IMPORTANCE: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). OBJECTIVE: To evaluate the effect of a ...strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. INTERVENTIONS: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. RESULTS: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths 14.4%) and in 111 patients (27.8%) in the usual care group (including 61 deaths 15.3%) (absolute difference for the primary end point, 2.8% 95% CI, −3.7% to 9.3%; adjusted hazard ratio, 1.07 95% CI, 0.83-1.39; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). CONCLUSIONS AND RELEVANCE: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00512759
Aims
We aimed to assess the long‐term effect of a strategy of comprehensive vasodilation versus usual care on health‐related quality of life (HRQL) among patients with acute heart failure (AHF).
...Methods and results
Health‐related quality of life was prospectively assessed by the generic 3‐levelled EQ‐5D and the disease‐specific Kansas City Cardiomyopathy Questionnaire (KCCQ) among adult AHF patients enrolled in an international, multicentre, randomised, open‐label blinded‐end‐point trial of a strategy that emphasized early intensive and sustained vasodilation using maximally tolerated doses of established oral and transdermal vasodilators according to systolic blood pressure. Changes in EQ‐5D and KCCQ from admission to 180 day follow‐up were individually compared between the intensive vasodilatation and the usual care group. Among 666 patients eligible for 180 day follow‐up, 284 (43%, median age 79 years, 35% women) and 198 (30%, median age 77 years, 35% women) had completed the EQ‐5D and KCCQ at baseline and follow‐up, respectively. There was a significant improvement in HRQL as quantified by both, EQ‐5D and KCCQ, from hospitalization to 180 day follow‐up, with no significant differences in the change of HRQL between both treatment strategies. For instance, 39 (26%) versus 33 (25%) patients had an improvement by at least one level in at least two categories in the EQ‐5D. Median increase in KCCQ overall summary score (KCCQ‐OSS) was 17.6 (IQR 2.0–42.6) in the intervention group versus 18.5 (IQR 3.9–39.3) in the usual care group (P < 0.001 vs. baseline, P = 0.945 between groups).
Conclusions
Among patients with AHF, long‐term HRQL quantified by EQ‐5D and KCCQ improved substantially, with overall no significant differences between a strategy of comprehensive vasodilation versus usual care.
Aims
Sex‐specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF ...therapies in women and men separately.
Methods and results
We performed a pre‐defined sex‐specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open‐label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2). The primary endpoint, a composite of all‐cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05–2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up‐titration of renin–angiotensin–aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men).
Conclusion
Rapid up‐titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all‐cause mortality and rehospitalization for AHF.
Clinical Trial Registration:
ClinicalTrials.gov, unique identifier NCT00512759.
In patients randomized to a strategy of early intensive and sustained vasodilatation or usual care, the combined primary endpoint showed a significant interaction of treatment strategy and sex. Women randomized to intervention significantly more often experienced the combined endpoint when comapred to standard of care. AHF, acute heart failure. Correction added on 15 January 2024, after first online publication: abbreviation has been added in this version.
Heart failure (HF) is a syndrome, whose advanced forms have a poor prognosis, which is aggravated by the presence of comorbidities.
We assessed the impact of infection in patients with decompensated ...HF admitted to a tertiary university-affiliated hospital in the city of São Paulo.
This study assessed 260 patients consecutively admitted to our unit because of decompensated HF. The presence of infection and other morbidities was assessed, as were in-hospital mortality and outcome after discharge. The chance of death was estimated by univariate logistic regression analysis of the variables studied. The significance level adopted was P < 0.05.
Of the patients studied, 54.2% were of the male sex, and the mean age ± SD was 66.1 ± 12.7 years. During hospitalization, 119 patients (45.8%) had infection: 88 (33.8%) being diagnosed with pulmonary infection and 39 patients (15.0%), with urinary infection. During hospitalization, 56 patients (21.5%) died, and, after discharge, 36 patients (17.6%). During hospitalization, 26.9% of the patients with infection died vs 17% of those without infection (p = 0.05). However, after discharge, mortality was lower in the group that had infection: 11.5% vs 22.2% (p = 0.046).
Infection is a frequent morbidity among patients with HF admitted for compensation of the condition, and those with infection show higher in-hospital mortality. However, those patients who initially had infection and survived had a better outcome after discharge.
•We explore cardiac/inflammatory biomarkers to predict in-hospital mortality in endocarditis.•Troponin concentration measured at admission showed the highest accuracy for mortality ...prediction.•Inflammatory biomarkers had better accuracy at the 7th day than at admission.
Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE.
Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality.
Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8–6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4–5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3–3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1–3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1–2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0–3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759).
S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.
The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments.
The extent ...of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324).
In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF 1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both
< 0.001, respectively. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF 41 (24-71) versus 33 (19-59) ng/L,
< 0.001. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10;
< 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort.
Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.
A recently published study raised doubts about the need for percutaneous treatment of nonculprit lesions in patients with acute coronary syndromes (ACS).
Retrospective, unicentric, observational ...study.
To analyze the long-term outcomes in patients undergoing treatment of the culprit artery, comparing those who remained with significant residual lesions in nonculprit arteries (group I) versus those without residual lesions in other coronary artery beds (group II). The study included 580 patients (284 in group I and 296 in group II) between May 2010 and May 2013. We obtained demographic and clinical data, as well as information regarding the coronary treatment administered to the patients. In the statistical analysis, the primary outcome included combined events (reinfarction/angina, death, heart failure, and need for reintervention). The comparison between groups was performed using the chi-square test and ANOVA. The long-term analysis was conducted with the Kaplan-Meier method, with a mean follow-up of 9.86 months.
The mean ages were 63 years in group I and 62 years in group II. On long-term follow-up, there was no significant difference in combined events in groups I and II (31.9% versus 35.6%, respectively, p = 0.76).
The strategy of treating the culprit artery alone seems safe. In this study, no long-term differences in combined endpoints were observed between patients who remained with significant lesions compared with those without other obstructions.
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