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.
Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact ...of relative hypochromia in acute heart failure (AHF).
We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points.
Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4–2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3–1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21–1.76) and eGFR (HR 1.5, 95% CI 1.3–1.8, p < 0.001).
Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker.
•Relative hypochromia reflects iron status of acute heart failure patients.•Relative hypochromia is associated with adverse outcomes in acute heart failure.•Relative hypochromia independently predicts mortality even after adjusting for multiple comorbidities.•Testing for relative hypochromia is inexpensive and universally available and gives a chance for improving patient care in acute heart failure.
Beneficial microorganisms on the skin contribute to the first line of defense against attacking pathogens. However, instability of the skin microbiota is associated with skin diseases. Hence, ...temporal analyses are crucial because they serve as a baseline to understand the development of dysbiosis in disease. In this study, we aim to improve the understanding of the fungal skin microbiota, the mycobiota, in healthy subjects. Skin swabs were taken monthly for a year from four different skin sites, that is, antecubital crease, dorsal neck, glabella, and vertex, and analyzed by DNA sequencing of the internal transcribed spacer 1 region. The mycobiota on the skin was dominated by the class Malasseziomycetes, and the core community was composed of Malassezia restricta, M. globosa, and M. sympodialis at all skin sites. Over the period of 1 year, the intrapersonal mycobiota remained largely stable, with some fluctuations of low abundant non-Malassezia fungi. We conclude that despite fluctuations of low abundant classes, fungal skin communities form a temporally robust and individual fingerprint in healthy subjects.
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Commensal fungi such as
Malassezia
,
Candida
, and
Rhodotorula
are common on healthy skin but are also associated with opportunistic invasive and superficial infections. Skin microbial community ...characterization has been extensively performed worldwide, with a focus on the 16S bacterial community. These studies have focused on geographically distinct or targeted cohorts with variable reported species distributions of commensal yeast species. To determine the effects of extrinsic environmental factors such as geography, climate, and ethnicity on detected healthy skin commensal yeast diversity, we compared cohorts from Singapore and Zürich, Switzerland, representative of two geographically and climatically distinct regions comprising multi-ethnic (Chinese, Malay, Indian, Caucasian) and predominantly white Caucasian cohorts, respectively, using identical skin sampling and culture methods. We chose to use a culture-based approach as cultures isolated from patients are still required for studies of pathogenicity and antifungal susceptibility. Detection of yeast species by culture-dependent and independent sequencing-based methods suggest healthy skin diversity reflects a species distribution representative of the geography, climate and ethnic background of their local populations. Culture success and species diversity was also found to be dependent on climate, with warm tropical climates favoring high positive culture rates and greater species diversity. Multilocus sequence typing data suggests some strains are geographically distinct and may be used to segregate potential disease-causing commensals. For accurate collection and characterization of skin microbial communities, it remains recommended to employ a combination of culture-dependent and sequence-based culture-independent methods. Characterization of healthy mycobiomes in geographically distinct local populations will be useful in defining the role of commensal fungi in health and disease.
Highlights • Self-care/self-management is an essential part of chronic heart failure treatment. • Information on successful group program features/educational strategies is lacking. • A ...patient-centred self-management group program might be effective. • Dissemination within inpatient cardiac rehabilitation can be recommended.
Candidatus Neoehrlichia mikurensis DNA was discovered in Ixodes ricinus ticks in 1999 and is referred to as an emerging human pathogen since its first detection in patients with febrile illness ...reported in 2010. In recent years, Ca. Neoehrlichia mikurensis has been detected in ticks from several European, Asian, and African countries. However, no epidemiological data exist for Austria, which is a highly endemic region for tick-transmitted diseases. To assess the geographic spread and prevalence of Ca. Neoehrlichia mikurensis sympatric with other tick-transmitted pathogens, we analysed 518 I. ricinus ticks collected in 2002 and 2003 in Graz, Austria. The prevalence of Ca. Neoehrlichia mikurensis was 4.2%, that of Borrelia burgdorferi sensu lato 25.7%, and that of Anaplasma phagocytophilum 1%. Coinfections with Ca. Neoehrlichia mikurensis and B. burgdorferi sensu lato were found in 2.3% of all ticks. Thus, the results show a relatively high prevalence of Ca. Neoehrlichia mikurensis in Austrian ticks suggesting a high probability for the occurrence of undiagnosed human infections in Austria.
Chronic heart failure requires a complex treatment regimen on a life-long basis. Therefore, self-care/self-management is an essential part of successful treatment and comprehensive patient education ...is warranted. However, specific information on program features and educational strategies enhancing treatment success is lacking. This trial aims to evaluate a patient-oriented and theory-based self-management educational group program as compared to usual care education during inpatient cardiac rehabilitation in Germany.
The study is a multicenter cluster randomized controlled trial in four cardiac rehabilitation clinics. Clusters are patient education groups that comprise HF patients recruited within 2 weeks after commencement of inpatient cardiac rehabilitation. Cluster randomization was chosen for pragmatic reasons, i.e. to ensure a sufficient number of eligible patients to build large-enough educational groups and to prevent contamination by interaction of patients from different treatment allocations during rehabilitation. Rehabilitants with chronic systolic heart failure (n = 540) will be consecutively recruited for the study at the beginning of inpatient rehabilitation. Data will be assessed at admission, at discharge and after 6 and 12 months using patient questionnaires. In the intervention condition, patients receive the new patient-oriented self-management educational program, whereas in the control condition, patients receive a short lecture-based educational program (usual care). The primary outcome is patients' self-reported self-management competence. Secondary outcomes include behavioral determinants and self-management health behavior (symptom monitoring, physical activity, medication adherence), health-related quality of life, and treatment satisfaction. Treatment effects will be evaluated separately for each follow-up time point using multilevel regression analysis, and adjusting for baseline values.
This study evaluates the effectiveness of a comprehensive self-management educational program by a cluster randomized trial within inpatient cardiac rehabilitation in Germany. Furthermore, subgroup-related treatment effects will be explored. Study results will contribute to a better understanding of both the effectiveness and mechanisms of a self-management group program as part of cardiac rehabilitation.
German Clinical Trials Register: DRKS00004841; WHO International Clinical Trials: = DRKS00004841.
We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans (EM), the hallmark of early Lyme borreliosis.
In 50 patients, ...seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin-binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters.
Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing (60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i IgM response was significantly decreased to 24%.
No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment.
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