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In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events, or cardiovascular death in patients with HF and reduced ejection fraction. The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting, that is, whether participants were enrolled as outpatients or inpatients. Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department visit). The primary outcome was a composite of worsening HF event (HF hospitalization or an urgent emergency department or clinic visit) or cardiovascular death. Of the 8232 patients analyzed, 2084 (25%) were hospitalized at randomization. Hospitalized patients had higher N-terminal prohormone of B-type natriuretic peptide concentrations, lower systolic blood pressure, reported more symptoms, and were less frequently treated with a renin–angiotensin system blocker or a beta-blocker than outpatients. The rate (per 100 person-years) of the primary outcome was higher in hospitalized patients (placebo group = 38.3/100 person-years) than in outpatients (23.1/100 person-years); adjusted hazard ratio 1.21 (95% confidence interval 1.12–1.31). The effect of omecamtiv mecarbil versus placebo on the primary outcome was similar in hospitalized patients (hazard ratio 0.89, 95% confidence interval 0.78–1.01) and outpatients (hazard ratio 0.94, 95% confidence interval 0.86–1.02) (interaction P =.51). Hospitalized patients with HF with reduced ejection fraction had a higher rate of the primary outcome than outpatients. Omecamtiv mecarbil decreased the risk of the primary outcome both when initiated in hospitalized patients and in outpatients. [ABSTRACT FROM AUTHOR]

Background: The tolerability and utility of combination doxycycline and ursodeoxycholic acid (ursodiol) amyloid fibril disruption therapy for transthyretin cardiac amyloidosis (ATTR CA) in clinical practice is poorly described.Methods and Results: We report the clinical experience of 53 ATTR CA patients treated with doxycycline and ursodiol. Six patients (11%) did not tolerate the therapy owing to dermatologic and gastrointestinal effects. Of those remaining, the median follow-up was 22 months (range 8-30), mean age was 71 ± 11years, 41 (87%) were male, and 42 (89%) had wild-type and 5 (11%) mutant ATTR. Five patients (11%) died during follow-up. There was no significant change in New York Heart Association (NYHA) functional class, cardiac biomarkers, or echocardiographic parameters during follow-up. Left ventricular (LV) global longitudinal systolic strain (GLS) improved in 16 patients (38%) (-12 ± 4% to -17 ± 4%; P < .01). Patients whose LV GLS improved were significantly younger and had lower NYHA functional class, troponin-T, N-terminal pro-B-type natriuretic peptide (BNP), and baseline LV GLS levels compared with those whose LV GLS did not improve. Troponin-T improved in follow-up for patients whose LV GLS improved (35 ± 21 to 20 ± 14 ng/L; P = .06).Conclusions: Doxycycline and ursodiol therapy for treatment of ATTR CA was tolerable and was associated with stabilized markers of disease progression. LV GLS improved in patients with less advanced disease. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF), and especially HF with preserved ejection fraction (HFpEF), remains a challenging condition to define. The heterogenous nature of this population may be related to a variety of underlying etiologies interacting myocardial dysfunction.Method: Alberta HEART study was a prospective, observational cohort that enrolled participants along the spectrum of heart failure including: healthy controls, people at risk of HF, and patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF). We aimed to explore phenotypes of patients with HF and at-risk of developing HF. Utilising 27 detailed clinical, echocardiographic and biomarker variables, latent class analysis with and without multiple imputation was undertaken to identify distinct clinical phenotypes.Results: Of 621 participants, 191 (30.8%) and 169 (27.2%) were adjudicated by cardiologists to have HFpEF and HFrEF respectively. In the overall cohort, latent class analysis identified four distinct phenotypes. Phenotype A (n=152, 24.5%) was a healthy and low risk group. Phenotype B (n=129, 20.8%) demonstrated increased left ventricular mass and end-diastolic volumes, with elevated natriuretic peptides and clinical features of congestion. Phenotype C (n=128, 20.6%) was primarily characterised by obesity (80%) and normal indexed cardiac chamber sizes, low natriuretic peptide levels and minimal features of congestion.  Phenotype D (n=212, 34.1%) consisted of elderly patients with clinical features of congestions. Phenotypes B and D demonstrated the highest risk of mortality and hospitalization over a median follow-up of 3.7 years.Conclusion: Phenotypes with congestive features demonstrated increased risk profiles. Heart failure is a heterogenous classification which requires further work to appropriately categorise patients based on the underlying etiology or mechanism of impairment. [ABSTRACT FROM AUTHOR]

Cardiac retransplantation accounts for approximately 3% of cardiac transplantation and is considered a risk factor for increased mortality. However, factors inherent to retransplantation including previous sternotomy, sensitization, and renal dysfunction may account for the increased mortality. We assessed whether retransplantation was associated with all-cause mortality after adjusting for such patient risk factors. We conducted a retrospective cohort study of adult and pediatric patients enrolled in the United Network for Organ Sharing database. We identified patients undergoing cardiac retransplantation based on transplant listing diagnosis and history of previous transplant. We used propensity-score matching to identify a matched cohort undergoing initial heart transplantation. In total, 62,112 heart transplant recipients were identified, with a mean age 46.6 ± 19.1 years. Of these, 2,202 (3.4%) underwent late cardiac retransplantation (>1 year after initial transplant and not for acute rejection). Compared with a matched group of patients undergoing initial heart transplantation, patients undergoing late retransplantation had comparable rates of all-cause mortality at 1 year (13.6% vs 13.8%, p = 0.733). In addition, overall mortality was not significantly different after matching (unadjusted hazard ratio [HR] 1.08, p = 0.084). In contrast, patients undergoing retransplantation within 1 year of initial transplant or for acute rejection remained at increased risk of mortality post-transplant after similar matching (unadjusted HR 1.79, p < 0.001). After matching for comorbidities, late retransplantation in the adult population was not associated with an increase in all-cause mortality. Our findings highlight the importance of assessing indication acuity and comorbid conditions when considering retransplant candidacy. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified.Objectives: This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy.Methods: All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m(2)). Patients were categorized as having 0 to 1 or 2 to 3 of these factors.Results: Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535).Conclusions: Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). [ABSTRACT FROM AUTHOR]