Gilbert Beran

Intracoronary Thrombectomy With the X-Sizer Catheter System Improves Epicardial Flow and Accelerates ST-Segment Resolution in Patients With Acute Coronary Syndrome A Prospective, Randomized, Controlled Study

Background—In patients with acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) may cause thrombus dislodgment followed by reduced flow and impaired microcirculatory function. We prospectively compared conventional PCI to a strategy of additional pretreatment using the X-sizer thrombectomy system. Methods and Results—Sixty-six patients (51 [77%] men; 54.9±9.9 years) with ACS (49 with ST-elevation infarction [STEMI]) and suspected intracoronary thrombus were randomized 1:1 to pretreatment with X-sizer and conventional PCI alone. Various aspects of epicardial flow and microvascular function were studied. Baseline data were similar in both groups. Postprocedural TIMI 3 flow was obtained in 90% of X-sizer–treated patients and in 84% of controls (NS); however, corrected TIMI frame count was lower in X-sizer– treated patients (18.3±10.2 versus 24.7±14.1;P <0.05). No significant group differences were observed in final coronary flow reserve, myocardial blush grade, and myocardial dye intensity. In STEMI, the sum of ST elevation was significantly lower in X-sizer–treated patients immediately after (2.78±3.05 versus 6.15±6.32 mm;P <0.03) and 6 hours after (2.17±2.31 versus 4.14±3.7 mm;P <0.05) intervention. ST-segment resolution >50% was observed in 83% of X-sizer–treated patients and in 52% of controls (P <0.03). Multivariate analysis identified X-sizer treatment as the single independent predictor of ST-segment resolution >50% (OR 4.35; 95% CI, 1.13 to 16.9;P <0.04). Major adverse cardiac events after 30 days occurred in 2 patients in each group. Conclusions—In ACS with suspected thrombus, pretreatment with the X-sizer catheter system improves epicardial flow and accelerates ST-segment resolution compared with conventional PCI alone.

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 × 106 and 194.8 ± 60.4 × 106 stem cells, respectively, were delivered to the myocardium, and 1.30 ± 0.68 × 109 and 1.29 ± 0.41 × 109 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.

Role of adult bone marrow stem cells in the repair of ischemic myocardium: Current state of the art

OBJECTIVE To review the milestones in stem cell therapy for ischemic heart disease from early basic science to large clinical studies and new therapeutic approaches. MATERIALS AND METHODS Basic research and clinical trials (systematic review) were used. The heart has the ability to regenerate through activation of resident cardiac stem cells or through recruitment of a stem cell population from other tissues, such as bone marrow. Although the underlying mechanism is yet to be made clear, numerous studies in animals have documented that transplantation of bone marrow-derived stem cells or circulating progenitor cells following acute myocardial infarction and ischemic cardiomyopathy is associated with a reduction in infarct scar size and improvements in left ventricular function and myocardial perfusion. RESULTS Cell-based cardiac therapy has expanded considerably in recent years and is on its way to becoming an established cardiovascular therapy for patients with ischemic heart disease. There have been recent insights into the understanding of mechanisms involved in the mobilization and homing of the imported cells, as well as into the paracrine effect, growth factors, and bioactive molecules. Additional information has been obtained regarding new stem cell sources, cell-based gene therapy, cell-enhancement strategies, and tissue engineering, all of which should enhance the efficacy of human cardiac stem cell therapy. CONCLUSIONS The recently published trials using bone marrow-origin stem cells in cardiac repair reported a modest but significant benefit from this therapy. Further clinical research should aim to optimize the cell types utilized and their delivery mode, and pinpoint optimal time of cell transplantation.

Active endothelin is an important vasoconstrictor in acute coronary thrombi.

Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. We have previously shown that thrombectomy in ST-elevation myocardial infarction (STEMI) accelerates ST-segment resolution, possibly by preventing distal embolization. We hypothesized that thrombus constituents contribute to microcirculatory dysfunction. Therefore, we analyzed the molecular and cellular composition of acute coronary thrombi, and correlated vasoconstrictive mediators with the magnitude of ST-segment resolution within one hour of percutaneous coronary intervention (PCI). Fresh coronary thrombi were retrieved in 35 consecutive STEMI patients who were treated with the X-Sizer thrombectomy catheter, and thrombus cell counts and vasoconstrictor concentrations were assessed. Twelve-lead ECG recordings were analyzed prior to and one hour after PCI. Concentration of endothelin (ET) was 20.0 (7.9-52.2) fmol/ml in thrombus compared with 0.1 (0.1-0.3) fmol/ml in corresponding peripheral plasma (p < 0.0001), representing a selective 280 (70.0-510.0)-fold enrichment, exceeding enrichment of noradrenaline, angiotensin II and serotonin. Human coronary thrombus homogenates exerted vasoconstriction of porcine coronary artery rings that was inhibited by the dual ET receptor blocker tezosentan. Extracted ET (r = 0.523 p = 0.026) and number of leukocytes (r = 0.555 p = 0.017) were correlated with the magnitude of ST-segment resolution. In conclusion, the amount of active ET and white blood cells aspirated from STEMI target vessels correlated with improvement of territorial microcirculatory function as illustrated by enhanced ST-segment resolution.

Mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients.

BackgroundDiabetic patients show an increased incidence of restenosis after coronary angioplasty than non-diabetic patients. This may be because of differences in the mechanism of lumen gain during coronary revascularization in this population cohort. DesignThis study analyses the mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients with intravascular ultrasound (IVUS). MethodsIVUS images were obtained prior to and after revascularization in 26 diabetic and 97 non-diabetic patients. The external elastic membrane cross-sectional area (EEM) and lumen cross-sectional area (LA) were measured. Plaque area (PA) was calculated as EEM minus LA. Differences between pre- and post-LA (ΔLA), EEM (ΔEEM) and PA (ΔPA) were calculated. ResultsPre-interventional PA (diabetic patients: 12.4 ± 4.4 mm2 compared with non-diabetic patients: 10.7 ± 3.6 mm2, P = 0.04) and pre-interventional EEM (15.5 ± 4.4 mm2 compared with 13.6 ± 3.7 mm2 respectively, P = 0.02) were larger in the diabetic group. Postinterventional PA (10.2 ± 3.2 mm2 compared with 8.0 ± 3.4 mm2, P = 0.004) was also larger and postinterventional LA (6.3 ± 2.2 mm2 compared with 7.4 ± 2.4 mm2 P = 0.04), ΔEEM (0.9 ± 1.8 mm2 compared with 1.8 ± 1.8 mm2 P = 0.04) and ΔLA (3.1 ± 1.6 mm2 compared with 4.2 ± 2.2 mm2, P = 0.03) were smaller in the diabetic group. The diabetic group exhibited longer lesion lengths (P = 0.04) and a higher inflation pressure was used during revascularization in this patient cohort (P = 0.02). ConclusionDiabetic patients have less reduction of PA during revascularization and because the vessel wall cannot be stretched outwards despite higher inflation pressure, postinterventional LA remains smaller than in the non-diabetic population cohort. This might be a rudiment for consideration of different treatment strategies such as cutting balloon or atherectomy prior to stenting in this population group in order to achieve better procedural outcome.

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.

Long-term outcome after thrombectomy in acute myocardial infarction.

Eur J Clin Invest 2010; 40 (3): 233–241

Left ventricular pseudoaneurysm following mitral valve repair

We present a rare case of a left ventricular pseudoaneurysm following mitral valve repair probably due to testing the valve’s competence. The pseudoaneurysm was treated successfully with a sutureless technique in which layers of a biodegradable collagen system with fibrinogen-based coating were used. We reviewed the literature regarding left ventricular rupture following mitral valve surgery published from 1990 until 2006. Overall, the incidence of this complication was 0.56% for 10978 operations, and the mortality rate was 57.4%. We also describe a possible mechanism common to all forms of left ventricular rupture.

Percutaneous Interventions in Radiation-Associated Coronary In-Stent Restenosis

AbstractThis study was performed to evaluate the outcome of percutaneous revascularization in “edge restenoses” developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P < 0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.