Pre-clinical In Vitro and In Vivo Models for Heart Valve Therapies

Heart valve disease is a frequently encountered pathology, related to high morbidity and mortality rates. Animal models are interesting to investigate the causality but also underlying mechanisms and potential treatments of human heart valve diseases. Strongly believing that both in vivo and ex vivo models are fundamental to support research and development of new technologies, we here report some examples of heart valve disease models, which in our experience have been actively used to support the development of new valve therapies

Long-term results of intensified, N-terminal-pro-B-type natriuretic peptide-guided versus symptom-guided treatment in elderly patients with heart failure: five-year follow-up from TIME-CHF

BACKGROUND Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left ventricular ejection fraction. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP-guided treatment strategy. METHODS AND RESULTS Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged≥60 years with left ventricular ejection fraction≤45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into prespecified age groups (60-74 and ≥75 years) during 18 months. A total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP-guided group. During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP-guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged≥75 years did not (P<0.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP-guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival. CONCLUSIONS Intensified, NT-proBNP-guided therapy did not improve the primary end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. These effects did not disappear after cessation of the NT-proBNP-guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP-guided group. CLINICAL TRIAL REGISTRATION URL: http://www.isrctn.org. Unique identifier: ISRCTN43596477

Long-term outcomes after intracoronary Beta-irradiation for in-stent restenosis in bare-metal stents

OBJECTIVE: We sought to characterize the long-term outcomes of patients undergoing intracoronary brachytherapy using Beta- irradiation (Beta-BT). BACKGROUND: Beta-BT is effective in reducing angiographic restenosis as well as target vessel revascularization (TVR) in patients with in-stent restenosis (ISR) after bare-metal stenting (BMS). METHODS: 81 consecutive patients undergoing Beta-BT for ISR (irradiated length 32 [32-54] mm) after BMS in native vessels (n = 79) or saphenous vein grafts (n = 2) between 2001 and 2003 were followed. Major cardiac events (MACE), including cardiac death, nonfatal myocardial infarction (MI), and TVR occurring < 1 year or < 1 year were assessed 5.2 (4.4-5.6) years after the index procedure. RESULTS: During the entire follow-up period, the total MACE rate was 49.4%. Within the first year and at < 1 year, MACE rates were 25.9% and 23.5%, cardiac death occurred in 2.4% and 6.2%, and nonfatal MI in 6.2% and 12.3% for annual cardiac death/MI rates of 8.7% at 32 mm (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.10-6.78; p = 0.03). The best, albeit not statistically significant, predictor of MACE occurring at < 1 year was the presence of diabetes mellitus (OR 2.49, 95% CI 0.94-6.57; p = 0.07). CONCLUSIONS: Patients undergoing Beta-BT for ISR after BMS carry a substantial risk of MACE also beyond the first year, with annual cardiac death and nonfatal MI rates of 1.5% and 2.9% up to 5 years postprocedure

Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale-Associated Stroke

Importance Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Observations Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. Conclusions and Relevance These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use