Jiangtao Yu

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Background—The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results—Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001). Conclusions—Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00279175.

Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial

Depressed left ventricular ejection fraction (LVEF) despite successful reperfusion therapy is the single most powerful predictor of progressive LV enlargement after acute myocardial infarction (AMI) and independently determines adverse outcome in these patients.

Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival

BACKGROUND In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years. METHODS AND RESULTS In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome. CONCLUSION In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.

Exercise training in patients with severe chronic heart failure: impact on left ventricular performance and cardiac size. A retrospective analysis of the Leipzig Heart Failure Training Trial

Background Exercise training (ET) has been shown to improve functional work capacity in patients with stable chronic heart failure (CHF) having moderate symptoms (NYHA class II). This analysis was conducted, to evaluate the effects of ET on left ventricular function and haemodynamics in patients with advanced CHF (NYHA class III) fulfilling the inclusion criteria of the COPERNICUS trial. Methods Seventy-three patients with moderate and advanced CHF were prospectively randomised to a training (n = 36), or to a control group (n = 37). At baseline and after six months, patients underwent echocardiography and symptom-limited ergospirometry with measurement of central haemodynamics by thermodilution. Results Nine out of 37 patients in the control group (C) and 10 out of 36 patients in the training group (T) had symptoms of advanced CHF. Exercise training over a period of six months resulted in an improvement of functional status on average by one NYHA class in patients with advanced CHF. Moreover, oxygen uptake at the ventilatory threshold increased by 49% (from 7.7 ± 1.0 to 11.4 ± 0.4 mL/min/kg, P<0.01 versus baseline) and at peak exercise by 32% (from 16.3 ± 1.6 to 21.5 ± 1.2 mL/min/kg, P<0.01 versus baseline) in training patients. The small, but significant reduction in left ventricular end-diastolic diameter by 7% (from 70 ± 2 to 66 ± 2 mm; P<0.05 versus baseline) was accompanied by an augmentation in stroke volume at rest by 32% (from 45 ± 3 to 60 ± 6 mL, P<0.05 versus baseline) and at peak exercise by 27% (63 ± 9 to 81 ±9 mL, P<0.05 versus baseline) as a result of ET in patients with advanced CHF. Conclusion In patients with advanced CHF (NYHA class III), long-term exercise training is associated with an enhanced physical work capacity, an improvement in stroke volume and a reduction in cardiomegaly.

Interventional Therapy of Bifurcation Lesions A TIMI Flow-Guided Concept to Treat Side Branches in Bifurcation Lesions—A Prospective Randomized Clinical Study (Thueringer Bifurcation Study, THUEBIS Study as Pilot Trial)

Background—Treatment of bifurcations is a complex problem. The clinical value of treating side branches is an unsolved problem in the field of interventional cardiology. Methods and Results—We initiated a prospective randomized controlled trial. One hundred and ten patients with bifurcations were randomly assigned to 2 arms: Stenting of the main branch (MB, Taxus-stent, paclitaxel-eluting stents) and mandatory side branch (SB) percutaneous coronary intervention (PCI; kissing balloons) with provisional SB stenting (therapy A), or stenting of the MB (paclitaxel-eluting stents) with provisional SB-PCI only when the SB had a thrombolysis in myocardial infarction flow <2 (therapy B). The primary end point was target lesion revascularization. The mean ages were 66.8 years (A) versus 65.1 years (B, P=0.4), 71.4% (A) versus 77.8% were men (P=0.4), patients with diabetes were present in 25.0% versus 25.9% (P=0.9). The MB was left anterior descending artery in 80.4% versus 81.5% (A versus B, P=0.9). The SB-PCI and kissing balloon-PCI were performed according to the study protocol in 82.1%/73.2% versus 16.7%/13.0% (P<0.05 for both), while changing of the intended therapy was necessary in 17.9% versus 16.7% (A versus B, P=0.9). A final thrombolysis in myocardial infarction flow 3 (MB) was reached in all patients (groups A and B), final thrombolysis in myocardial infarction flow 3 (SB) was observed in 96.4% versus 88.9% (A versus B, P=0.3). Radiation time (min) and contrast medium (mL) were 14.2/210 (group A) versus 7.8/151.6 (group B; P for both <0.05). Six month – follow up: major adverse cardiac events was 23.2% (A) versus 24.1% (B, P=0.9), target lesion revascularization was 17.9% (A) versus 14.8% (B, P=0.7), and late lumen loss (MB) was 0.2 mm (A) versus 0.3 mm (B, P=0.5). In group B, no PCI of the SB was done during follow up. Conclusion—A simple strategy using paclitaxel-eluting stents with only provisional SB-PCI may be of equal value to a more complex strategy with mandatory SB-PCI. Clinical Trial Registration—URL: http://www.controlled.trials.com. Unique identifier: ISRCTN22637771.

