Although B-type natriuretic peptide (BNP) is widely used as a biomarker for heart failure, the in vivo mechanical stimulus for its cardiac release remains poorly defined. We aimed to characterize the ...hemodynamic determinants of the transcardiac BNP gradient as a measure of myocardial BNP release by performing a detailed hemodynamic assessment in subjects with a broad spectrum of systolic and diastolic left ventricular dysfunction. Forty-two subjects underwent a detailed transthoracic echocardiographic study, right heart catheterization, and simultaneous BNP measurement in arterial and coronary sinus plasma. The transcardiac BNP gradient was lowest in subjects with normal left ventricular ejection fraction/high peak early diastolic annular velocity (n=11), intermediate in those with normal left ventricular ejection fraction/low peak early diastolic annular velocity (n=13), and highest in those with low left ventricular ejection fraction/low peak early diastolic annular velocity (n=18; 29 ng/L (range: 15 to 78 ng/L) versus 88 ng/L (range: 34 to 172 ng/L) versus 1566 ng/L (range: 624 to 2349 ng/L; P<0.001). Across the range of patients, left ventricular end-systolic wall stress (r(2)=0.51) and peak systolic mitral annular velocity (r(2)=0.47) showed the strongest correlation with higher transcardiac BNP gradient. In contrast, the transcardiac BNP gradient was weakly related to indices of diastolic load, including pulmonary capillary wedge pressure (r(2)=0.27) and left ventricular end-diastolic wall stress (r(2)=0.21). Across this spectrum of pathophysiology, left ventricular end-systolic wall stress appears to be the key mechanical stimulus influencing cardiac BNP release.
The pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using ...comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism.
In 65 patients with moderate or severe OSAS apnea–hypopnea index (AHI) 39±20/h and 33 patients with no or mild OSAS (AHI 8+4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP).
Patients with moderate/severe OSAS had higher insulin before sleep median (interquartile range), 36.4 (21.9–52.1) vs. 20.8 (10.6–32.8)mU/mL; p=0.006, higher IL-6 after sleep 1.00 (0.73–1.58) vs. 0.72 (0.48–0.94)pg/mL; p=0.005, and larger relative overnight reduction in BNP −9 (−35–0) vs. −3 (−21–13)%; p=0.04 than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69–0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep.
Significant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.
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•We measured a panel of biomarkers in patients with and without significant OSAS.•We found a relevant diurnal variation of a number of biomarkers in OSAS patients.•The association between biomarkers and OSAS depended on the time of measurement.•Insulin measured before sleep was an independent predictor of severe OSAS.•Interleukin-6 measured after sleep was an independent predictor of severe OSAS.
Background Contemporary heart failure (HF) patients are elderly and have a high rate of early rehospitalization or death, resulting in a high burden for both the patients and the health care system. ...Prior studies were focused on younger and less well-characterized patients. We aimed to identify predictors of early hospital readmission and death in elderly patients with HF. Methods Patients with chronic HF taking part in the TIME-CHF study (n = 614, age 77 ± 8 years, 41% female, left ventricular ejection fraction 35% ± 13%) were evaluated with respect to predictors of hospital readmission or death 30 and 90 days after inclusion. Demographic, clinical, laboratory, echocardiographic, and social variables were obtained at baseline and included in a multivariable logistic regression analysis to identify predictors of early events. Results The rate of hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason for hospitalization was HF in 33%, other cardiovascular in 32%, and noncardiovascular in 45% of the cases, respectively. Predictors of readmission or death at 30 days were angina, lower systolic blood pressure, anemia, more extensive edema, higher creatinine levels, and dry cough; and at 90 days were coronary artery disease, prior pacemaker implantation, high jugular venous pressure, pulmonary rales, prior abdominal surgery, older age, and depressive symptoms. Conclusions Early hospital readmission or death was frequent among elderly HF patients. A very large proportion of readmissions were due to noncardiovascular causes. In addition to clinical signs of HF, comorbidities are important predictors of early events in elderly HF patients.
