Prevalence of Microvascular and Endothelial Dysfunction in the Nonculprit Territory in Patients With Acute Myocardial Infarction.

BACKGROUND: Approximately half of the patients presenting with ST-segment-elevation myocardial infarction (STEMI) have multivessel disease. The physiology of the nonculprit artery has not been thoroughly studied to date. We sought to characterize the coronary physiology of the nonculprit artery in the early phase after STEMI and determine the real prevalence of microvascular and endothelial dysfunction. METHODS AND RESULTS: Patients with STEMI and another coronary artery lesion in a different territory were prospectively included in an observational single-center study. The protocol took place after revascularization of the culprit artery and comprised 3 phases: first, epicardial endothelial functional assessment using intracoronary acetylcholine; second, epicardial severity quantification based on fractional flow reserve, and nonendothelial microvascular function with coronary flow reserve and the index of microvascular resistance; third, endothelium-dependent microvascular function assessment based on the endothelial coronary flow reserve. Eighty-four patients were included. Mean age was 62±10 years, and 86.9% were men. Only 6 subjects had a nonpathological study: macrovascular endothelial dysfunction was present in 60% of the patients; fractional flow reserve ≤0.8, coronary flow reserve <2, and index of microvascular resistance >25 were evident in 34%, 37%, and 28% of the subjects respectively; and microvascular endothelial dysfunction (endothelial coronary flow reserve <1.5) was observed in 44%. In hospital-mortality was 0%, and no major complications occurred. At 6-month follow-up, there were no events related to the nonculprit artery. CONCLUSIONS: Microvascular and endothelial dysfunction in the nonculprit artery territory in patients with STEMI are very common. In 93% of the patients, we found functional abnormalities. Acetylcholine administration in the early phase post-STEMI in patients with multivessel disease is safe.

Determinants of platelet count are different in patients with compensated and decompensated cirrhosis.

BACKGROUND & AIMS: Different mechanisms including portal hypertension and hypersplenism have been involved in the development of thrombocytopenia in cirrhosis. However, the relative contribution of each one is unknown. The aim was to evaluate simultaneously different mechanisms that determine platelet count in cirrhosis. METHODS: Cross-sectional study including cirrhotics (n = 120) with hepatic venous pressure gradient (HVPG) measurement. Samples were obtained from peripheral (P) veins to evaluate thrombopoietin (TPO), stem cell factor, hepatocyte growth factor (HGF), tumour necrosis factor, interleukin-(IL6) and (IL11) and from hepatic (H) veins to evaluate TPO. A subgroup (n = 72) had spleen volume estimation. H and P-TPO were also measured in non-cirrhotic patients (n = 15). RESULTS: Patients (Child A: 55, B: 43, C: 22) had a median platelet count of 81 000/mm(3) (IQR 60 500, 110 750), which correlated with spleen volume (r = -0.38, P < 0.001). Platelets were associated also to HVPG (r = -0.47, P = 0.004) and P-TPO (r = 0.31, P = 0.050) only in compensated patients. H-TPO decreased, and the proportion of patients with P-TPO > H-TPO increased, with the presence and the severity of liver disease. H-TPO was correlated with liver function (bilirubin r = -0.350, P < 0.001 and international normalized ratio r = -0.227, P = 0.011). Patients with H-TPO < P-TPO had higher levels of IL-11 and HGF. CONCLUSION: Platelet count in cirrhosis is associated mainly to spleen volume, although portal hypertension as estimated by HVPG and liver function plays a significant role in compensated patients. H-TPO and the proportion of patients with P-TPO > H-TPO were associated to the presence and severity of liver disease.

Acellular human heart matrix: A critical step toward whole heart grafts.

