Non-ischaemic Systolic Heart Failure Research Articles

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

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). 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). 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.

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

BackgroundChanges 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. MethodsWe 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. ResultsComplete 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). ConclusionIn 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.

Effect of implantable cardioverter-defibrillator in non-ischaemic systolic heart failure according to the Heart Failure Collaboratory Medical Therapy Score: extended follow-up of the DANISH trial

Abstract Background The Heart Failure Collaboratory (HFC) has developed a medical therapy score which integrates types and doses of guideline-directed pharmacotherapies in patients with systolic heart failure, providing a measure of treatment quality. In clinical trials, this score may help determine the additive effect of new treatments. In the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. Purpose Adding four years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to baseline modified HFC (mHFC) medical therapy score. Methods In the DANISH trial, 1,116 patients with non-ischaemic systolic heart failure were randomised to receive an ICD (N = 556) or usual clinical care (N = 560, control group). The primary outcome was death from any cause. In the mHFC score, patients were assigned a score for each drug class of the original cornerstones of systolic heart failure treatment (renin-angiotensin-system inhibitor, beta-blocker, and mineralocorticoid receptor antagonist). The maximum score was 100%, corresponding to optimal medical therapy with all three types of medication (=&amp;gt;50% of target dose). Results The median mHFC score at baseline was 67% (25th-75th percentile, 67%-100%; range, 17%-100%). During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74-1.08]). The results were independent of the mHFC score at baseline (mHFC score = &amp;lt; median: HR 0.91 [95% CI, 0.70-1.19]; mHFC score &amp;gt; median: HR 0.87 [95% CI, 0.66-1.14]; P for interaction, 0.94). Similarly, ICD implantation did not reduce the rate of cardiovascular death overall (HR 0.87 [95% CI, 0.70-1.09]), and this association was not modified by the mHFC score (mHFC score = &amp;lt; median: HR 0.90 [95% CI, 0.65-1.24]; mHFC score &amp;gt; median: HR 0.84 [95% CI, 0.61-1.15]; P for interaction, 0.89). The ICD group had a significantly lower rate of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40-0.92]), and this association was not modified by the mHFC score (mHFC score = &amp;lt; median: HR 0.72 [95% CI, 0.40-1.29]; mHFC score &amp;gt; median: HR 0.53 [95% CI, 0.28-0.99]; P for interaction, 0.59). See Figure for results. Conclusions In this extended follow-up study of the DANISH trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure regardless of baseline medical heart failure therapy, assessed by the mHFC score.Modified HFC score in the DANISH trial

Efficacy of implantable cardioverter-defibrillator in non-ischemic systolic heart failure in patients with and without chronic kidney disease: an extended follow-up analysis of the DANISH trial

Abstract Background Patients with heart failure (HF) 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). Purpose In this extended follow-up study 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-prevention ICD implantation, compared with usual medical care, according to baseline CKD status. Methods In the DANISH trial, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (eGFR ≥/&amp;lt; 60 mL/min/1.73 m2) at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results In total, 1,113 patients had an available eGFR measurement at baseline (median eGFR 73 ml/min/1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual medical care, did not reduce the rate of death from any cause (no CKD, HR 0.81 [95% CI, 0.64-1.03]; CKD, HR 0.92 [0.68-1.26]; P for interaction=0.31) or cardiovascular death (no CKD, HR 0.76 [0.57-1.02]; CKD, HR 0.95 [0.66-1.36]; P for interaction=0.21), 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 [0.32-1.00]; CKD, HR 0.60 [0.31-1.14]; P for interaction=0.70). Conclusions Primary-prevention ICD implantation did not provide an overall survival benefit regardless of baseline kidney function in patients with non-ischemic systolic heart failure.Figure

Clinical characteristics, etiological profile, treatment and long term outcomes in patients with non ischemic systolic heart failure; Himachal Pradesh heart failure registry (HP–HF registry)