Interventional Therapy of Bifurcation Lesions

Background—Treatment of bifurcations is a complex problem. The clinical value of treating side branches is an unsolved problem in the field of interventional cardiology. Methods and Results—We initiated a prospective randomized controlled trial. One hundred and ten patients with bifurcations were randomly assigned to 2 arms: Stenting of the main branch (MB, Taxus-stent, paclitaxel-eluting stents) and mandatory side branch (SB) percutaneous coronary intervention (PCI; kissing balloons) with provisional SB stenting (therapy A), or stenting of the MB (paclitaxel-eluting stents) with provisional SB-PCI only when the SB had a thrombolysis in myocardial infarction flow <2 (therapy B). The primary end point was target lesion revascularization. The mean ages were 66.8 years (A) versus 65.1 years (B, P=0.4), 71.4% (A) versus 77.8% were men (P=0.4), patients with diabetes were present in 25.0% versus 25.9% (P=0.9). The MB was left anterior descending artery in 80.4% versus 81.5% (A versus B, P=0.9). The SB-PCI and kissing balloon-PCI were performed according to the study protocol in 82.1%/73.2% versus 16.7%/13.0% (P<0.05 for both), while changing of the intended therapy was necessary in 17.9% versus 16.7% (A versus B, P=0.9). A final thrombolysis in myocardial infarction flow 3 (MB) was reached in all patients (groups A and B), final thrombolysis in myocardial infarction flow 3 (SB) was observed in 96.4% versus 88.9% (A versus B, P=0.3). Radiation time (min) and contrast medium (mL) were 14.2/210 (group A) versus 7.8/151.6 (group B; P for both <0.05). Six month – follow up: major adverse cardiac events was 23.2% (A) versus 24.1% (B, P=0.9), target lesion revascularization was 17.9% (A) versus 14.8% (B, P=0.7), and late lumen loss (MB) was 0.2 mm (A) versus 0.3 mm (B, P=0.5). In group B, no PCI of the SB was done during follow up. Conclusion—A simple strategy using paclitaxel-eluting stents with only provisional SB-PCI may be of equal value to a more complex strategy with mandatory SB-PCI. Clinical Trial Registration—URL: http://www.controlled.trials.com. Unique identifier: ISRCTN22637771.

Incidence and outcome of femoral vascular complications among 18,165 patients undergoing cardiac catheterisation

BACKGROUND Arteriovenous fistulas (AVF) and arterial pseudoaneurysms (PSA) are potentially harmful complications of diagnostic and interventional cardiac catheterisation. Incidence, risk factors and clinical outcome are not well defined yet, although important for stratification and treatment. METHODS A total of 18,165 consecutive patients undergoing cardiac catheterisation were enrolled in our prospective registry. For the diagnosis of AVF and PSA a clinical examination was performed in every patient followed by a Duplex examination in case of clinical suspicion of AVF/PSA. The impact of the following risk factors was assessed: age, body mass index, puncture of left vs. right groin, gender, hypertension, sheath size, peripheral artery disease, coumadin therapy, glycoprotein IIb/IIIa-inhibitors, pre-treatment with thrombolytics, and emergency procedures. RESULTS Within 3 years a total of 334 complications were found (1.8%). The incidence of AVF and PSA was 0.6% (n = 107) and 1.2% (n = 227), respectively. The following significant independent risk factors were identified: arterial hypertension (odds ratio [OR]) = 1.86, female gender (OR = 1.65), and emergency procedures (OR = 2.13). During follow-up (mean 48 +/- 10 months) only 11% of all AVF underwent operative repair due to symptoms. All PSA could be treated successfully either by manual compression, thrombin injection, or surgery. The overall mortality was 0.8%. CONCLUSION Almost 2% of patients undergoing cardiac catheterisation acquire femoral AVF or PSA, for which patient- or procedure-related risk factors could be identified. Most of AVF and PSA could be managed conservatively or without any treatment, the overall mortality is low.

