Polyunsaturated fatty acids supplementation impairs anti-oxidant high-density lipoprotein function in heart failure.

BACKGROUND: The underlying reasons for the highly inconsistent clinical outcome data for omega-3-polyunsaturated fatty acids (n3-PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, double-blind, placebo controlled study was to determine the effects of oral treatment with n3-PUFAs on the anti-oxidant capacity of HDL in heart failure (HF) patients. METHODS: A total of 40 patients with advanced HF of nonischaemic origin, defined by NT-proBNP levels of >2000 pg/mL, NYHA class III or IV and a LVEF <35% who were on stable optimized medical therapy for ≥3 months, were consecutively enrolled into this prospective, double-blind, placebo-controlled trial and randomized in a 1:1:1 fashion to receive 1 g/day or 4 g/day of n3-PUFA, or placebo, respectively, for 12 weeks. RESULTS: After 12 weeks of treatment, the anti-oxidant function of HDL, measured by the HDL inflammatory index, was found significantly impaired in the treatment group in a dose-dependent fashion with 0.67 [IQR 0.49-1.04] for placebo vs 0.71 [IQR 0.55-1.01] for 1 g/day n3-PUFA vs 0.98 [IQR 0.73-1.16] for 4 g/day n3-PUFA (P for trend = 0.018). CONCLUSION: We provide evidence for an adverse effect of n3-PUFA supplementation on anti-oxidant function of HDL in nonischaemic heart failure patients, establishing a potential mechanistic link for the controversial outcome data on n3-PUFA supplementation.

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.

Repeat measurements of glycated haemoglobin A(1c) and N-terminal pro-B-type natriuretic peptide: divergent behaviour in diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus have a substantially increased risk of developing cardiovascular disease. However, the absolute risk greatly varies not only among patients, but the risk profile for an individual patient may also change over time. We investigated the prognostic role of repetitive measurements of Glycated haemoglobin A(1c) (HbA(1c) ) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with longstanding diabetes. MATERIALS AND METHODS: For this prospective, observational study data from 544 consecutive patients were collected between 2005 and 2008. HbA(1c) and NT-proBNP were measured at baseline and after 1 year. The median observation period was 40 months. Endpoints were all-cause mortality, cardiac, cardiovascular and all-cause hospitalizations. RESULTS: N-terminal pro-B-type natriuretic peptide concentrations significantly increased from 230 ± 385 to 280 ± 449 pg mL(-1) (P < 0·001); during the same time, HbA(1c) significantly decreased from 7·6 ± 1·5 to 7·3 ± 1·2 (P < 0·001). NT-proBNP was the best baseline predictor in a Cox regression model consisting of NT-proBNP, HbA(1c) , age, gender and duration of diabetes for all endpoints (P < 0·001). NT-proBNP at follow-up was the best predictor for the remaining period (P < 0·001, all endpoints). HbA(1c) at baseline and follow-up was predictive for all-cause hospitalizations (P = 0·005 both). In a third model that investigated the plasticity of both markers, changes in HbA(1c) concentration had no predictive value, but a change of NT-proBNP concentration was highly predictive (P = 0·025 all-cause mortality, P < 0·001 all other endpoints). CONCLUSIONS: N-terminal pro-B-type natriuretic peptide and HbA(1c) concentrations significantly diverged over a 1-year period. NT-proBNP was the most potent predictor of outcome at baseline and follow-up, and changes in NT-proBNP concentrations were linked to an altered risk profile, unlike changes in HbA(1c) levels.

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

BACKGROUND: Heart failure management programmes have been shown to reduce re-hospitalizations. We recently investigated a new disease management programme comparing usual care (UC) to home-based nurse care (HNC) and a HNC group in which decision-making was based on NT-proBNP levels (BNC). As re-hospitalization is the main contributing economic factor in heart failure expenditures, we hypothesized that this programme might be able to reduce costs and could be conducted cost effectively compared to UC. METHODS: One hundred and ninety congestive heart failure patients, who were included in a randomized trial to receive UC, HNC or BNC at discharge, were analysed in a cost-effectiveness model. Different models were applied to perform analysis of all medical costs, and the costs per year survived were chosen as an effectiveness parameter. RESULTS: Per patient costs because of heart failure treatment in the UC and the BNC group were € 7109 ± 11,687 and € 2991 ± 4885 (P=0·027), respectively. Corrected for death as a competing risk, the costs in the UC group were € 7893 ± 11,734 and were reduced by BNC to €3148 ± 4949 (P=0·012). Considering costs because of all-cause re-hospitalizations, calculated costs per year survived after discharge were € 19,694 ± 26,754 for UC, € 14,262 ± 25 330 for HNC (P > 0·05) and € 8784 ± 14,728 for BNC (t-test-based contrast P=0·015). In all models calculated, HNC was cost neutral. CONCLUSIONS: NT-BNP-guided heart failure specialist care in addition to home-based nurse care is cost effective and cheaper than standard care, whereas HNC is cost neutral.