BackgroundThe data on clinical characteristics, treatment practices and out comes in patients with Non- ischemic Systolic Heart Failure (NISHF) is limited. We report clinical characteristics, treatment and outcomes in patients with NISHF. Methods1004 patients with NISHF were prospectively enrolled and their demographics, clinical characteristics, and treatment were recorded systematically. Patients were followed annually for a median of 3 years (1 year to 8 years) for allcause death, major adverse cardiovascular events (MACE); composite of all-cause death, hospitalization of heart failure, and or for stroke. ResultsPatients of NISHF were middle-aged (58.8±16.2 years) population with severely depressed left ventricular ejection fraction (29.3±7.02%) and 31.1% had symptoms of advanced Heart failure. Hypertension (43.6%), obesity and or overweight (28.0%), Diabetes (15.0%), and valvular heart disease (11.8%) were the common risk factors. The guideline directed medical treatment was prescribed in more than 80% of the study cohort. Incidence of all cause death and MACE was 7 (6.8, 8.8) per 100 person years and 11(10, 13) per 100 person years respectively. The cumulative incidence of deaths and MACE was 35% (30%, 40%) and 49% (44%, 53%) at 8 years of follow-up. ConclusionsPatients of NISHF were middle-aged population with severely depressed LV systolic function with significant incident morbidity and mortality. Early detection of risk factors and their risk management and enhancing the use of guideline directed treatment may improve the outcomes. Keywords: Non-ischemic systolic heart failure, risk factors, outcomes, guideline directed treatment.

Incidence, determinants, and outcomes of recovered left ventricular ejection fraction (LVEF) in patients with non-ischemic systolic heart failure; a hospital-based cohort study

BackgroundThe data on incidence of recovered Left Ventricular Ejection Fraction (LVEF) and outcome in patients with non ischemic systolic heart failure is limited. We report the incidence, determinants and mortality in patients with recovered LVEF. Methods: The 369 patients with HFrEF with LVEF of less than 40% of non ischemic etiology with available follow up echocardiography study at one year were enrolled. The baseline data of clinical characteristics and treatment was recorded prospectively and were followed up annually for mean of 3.6 years (range 2 to 5 years) to record all cause death and LVEF measured echocardiographically. The recovered, partially recovered and no recovery of LVEF was defined based on increase in LVEF to 50% and more, 41% to 49% and to persistently depressed LVEF to 40% or lower respectively. ResultsThe LVEF recovered in 36.5%% of the cohort at 5 years. The rate of recovery of LVEF was slower in patients with no recovery of LVEF at one year compared to cohort with partially recovered LVEF (18% vs.53%) at five year. The Baseline LVEF was significantly associated with recovered LVEF, odd ratio (95% C.I.) 1.09(1.04, 1.14). The cumulative mortality at five years was significantly lower in cohort with recovered LVEF (18.1% vs. 57.1%). ConclusionsOne third of the patients had recovered LVEF and was significantly associated with baseline LVEF and lower mortality rate.

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

BackgroundPatients 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 ResultsIn 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). ConclusionsIn 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.

Cardiac resynchronisation therapy and implantable cardioverter-defibrillator in non-ischaemic systolic heart failure: extended follow-up of the DANISH trial

