Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

RATIONALE: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. OBJECTIVE: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). METHODS AND RESULTS: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. CONCLUSIONS: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591.

Association of the Polymorphism rs3918242 of the Matrix Metalloproteinase-9 Gene with Coronary Artery Disease in a Younger Population.

Coronary artery disease (CAD) is a complex disease resulting from the interaction of numerous so-called traditional risk factors and comorbid conditions on the one side (such as dyslipidemia, smoking, obesity, diabetes, hypertension) and genetic factors on the other. The evidence of a genetic contribution to the development of CAD, especially in the last 2 decades is consistent. It is important that a number of established gene polymorphisms in the younger CAD population are in the genes involved in the inflammatory response and tissue maintenance and remodeling processes. The aim of this study is to investigate the association of the rs3918242 polymorphism of the matrix metal-loproteinase 9 (MMP9) gene with the coronary artery disease in the younger population. In this observational genetic-association study of cases and controls, the demographic, clinical, laboratory and genetic data of the younger population in a group of selected 70 CAD patients aged up to 45 years were analyzed, of which 35 patients have negative and 35 have positive coronary angiography finding, and 43 are men and 27 are women. The analysis of the genotypic and allelic frequency determined an association of the polymorphism and the occurrence of the positive coronary angiographic findings in the population of patients under the age of 45. The carriers of the heterozygous genotype CT have almost 5 times higher probability of having a positive coronary angiography finding compared to the carriers of the reference homozygous genotype CC (p=0.012). Thus, this parameter could be used for clinical risk assessment for the development of CAD.

Design and rationale for the Myocardial Stem Cell Administration After Acute Myocardial Infarction (MYSTAR) Study: a multicenter, prospective, randomized, single-blind trial comparing early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of nonselected autologous bone marrow cells to patients after acute myocardial infarction.

BACKGROUND: Previous data suggest that bone marrow-derived stem cells (BM-SCs) decrease the infarct size and beneficially affect the postinfarction remodeling. METHODS: The Myocardial Stem Cell Administration After Acute Myocardial Infarction Study is a multicenter, prospective, randomized, single-blind clinical trial designed to compare the early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of BM-SCs to patients after acute myocardial infarction (AMI) with reopened infarct-related artery. The primary end points are the changes in resting myocardial perfusion defect size and left ventricular ejection fraction (gated single photon emission computed tomography [SPECT] scintigraphy) 3 months after BM-SCs therapy. The secondary end points relate to evaluation of (1) the safety and feasibility of the application modes, (2) the changes in left ventricular wall motion score index (transthoracic echocardiography), (3) myocardial voltage and segmental wall motion (NOGA mapping), (4) left ventricular end-diastolic and end-systolic volumes (contrast ventriculography), and (5) the clinical symptoms (Canadian Cardiovascular Society [CCS] anina score and New York Heart Association [NYHA] functional class) at follow-up. Three hundred sixty patients are randomly assigned into 1 of 4 groups: group A, early treatment (21-42 days after AMI) with intracoronary injection; group B, early treatment with combined application; group C, late treatment (3 months after AMI) with intracoronary delivery; and group D, late treatment with combined administration of BM-SCs. Besides the BM-SCs therapy, the standardized treatment of AMI is applied in all patients. CONCLUSIONS: The Myocardial Stem Cell Administration After Acute Myocardial Infarction Trial is the first randomized trial to investigate the effects of the combined (intramyocardial and intracoronary) and the intracoronary mode of delivery of BM-SCs therapy in the early and late periods after AMI.

Transition Towards Transradial Approach Improves Outcomes of Acute Myocardial Infarction PCI.

INTRODUCTION AND AIM: Transradial (TRA) instead of transfemoral (TFA) approach strategy has been presented in research literature as superior access strategy especially for acute ST elevation myocardial infarction (STEMI) primary percutaneous coronary intervention (PCI). There is a paucity of registry-based data of outcomes from default TRA strategy compared to TFA. MATERIALS AND METHODS: All-comers STEMI PCI institutional Registry identified 1808 consecutive patients in time-frame of 40 months from 2007 to 2010, without making any exclusions. Moreover, we applied Propensity Score Matching (PSM) to replace randomization, address the potential confounding and selection bias. PSM derived 565 congruent pairs of patients from the groups. RESULTS: After 30 days the primary composite endpoint of major adverse cardiovascular events (MACE) was in favor of TRA 6.5% vs. 12.4% in TFA group, simultaneously secondary endpoints of death in TRA with rate of 4.8% and with rate of 10.1% in TFA. Moreover, the rate of major access related bleeding was 1.1% in TRA vs. 8.5% in TFA, in contrast the major non-access related bleeding was 1.8% and 2.4% respectively showed no significant difference. One year Kaplan Meier survival plots were in favor of TRA. CONCLUSIONS: Default transradial access strategy is associated with improved STEMI PCI outcomes.

