Martin Huelsmann

N-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study

OBJECTIVES This study was designed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided, intensive patient management (BM) to multidisciplinary care (MC) improves outcome in patients following hospitalization due to heart failure (HF). BACKGROUND Patients hospitalized due to HF experience frequent rehospitalizations and high mortality. METHODS Patients hospitalized due to HF were randomized to BM, MC, or usual care (UC). Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. NT-proBNP was used to define the level of risk and to monitor wall stress. This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance. RESULTS A total of 278 patients were randomized in 8 Viennese hospitals. After 12 months, the BM group had the highest proportion of antineurohormonal triple-therapy (difference among all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p = 0.01). Moreover, the combined end point of death or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Death rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02). CONCLUSIONS Compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization. (BNP Guided Care in Addition to Multidisciplinary Care; NCT00355017).

Comparison of Copeptin, B-Type Natriuretic Peptide, and Amino-Terminal Pro-B-Type Natriuretic Peptide in Patients With Chronic Heart Failure: Prediction of Death at Different Stages of the Disease

OBJECTIVES This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). BACKGROUND Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality. METHODS This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%]). RESULTS The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent single predictor of mortality in patients with NYHA functional class II (p < 0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of patients was best predicted by serum sodium, but again, copeptin added additional independent information. CONCLUSIONS Increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

Clinical ResearchHeart FailureN-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study

OBJECTIVES This study was designed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided, intensive patient management (BM) to multidisciplinary care (MC) improves outcome in patients following hospitalization due to heart failure (HF). BACKGROUND Patients hospitalized due to HF experience frequent rehospitalizations and high mortality. METHODS Patients hospitalized due to HF were randomized to BM, MC, or usual care (UC). Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. NT-proBNP was used to define the level of risk and to monitor wall stress. This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance. RESULTS A total of 278 patients were randomized in 8 Viennese hospitals. After 12 months, the BM group had the highest proportion of antineurohormonal triple-therapy (difference among all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p = 0.01). Moreover, the combined end point of death or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Death rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02). CONCLUSIONS Compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization. (BNP Guided Care in Addition to Multidisciplinary Care; NCT00355017).

N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients.

Objectives:Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. Design:Prospective, observational study. Setting:A tertiary intensive care unit in a university hospital. Patients:A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 ± 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 ± 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). Interventions:None. Measurements and Main Results:Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24–35,000] vs. 6776 [303–35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24–35,000] vs. 8390 [303–35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26–35,000], n = 202 vs. 3349 [24–35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (&khgr;2 = 35.6, p = .0001 and &khgr;2 = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome. Conclusions:NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.

Comparison of Midregional Pro-Atrial and B-Type Natriuretic Peptides in Chronic Heart Failure Influencing Factors, Detection of Left Ventricular Systolic Dysfunction, and Prediction of Death

OBJECTIVES Midregional pro-atrial natriuretic peptide (MR-proANP) was assessed for the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power compared with B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (HF). BACKGROUND MR-proANP is a biologically stable natriuretic peptide measured by a recently developed assay, with potential advantages over conventional natriuretic peptides such as BNP and NT-proBNP. METHODS We measured MR-proANP, BNP, and NT-proBNP in 797 patients with chronic HF. RESULTS All 3 natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [95% confidence interval (CI): 0.753 to 0.844]), BNP (0.803 [95% CI: 0.757 to 0.849]), and NT-proBNP (0.730 [95% CI: 0.681 to 0.778]). During a median observation time of 68 months, 492 (62%) patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables. Proportion of explained variation showed that NT-proANP (4.36%) was a significantly stronger predictor of death than both NT-proBNP (2.47%, p < 0.0001) and BNP (2.42%, p < 0.0001). CONCLUSIONS Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

Impact of tricuspid regurgitation on survival in patients with chronic heart failure: unexpected findings of a long-term observational study