Abstract Background In the Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators [ICDs] in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. A high proportion of patients in the DANISH trial received a cardiac resynchronisation therapy (CRT) device, which improves the prognosis in patients with heart failure. Therefore, it is of interest to examine whether the effect of ICD implantation in patients with non-ischaemic systolic heart failure is modified by CRT. Purpose Adding 4 years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to status with respect to CRT implantation at baseline. Methods In the DANISH trial, 556 patients with non-ischaemic systolic heart failure were randomised to receive an ICD and 560 to receive usual clinical care (control). Patients fulfilling indications for a CRT device received a CRT-defibrillator (if randomised to ICD arm) or CRT-pacemaker (if randomised to control arm). In the ICD group, 322 patients (57.9%) received a CRT device; in the control group, 323 patients (57.7%) received a CRT device. In this extended follow-up study, patients were followed until May 18, 2020. The primary outcome was death from any cause; secondary outcomes were cardiovascular death and sudden cardiovascular death. Results During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74–1.08]). The results were independent of whether the patient received a CRT device at randomisation (patients with a CRT device: HR 0.92 [95% CI, 0.72–1.18]; patients without a CRT device: HR 0.86 [95% CI, 0.64–1.14]; P for interaction, 0.72). Similarly, ICD implantation did not reduce rates of cardiovascular death overall (HR 0.87 [95% CI, 0.70–1.09]), and this association was not modified by CRT (patients with a CRT device: HR 0.89 [95% CI, 0.66–1.19]; patients without a CRT device: HR 0.85 [95% CI, 0.60–1.20]; P for interaction, 0.86). The ICD group had significantly lower rates of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40–0.92]), and this association was not modified by CRT (patients with a CRT device: HR 0.69 [95% CI, 0.40–1.21]; patients without a CRT device: HR 0.51 [95% CI, 0.26–0.97]; P for interaction, 0.47). See Figure 1 for all results. Conclusions In this extended follow-up study of the DANISH trial, the effect of ICD implantation in patients with non-ischaemic systolic heart failure was not modified by CRT. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The DANISH trial was supported by unrestricted grants from Medtronic, St Jude Medical, Tryg Fonden, and the Danish Heart Foundation. No further funding was obtained for this follow-up study.

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.

Elevated α-hydroxybutyrate dehydrogenase is associated with in-hospital mortality in non-ischemic dilated cardiomyopathy.

BackgroundPrevious Study Found That Implantation of a Cardioverter-Defibrillator Likely Caused a Worse Prognosis in Older Patients With non-Ischemic Systolic Heart Failure. This Suggests That More Precise Risk Stratification Is Needed in Elderly Patients. We Conducted a Retrospective Study to Evaluate the Association of α-Hydroxybutyrate Dehydrogenase (α-HBDH) With Mortality During Hospitalization in Elderly Patients With non-Ischemic Dilated Cardiomyopathy (NIDCM).Methods1,019 Elderly Patients (age ≥60 Years) Diagnosed With NIDCM Were Retrospectively Enrolled From January 2010 to December 2019. Univariate and Multivariate Analyses Were Showed to Explore the Relationship Between α-HBDH and in- Hospital Death.ResultsPatients in elevated α-HBDH group (>182 U/L) had a longer hospital stays and higher in-hospital mortality. Univariate logistics regression analysis showed that elevated α-HBDH was significantly related to mortality (OR: 7.004, 95% CI: 3.583–13.693, p < 0.001). Receiver operator characteristic (ROC) curve analysis reflected that α-HBDH levels had excellent predictive power for in-hospital death (AUC = 0.810, 95% CI: 0.745–0.876, p < 0.001). After adjustment of age, serum creatine, albumin and LVEF, multivariate regression analysis validated the association of elevated α-HBDH with increased risk of in-hospital death (p < 0.05).ConclusionsElevated α-HBDH level is significantly related to in-hospital mortality in older patients with NIDCM.

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

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. 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. 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). In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex. URL: https://www. gov; Unique identifier: NCT00542945.