Macedonia: coronary and structural heart interventions from 2010 to 2015.

The aim of this report is to describe invasive cardiology procedural practice in Macedonia during the period from 2010 to 2015. Details of all consecutive 39,899 patients who underwent cardiovascular, peripheral or structural heart procedures during the period from 2010 until 2015 were examined. Clinical and procedure characteristics, access site, procedural success and complications were analysed. The number of coronary angiographies increased from 5,540 in 2010 to 8,550 in 2015. Transfemoral access (TFA) was present in 4% of coronary angiographies in 2010 and had decreased to 1% in 2015. The number of primary percutaneous coronary interventions (PCI) for acute ST-segment elevation myocardial infarction increased from 763 to 1,175 and both chronic total occlusion and left main coronary artery interventions also increased over time. In 2015, the drug-eluting stent penetration rate was 65%. Structural heart interventions, including transcatheter aortic valve implantations (TAVI) were introduced in 2014 and 23 TAVI cases have since been performed. Transradial access was performed in 38,455 (96%) of all patients. Wrist access adoption in the majority of cardiovascular interventions is possible in all PCI centres in Europe if an appropriate national strategy is developed.

Transradial versus transfemoral access for female patients who underwent primary PCI in STEMI: Two years follow-up data from acute STEMI interventional registry.

BACKGROUND: Female patients possess a higher risk for poorer outcome in ST segment elevation myocardial infarction (STEMI). There is possibility that transradial access (TRA) for primary percutaneous coronary intervention (PPCI) could provide better outcome than transfemoral access (TFA) in female patients with STEMI. METHODS: From 2008 to 2010, 418 female patients (out of 1808 patients) underwent PPCI for acute STEMI. The registry recruited all-comers patients with acute STEMI. Cardiac mortality, major bleeding, and overall MACE rates (composite of death, stroke, re MI and target vessel revascularization-TVR) after 2years follow-up were compared between TRA and TFA. RESULTS: TRA for PPCI was performed in 261 patients and 157 underwent TFA PPCI. The 30-days, 1year mortality and 2year mortality rates were lower in TRA compared to TFA (6.9% vs.14.6%, p=0.012, 8.8% vs. 15.3%, p=0.045, and 9.2% vs. 16.6%, p=0.027respectively). After 2years follow-up, the overall MACE rates were similar (26.4% vs. 31.2%, p=0.336). The overall major bleeding and major vascular access site bleeding were more favorable for TRA than TFA (4.4 vs. 14%, p<0.001, and 2.7 vs. 10.8%, p<0.001, respectively). CONCLUSION: Transradial access for primary PCI in female patients provided better clinical outcomes with lower cardiac mortality and reduced major bleeding in comparison to TFA. There was no significant difference at 2years MACE between TRA and TFA.

Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis.

AIM: We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. CASE PRESENTATION: A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis.

Complete transitioning to the radial approach for primary percutaneous coronary intervention: a real-world single-center registry of 1808 consecutive patients with acute ST-elevation myocardial infarction.

OBJECTIVES: To compare the short- and long-term outcomes of transradial approach (TRA) versus transfemoral approach (TFA) for primary percutaneous coronary intervention (PPCI) during a complete institutional transition from TFA to TRA. METHODS AND RESULTS: An all-comer population of ST-elevation myocardial infarction (STEMI) patients (n=1808) who underwent PPCI using TRA (n=1162) and TFA (n=646) from October 2007 to December 2010 were enrolled. TRA was used in 25% of PPCIs by 2007 and in 96% of PPCIs in 2010. Primary endpoints were cardiovascular death and major adverse cardiac event (MACE), defined as a composite of death, stroke, reinfarction, and target vessel revascularization at 30 days and 1 year. At 30 days, TRA compared to TFA was associated with a significant reduction of cardiovascular mortality (5.2% vs 10.5%; P<.001), significant MACE reduction (7.3% vs 12.5%; P<.001), fewer access-site complications (0.9% vs 8.2%; P<.001), and lower TIMI major bleeding (1.1% vs 4.3%; P<.001). At 1 year, the cardiovascular mortality and MACE rates were also in favor of the TRA group (6.9% vs 11.5%; P<.001 and 11.6% vs 20.1%; P<.001), respectively. CONCLUSION: Complete transition from femoral access to a preferred radial access is safe and effective for STEMI patients undergoing PPCI, with a favorable effect on short- and long-term outcomes.

