Extended heart failure clinic follow-up in low-risk patients: a randomized clinical trial (NorthStar).

BACKGROUND: Outpatient follow-up in specialized heart failure clinics (HFCs) is recommended by current guidelines and implemented in most European countries, but the optimal duration of HFC programmes has not been established. Nor is it known whether all or only high-risk patients, e.g. identified by NT-proBNP, might benefit from an extended HFC follow-up. METHODS AND RESULTS: In a multi-centre setting, we randomly assigned 921 clinically stable systolic heart failure (HF) outpatients on optimal medical therapy to undergo either an extended follow-up in the HFC (n = 461) or referral back to their general practitioner (GP) (n = 460). The primary composite endpoint was death or a cardiovascular admission. Secondary endpoints included mortality, an HF admission, quality of life, number of days admitted, and number of admissions. The median age of the patients was 69 years; 23% were females; the median left ventricular ejection fraction was 0.30; and the median NT-proBNP was 801 pg/mL; 89% were in NYHA class I-II. The median follow-up was 2.5 years. Time-to-event did not differ between groups (HFC vs. GP) (HR: 1.17, 95% CI: 0.95-1.45, P = 0.149). The two groups did not differ with respect to any of the secondary endpoints at the follow-up (P> 0.05 for all). In high-risk patients identified by NT-proBNP ≥1000 pg/mL, no benefit from HFC follow-up was found (P = 0.721). CONCLUSION: Irrespective of the level of NT-proBNP stable HF patients on optimal medical therapy do not benefit from long-term follow-up in a specialized HFC in a publicly funded universal access healthcare system. Heart failure patients on optimal medical therapy with mild or moderate symptoms are safely managed by their personal GP. TRIAL REGISTRATION: www.Centerwatch.com: 173491 (NorthStar).

Prevalence and inter-relationship of different Doppler measures of dyssynchrony in patients with heart failure and prolonged QRS: a report from CARE-HF.

BACKGROUND: Cardiac resynchronisation therapy (CRT) improves mortality and morbidity in heart failure patients with wide QRS. Observational studies suggest that patients having more left ventricular dyssynchrony pre-implantation obtain greater benefit on ventricular function and symptoms with CRT. AIM: To provide an analysis of the prevalence and type of dyssynchrony in patients included in the CARE-HF trial. METHODS: 100 patients 67 (58 to 71) years were examined with echocardiography including tissue doppler imaging before receiving a CRT-pacemaker. Atrio-ventricular dyssynchrony (LVFT/RR) was defined as left ventricular filling time <40% of the RR-interval. Inter-ventricular mechanical delay (IVMD) was measured as the difference in onset of Doppler-flow in the pulmonary and aortic outflow tracts >40 ms. Intra-ventricular (regional) dyssynchrony in a 16-segment model was expressed either as a delayed longitudinal contraction (DLC) during the postsystolic phase or by tissue synchronisation imaging (TSI) with a predefined time-difference in systolic maximal velocities >85 ms. RESULTS: LVFT/RR was present in 34% and IVMD in 60% of patients while intra-ventricular dyssynchrony was present in 85% (DLC) and 86% (TSI) with a high agreement between the measures (Kappascore 0.86-1.00), indicating the methods being interchangeable. Patients with cardiomyopathy (53%) were more likely to have LVFT/RR <40% (45% vs. 21% (p= 0.02)) and more segments affected by intra-ventricular dyssynchrony 4(3, 5) vs. 3(1, 4), p = 0.002, compared to patients with ischemic heart disease. CONCLUSION: The prevalence of intra-ventricular dyssynchrony is high in patients with heart failure, wide QRS and depressed systolic function. Most important, TSI appears to be a fast and reliable method to identify patients with intra-ventricular dyssynchrony likely to benefit from CRT.

Design and methodology of the NorthStar Study: NT-proBNP stratified follow-up in outpatient heart failure clinics -- a randomized Danish multicenter study.

BACKGROUND: Randomized clinical trials have shown that newly discharged and symptomatic patients with chronic heart failure (CHF) benefit from follow-up in a specialized heart failure clinic (HFC). Clinical stable and educated patients are usually discharged from the HFC when on optimal therapy. It is unknown if risk stratification using natriuretic peptides could identify patients who would benefit from longer-term follow-up. Furthermore, data on the use of natriuretic peptides for monitoring of stable patients with CHF are sparse. AIMS: The aims of this study are to test the hypothesis that clinical stable, educated, and medical optimized patients with CHF with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > or = 1,000 pg/mL benefit from long-term follow-up in an HFC and to assess the efficacy of NT-proBNP monitoring. METHODS: A total of 1,250 clinically stable, medically optimized, and educated patients with CHF will be enrolled from 18 HFCs in Denmark. The patients will be randomized to treatment in general practice, to a standard follow-up program in the HFC, or to NT-proBNP monitoring in the HFC. The patients will be followed for 30 months (median). RESULTS: Data will be collected from 2006 to 2009. At present (March 2008), 720 patients are randomized. Results expect to be presented in the second half of 2010. CONCLUSIONS: This article outlines the design of the NorthStar study. If our hypotheses are confirmed, the results will help cardiologists and nurses in HFCs to identify patients who may benefit from long-term follow-up. Our results may also indicate whether patients with CHF will benefit from adding serial NT-proBNP measurements to usual clinical monitoring.

Effects of pentoxifylline on the vascular response to injury after angioplasty in rabbit iliac arteries.

Pentoxifylline (PTX) inhibits the effects of several cytokines and reduces injury-related collagen accumulation. The aim of the present study was to investigate the effect of PTX on the vascular response to injury. We treated rabbits with PTX (100 mg/kg/day) or placebo (saline) subcutaneously from 2 days before angioplasty of an iliac artery until euthanasia 7 or 28 days later. At 7 days after injury, PTX treatment was associated with a more differentiated (less proliferation, more smoothelin-positive) intimal smooth muscle cell phenotype. Furthermore, PTX reduced myofibroblast accumulation in adventitia. At 28 days after injury, PTX-treated rabbits had a 48.5% larger lumen area (P = 0.03) and a 28.1% larger area within the external elastic lamina (P = 0.04). There were no significant differences between PTX-treated rabbits and the placebo group with regard to neointima and media area. Angioplasty induced marked neoadventitial hyperplasia, which was reduced by 20.5% (P = 0.01) in the PTX-treated group. Finally, PTX reduced collagen density in all three arterial layers. We conclude that PTX treatment induces less proliferation within the vessel wall early after angioplasty and increases late lumen size after angioplasty by a positive effect on vascular remodeling.

Adventitial myofibroblasts play no major role in neointima formation after angioplasty.

OBJECTIVE: Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts. DESIGN: Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for alpha-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype). RESULTS: Adventitial cells became transiently actin-positive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82 +/- 10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen. CONCLUSION: At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.