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.

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure.

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.

B-type natriuretic peptide predicts benefit from a home-based nurse care in chronic heart failure.

BACKGROUND: Home-based nurse care (HBNC) can reduce adverse events in patients with chronic heart failure. However, which patients really benefit from such an intervention remains unclear. We investigated if B-type natriuretic peptide (BNP), a strong prognostic marker in chronic heart failure, can predict benefit from HBNC. METHODS AND RESULTS: After discharge from heart failure hospitalization, 96 patients were randomized to either HBNC for 12 months or usual care. The combined endpoint of death or heart failure hospitalization was evaluated after 12 and 24 months. The median value of BNP (267 pg/mL) was used as a cutoff value to predict benefit from the HBNC. HBNC reduced the endpoint after 12 (P = .013) and 24 months (P = .033, relative risk [RR] (95% confidence intervals): 0.42 [0.20-0.78] and 0.55 [0.31-0.98], respectively). This benefit from HBNC was dependent on BNP. In patients with supramedian BNP, the endpoint was significantly reduced after 12 (P = .002) and 24 months (P = .003, RR: 0.39 [0.20-0.76] and 0.50 [0.30-0.83], respectively), whereas in patients with inframedian BNP no significant changes occurred. CONCLUSIONS: A high BNP can predict benefit from HBNC in patients with chronic heart failure and may assist in selecting patients for such an intervention.

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.

Prognostic value of sequential measurements of amino-terminal prohormone of B-type natriuretic peptide in ambulatory heart failure patients.

BACKGROUND: We evaluated the prognostic value of sequential NT-proBNP values in ambulatory heart failure patients after discharge, investigating whether the current value or the recent percent change is more important. METHODS AND RESULTS: In 166 patients, NT-proBNP was measured at discharge from heart failure hospitalisation and three months later. The combined endpoint of death or heart failure rehospitalisation was evaluated after a maximum of 18 months or at follow-up closure. During a mean observation time of 14+/-4 months, 63 patients (38%) reached the endpoint. In multiple Cox analysis, NT-proBNP three months after discharge (NT-proBNP-3Mo) and NT-proBNP percent change (NT-proBNP-%change) were the only independent predictors of the endpoint among various clinical and laboratory variables. After definition of a high- (n=83, 57% endpoints) and a low-NT-proBNP patient subgroup (n=83, 19% endpoints) according to the median NT-proBNP-3Mo (1751 pg/ml), NT-proBNP-%change was the strongest predictor in the high-NT-proBNP subgroup. In the low-NT-proBNP subgroup, NT-proBNP-3Mo was the only independent predictor. CONCLUSIONS: In ambulatory heart failure patients, the prognostic value of sequential NT-proBNP measurements depends on the magnitude of the current NT-proBNP value. Recent percent changes in NT-proBNP provide important prognostic information in patients with high NT-proBNP but not in patients with low NT-proBNP.

Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure.

BACKGROUND: In advanced chronic heart failure (CHF) 20% of patients do not tolerate beta-blockers and 50% do not reach target doses. AIM: To test whether levosimendan or prostaglandin E1 (PGE1) can facilitate uptitration of beta-blockers in advanced CHF. METHODS AND RESULTS: Seventy-five advanced CHF patients (LVEF<35%, NYHA class IIIb or IV) intolerant to beta-blocker uptitration to target doses (10 mg bisoprolol/day) were randomised to a monthly 24 h infusion with levosimendan (n=39) or a chronic infusion with PGE1 (n=36) for 3 months. Bisoprolol was uptitrated following predefined criteria. At 12 weeks, bisoprolol dose increased from 4 mg to 10 mg in both groups. Heart failure worsening occurred in 29 levosimendan patients (74%) versus 16 PGE1 patients (44%, p=0.008). Uptitration was impossible in 9 levosimendan patients (23%) versus 2 PGE1 patients (6%, p=0.03). The combined endpoint of death or urgent heart transplantation or implantation of a ventricular assist device was reached by 12 levosimendan patients (31%) versus 4 PGE1 patients (11%, p=0.04). After 1 year, LVEF increased from 23+/-7% to 28+/-11% (p=0.0004), and BNP decreased from 994+/-806 to 659+/-564 pg/ml (p=0.03). CONCLUSION: Levosimendan and PGE1 facilitate uptitration of beta-blockers in previously intolerant CHF patients. PGE1 treatment allowed uptitration in more patients and resulted in a better clinical outcome compared to levosimendan. This approach increased LVEF and decreased BNP after 1 year.

