazard ratio [HR] 1.44; confidence interval [CI] 1.04-1.99; P = .03) and CVD (HR 1.59; CI 1.07-2.36; P = .02). ESVEA was associated with all-cause mortality (HR 1.73; CI 1.16-2.57; P = .0073) and CVD (HR 1.76; CI 1.06-2.92; P = .03). Neither AF nor ESVEA was associated with SCD. ICD implantation was not associated with an improved prognosis for neither AF (P value for interaction = .17), nor ESVEA (P value for interaction = .68). CONCLUSIONS: Both AF and ESVEA were associated with worsened prognosis in nonischemic HF. However, ICD implantation was not associated with an improved prognosis for either group.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Anxiety and depression symptoms in Danish patients with an implantable cardioverter-defibrillator: prevalence and association with indication and sex up to 2 years of follow-up (data from the national DEFIB-WOMEN study).

AIMS: To investigate (i) the prevalence of anxiety and depression and (ii) the association between indication for implantable cardioverter-defibrillator (ICD) implantation and sex in relation to anxiety and depression up to 24 months' follow-up. METHODS AND RESULTS: Patients with a first-time ICD, participating in the national, multi-centre, prospective DEFIB-WOMEN study (n = 1496; 18% women) completed the Hospital Anxiety and Depression Scale at baseline, 3, 6, 12, and 24 months. Data were analysed using linear mixed modelling for longitudinal data. Patients with a secondary prophylactic indication (SPI) had higher mean anxiety scores than patients with a primary prophylactic indication (PPI) at baseline, 3, and 12 months and higher mean depression scores at all-time points, except at 24 months. Women had higher mean anxiety scores as compared to men at all-time points; however, only higher mean depression scores at baseline. Overall, women with SPI had higher anxiety and depression symptom scores than men with SPI. Symptoms decreased over time in both women and men. From baseline to follow-up, the prevalence of anxiety (score ≥8) was highest in patients with SPI (13.3-20.2%) as compared to patients with PPI (range 10.0-14.7%). The prevalence of depression was stable over the follow-up period in both groups (range 8.5-11.1%). CONCLUSION: Patients with a SPI reported higher anxiety and depression scores as compared to patients with PPI. Women reported higher anxiety scores than men, but only higher depression scores at baseline. Women with SPI reported the highest anxiety and depression scores overall.

Long-term follow-up of abandoned transvenous defibrillator leads: a nationwide cohort study.

AIMS: Commonly, a dysfunctional defibrillator lead is abandoned and a new lead is implanted. Long-term follow-up data on abandoned leads are sparse. We aimed to investigate the incidence and reasons for extraction of abandoned defibrillator leads in a nationwide cohort and to describe extraction procedure-related complications. METHODS AND RESULTS: All abandoned transvenous defibrillator leads were identified in the Danish Pacemaker and ICD Register from 1991 to 2019. The event-free survival of abandoned defibrillator leads was studied, and medical records of patients with interventions on abandoned defibrillator leads were audited for procedure-related data. We identified 740 abandoned defibrillator leads. Meantime from implantation to abandonment was 7.2 ± 3.8 years with mean patient age at abandonment of 66.5 ± 13.7 years. During a mean follow-up after abandonment of 4.4 ± 3.1 years, 65 (8.8%) abandoned defibrillator leads were extracted. Most frequent reason for extraction was infection (pocket and systemic) in 41 (63%) patients. Procedural outcome after lead extraction was clinical success in 63 (97%) patients. Minor complications occurred in 3 (5%) patients, and major complications in 1 (2%) patient. No patient died from complication to the procedure during 30-day follow-up after extraction. CONCLUSION: More than 90% of abandoned defibrillator leads do not need to be extracted during long-term follow-up. The most common indication for extraction is infection. Abandoned defibrillator leads can be extracted with high clinical success rate and low risk of major complications at high-volume centres.

Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure.

BACKGROUND: The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT). METHODS: In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death. RESULTS: After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29). CONCLUSIONS: In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).

The effect of implantable cardioverter-defibrillator in patients with diabetes and non-ischaemic systolic heart failure.

