Impaired myocardial perfusion is associated with increasing end-systolic- and end-diastolic volumes in patients with non-ischemic systolic heart failure: a cross-sectional study using Rubidium-82 PET/CT.

BACKGROUND: Myocardial flow reserve (MFR, stress/rest myocardial blood flow) is a strong marker of myocardial vasomotor function. MFR is a predictor of adverse cardiac events in patients with non-ischemic systolic heart failure and previous studies using different methods have found association between myocardial blood flow and left ventricular dilatation. The aim of this study was to investigate whether there is an association between increasing end-systolic- and end-diastolic volumes (ESV and EDV) and MFR in these patients measured with Rubidium-82 positron emission tomography computed tomography (82Rb-PET/CT) as a quantitative myocardial perfusion gold-standard. METHODS: We scanned 151 patients with non-ischemic heart failure with initial left ventricular ejection fraction ≤35% with 82Rb-PET/CT at rest and adenosine-induced stress to obtain MFR and volumes. To account for differences in body surface area (BSA), we used indexed ESV (ESVI): ESV/BSA (ml/m2) and EDV (EDVI). We identified factors associated with MFR using multiple regression analyses. RESULTS: Median age was 62 years (55-69 years) and 31% were women. Mean MFR was 2.38 (2.24-2.52). MFR decreased significantly with both increasing ESVI (estimate - 3.7%/10 ml/m2; 95% confidence interval [CI] -5.6 to - 1.8; P < 0.001) and increasing EDVI (estimate - 3.5%/10 ml/m2; 95% CI -5.3 to - 1.6; P < 0.001). Results remained significant after multivariable adjustment. Additionally, coronary vascular resistance during stress increased significantly with increasing ESVI (estimate: 3.1 mmHg/(ml/g/min) per (10 ml/m2); 95% CI 2.0 to 4.3; r = 0.41; P < 0.0001) and increasing EDVI (estimate: 2.7 mmHg/(ml/g/min) per (10 ml/m2); 95% CI 1.6 to 3.8; r = 0.37; P < 0.0001). CONCLUSIONS: Impaired MFR assessed by 82Rb-PET/CT was significantly associated with linear increases in ESVI and EDVI in patients with non-ischemic systolic heart failure. Our findings support that impaired microvascular function may play a role in heart failure development. Clinical trials investigating MFR with regard to treatment responses may elucidate the clinical use of MFR in patients with non-ischemic systolic heart failure. TRIAL REGISTRATION: Sub study of the randomized clinical trial: A DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillator in patients with non-ischemic Systolic Heart failure on mortality (DANISH), ClinicalTrials.gov Identifier: NCT00541268 .

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).

BACKGROUND: The 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. METHODS: 1004 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. RESULTS: Patients 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. CONCLUSIONS: Patients 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.

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

BACKGROUND: The 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. RESULTS: The 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%). CONCLUSIONS: One third of the patients had recovered LVEF and was significantly associated with baseline LVEF and lower mortality rate.

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.