Quality of medical therapy in heart failure patients undergoing elective revascularisation: A protective effect of disease modifying therapy at discharge.

The STICH(-ES) trial showed that coronary artery bypass grafting was superior to medical therapy alone in treating ischemic heart failure. However, dosages of disease modifying drugs were not reported. We included 128 (84% male, mean age 66 ± 11 years) consecutive patients with ischemic heart failure and an ejection fraction ≤35% undergoing isolated elective coronary artery bypass grafting. We defined optimal medical therapy (OMT) as prescription of ≥50% dosages of guideline recommended medications (i.e. beta-blocker (BB) and renin angiotensin system (RAS) antagonist) plus prescription of a mineralocorticoid receptor antagonist (MRA). The mean logistic EuroSCORE was 12.3 ± 13.8%. The five year survival was 74%. At discharge, 111 patients (87%) were on a BB and 106 (83%) were on a RAS antagonist. Forty-nine patients (38%) received an MRA. Only 8 patients (6%) received OMT. A Cox regression analysis revealed EuroSCORE (p < 0.001) and the use of MRA (p = 0.003) and BB (p = 0.037) at discharge as significant predictors of 5 year survival. Prescription rates of heart failure medication are comparable to those reported in the STICH trial, but rates of OMT are very low at admission and discharge. Prescription of BB and MRA was associated with improved survival, highlighting the need for disease management programs and rigorous discharge management.

Heart transplantation provides long-term survival benefit in stable patients experiencing heart failure without reverse left ventricular remodeling.

BACKGROUND: Heart transplantation does not provide short-term survival benefit in stable patients experiencing chronic heart failure (CHF) with optimized medical therapy. This study compared the outcome of stable patients with CHF with patients after heart transplantation in the long-term. METHODS: Between January 1995 and September 1997, 318 potential transplant candidates (New York Heart Association class III or IV, left ventricular ejection fraction [LVEF] <35%) were evaluated. After three months of therapeutic optimization, 108 patients were stable outpatients with maximally uptitrated neurohormonal antagonists. Seventy of the 318 patients underwent transplantation between January 1995 and December 1997. RESULTS: After an observation period of 7 to 10 years, stable patients with CHF had a significantly lower survival compared with transplanted patients (hazard ratio, 0.90; 95% confidence interval, 0.83-0.98; P=0.01). One-year LVEF (> or =30%) was the best independent predictor of long-term survival. Patients with an LVEF > or =30% had a similar survival; patients with an LVEF <30% had a significantly lower survival (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001) compared with transplanted patients. CONCLUSION: Not in the short term (1.5 years) but in the long term (7-10 years), heart transplantation seems to provide survival benefit in stable patients with CHF except in patients with improved LVEF (> or =30%) after medical optimization.

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

BACKGROUND: Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects on hemodynamic parameters and outcome compared to dobutamine in decompensated chronic heart failure (CHF). AIMS: We compared short-term effects of levosimendan versus PGE1 on hemodynamic parameters and B-type natriuretic peptide levels (BNP) in patients with decompensated CHF. METHODS AND RESULTS: 73 patients (cardiac index < 2.5 L/min/m2, pulmonary capillary wedge pressure (PCP) >15 mmHg) with decompensated CHF were randomised to treatment with either a 24 h-infusion of levosimendan (n=38) or a chronic infusion of PGE1 (n = 35). Hemodynamic parameters and BNP were measured at baseline, 24 and 48 h, BNP levels were also measured after 1 week. Baseline characteristics including concomitant medication were similar in both groups. Levosimendan and PGE1 increased cardiac output (CO) after 24 and 48 h. Levosimendan increased CO twice as much as PGE1 (24 h: Levosimendan +1.1 +/- 0.1 L/min, PGE1 +0.6 +/- 0.1 L/min, p < 0.001). Both drugs produced a comparable reduction in PCP and pulmonary artery pressure after 24 and 48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but effects disappeared after 1 week. In contrast, PGE1 decreased BNP by 15% after 48 h (no change at 24 h), but a decrease of 20% was sustained at 1 week. CONCLUSIONS: The differential beneficial effects of levosimendan (greater increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact on clinical outcome.

Prognostic impact of workload in patients with congestive heart failure.

