Intracoronary cell therapy following percutaneous coronary intervention for AMI appears to provide statistically and clinically relevant benefits on cardiac function and remodeling. These data confirm the beneficial impact of this novel therapy and support further multicenter randomized trials targeted to address the impact of intracoronary cell therapy on overall and event-free long-term survival.

Background-Cardiac resynchronization therapy was shown to reverse left ventricular (LV) remodeling in patients with congestive heart failure (CHF). However, the prediction of benefit is controversial. We aimed to investigate predictive factors of LV functional recovery and reversed remodeling after biventricular pacing. Methods and Results-Forty-nine consecutive patients with CHF and a wide QRS complex (182Ϯ32 ms) were studied by echocardiography before resynchronization. Intraventricular and interventricular asynchrony and their combination were assessed by pulsed-wave tissue Doppler imaging from measurements of regional electromechanical coupling times in basal segments of the right and left ventricle. At 6-month follow-up, responders were defined by a relative increase in LV ejection fraction Ն25% compared with baseline (nϭ27). Receiver operating curve analysis revealed the degree of intraventricular asynchrony (area under the curveϭ0.77), interventricular asynchrony (area under the curveϭ0.69), and their combination (area under the curveϭ0.84) as the best predictors of functional recovery after resynchronization. In addition, the degree of intraventricular and interventricular asynchrony correlated significantly with the improvement of LV ejection fraction (rϭ0.

Background-Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR. Methods and Results-In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was Ն0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; nϭ138). When FFR was Ͻ0.80, coronary artery bypass grafting was performed (surgical group; nϭ75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (Pϭ0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (Pϭ0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (rϭϪ0.38, PϽ0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis Ͻ50%, the left main coronary artery stenosis was hemodynamically significant by FFR. Conclusions-In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made "blindly" about the need for revascularization. (Circulation. 2009;120:1505-1512.)

Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides-ANP, BNP, CNP-that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor-mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre-proBNP and then enzymatically cleaved to BNP and the Nterminal portion of BNP(NT-proBNP). Blood measurements of BNP and NT-proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.

Objectives Aims were to investigate 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; 3) expression of ST2, membrane-anchored ST2L, and its ligand, IL-33, in myocardium, endothelium and leukocytes from patients with LV pressure overload and congestive cardiomyopathy. Background Serum levels of ST2 are elevated in heart failure. Relationship of ST2 with hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown. Methods Serum ST2 (pg/mL; median [25th-75th]) was measured in patients with LV hypertrophy (aortic stenosis, AS, N=45), congestive cardiomyopathy (CCM N=53), and Controls (N=23). ST2 was correlated to NT-pro BNP, CRP and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. ST2, ST2L and IL-33 were measured (RT-PCR) in myocardial biopsies and leukocytes; ST2 protein production was evaluated in human endothelial cells. IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium Results ST2 was elevated in AS (103[65-165], p<0.05) and CCM (194[69-551], p<0.01) vs. Controls (49[4-89]) and correlated with BNP (r=0.5; p<0.05), CRP (r=0.6; p<0.01) and LV EDP (r=0.38, p<0.03). LV ST2 mRNA was similar in AS and CCM vs. Control (NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r=0.97, p<0.001). Conclusions In human hypertrohy and failure, serum ST2 correlates with diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.

The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238).

AimsCardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort.Methods and resultsThis multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death.ConclusionThe primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

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