Impact of signal-averaged electrocardiography findings on appropriate shocks in prophylactic implantable cardioverter defibrillator patients with nonischemic systolic heart failure

BackgroundAppropriate shock therapy is associated with subsequent all-cause death in heart failure (HF) patients who receive an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death. To evaluate the impact of signal-averaged electrocardiography (SAECG) findings on appropriate shocks in prophylactic ICD patients with nonischemic systolic HF.MethodsWe studied 86 patients with nonischemic HF and a left ventricular ejection fraction ≤ 35% who underwent new ICD implantation for the primary prevention of sudden cardiac death. We excluded patients who had a previously implanted permanent pacemaker and patients who received cardiac resynchronization therapy with an ICD. SAECG was performed before implantation. Abnormal SAECG findings were defined if 2 of the following 3 conditions were identified: filtered QRS duration (fQRS) ≥ 114 ms, root-mean-square voltage during the last 40 ms of the fQRS (RMS 40) < 20 μV, and duration of the low-amplitude potentials < 40 μV (LAS 40) > 38 ms; additionally, patients with a QRS complex ≥ 120 ms who met both the RMS 40 and LAS 40 criteria were also considered to have abnormal SAECG findings. The primary outcome was the first occurrence of appropriate shock after implantation of the ICD. The secondary outcomes were the first occurrence of inappropriate shock and all-cause mortality.ResultsForty-two patients met the criteria for abnormal SAECG findings (49%). During a median follow-up period of 61 months, 17 patients (20%) died, 24 (28%) received appropriate shock therapy, and 19 (22%) received inappropriate shock therapy. There was a significantly higher incidence of appropriate shocks in patients with abnormal SAECG findings than in those with normal SAECG findings (log-rank test, p = 0.025). Multivariate analysis revealed that abnormal SAECG findings were independently associated with the occurrence of appropriate shock (hazard ratio 2.67, 95% confidential interval 1.14–6.26). However, abnormal SAECG findings were not related to inappropriate shock. There was no difference in the incidence of all-cause death between patients with abnormal and normal SAECG findings.ConclusionsOur results suggest that abnormal SAECG findings are associated with a high probability of appropriate shocks in prophylactic ICD patients with nonischemic systolic HF.

EP News: Clinical

Yafasova et al (Circulation 2022;145:427, PMID 34882430) evaluated long-term follow-up (9.5 years) of 556 patients with nonischemic systolic heart failure randomized to receive an implantable cardioverter-defibrillator (ICD) and 560 to receive usual clinical care in DANISH (The Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). Overall 208 of 556 patients (37%) in the ICD group and 226 of 560 patients (40%) in the control group died (hazard ratio [HR] 0.89; P = .24).

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

ObjectivesIn 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. BackgroundIn the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation. MethodsIn 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. ResultsAll 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). ConclusionsLower 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.

AimsProphylactic 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 resultsPatients 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).ConclusionsIn 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.

Predictive value of electrophysiological study for risk stratification of ventricular tachyarrhythmias in patients with non-ischemic cardiomyopathy and chronic systolic heart failure

A systematic review and meta-analysis of studies providing information on the use of intracardiac electrophysiological study (EPS) to stratify the risk of ventricular tachyarrhythmia (VT) in patients with non-ischemic chronic heart failure with low left ventricle ejection fraction (HFrEF). Relevant publications were searched until 20.01.2021 by two independent researchers in major search engines, electronic archives of clinical research, and open access preservatives repository. The end point considered was an episode of sudden cardiac death or sustained paroxysm of VT, or an appropriate electrotherapy of an implanted cardiac defibrillator. Ten clinical trials with 608 relevant patients (mean age: 51.5 ± 12 years; mean left ventricle EF: 26.8±8.5%, NYHA class: I - 17.7%; II - 33.7%; III - 35.9%, IV - 12.7%) were selected. The end point was registered in 92 patients (15.1%): in 47 patients (43.9%) with previously induced VT during EPS and in 45 patients (8.9%) without VT. The diagnostic odds ratio was 5.57 (2.27-13.63). The combined sensitivity and specificity of the EPS were 42% (26-61%) and 88% (83-92%) respectively. The results indicate the potential of EPS to stratify the arrhythmic risk in patients with non-ischemic HFrEF.

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

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. 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). 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). 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.

Epicardial Adipose Tissue Measured From Computed Tomography Predicts Cardiac Resynchronization Therapy Response in Patients With Non-ischemic Systolic Heart Failure.