Background Incidence, predictors, and prognostic impact of worsening renal function (WRF) in elderly patients with chronic heart failure (HF) undergoing intensive contemporary medical therapy are ...unknown. Methods and Results In 566 patients (age 77 ± 8 years) included in the TIME-CHF, serum creatinine (sCr) was repeatedly measured up to 6 months. Worsening renal function was classified as increase in sCr by 0.2 to 0.3 (WRFI), 0.3 to 0.5 (WRFII), or ≥0.5 mg/dL (WRFIII) within the first 6 months. Outcome events were assessed for 18 months. Results The incidence of WRF I, II, and III was 12%, 19%, and 22%, respectively. Worsening renal function III was associated with increased mortality (hazard ratio 1.98 95% CI 1.27-3.07, P = .002 vs no WRF), whereas WRF I/II was not. History of renal failure, spironolactone treatment, higher baseline dose, and higher maximal increase in loop diuretic dose were independently associated with the occurrence of WRF III, whereas angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and β-blocker use and allocation to N-terminal pro–B-type natriuretic peptide–guided management were not. Worsening renal function III was an independent predictor of death, death or hospitalization, and death or HF hospitalization also after adjusting for baseline characteristics. Conclusions One fifth of elderly patients with chronic HF experienced WRF III on 6-month intensive HF treatment. These patients had higher mortality, whereas patients with smaller sCr rises did not. Occurrence of WRF III was associated with high doses of loop diuretics and spironolactone use but not with other treatments.
Background
The new 2018 pulmonary hypertension (PH) definition includes a lower mean pulmonary artery pressure (mPAP) cut‐off (>20 mmHg rather than ≥25 mmHg) and the compulsory requirement of a ...pulmonary vascular resistance (PVR) ≥3 Wood units (WU) to define precapillary PH. We assessed the clinical impact of the 2018 compared to the 2015 PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR).
Methods
Severe AS patients (n = 487) undergoing pre‐AVR right heart catheterization were classified according to the 2015 and 2018 definitions. Post‐AVR mortality (median follow‐up 44 months) was assessed.
Results
Based on the 2015 definition, 66 (13%) patients exhibited combined pre and postcapillary PH (CpcPH), 116 (24%) isolated post‐capillary PH (IpcPH), 28 (6%) precapillary PH, and 277 (57%) no PH at all. Overall, 52 (11%) patients were reclassified: 23 no PH into IpcPH; 8 no PH into precapillary PH; 20 precapillary PH into no PH; 1 CpcPH into IpcPH. By the 2015 definition, only CpcPH patients displayed increased mortality, whereas by the 2018 definition, precapillary PH patients also experienced higher mortality than those without PH. Among the PH definition components, PVR ≥3 WU was the strongest predictor of death (hazard ratio > 4).
Conclusions
In severe AS, a higher number of IpcPH patients are diagnosed by the 2018 definition, even though they have the same prognosis as those without PH. Patients with true precapillary PH are more accurately identified by the 2018 definition that includes a pulmonary vascular disease criterion, that is, PVR ≥3 WU, a strong mortality predictor.
Aims
A budget impact analysis compared treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and iron deficiency (ID) in Switzerland with intravenous ferric carboxymaltose ...(FCM) or placebo.
Methods
Clinical data from four international randomized trials showed that FCM versus placebo treatment was associated with a reduced hospitalization rate due to HF. The budget impact of this was modelled over 1 year. Hospital treatment costs for HFrEF, FCM drug costs, and estimated patient numbers were based on published data, official tariffs, specially commissioned analyses of SwissDRG data, and clinical and diagnosis-related groups (DRG) coding expert opinion. The original cost year was 2015. Sensitivity analyses were conducted including updated unit costs from 2019/2020.
Results
FCM treatment was associated with average cost savings of Swiss Francs (SFr) 503 per patient per year from the perspective of the Swiss mandatory health insurance system. Extrapolating across all eligible HFrEF patients with ID in Switzerland, this amounted to estimated savings of SFr 23,336,873. Sensitivity analyses showed these results to be robust in the face of changes to input parameters like treatment costs, different hospital settings, updated unit costs, and including outpatient treatment and patient co-payments in the analysis.
Conclusions
The present analysis shows that using FCM to treat HFrEF patients with ID in line with current guideline recommendations resulted not only in medical benefits but also in significant cost savings. The analysis also provides an example of the pitfalls of transferring economic evaluation results, even between countries with similar hospital reimbursement systems.
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