Search

AIMS In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. METHODS AND RESULTS MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C-terminal fragment of pre-pro-vasopressin (copeptin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and C-terminal pro-endothelin-1 (CT-proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow-up visits. Their performance to predict all-cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P

Aims Whereas guidelines recommend the routine use of natriuretic peptides (NPs) in heart failure (HF) care, the clinical relevance and prognostic potential of midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to compare the prognostic potential of MR-proADM after acute decompensation for systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial NP (MR-proANP), to investigate the significance of high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat measurements. Methods and results The Interdisciplinary Network Heart Failure (INH) programme enrolled patients hospitalized for acute systolic HF and followed them for 18 months (100% complete). Of 1022 INH participants, 917 (68 ± 12 years, 28% female) who had biomaterials available were enrolled. High MR-proADM was associated with more impaired left ventricular function, higher comorbidity burden, lower doses of HF medications, and lower likelihood of left ventricular reverse remodelling. Compared with NPs, MR-proADM had superior prognostic significance (concordance index 0.72 for all-cause mortality), improved Cox regression models including NPs (P < 0.001), and was the only biomarker also predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low NPs, patients with high MR-proADM experienced non-cardiac death more often. Six month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for prediction of all-cause death (net reclassification index: 0.48, 95% confidence interval 0.19–0.78). Conclusion MR-proADM was found to correlate with the global disease burden in HF and proved a potent prognostic indicator, capturing the risk for both cardiac and non-cardiac death. Serial MR-proADM measurements further enhanced risk assessment, thus facilitating substantial reclassification.

Background This study investigated the correlation of levels of and changes in serial high-sensitivity cardiac troponin I (hsTnI) with subsequent clinical event rates and changes in cardiac morphology and function in patients hospitalized for acutely decompensated heart failure (ADHF). Methods and results HsTnI levels were determined in 875 ADHF patients before discharge from hospital (baseline cohort) and clinical outcomes assessed after 180days. HsTnI was re-measured at 180days in 456/875 patients (follow-up cohort). Follow-up hsTnI values were grouped according to baseline hsTnI tertiles; echocardiographic changes from 0–180days and event rates from 180–540days were assessed in these subgroups. At baseline and 180-day follow-up, hsTnI levels were elevated (>0.06ng/mL) in 322/875 (37%) and 68/456 (15%) patients, respectively. At 180days, 85/875 patients (9.7%) had died (cardiovascular causes: 56/875 [6.4%]). Hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality (per two-fold hsTnI increase) were 1.2 (1.0–1.3; p=0.004) and 1.2 (1.1–1.4; p=0.001), respectively. In the follow-up cohort, 35/456 patients (7.7%) died between days 180 and 540 (cardiovascular death: 20/456, 4.4%). HsTnI was a significant predictor of cardiovascular re-hospitalization within 180–540days (HR 1.2, 95% CI 1.0–1.4; p=0.028). Patients with hsTnI in the lowest tertile at follow-up had more frequent and more pronounced reverse cardiac remodelling on echocardiography. Conclusions Elevated baseline hsTnI was common and associated with adverse clinical outcomes. Changes in hsTnI from baseline to 180-day follow-up predicted longer-term risk. Low or decreasing hsTnI was associated with better reverse cardiac remodelling and more favourable long-term outcomes. Clinical Trial Registration URL http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.

AIMS Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T-allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all-cause death and re-hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype. METHODS AND RESULTS Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing (n = 924) and randomization to usual care (UC, n = 464) or nurse-co-ordinated disease management (DM, n = 460). Follow-up was 180 days (100% complete). Compared with AT/AA carriers (n = 726), TT genotype carriers (n = 198) had more CPEP events [47% vs. 39%, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.01-1.61, P = 0.044] and were more frequently re-hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02-1.67, P = 0.033); mortality rate was similar in both groups (HR 1.11, 95% CI 0.68-1.81, P = 0.664). In subjects undergoing DM, CPEP and re-hospitalization occurred more often in TT (51% and 47%) than in AT/AA carriers (36% and 33%; HR 2.14, 95% CI 1.44-3.19, and HR 2.29, 95% CI 1.52-3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT/AA carriers (P = 0.009 and P = 0.005). With UC, event rates did not differ between genotype subgroups. CONCLUSION We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF, which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of 'personalized' medicine in HF. TRIAL REGISTRATION ISRCTN23325295.