Background: Epicardial adipose tissue (EAT) has been linked with the pathogenesis of heart failure (HF). Limited data have been reported about the clinical value of EAT for cardiac resynchronization therapy (CRT) in non-ischemic systolic HF. We aimed to explore the values of EAT measured from CT to predict the response to CRT in patients with non-ischemic systolic HF.Methods: Forty-one patients with CRT were consecutively recruited for our study. All patients received both gated resting Single Photon Emission CT (SPECT) myocardial perfusion imaging (MPI) and dual-source multi-detector row CT scans. EAT thickness was assessed on both the parasternal short and horizontal long-axis views. The area of EAT was calculated at the left main coronary artery level. Left ventricular systolic mechanical dyssynchrony (LVMD) was measured by phase standard deviation (PSD) and phase histogram bandwidth (PBW). The definition of CRT response was an improvement of 5% in left ventricular ejection fraction (LVEF) at 6 months after CRT implantation.Results: After 6 months of follow-up, 58.5% (24 of 41) of patients responded to CRT. A greater total perfusion deficit (TPD) was observed in the left ventricle, and a narrower QRS complex was observed in the nonresponse group than in the response group (p < 0.05). Meanwhile, the systolic PSD and systolic PBW were statistically greater in the CRT group with no response than in the response group (p < 0.05). Meanwhile, the baseline QRS duration, TPD, systolic PSD, systolic PBW, EAT thicknesses of the left ventricular (LV) apex, right atrioventricular (AV) groove, and left AV groove were all significantly related to the CRT response in the univariate logistic regression analysis. Furthermore, the QRS duration and EAT thicknesses of the right AV groove and left AV groove were independent predictors of CRT response in the multivariate logistic regression analysis.Conclusions: The EAT thickness of the left AV groove in patients with non-ischemic systolic HF is associated with the TPD of LV and LV systolic dyssynchrony. The EAT thickness of the AV groove has a good predictive value for the CRT response in patients with non-ischemic systolic HF.

Morphologies and prognostic significance of left ventricular volume/time curves with cardiac magnetic resonance in patients with non-ischaemic heart failure and left bundle branch block

Patients with non-ischaemic systolic heart failure (HF) and left bundle branch block (LBBB) can display a wide or narrow pattern (WP/NP) of the systolic phase of the left ventricular (LV) volume/time (V/t) curve in cardiac magnetic resonance (CMR). The clinical and prognostic significance of these patterns is unknown. Consecutive patients with non-ischaemic HF, LV ejection fraction < 50% and LBBB underwent 1.5 T CMR. Maximal dyssynchrony time (time between the earliest and latest end-systolic peaks), systolic dyssynchrony index (standard deviation of times to peak volume change), and contractility index (maximum rate of change of pressure-normalized stress) were calculated. The endpoint was a composite of cardiovascular death, HF hospitalization, and appropriate defibrillator shock. NP was found in 29 and WP in 72 patients. WP patients had higher volumes and NT-proBNP, and lower LVEF. WP patients had a longer maximal dyssynchrony time (absolute duration: 192 ± 80 vs. 143 ± 65 ms, p < 0.001; % of RR interval: 25 ± 11% vs. 8 ± 4%, p < 0.001), a higher systolic dyssynchrony index (13 ± 4 vs. 7 ± 3%, p < 0.001), and a lower contractility index (2.6 ± 1.2 vs 3.2 ± 1.7, p < 0.05). WP patients had a shorter survival free from the composite endpoint regardless of age, NT-proBNP or LVEF. Nonetheless, WP patients responded more often to cardiac resynchronization therapy (CRT) than those with NP (24/28 [86%] vs. 1/11 [9%] responders, respectively; p < 0.001). In patients with non-ischaemic systolic HF and LBBB, the WP of V/t curves identifies a subgroup of patients with greater LV dyssynchrony and worse outcome, but better response to CRT.

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.