AIMS: Recent data underline the prognostic value of cardiopulmonary exercise parameters (eg, peak oxygen consumption [PVO2]), percentage of predicted oxygen consumption [ppVO2], ventilation, and workload) in patients with congestive heart failure. These parameters were not yet compared in a multivariate analysis. METHODS AND RESULTS: To detect the superiority of one of these parameters, in a prospective 1-year follow-up study we investigated 226 patients with heart failure. The end point of the study was combined death and prioritization for urgent cardiac transplantation within 1 year. Cardiopulmonary exercise testing was performed with evaluation of peak oxygen consumption, percentage of predicted peak oxygen consumption, peak carbon dioxide production, ventilation, workload, anaerobic threshold, and ventilation/carbon dioxide production ratio. All variables were univariate predictors of 1-year mortality and urgent transplantation. Multivariate analysis demonstrated that only workload and ventilation were independently related to 1-year mortality and urgent cardiac transplantation, whereas peak oxygen consumption or percentage of predicted peak oxygen consumption did not reach statistical significance in this model. CONCLUSION: Workload on bicycle stress test correlates to 1-year mortality. More important, workload is a more powerful predictor of 1-year survival compared with established markers such as pVO2 or ppVO2.

Prognostic power of neurohumoral parameters in chronic heart failure depends on clinical stage and observation period.

BACKGROUND: Endothelin (ET) and natriuretic peptides have prognostic significance in chronic heart failure (CHF). Because stimuli for forming these neurohormones differ, this study investigates whether their prognostic power depends on clinical stage and on length of the observation period. METHODS: Plasma big ET, B-type natriuretic peptide (BNP), N-terminal BNP (N-BNP), and N-terminal atrial natriuretic peptide (N-ANP), in addition to 11 clinical and hemodynamic variables, were obtained from 452 patients with left ventricular ejection fraction (LVEF)

Circadian variation in ventricular tachycardia and atrial fibrillation in a medical-cardiological ICU.

OBJECTIVE: To assess the diurnal distribution of ventricular tachycardia (VT) and atrial fibrillation (AF) in critically ill patients. DESIGN AND SETTING: Prospective observational study (episode-based design) in an eight-bed medical/cardiological ICU at a university hospital that also admits postoperative patients. PATIENTS: 98 consecutive patients with AF ( n=55) or ventricular tachycardia ( n=43). MEASUREMENTS AND RESULTS: There were a total of 218 arrhythmia episodes (83 AF, 136 VT). The time of arrhythmia onset was not evenly distributed. Circadian variation in VT but not AF onset was well represented by a sine wave function. Both VT and AF fibrillation showed a trough during the night. The distribution of VT and AF episodes did not differ significantly with or without analgosedation. CONCLUSIONS: In critically ill patients the onset of VT and AF over 24-h is nonuniformly distributed. In VT this circadian pattern of occurrence is well modeled by a sine wave function peaking between noon and 2 p.m. The circadian pattern is less clear for AF. The circadian variation is seen irrespective of the presence of absence of analgosedation for both arrhythmias.

Portable recording for detecting sleep disorder breathing in patients under the care of a heart failure clinic.

BACKGROUND: Sleep disordered breathing (SDB) has important clinical implications in patients with congestive heart failure (CHF). We performed portable recording in unselected CHF patients on contemporary therapy. Data on the interactions of SDB in patients supervised at heart failure clinics are rare and we illustrate diversities of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA). METHODS: We studied 176 consecutive subjects on contemporary medical therapy with a median left ventricular ejection fraction of 25.0 % (range 7-35%) and median NT-pro BNP levels of 3,413.0 pg/ml (range 305.1-35,000.0 pg/ml). Participants underwent prospective overnight portable recording. RESULTS: 50% presented with an at least moderate form of nocturnal breathing disorder [apnoea-hypopnoea index (AHI) ≥15/h]. Only 15 patients (17.1%) with AHI ≥15/h reported excessive daytime sleepiness. Irrespective of left ventricular ejection fraction, patients with CSA had higher levels of NT-pro BNP compared to patients with OSA (differences in medians = 2,639.0 pg/ml, p = 0.016), and compared to patients with an AHI <15/h (differences in medians = 2,710.0 pg/ml, p < 0.001). OSA affected 26 patients (14.8%). CONCLUSIONS: Patients with severe stable CHF on contemporary therapy have a prevalence of 50.0% of moderate to severe SDB. The natural cascade of the failing heart is initially characterised by absent SDB or OSA, whereas end-stage CHF is associated with CSA.

PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.

OBJECTIVES: The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP). BACKGROUND: Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context. METHODS: A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years. RESULTS: At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all). CONCLUSIONS: Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952).