Differences in socio-demographic and risk factor profile, clinical presentation, and outcomes between patients with and without RHD heart failure in Sub-Saharan Africa: results from the THESUS-HF registry

Background: Rheumatic heart disease (RHD) was found in the THESUS-HF registry to be the third most common cause of acute heart failure (AHF) in Sub-Saharan Africa. Methods: One thousand six patients with AHF from 9 Sub-Saharan African countries were recruited in THESUS-HF, of which 143 (14.3%) had RHD-AHF. Clinical characteristics and outcomes in patients with RHD-AHF and non-RHD-AHF were compared. Kaplan-Meier plots for time to all-cause death and/or HF readmission according to the presence of RHD-AHF and non-RHD-AHF were performed and survival distributions compared using the log-rank test. Cox regression was used to determine the hazard ratio of death to day 180 and death or readmission to day 60 after adjusting for confounders. Results: Patients with RHD-AHF were younger, more often females, had higher rates of atrial fibrillation, had less hypertension, hyperlipidemia and diabetes, had lower BP, and higher pulse rate and better kidney function and echocardiographic higher ejection fraction larger left atria and more diastolic dysfunction. Patients with RHD-AHF had a numerically longer mean stay in the hospital (10.5 vs. 8.8 days) and significantly higher initial hospitalization mortality (9.1% vs. 3.4%). Conclusions: In conclusion, patients with HF related to RHD were younger, have higher rate of atrial fibrillation and have a worse short-term outcome compared to HF related to other etiologies in Sub-Saharan Afric

Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?

Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions: In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients

Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS

Background: The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs. Methods and Results: We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P < .001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission. Conclusions: In patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality. Clinical Trial Registration: VERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433

Response to Letter Regarding Article, "Is Worsening Renal Function an Ominous Prognostic Sign in Patients With Acute Heart Failure? The Role of Congestion and Its Interaction With Renal Function"

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Glioblastoma and glioblastoma stem cells are dependent on functional MTH1

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target. We found MTH1 expression levels elevated and correlated with GBM aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. We revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. We used an orthotopic zebrafish model to confirm our results in vivo and light-sheet microscopy to follow the effect of MTH1 inhibition in GBM in real time. In conclusion, MTH1 represents a promising target for GBM therapy and MTH1 inhibitors may also be effective in patients that suffer from recurring disease

The causes, treatment, and outcome of acute heart failure in 1006 Africans From 9 countries

Background: Acute heart failure (AHF) in sub-Saharan Africa has not been well characterized. Therefore,wesought to describe the characteristics, treatment, and outcomes of patients admitted with AHF in sub-Saharan Africa. Methods: The Sub-Saharan Africa Survey of Heart Failure (THESUS–HF) was a prospective, multicenter, observational survey of patients with AHF admitted to 12 university hospitals in 9 countries. Among patients presenting with AHF, we determined the causes, treatment, and outcomes during 6 months of follow-up. Results: From July 1, 2007, to June 30, 2010, we enrolled 1006 patients presenting with AHF. Mean (SD) age was 52.3 (18.3) years, 511 (50.8%) were women, and the predominant race was black African (984 of 999 [98.5%]). Mean (SD) left ventricular ejection fraction was 39.5% (16.5%)... Conclusions: In African patients, AHF has a predominantly nonischemic cause, most commonly hypertension. The condition occurs in middle-aged adults, equally in men and women, and is associated with high mortality. The outcome is similar to that observed in non- African AHF registries, suggesting that AHF has a dire prognosis globally, regardless of the cause

Prognostic significance of creatinine increases during an acute heart failure admission in patients with and without residual congestion

Background: The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. Methods and Results: In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29–5.73) more days (P=0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06–2.09) times higher (P=0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. Conclusions: In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment

Gender differences in clinical characteristics and outcome of acute heart failure in sub-Saharan Africa: results of the THESUS-HF study

Background: The impact of gender on the clinical characteristics, risk factors, co-morbidities, etiology, treatment and outcome of acute heart failure in sub-Saharan Africa has not been described before. The aim of this study was to evaluate the sex diffe rences in acute heart failure in sub-Saharan Africa using the data from The sub-Saharan Africa Survey of Heart Failure (THESUS-HF). Methods and results: 1,006 subjects were recruited into this prospective multicenter, international observational heart failure survey. The mean age of total population was 52.4 years (54.0 years for men and 50.7 years for women). The men were significantly older (p = 0.0045). Men also presented in poorer NYHA functional class (III and IV), p = 0.0364). Cigarette smoking and high blood pressure were significantly commoner in men (17.3 vs. 2.6 % and 60.0 vs. 51.0 % respectively). On the other hand, atrial fibrillation and valvular heart disease were significantly more frequent in women. The mean hemoglobin concentration was lower in women compared to men (11.7 vs. 12.6 g/dl, p ≤ 0.0001), while the blood urea and creatinine levels were higher in men (p \u3c 0.0001). LV systolic dysfunctional was also seen more in men. Men also had higher E/A ratio indicating higher LV filling pressure. Outcomes were similar in both sexes. Conclusions: Although the outcome of patients admitted for AHF in sub-Saharan regions is similar in men and women, some gender differences are apparent suggesting that in men more emphasis should be put on modifiable life risk factors, while in women prevention of rheumatic heart diseases and improved nutrition should be addressed vigorously

Effects of serelaxin in patients admitted for acute heart failure:a meta-analysis

Aims: The effectiveness and safety of 48 h intravenous 30 μg/kg/day serelaxin infusion in acute heart failure (AHF) has been studied in six randomized, controlled clinical trials. Methods and results: We conducted a fixed-effect meta-analysis including all studies of intravenous serelaxin initiated within the first 16 h of admission for AHF. Endpoints considered were the primary and secondary endpoints examined in the serelaxin phase III studies. In six randomized controlled trials, 6105 total patients were randomized to receive intravenous serelaxin 30 μg/kg/day and 5254 patients to control. Worsening heart failure to day 5 occurred in 6.0% and 8.1% of patients randomized to serelaxin and control, respectively (hazard ratio 0.77, 95% confidence interval 0.67–0.89; P = 0.0002). Serelaxin had no statistically significant effect on length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration resulted in statistically significant improvement in markers of renal function and reductions in both N-terminal pro-B-type natriuretic peptide and troponin. No significant adverse outcomes were noted with serelaxin. Through the last follow-up, which occurred at an average of 4.5 months (1–6 months), serelaxin administration was associated with a reduction in all-cause mortality, with an estimated hazard ratio of 0.87 (95% confidence interval 0.77–0.98; P = 0.0261). Conclusions: Administration of intravenous serelaxin to patients admitted for AHF was associated with a highly significant reduction in the risk of 5-day worsening heart failure and in changes in renal function markers, but not length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration was safe and associated with a significant reduction in all-cause mortality.</p