AIMS: Implantable cardioverter-defibrillator (ICD) implantation reduce the risk of sudden cardiac death, but not all-cause death in patients with non-ischaemic systolic heart failure (HF). Whether co-existence of diabetes affects ICD treatment effects is unclear. METHODS AND RESULTS: We examined the effect of ICD implantation on risk of all-cause death, cardiovascular death, and sudden cardiac death (SCD) according to diabetes status at baseline in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial. Outcomes were analysed by use of cumulative incidence curves and Cox regressions models. Of the 1116 patients enrolled, 211 (19%) had diabetes at baseline. Patients with diabetes were more obese, had worse kidney function and more were in New York Heart Association Class III/IV. The risk of device infections and other complications in the ICD group was similar among patients with and without diabetes (6.1% vs. 4.6% P = 0.54). Irrespective of treatment group, diabetes was associated with higher risk of all-cause death, cardiovascular death, and SCD. The treatment effect of ICD in patients with diabetes vs. patients without diabetes was hazard ratio (HR) = 0.92 (0.57-1.50) vs. HR = 0.85 (0.63-1.13); Pinteraction = 0.60 for all-cause mortality, HR = 0.99 (0.58-1.70) vs. HR = 0.70 (0.48-1.01); Pinteraction = 0.25 for cardiovascular death, and HR = 0.81 (0.35-1.88) vs. HR = 0.40 (0.22-0.76); Pinteraction = 0.16 for sudden cardiac death. CONCLUSION: Among patients with non-ischaemic systolic HF, diabetes was associated with higher incidence of all-cause mortality, primarily driven by cardiovascular mortality including SCD. Treatment effect of ICD therapy was not significantly modified by diabetes which might be due to lack of power.

The impact of implantable cardioverter-defibrillator implantation on health-related quality of life in the DANISH trial.

AIM: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH. METHODS AND RESULTS: In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0-105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months [least square mean -7.0 vs. -4.2 (P = 0.13)]. A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group [55% vs. 51%, respectively (P = 0.25)]. CONCLUSION: Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care.

Association between Type D personality and outcomes in patients with non-ischemic heart failure.

PURPOSE: The "distressed" (Type D) personality trait has been reported to be over-represented in patients with heart failure (HF) compared to the background population and may provide prognostic information for mortality. We examined the association between Type D personality and outcomes in the DANISH trial (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality). METHODS: The DANISH trial included a total of 1116 patients with non-ischemic HF on guideline-recommended therapy. Type D personality was assessed with the Type D Scale (DS14) at baseline and investigated through follow-up accordingly. Multivariable Cox proportional hazard models were used to compare hazard ratios (HR) of cardiovascular and all-cause mortality. RESULTS: Type D personality assessment was completed by 873 (78%) patients at baseline and Type D personality was found in 120 (14%) patients. The median follow-up was 67 months (interquartile range [IQR] 48-83). Among patients with versus without Type D personality, 22% versus 19% died from all-cause yielding similar incidence rates of 4.62 (95% CI 3.14-6.87) versus 3.95 (95% CI 3.37-4.66) per 100 person-years. The adjusted risk of all-cause mortality was not significantly different in patients with versus without Type D personality with an adjusted HR of 1.31 (95% CI 0.84-2.03, p = 0.23) with similar results for cardiovascular death (HR 1.46 (95% CI 0.88-2.44, p = 0.15). CONCLUSION: Type D personality was not significantly associated with increased risk of all-cause mortality or cardiovascular death in patients with non-ischemic HF.

Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation. METHODS: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ2 analysis. RESULTS: Median age of the study population was 63 years (range, 21-84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003-1.06; P=0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51-0.96; P=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68-1.62; P=0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3-2.5) and nonsudden death rate was 2.7 (95% CI, 2.1-3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8-3.2) and nonsudden death rate was 5.4 (95% CI, 3.7-7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (P=0.01). CONCLUSIONS: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Association between right ventricular lead position and clinical outcomes in patients with cardiac resynchronization therapy.

Aims: To evaluate the association between an apical vs. non-apical right ventricular lead position (RV-LP) and clinical outcome in a large nationwide cohort of patients treated with cardiac resynchronization therapy (CRT). Methods and results: We included consecutive Danish patients receiving a CRT device from 2008 to 2012, identified from the Danish Pacemaker and ICD Register. Endpoints were mortality, mortality or hospitalization for heart failure (HF), and clinical response (improvement ≥1 New York Heart Association class at follow-up). Subgroup analysis was made for ischaemic heart disease (IHD) and non-IHD. Cox and logistic regression analyses were used to calculate adjusted HR (aHR) and adjusted odds ratios with 95% confidence intervals (CI). A total of 2883 patients received a CRT device during the period. We excluded 301 patients that did not meet standard CRT indication. In 2391 (93%) of the remaining 2582 patients the RV-LP was defined as apical in 647 (27%) and non-apical in 1744 (73%). After mean 3.2 ± 2 years, 660 patients had died, 1275 patients were hospitalized for HF, and 1021 were responders. With a non-apical RV-LP the aHR for mortality was 0.93 (95% CI 0.0.79-1.10, P = 0.40) and the aHR for the combined endpoint of mortality or HF-hospitalization was 0.89 (95% CI 0.79-0.99, P = 0.03). These findings were significant only in patients with non-IHD. There was no association between clinical response and RV-LP. Conclusion: A non-apical RV-LP is associated with lower risk of meeting the combined endpoint of mortality or hospitalization for HF in patients with CRT. In subgroup analysis, this association was present only in patients with non-IHD.