The best definitive treatment option for end-stage heart failure currently is transplantation, which is limited by donor availability and immunorejection. Generating an autologous bioartificial heart could overcome these limitations. Here, we have decellularized a human heart, preserving its 3-dimensional architecture and vascularity, and recellularized the decellularized extracellular matrix (dECM). We decellularized 39 human hearts with sodium-dodecyl-sulfate for 4-8 days. Cell removal and architectural integrity were determined anatomically, functionally, and histologically. To assess cytocompatibility, we cultured human cardiac-progenitor cells (hCPC), bone-marrow mesenchymal cells (hMSCs), human endothelial cells (HUVECs), and H9c1 and HL-1 cardiomyocytes in vitro on dECM ventricles up to 21 days. Cell survival, gene expression, organization and/or electrical coupling were analyzed and compared to conventional 2-dimensional cultures. Decellularization removed cells but preserved the 3-dimensional cardiac macro and microstructure and the native vascular network in a perfusable state. Cell survival was observed on dECM for 21 days. hCPCs and hMSCs expressed cardiocyte genes but did not adopt cardiocyte morphology or organization; HUVECs formed a lining of endocardium and vasculature; differentiated cardiomyocytes organized into nascent muscle bundles and displayed mature calcium dynamics and electrical coupling in recellularized dECM. In summary, decellularization of human hearts provides a biocompatible scaffold that retains 3-dimensional architecture and vascularity and that can be recellularized with parenchymal and vascular cells. dECM promotes cardiocyte gene expression in stem cells and organizes existing cardiomyocytes into nascent muscle showing electrical coupling. These findings represent a first step toward manufacturing human heart grafts or matrix components for treating cardiovascular disease.

Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement.

BACKGROUND: Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial tree's behavior could be influenced by the valvular obstruction. OBJECTIVES: This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention. METHODS: Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up. RESULTS: Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy. CONCLUSIONS: Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedure's acute afterload relief.

Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial.

BACKGROUND: The effect of intracoronary adenosine (ADO) on ST-segment elevation myocardial infarction (STEMI) size and adverse remodeling is not well established. METHODS: In a double-blind trial, 201 patients with STEMI were randomized to receive percutaneous coronary intervention (PCI) within 6 hours of symptom onset, 4.5mg ADO or saline immediately prior to reperfusion. Primary end-point: percentage of total myocardial necrotic mass by cardiac magnetic resonance (CMR) 2-7 days post-reperfusion. Secondary end-points: changes in left ventricular volumes and ejection fraction (LVEF) at baseline and at 6 months. RESULTS: Baseline CMR could not be performed in 20 patients. Overall, no significant differences were observed between ADO and placebo regarding infarct size (20.8% vs. 22.5%; p=0.40). However, infarct size was significantly reduced (19.4% vs. 25.7%; p for interaction=0.031) in those with ischemia duration below the median (200 min). CMR at 6 months, performed in 138 patients, did not show statistically significant differences between groups in the rate of LVEF increase (3.3 units (SD 9.6) in ADO group vs. 1.5 units (SD 9) in placebo group; p=0.25). In the subgroup analysis, among patients with ischemia time below 200 min, the increase in LVEF was slightly higher with ADO (3.59% vs. 0.43%; p for interaction=0.06). CONCLUSIONS: Although our study failed to demonstrate that intracoronary administration of ADO prior to PCI limits infarct size, in patients receiving early PCI ADO might enhance myocardial salvage and has a favorable effect on LVEF evolution, which may help to reconcile apparently contradictory results of previous studies. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov (NCT00781404).

Direct injury to right coronary artery in patients undergoing tricuspid annuloplasty.

BACKGROUND: Direct injury to the right coronary artery as a result of reparative operation on the tricuspid valve is a rare, probably underdiagnosed, but serious complication, which often involves dramatic clinical consequences. So far, only five cases have been described in the literature. METHODS: We describe our single-center experience of this complication, and review and analyze relevant clinical and anatomic considerations related to this entity. Cases previously reported in the literature were also reviewed. RESULTS: We describe four cases of direct injury to the right coronary artery in patients undergoing tricuspid annuloplasty (DeVega annuloplasty, 3; ring annuloplasty, 1) in our institution since 2005. All patients had right ventricular dilatation and severely dilated tricuspid annulus. Right coronary artery occlusion always occurred between the right marginal artery and the crux of the heart. Patients presented with hemodynamic or electrical instability. Coronary flow could be restored in 2 patients (percutaneously 1; surgically 1), both of whom finally survived, while it was not technically possible in the other 2 (1 died). CONCLUSIONS: Occlusion of the right coronary artery in patients undergoing tricuspid annuloplasty is a rare complication that may occur if great annulus dilatation is present, thus altering both normal annular geometry and the relationship between the right coronary artery and the tricuspid annulus, particularly when DeVega annuloplasty is performed. Such an entity should be considered in the immediate postoperative period in an unstable patient, especially when complementary tests support this diagnosis. Prompt recognition and treatment can positively affect the patient's outcome, most often by means of an emergency revascularization strategy.

