Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).
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.
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.
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.
The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days.
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%).
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.
ClinicalTrials.gov Identifier: NCT00512759.
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.
Abstract Background This study aims
to determine whether small vessel disease (SVD) or vasospastic disease (VSD) has an impact on prognosis. Methods The prospective cohort embraced 718 patients with ...angina equivalent symptoms and no coronary stenosis ≥ 50% recruited between 1997 and 2008. At baseline, patients were classified as having
SVD, VSD, other cardiac disease or non-cardiac problem based on intracoronary acetylcholine application and fast atrial pacing during coronary angiography. Patients underwent follow-up between 2007 and 2015. Prognostic significance of the diagnosis on cardiovascular events (cardiovascular death or non-fatal myocardial infarction) was evaluated using Cox proportional hazards models adjusted for age and sex. Results The mean follow-up duration was 11.3 ± 2.7 years. Only 11 patients (1.5%) were lost to follow-up, resulting in an analyzed population of 707 patients. Patients with SVD (HR: 4.9, 95% CI: 1.1–22.4, P = 0.040) and VSD (HR: 4.8, 95% CI: 1.0–23.4, P = 0.050) had an increased risk of suffering cardiovascular events compared to patients with non-cardiac problems. Among SVD patients, those with the presence of endothelial dysfunction had a particularly high risk (HR: 7.3, 95% CI: 1.5–35.5, P = 0.015). Among patients with SVD or VSD, those having persisting or worsening angina during follow-up had a higher risk than patients in whom angina improved (HR: 4.8, 95% CI: 1.9–12.3, P = 0.001). Conclusions Our study shows that patients with SVD or VSD have an increased risk of cardiovascular events. This particularly applies to SVD patients with endothelial dysfunction. Symptoms should be taken seriously in SVD and VSD patients. Trial registration : ClinicalTrials.gov Identifier: NCT01318629
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Abstract Background The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective ...cohort. This study is aimed to identify the cause of angina in these patients. Methods This prospective cohort comprised 718 consecutive patients with angina equivalent symptoms and no CAD (defined as no coronary stenosis ≥ 50%) between January 1st 1997 and July 31st 2008. All patients underwent additional invasive testing (intracoronary acetylcholine administration, fast atrial pacing). Small vessel and vasospastic diseases were diagnosed according to symptoms and vessel reaction during testing. Results Mean age was 56.3 ± 11.0 years (range 15 to 81 years). A majority of 431 patients (60.0%) had small vessel and/or vasospastic disease (233 patients had small vessel disease, 145 vasospastic disease and 53 a combination of both). Additional 87 patients (12.1%) had another cardiac disease. Only in a minority of 200 study participants (27.9%) that the symptoms were attributed to an extracardiac problem. Patients with small vessel disease were more likely to be female, to have hypertension, to have a family history of CAD and to have effort-related symptoms. Patients with vasospastic disease were more likely to be current smokers, to have angina at rest or to present as myocardial infarction, and to have coronary sclerosis and/or endothelial dysfunction. Conclusions In a majority of patients with angina but no significant CAD, a cardiac cause of their symptoms can be found. Systematical invasive testing may help optimizing the medical management of these patients.
PCDD/PCDF were determined in solid samples from wood combustion. The samples included grate ashes, bottom ashes, furnace ashes as well as fly and cyclone ashes. The solid waste samples were ...classified into bottom and fly ash from native wood and bottom and fly ash from waste wood. For each of the four classes concentration distribution patterns from individual congeners, the sums of PCDD/PCDF and the international toxicity equivalents (I-TEQ) values are given. The I-TEQ levels of fly ash from waste wood burning can be approximately up to two thousand times higher than the values from fly ashes of natural wood. The I-TEQ levels in bottom ashes from waste wood combustion systems are as low as the corresponding ashes from the combustion of native wood. Grate ash samples from waste wood combustion systems with low carbon burnout show high levels of PCDD/PCDF.
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