Randomized Comparison of a Polymer-Free Sirolimus-Eluting Stent Versus a Polymer-Based Paclitaxel-Eluting Stent in Patients With Diabetes Mellitus: The LIPSIA Yukon Trial

OBJECTIVES The objective of the study was to assess noninferiority of the polymer-free sirolimus-eluting Yukon Choice stent (Translumina GmbH, Hechingen, Germany) compared with the polymer-based Taxus Liberté stent (Boston Scientific, Natick, Massachusetts) with regard to the primary endpoint, in-stent late lumen loss, at 9 months in patients with diabetes mellitus. BACKGROUND The Yukon Choice stent has been evaluated in several randomized controlled trials before, albeit to date, there has been no trial that exclusively enrolled patients with diabetes mellitus. METHODS Patients with diabetes mellitus undergoing percutaneous coronary intervention for clinically significant de novo coronary artery stenosis were randomized 1:1 to receive either the polymer-free sirolimus-eluting Yukon Choice stent or the polymer-based paclitaxel-eluting Taxus Liberté stent. RESULTS A total of 240 patients were randomized. Quantitative coronary angiography was available for 79% of patients. Mean in-stent late lumen loss was 0.63 ± 0.62 mm for the Yukon Choice stent and 0.45 ± 0.60 mm for the Taxus Liberté stent. Based on the pre-specified margin, the Yukon Choice stent failed to show noninferiority for the primary endpoint. During follow-up, there were no significant differences between groups regarding death, myocardial infarction, stent thrombosis, target lesion revascularization, target vessel revascularization, or nontarget vessel revascularization. CONCLUSIONS Compared with the Taxus Liberté stent, the polymer-free sirolimus-eluting Yukon Choice stent failed to show noninferiority with regard to the primary endpoint, in-stent late lumen loss, in patients with diabetes mellitus after 9-month follow-up. Both stents showed comparable clinical efficacy and safety. (Yukon Choice Versus Taxus Liberté in Diabetes Mellitus; NCT00368953).

Tako-Tsubo-Like Cardiomyopathy: Specific ECG Findings, Characterization and Clinical Findings in a European Single Center

Objectives: A newly discovered heart syndrome mimicking acute coronary syndrome has been termed ‘Tako-Tsubo cardiomyopathy’ (TTC). Differentiation from acute myocardial infarction using the ECG is an important issue in clinical practice. Methods: We retrospectively analyzed patients admitted for cardiac catheterization between September 2003 and September 2006. Results: From 26,593 cardiac catheterization procedures, we identified 21 patients with suggested TTC (0.08%). Trigger mechanisms were present in 38.1%; all patients had elevated troponin levels (mean 3.9 ng/ml). Median age was 68.4 years; 90.5% were female. Hypertension was seen in 85.7% and atrial fibrillation in 19.1%. Specific ECG findings related to a TTC are: a mild elevation of the ST segment arising from the S curve of the QRS complex, where the maximum ST segment elevation at the basis of the T wave is <1.5 mm, T-wave inversion, absence of ST segment depression and a summated amplitude of the S curve in V1 plus R in V6 <1.5 mV. An intraventricular gradient was seen in 9.5%; coronary atherosclerosis was detected in 57.1%. Follow-Up Data: Mean follow-up was 13.2 months. 47.6% were free from angina or dyspnea, most of the patients received β-blockers/ACE inhibitors (76.2%). One patient had a sudden cardiac death (4.8%), 1 patient became an implantable cardioverter-defibrillator primarily due to resuscitation. Conclusion: TTC is a rare syndrome mimicking acute coronary syndrome that shows a specific ECG pattern and does not appear to be an unambiguously benign disease.

Simultaneous combined interventional percutaneous left atrial auricle and atrial septal defect closure

A 79-year-old man presented with atrial fibrillation, cerebral embolic events and intracerebral bleeding under oral anticoagulation and a haemodynamically significant secundum atrial …