The Ibero-American transcatheter aortic valve implantation registry with the CoreValve prosthesis. Early and long-term results.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The aim of this study was to describe early experience and long-term follow-up with the CoreValve self-expanding aortic prosthesis at 42 Ibero-American hospitals. METHODS: Multiple centre observational study including 1220 consecutive patients with symptomatic severe aortic stenosis who are not suitable candidates for surgery and underwent transcatheter aortic valve implantation with the self-expanding Medtronic CoreValve System between December 2007 and May 2012. RESULTS: The registry included 1220 consecutive patients with a mean age of 80.8 ± 6.3 years and a mean logistic euroSCORE of 17.8% ± 13%. The procedural success rate was 96.1%. Hospital mortality was 7.3% and combined end-point was 21.3%. Aortic regurgitation after TAVI was present in 24.5% (Sellers grade ≥ 2). The estimated 1-year and 2-year survival rates were 82.1% and 73.4% respectively. The following issues were significant independent risk factors for hospital mortality: acute kidney failure (odds ratio 3.55); stroke (odds ratio 5.72); major bleeding (odds ratio 2.64) and euroSCORE (odds ratio 1.02). Long-term predictors of mortality were diabetes mellitus (hazard ratio 1.59, 95% confidence interval 1.09-2.31), severe chronic obstructive pulmonary disease (hazard ratio 1.85, 95% confidence interval 1.85-2.88), and functional classes NYHA III-IV (hazard ratio 1.31, 95% confidence interval 1.01-1.70). CONCLUSIONS: Transcatheter aortic valve implantation constitutes a safe and viable therapeutic option for high operative risk patients with severe aortic stenosis. Long-term prognosis is conditioned by associate comorbidities.

Comparison of paclitaxel-eluting stents (Taxus) and everolimus-eluting stents (Xience) in left main coronary artery disease with 3 years follow-up (from the ESTROFA-LM registry).

Evidence regarding therapy with drug-eluting stents in the left main coronary artery (LM) is based mostly on trials performed with first-generation drug-eluting stents. The aim of this study was to evaluate long-term clinical outcomes after treatment for unprotected LM disease with paclitaxel-eluting stents (PES) and everolimus-eluting stents (EES). The ESTROFA-LM is a multicenter retrospective registry including consecutive patients with unprotected LM disease treated with PES or EES. A total of 770 patients have been included at 21 centers, 415 with treated PES and 355 with EES. Treatment with 2 stents was more frequent with PES (17% vs 10.4%, p = 0.007), whereas intravascular ultrasound was more frequently used with EES (35.2% vs 26%, p = 0.006). The 3-year death and infarction survival rates were 86.1% for PES and 87.3% for EES (p = 0.50) and for death, infarction, and target lesion revascularization were 83.6% versus 82% (p = 0.60), respectively. Definite or probable thrombosis was 1.6% for PES and 1.4% for EES (p = 0.80). The use of 2 stents, age, diabetes, and acute coronary syndromes were independent predictors of mortality. In the subgroup of distal lesions, the use of intravascular ultrasound was an independent predictor of better outcome. Comparison of propensity score-matched groups did not yield differences between the 2 stents. In conclusion, the results of this multicenter registry show comparable safety and efficacy at 3 years for PES and EES in the treatment of LM disease. The use of bifurcation stenting techniques in distal lesions was a relevant independent predictor for events. The use of intravascular ultrasound appears to have a positive impact on patients treated for LM distal disease.

Panoramic view of the Fifth International Symposium on Stem Cell Therapy and Applied Cardiovascular Biotechnology, April 2008, Madrid (Spain).

The Fifth International Symposium on Stem Cell Therapy and Applied Cardiovascular Biotechnology was held on April 24th-25th, 2008, at the Auditorium of the High Council of Scientific Research of Spain (CSIC) in Madrid, as a continuation of a series of yearly meetings, organized in an attempt to encourage translational research in this field and facilitate a positive interaction among experts from several countries, along with industry representatives and journalists. In addition, members of the Task Force of the European Society concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart gathered and discussed an update of the previous consensus, still pending of publication. In this article, we summarize some of the main topics of discussion, the state-of-the-art and latest advances in this field, and new challenges brought up for the near future.