Value-based health care in heart failure: Quality of life and cost analysis

Abstract Objectives: To measure Quality of Life (QoL) and costs of Heart Failure (HF) outpatients in Brazil as an introduction to the Value-Based Health Care (VBHC) concept. Materials and methods: Cross-sectional study, patients with HF, with ejection fraction <50%, were recruited from three hospitals in Brazil. Two QoL (36-Item Short Form Survey [SF-36] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and two anxiety/depression questionnaires were applied. SF-36 scores were stratified by domains. Treatment costs were calculated using the Time-Driven Activity-Based Costing (TDABC) method. Results were stratified by NYHA functional class and sex. Results: From October 2018 to January 2021, 198 patients were recruited, and the median MLHFQ (49.5 [IQR 21.0, 69.0]) and SF-36 scores demonstrated poor QoL, worse at higher NYHA classes. A third of patients had moderate/severe depression and anxiety symptoms, and women had higher anxiety scores. Mean costs of outpatient follow-up were US$ 215 ± 238 for NYHA I patients, US$ 296 ± 399 for NYHA II and US$ 667 ± 1012 for NYHA III/IV. Lab/exam costs represented 30% of the costs in NYHA I, and 74% in NYHA III/IV (US $ 63.26 vs. US$ 491.05). Conclusion: Patients with HF in Brazil have poor QoL and high treatment costs; both worsen as the NYHA classification increases. It seems that HF has a greater impact on the mental health of women. Costs increase mostly related to lab/exams. Accurate and crossed information about QoL and costs is essential to drive care and reimbursement strategies based on value.

Lung ultrasound in congestion assessment of patients with advanced heart failure referred for heart transplant: Correlations with right heart catheterization findings.

Background: In advanced heart failure (HF), diagnostic performance of physical exam may be poor. Physical examination associated with lung ultrasound (LUS) may be an important tool to facilitate congestion screening. Objective: To evaluate performance of LUS for congestion screening in advanced HF referred for transplant, as compared to findings of right heart catheterization (RHC). Methods: Prospective study of 23 subjects with advanced HF referred for RHC. LUS was performed in association with clinical congestion score (CCS), analogue-visual dyspnea scale (AVDS) and presence of trepopnea/bendopnea prior to catheterization. Congestion was assessed by the number of B-lines in the LUS, and by findings of physical examination as well as by NT-proBNP serum values. Results: Congestion was present in 43.4 % of patients by LUS (B-lines ≥ 15), as compared to 21.7 % by CCS (score greater than or equal to 5), 56.5 % by NT-proBNP (>1000 pg/ml), and 60.8 % by pulmonary capillary wedge pressure (PCWP) (>15 mm Hg). The number of B-lines was correlated to cardiac index (CI) (rho = -0.619; p 0.002), but not with PCWP (rho 0.190; p 0.386), RAP (rho -0.244; p 0.262), CCS (rho 0.198; p 0.36) and neither with NT-proBNP (rho 0.282; p 0.193). Otherwise, NT-proBNP was correlated with PCWP (rho = 0.636; p = 0.001) and with CI (rho -0.667 p 0.001). Conclusions: In advanced HF patients referred for transplant, number of B-lines in LUS was not correlated with PCWP or RAP. Advanced HF patients seem to have increased filling pressures, but no interstitial pulmonary congestion that LUS could detect.

Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial.

Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65 years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics. To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF. This randomized clinical trial compared HCTZ 50 mg versus placebo for 3 days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay. Fifty-one patients were randomized-26 to the HCTZ group and 25 to the placebo group. There was an increment of 0.73 kg/day towards additional weight reduction in the HCTZ group (HCTZ: - 1.78 ± 1.08 kg/day vs placebo: - 1.05 ± 1.51 kg/day; p = 0.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40 mg of intravenous furosemide (HCTZ: - 0.74 ± 0.47 kg/40 mg vs placebo: - 0.33 ± 0.80 kg/40 mg; p = 0.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50 ± 0.37 vs placebo: 0.27 ± 0.40; p = 0.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%; p = 0.38). No differences were found in the remaining outcomes. Adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure did not cause significant difference in daily body weight reduction compared to placebo. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50 mg to furosemide resulted in a significant synergistic effect on weight loss.Trial registration: The Brazilian Clinical Trials Registry (ReBEC), a publically accessible primary register that participates in the World Health Organization International Clinical Trial Registry Platform; number RBR-5qkn8h. Registered in 23/07/2019 (retrospectively), http://www.ensaiosclinicos.gov.br/rg/RBR-5qkn8h/ .

HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma.

Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant brain tumor of childhood. Recurrent and metastatic disease is the principal cause of death and may be related to resistance within cancer stem cells (CSCs). Chromatin state is involved in maintaining signaling pathways related to stemness, and inhibition of histone deacetylase enzymes (HDAC) has emerged as an experimental therapeutic strategy to target this cell population. Here, we observed antitumor actions and changes in stemness induced by HDAC inhibition in MB. Analyses of tumor samples from patients with MB showed that the stemness markers BMI1 and CD133 are expressed in all molecular subgroups of MB. The HDAC inhibitor (HDACi) NaB reduced cell viability and expression of BMI1 and CD133 and increased acetylation in human MB cells. Enrichment analysis of genes associated with CD133 or BMI1 expression showed mitogen-activated protein kinase (MAPK)/ERK signaling as the most enriched processes in MB tumors. MAPK/ERK inhibition reduced expression of the stemness markers, hindered MB neurosphere formation, and its antiproliferative effect was enhanced by combination with NaB. These results suggest that combining HDAC and MAPK/ERK inhibitors may be a novel and more effective approach in reducing MB proliferation when compared to single-drug treatments, through modulation of the stemness phenotype of MB cells.