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.
Objectives The purpose of this study was to invasively investigate the hemodynamic response to exercise in patients with heart failure with normal ejection fraction (HFNEF) and to evaluate the ...ability of the peak early diastolic transmitral velocity to peak early diastolic annular velocity ratio (E/e′) to reflect exercise hemodynamics. Background There is little information regarding the hemodynamic response to exercise in HFNEF. Methods Patients with HFNEF (n = 14) and asymptomatic controls (n = 8) underwent right-side heart catheterization at rest and during supine cycle ergometer exercise and echocardiography with measurement of resting and peak exercise E/e′. Results Resting pulmonary capillary wedge pressure (PCWP) (10 ± 4 mm Hg vs. 10 ± 4 mm Hg; p = 0.94) was similar in HFNEF patients and controls, but stroke volume index (SVI) (p = 0.02) was lower, and systemic vascular resistance index (SVRI) (p = 0.01) was higher in patients. Patients stopped exercise at lower work rate (0.63 ± 0.29 W/kg vs. 1.13 ± 0.49 W/kg; p = 0.006). Although peak exercise PCWP was similar in both groups (23 ± 6 mm Hg vs. 20 ± 7 mm Hg; p = 0.31), the peak PCWP/work rate ratio was higher in patients compared with controls (46 ± 31 mm Hg/W/kg vs. 20 ± 9 mm Hg/W/kg; p = 0.03). Peak exercise SVI (p = 0.001) was lower and SVRI was higher (p = 0.01) in patients. Resting E/e′ was modestly elevated in patients (13.2 ± 4.1 vs. 9.5 ± 3.4; p = 0.04). Peak exercise E/e′ did not differ between the groups (11.1 ± 3.4 vs. 9.4 ± 3.4; p = 0.28). Conclusions The HFNEF patients achieved a similar peak exercise PCWP to that of asymptomatic controls, at a much lower workload. This occurs at a lower SVI and in the setting of higher SVRI. The E/e′ does not reflect the hemodynamic changes during exercise in HFNEF patients.
Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there ...are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP) has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA.
Non-invasive testing is recommended as a basis to decide about the indication for invasive coronary angiography (ICA) in patients with suspected stenotic coronary artery disease (CAD). However, a ...recent study based on insurance claims data reported that one third of patients undergoing ICA in Switzerland did not have non-invasive testing beforehand. We aimed to re-evaluate the practice of testing prior to ICA in Switzerland by manual review of patient histories.
Retrospective analysis of all 816 consecutive patients (age 67±9 years, 70% males) undergoing elective ICA solely for the evaluation of stenotic CAD during the year 2015 in a single center in Eastern Switzerland. The proportion of patients undergoing a non-invasive test was assessed, and predictors of the lack of such a test were determined.
764/816 (94%) patients had a non-invasive test prior to ICA. The majority of patients (728/816; 89%) had an exercise stress test, one fifth (160/816; 20%) underwent a test other than an exercise stress test (6% scintigraphy, 4% stress echocardiography, 6% stress magnetic resonance imaging, 4% computed tomography coronary angiography), and 122/816 (15%) patients had two tests. The use of antianginal drugs other than beta-blockers odds ratio 1.92 (95% confidence interval 1.01-3.66); p = 0.047 and a lower left ventricular ejection fraction odds ratio 0.97 (95% confidence interval 0.94-0.99) per one % point increase; p = 0.005 were independent predictors of the lack of a non-invasive test. ICA revealed stenotic CAD in 72% of patients, and 54% of patients underwent revascularization. Patients with and without non-invasive tests did not differ with respect to ICA findings and management.
The present analysis suggests that patients are appropriately selected for ICA based on clinical judgement and non-invasive testing in Switzerland. There is no evidence for an overuse of ICA.
This study sought to determine the potential pathophysiological link between anemia and disease severity, and adverse outcome in heart failure (HF).
Anemia frequently accompanies advanced HF; ...however, the pathophysiological mechanism responsible for the association between anemia and more severe HF remains uncertain. We hypothesized that a depletion of myocardial iron content may provide the biological link.
Complementary clinical and basic studies were performed. Hemodynamic, biochemical, and echocardiographic investigations were performed in 9 healthy controls and 25 patients with advanced HF (left ventricular ejection fraction: 23 ± 10%). Tissue iron content and type 1 transferrin receptor (Tfr1) expression were assessed in human myocardial tissue, and the regulation of Tfr1 expression was studied in isolated cardiomyocytes.
HF patients displayed evidence of iron deficiency as measured by lower serum iron (p < 0.05) and transferrin saturation (TFS) (p < 0.05). When subclassified according to the presence of anemia, TFS was lower in anemic compared with nonanemic HF patients, whereas TFS in nonanemic HF patients was intermediate. In association, myocardial iron content was reduced in HF versus non-HF samples (0.49 ± 0.07 μg/g vs. 0.58 ± 0.09 μg/g, p < 0.05), and there was a significant reduction (p < 0.05) in the myocardial mRNA expression of Tfr1, which plays a key role in cellular iron transport. In the context of HF, catecholamines and aldosterone both down-regulated Tfr1 expression in isolated cardiomyocytes.
This study suggests the presence of iron depletion in the failing human heart, providing a potential link for the association between anemia and adverse prognosis in HF.
Aims
We aimed to investigate the prevalence, detailed invasive haemodynamics, and prognostic impact of pulmonary hypertension (PH) in severe aortic stenosis (AS).