AIMS Tricuspid regurgitation (TR) is common in patients with chronic heart failure (CHF) but its prognostic impact is unclear. METHODS AND RESULTS A total of 576 consecutive patients with CHF were prospectively included. The impact of moderate and severe (significant) TR on the combined endpoint death/heart transplantation/left ventricular-assist device implantation was assessed. Patients were followed for 5.8 ± 4.2 (maximum 14.4) years. Kaplan-Meier analysis showed a worse outcome of patients with significant TR (P < 0.0001). By multivariable analysis, amino terminal pro B-type natriuretic peptide (NT-proBNP) (P = 0.0028), systolic left ventricular function (LVF) (P = 0.0014), serum sodium, NYHA functional class, systolic blood pressure, right atrial size (all P = 0.0001), but not TR were significantly related with the outcome. However, as soon as the strong interaction between TR and LVF was included in the model, significant TR determined outcome as well (P = 0.0059). Therefore, in a second analysis patients were stratified for LVF. In patients with mildly or moderately impaired LVF, TR was significantly related with the outcome (HR: 1.368, CI: 1.070-1.748, P = 0.0125), whereas in patients with severely depressed LVF it was not (P = 0.1401). As a proof of concept, we additionally stratified patients according to serum NT-proBNP concentrations. In patients with NT-proBNP concentrations below the median (≤ 280 fmol/mL), TR was related with the outcome (HR: 2.512, CI: 1.127-5.597, P = 0.0242) but it was not in patients with NT-proBNP concentrations above the median (P = 0.3935). CONCLUSION The prognostic impact of TR depends on the severity of CHF. While TR was significantly related with excess mortality in mild to moderate CHF, it provided no additive value in advanced disease when compared with established risk factors.

Prognostic value of emerging neurohormones in chronic heart failure during optimization of heart failure-specific therapy.

BACKGROUND Serial measurements of neurohormones have been shown to improve prognostication in the setting of acute heart failure (HF) or chronic HF without therapeutic intervention. We investigated the prognostic role of serial measurements of emerging neurohormones and BNP in a cohort of chronic HF patients undergoing increases in HF-specific therapy. METHODS In this prospective study we included 181 patients with chronic systolic HF after an episode of hospitalization for worsening HF. Subsequently, HF therapy was gradually increased in the outpatient setting until optimized. We measured copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide before and after optimization of HF therapy. The primary endpoint was all-cause mortality at 24 months. RESULTS Angiotensin-converting enzyme/angiotensin receptor blocker and beta-blockers were increased significantly during the 3-month titration period (P < 0.0001 for both). In a stepwise Cox regression analysis adjusted for age, sex, glomerular filtration rate, diabetes mellitus, and ischemic HF, baseline and follow-up neurohormone concentrations were predictors of the primary endpoint as follows (baseline hazard ratios): copeptin 1.92, 95% CI 1.233-3.007, P = 0.004; midregional proadrenomedullin 2.79, 95% CI 1.297-5.995, P = 0.009; midregional proatrial natriuretic peptide 2.05, 95% CI 1.136-3.686, P = 0.017; C-terminal endothelin-1 precursor fragment 2.24, 95% CI 1.133-4.425, P = 0.025; B-type natriuretic peptide 1.46, 95% CI 1.039-2.050, P = 0.029. CONCLUSIONS In pharmacologically unstable chronic HF patients, baseline values and follow-up measures of copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide were equally predictive of all-cause mortality. Relative change of neurohormone values was noncontributory.

Cost analysis and cost‐effectiveness of NT‐proBNP‐guided heart failure specialist care in addition to home‐based nurse care

Eur J Clin Invest 2011; 41 (3): 315–322

Short-term effects of levosimendan and prostaglandin E1 on hemodynamic parameters and B-type natriuretic peptide levels in patients with decompensated chronic heart failure

Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects on hemodynamic parameters and outcome compared to dobutamine in decompensated chronic heart failure (CHF).

NT-proBNP has a high negative predictive value to rule-out short-term cardiovascular events in patients with diabetes mellitus

AIMS This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events. METHODS AND RESULTS A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. Of all variables analysed (age, gender, history of hypertension, ischaemic heart disease/any cardiac disease, smoking, duration of diabetes, body mass index, blood pressure, New York Heart Association-class, Dyspnoea score, Minnesota Living with Heart Failure Questionnaire, LDL-cholesterol, HbA(1c), creatinine, glomerular filtration rate), the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis (P < 0.0001). Bootstrapping with 500 samples supports this result in 95% samples. The negative predictive value of a normal value (<125 pg/mL) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98%. CONCLUSION We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus. With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events. NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers, in this unselected cohort.