Myocardial fibrosis and ventricular ectopy in patients with non-ischemic systolic heart failure: results from the DANISH trial.

Patients with non-ischemic systolic heart failure (HF) have increased risk of sudden cardiovascular death (SCD). The initiation and substrate for ventricular arrhythmias remains poorly understood. Our purpose was to describe the relationship between cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and Holter recorded ventricular arrhythmic activity. Patients from the DANISH trial underwent a Holter-recording and a CMR-scan. The presence of non-sustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVC) were examined in relation to presence and amount of LGE. Outcome measures were all-cause mortality and SCD. Overall, 180 patients were included. LGE was present in 86 (47%). NSVT occurred in 72 (40%), not different according to LGE status (p = 0.65). The amount of LGE was not correlated to the occurrence of NSVT (p = 0.40). The occurrence of couplet PVCs (p = 0.997), frequent PVCs (p = 0.12), PVCs in bigemini (p = 0.29), in trigemini (p = 0.26), or in quadrimini (p = 0.35) did not differ according to LGE status. LGE was significantly associated with risk of all-cause mortality (HR 2.14; 95% CI 1.05-4.37, p = 0.04). NSVT did not increase risk of all-cause mortality in either patients with LGE (HR 1.00; 95% CI 0.46-2.16, p = 0.996) or without LGE (HR 1.37; 95% CI 0.46-4.08, p = 0.57). There was no interaction between LGE and NSVT for the risk of all-cause mortality (p = 0.62). In patients with non-ischemic systolic HF there was no relationship between the presence of LGE and NSVT or any other Holter recorded ventricular tachyarrhythmia. LGE was associated with increased risk of mortality, independent of the presence of NSVT.

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.

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.

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.