Methods and results
We studied 503 ...patients (mean age 74 ± 10 years) with severe AS (indexed aortic valve area 0.4 ± 0.1 cm2/m2, left ventricular ejection fraction 57 ± 12%) undergoing left and right heart catheterization prior to aortic valve replacement. Median follow‐up was 3.7 (interquartile range 2.6–5.4) years. Baseline PH (mean pulmonary artery pressure ≥ 25 mmHg) was found in 239 (48%) patients: 31 patients had pre‐capillary PH mean pulmonary artery wedge pressure (mPAWP) ≤ 15 mmHg, 144 had isolated post‐capillary PH IpcPH; mPAWP > 15 mmHg, pulmonary vascular resistance (PVR) ≤ 3 Wood units (WU), and 64 had combined pre‐ and post‐capillary PH (CpcPH; mPAWP > 15 mmHg, PVR > 3 WU). Patients with CpcPH had higher mortality than those with IpcPH, pre‐capillary PH, and without PH. In the multivariate analysis, CpcPH remained an independent predictor of death (hazard ratio 4.39, 95% confidence interval 2.40–8.03; P < 0.001). Patients with CpcPH had higher mPAWP (26 ± 7 vs. 22 ± 5 mmHg) and lower pulmonary arterial capacitance (1.5 ± 0.6 vs. 2.9 ± 1.2 mL/mmHg) than IpcPH patients but similar left ventricular end‐diastolic pressure (LVEDP; 25 ± 7 vs. 25 ± 7 mmHg). A smaller LVEDP–mPAWP difference was related to larger left atrial size, atrial fibrillation, and more severe mitral regurgitation.
Conclusions
In patients with severe AS, PH is common but underlying mechanisms differ. Patients with CpcPH have higher mPAWP, lower pulmonary arterial capacitance, and worse survival than all other groups. Left atrial dysfunction and mitral regurgitation seem to be drivers of high mPAWP in CpcPH.
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•Heart failure was identified in 2% of patients with type 1 diabetes.•Heart failure was identified in 16% of patients with type 2 diabetes.•Of the identified cases of heart failure, ...60% were previously undiagnosed.•Of the newly identified cases, 61 % had undergone echocardiography within 2 years.•There is a need to raise awareness of heart failure among healthcare professionals.
To evaluate the prevalence of heart failure (HF) in patients with diabetes in tertiary care, and the implementation of sodium-glucose co-transporter 2 inhibitor (SGLT2i).
Between 28.09.2020 and 31.03.2022, patients enrolled in the Swiss Diabetes Registry at one study centre were screened for HF based on the recommendations by the European Society of Cardiology. Indicated patients were referred for echocardiography and a clinical evaluation of HF, further stratified by preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) left ventricular ejection fraction.
In total, 534 patients were screened (31.5%, type 1 diabetes (T1D); 59.7%, type 2 diabetes (T2D); 8.8%, other forms). Overall, HF was present in 11.2% (HFpEF, 56.7%; HFmrEF, 11.7%; HFrEF, 31.7%). Prevalence by diabetes type was 2.4%, T1D; 16.0%, T2D; and 10.6%, other forms. Of the identified cases, 40.0% were previously diagnosed and 60.0% were diagnosed as a result of the screening. Of the 24 patients with previously known HF, 50.0% were prescribed SGLT2i (including 2 out of 3 patients with HFrEF).
The fact that most cases of HF were previously undiagnosed and treatment with SGLT2i could be improved highlights the need to increase awareness of HF among healthcare professionals treating patients with diabetes.
Aims
While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown ...whether patients with HF and mid‐range LVEF (HFmrEF, LVEF 40–49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy.
Methods and results
The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME‐CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be ‘intermediate’ regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow‐up of 794 days, mortality was 39.7% without significant differences between groups. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP)‐guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF.
Conclusion
Although the ‘intermediate’ clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT‐proBNP‐guided therapy in HFrEF and HFmrEF, in contrast to HFpEF.
There is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely ...defined.
Consecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed.
Among all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e′). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e′, left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up.
Approximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease.
Aims
The aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) ...and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF.
Methods and results
A total of 458 HFrEF (LVEF ≤40%) and 112 HFpEF (LVEF ≥50%) patients aged ≥60 years with NYHA class ≥II from TIME‐CHF were included. Endpoints are 18‐month overall and HF hospitalization‐free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor‐like 1 ST2; 37.6 (28.5–54.7) vs. 35.7 (25.6–52.2), P = 0.02, high sensitivity C‐reactive protein (hsCRP; 8.54 (3.39–25.86) vs. 6.66 (2.42–15.39), P = 0.01), and cystatin‐C 1.94 (1.57–2.37) vs. 1.75 (1.39–2.12), P = 0.01. In contrast, HFrEF patients exhibited higher NT‐proBNP 2142 (1473–4294) vs. 4202 (2239–7411), P < 0.001, high sensitivity troponin T hsTnT; 27.7 (16.8–48.0) vs. 32.4 (19.2–59.0), P = 0.03, and haemoglobin 124 (110–135) vs. 134 (122–145), P < 0.001. In addition to these clinical characteristics, NT‐proBNP, haemoglobin, cystatin‐C, hsTnT, and ST2 improved the area under the curve from 0.86 (0.82–0.89) to 0.91 (0.87–0.94; P < 0.001) for discriminating HFpEF from HFrEF. There were no significant interactions between HFpEF and HFrEF when considering the prognostic value of the investigated biomarkers (P > 0.10 for both endpoints), except for cystatin‐C which had less prognostic impact in HFpEF (P < 0.01).
Conclusion
Biomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin‐C, and for NT‐proBNP in the NT‐proBNP‐guided study arm only, both of which had less prognostic value in HFpEF.
Trial registration
ISRCTN43596477
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