Serum cortisol independently predicts mortality risk in patients with systolic heart failure. Salivary cortisol may provide advantages as it better reflects the biologically active free compound. Furthermore, sampling is non-invasive and may easily be performed in outpatients. We comparatively evaluated associations of morning (MSC) vs. evening salivary cortisol (ESC) and all-cause mortality risk.MSC (8 am) and ESC (9 pm) were determined in 229 patients with heart failure participating in the Interdisciplinary Network for Heart Failure program (66 ± 13 years; 21% female; 37% New York Heart Association (NYHA) class III/IV, median left ventricular ejection fraction 33%). The association of cortisol with mortality risk was determined by univariate and Cox multivariable regression analyses adjusting for age, sex, NYHA class, and N-terminal pro-hormone B-type natriuretic peptide. Compared to ESC, MSC was significantly higher and exhibited a higher variance: median 0.59 ng/ml (interquartile range 0.41-0.93) vs. 0.25 ng/ml (0.15-0.48), p0.001. During 18 months of follow-up, 25 (11%) patients died. In univariate and multivariable models mortality risk was not increased in the highest MSC quartile: crude hazard ratio (HR) 1.81 (95% confidence interval 0.79-4.14, p=0.160), adjusted HR 1.26 (0.51-3.13, p=0.616). However, patients in the highest ESC quartile had a significantly increased mortality risk, suggesting that associations of high ESC and increased mortality were independent of disease severity: crude HR 3.33 (1.50-7.42, p=0.003), adjusted HR 2.49 (1.01-6.14, p=0.047). ESC alone proved the best predictor of mortality.High ESC but not MSC levels independently predict increased mortality risk in heart failure.

Background Heart failure (HF) is a complex, chronic condition that is associated with debilitating symptoms, all of which necessitate close follow-up by health care providers. Lack of disease monitoring may result in increased mortality and more frequent hospital readmissions for decompensated HF. Remote patient management (RPM) in this patient population may help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a manifestation of HF decompensation. Objective The objective of the present article is to describe the design of a new trial investigating the impact of RPM on unplanned cardiovascular hospitalisations and mortality in HF patients. Methods The TIM-HF2 trial is designed as a prospective, randomised, controlled, parallel group, open (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. Eligible patients with HF are randomised (1:1) to either RPM + usual care or to usual care only and are followed for 12 months. The primary outcome is the percentage of days lost due to unplanned cardiovascular hospitalisations or all-cause death. The main secondary outcomes are all-cause and cardiovascular mortality. Conclusion The TIM-HF2 trial will provide important prospective data on the potential beneficial effect of telemedical monitoring and RPM on unplanned cardiovascular hospitalisations and mortality in HF patients.

Whereas guidelines recommend the routine use of natriuretic peptides (NPs) in heart failure (HF) care, the clinical relevance and prognostic potential of midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to compare the prognostic potential of MR-proADM after acute decompensation for systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial NP (MR-proANP), to investigate the significance of high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat measurements.The Interdisciplinary Network Heart Failure (INH) programme enrolled patients hospitalized for acute systolic HF and followed them for 18 months (100% complete). Of 1022 INH participants, 917 (68 ± 12 years, 28% female) who had biomaterials available were enrolled. High MR-proADM was associated with more impaired left ventricular function, higher comorbidity burden, lower doses of HF medications, and lower likelihood of left ventricular reverse remodelling. Compared with NPs, MR-proADM had superior prognostic significance (concordance index 0.72 for all-cause mortality), improved Cox regression models including NPs (P0.001), and was the only biomarker also predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low NPs, patients with high MR-proADM experienced non-cardiac death more often. Six month MR-proADM enhanced models including baseline MR-proADM (P0.001) for prediction of all-cause death (net reclassification index: 0.48, 95% confidence interval 0.19-0.78).MR-proADM was found to correlate with the global disease burden in HF and proved a potent prognostic indicator, capturing the risk for both cardiac and non-cardiac death. Serial MR-proADM measurements further enhanced risk assessment, thus facilitating substantial reclassification.

Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T-allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all-cause death and re-hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype.Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing (n = 924) and randomization to usual care (UC, n = 464) or nurse-co-ordinated disease management (DM, n = 460). Follow-up was 180 days (100% complete). Compared with AT/AA carriers (n = 726), TT genotype carriers (n = 198) had more CPEP events [47% vs. 39%, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.01-1.61, P = 0.044] and were more frequently re-hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02-1.67, P = 0.033); mortality rate was similar in both groups (HR 1.11, 95% CI 0.68-1.81, P = 0.664). In subjects undergoing DM, CPEP and re-hospitalization occurred more often in TT (51% and 47%) than in AT/AA carriers (36% and 33%; HR 2.14, 95% CI 1.44-3.19, and HR 2.29, 95% CI 1.52-3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT/AA carriers (P = 0.009 and P = 0.005). With UC, event rates did not differ between genotype subgroups.We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF, which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of 'personalized' medicine in HF.ISRCTN23325295.

AIM: This study investigates the prevalence and prognostic impact of central and small airways obstruction (CAO and SAO) in patients with stable heart failure (HF). METHODS & RESULTS: Spirometry was performed in 585 outpatients (mean age 65±12years, 75% male) six months after hospitalisation for acute decompensation secondary to HF with ejection fraction

Double sampling for stratification is a sampling design that is widely used for forest and other resource inventories in forest ecosystems. It is shown that this sampling design can be adapted to repeated inventories including estimators of net change, even for non-proportional allocation of second-phase units and periodically updated stratification. The method accounts for the transition of sampling units among strata. Moreover, it may outperform classical single phase designs if sample plots are appropriately allocated to strata with respect to predefined target variables, here: volume per ha of bigger trees of the main tree species. The latter requires a clear definition of predominant aims of the inventory and an appropriate optimization method. Access to inventory data of a state forest district from two occasions allowed for an optimization of the design based on the first occasion, which proved to be still advantageous on the following occasion. Estimators are developed under the infinite population approach, which is generally deemed more appropriate for forest inventories.

Our aim was to identify and validate DNA-methylation markers associated with very good outcome in node negative, hormone receptor positive breast cancer patients after adjuvant endocrine therapy which might allow identifying patients who could be spared the burden of adjuvant chemotherapy. Using a methylation microarray, we analysed 117 candidate genes in hormone receptor-positive tumours from 109 breast cancer patients treated by adjuvant tamoxifen. Results were validated in an independent cohort (n = 236, 5 centres). Independent methodological validation was achieved by a real-time polymerase chain reaction (PCR)-based technique. DNA methylation of PITX2 showed the strongest correlation with distant recurrence. Its impact on patient outcome was validated in the independent cohort: 86% of patients with low PITX2 methylation were metastasis-free after 10 years, compared to 69% with elevated PITX2 methylation. Moreover, PITX2 methylation added significant independent information to established clinical factors. All clinical and technical findings were confirmed by quantitative DNA-methylation PCR. These results provide strong evidence that DNA-methylation analysis allows clinically relevant risk assessment in tamoxifen-treated primary breast cancer. Based on PITX2 methylation, about half of hormone receptor-positive, node-negative breast cancer patients receiving adjuvant tamoxifen monotherapy can be considered low-risk regarding development of distant recurrences and may thus be spared adjuvant chemotherapy. In addition, these low-risk postmenopausal patients seem to respond sufficiently well to tamoxifen so that they may not require up-front aromatase inhibitor therapy.

Aim: To elucidate the prognostic role of procalcitonin (PCT) in patients with acute decompensated heart failure (ADHF) without clinical signs of infection at admission. Materials & Methods: Serial measurements of PCT and NT-proBNP were performed in 168 patients, aged 68 ± 10 years with ADHF followed by 3-month outcome evaluation. Results: Cox regression analysis demonstrated significant predictive value of baseline PCT for all-cause death/hospitalization (area under the curve: 0.67; p = 0.013) at 90th day. The patients with persistently elevated PCT or with an increase during the first 72 h of hospitalization had the worst prognosis (p = 0.0002). Conclusion: Baseline and serial in-hospital measurements of PCT have significant prognostic properties for 3-month all-cause mortality/hospitalization in patients with ADHF without clinical signs of infection at admission.