Atherosclerosis of coronary blood vessels - local or systemic inflamation?

The presence of atherosclerotic lesions in the blood vessels is a predisposition for the development and occurrence of acute ischaemic attacks. Bigger atherosclerotic lesions in the coronary blood vessels cause lumen occlusion, which is a cause of acute myocardial infarction. Endothelial dysfunction is defined as an ability of the endothelium to produce vasorelaxing nitric oxide (NO), or deregulation of the other vasoactive substances, such as angiotensin II and endothelin [13]. This definition describes endothelial dysfunction as an improper vasomotor constriction of the vessel, that leads to lumen occlusion of the already existing atherosclerotic lesions. According to the modern model, the development of atherosclerotic plaque and inappropriate endothelial NO production have a synergistic role in patho-physiological and molecular processes in the blood vessels [14]. Lesions in the coronary arteries are deposits of huge quantities of foamy cells and fibrous plaques. The thin fibrous plaques are 10-20% of the total plaque population and are the cause of 80-90% of clinical cases due to their ability to rupture [48]. According to all the results from published studies by far, it has been pointed out that the plaque stability, not the absolute size influences the rupture potential. Elucidating the risk factors that may modify in the atherogenesis and the consequent atherothrombic effect is the first step to this goal.

Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study.

BACKGROUND: Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches. METHODS: Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3-6 weeks or 3-4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy. RESULTS: A total of 60 patients were treated. The mean changes in infarct size at 3 months were -3.5 +/- 5.1% (95% CI -5.5% to -1.5%, P = 0.001) in the early group and -3.9 +/- 5.6% (95% CI -6.1% to -1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 +/- 5.6% (95% CI 1.3-5.6%, P = 0.003) and 3.4 +/- 7.0% (95% CI 0.7-6.1%, P = 0.017), respectively. At 9-12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 +/- 68.7 x 10(6) and 194.8 +/- 60.4 x 10(6) stem cells, respectively, were delivered to the myocardium, and 1.30 +/- 0.68 x 10(9) and 1.29 +/- 0.41 x 10(9) cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points. CONCLUSIONS: Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

Recurrent myocardial infarction in a young football player with antithrombin III deficiency.

Acute myocardial infarction is a rare condition in young athletes. One of the causes could be a hypercoagulable state due to congenital antithrombin III deficiency, together with a prothrombotic state soon after strenuous physical training. We present the case of myocardial reinfarction in young football player with antithrombin III deficiency, treated with primary percutaneous coronary intervention and drug eluting stent, as well as the functional repercussions of continuous intensive physical activity.

Stenting of coronary bifurcation lesions: case series.

AIM: To assess the procedural success and major cardiac event rate after stenting of coronary bifurcation lesions. METHODS: The prospective study included 36 patients with coronary artery bifurcation lesion treated with stenting between January 1999 and December 2001 at the Institute for Heart Disease, Skopje University Center. There were 23 men and 13 women, with a mean age of 62.5+/-12.3 years. Seventeen patients had acute myocardial infarction and 19 patients had unstable angina. The follow-up lasted 6 months. The strategy of systematic coronary stenting in the bifurcation lesions involving a side branch of >2.2 mm in diameter was prospectively evaluated according to the quantitative coronary angiography (QCA) measurements. Procedural success was defined as a residual stenosis of less than 20%. Major cardiac events included deaths, emergency coronary artery bypass grafting (CABG), Q-wave myocardial infarction, acute and subacute closure, repeated percutaneous transluminal coronary angioplasty (PTCA), and non-Q myocardial infarction. RESULTS: Out of a total of 36 bifurcation lesions, the left anterior descending/diagonal bifurcation lesion was found in 22 patients, circumflex/marginal in 8 patients, posterior descending artery/posterolateral artery in 4 patients, and left main coronary artery in 2 patients. The main branch of the coronary artery (mean+/-SD reference diameter, or the diameter of the normal coronary artery, 2.90+/-0.36 mm) was stented in 35 patients and the side branch of the main coronary artery (2.35+/-0.42 mm reference diameter) in 24 patients. The major cardiac events occured in 3 patients: one had Q-wave myocardial infarction, one developed acute and subacute closure, and one underwent PTCA. There were no deaths or emergency CABG. CONCLUSION: The development of new surgical strategies and stent design has improved the safety and immediate outcome of bifurcation stenting, but procedural success still needs to be matched by an equal clinical improvement and long-term patency.