Systematic Evaluation of Systemic Right Ventricular Function.

BACKGROUND: The right ventricle serves as the subaortic systemic ventricle (sysRV) in patients with congenitally corrected transposition of the great arteries (ccTGA) and in patients with transposition of the great arteries (TGA) surgically repaired by an atrial switch. SysRV can lead to late complications, primarily heart failure, significant regurgitation of the systemic atrioventricular (AV) valve, and ventricular arrhythmias with sudden cardiac death. We sought to investigate the value of 2D- and 3D-echocardiographic parameters of sysRV function. METHODS: Consecutive adult patients with sysRV who presented at the adult congenital heart disease outpatient clinic were prospectively enrolled. All patients received comprehensive transthoracic echocardiography, including 3D-echocardiography, cardiac magnetic-resonance-imaging (CMR), cardiopulmonary-exercise-testing, and blood analysis for NT-proBNP. RESULTS: A total of 27 patients were included, 18 with TGA and nine with ccTGA. Median age was 37 years (Q1 = 31, Q3 = 44), 44% were male, median NT-proBNP was 189 pg/mL (Q1 = 155, Q3 = 467); sufficient 3D-echocardiography datasets were acquired in 78% of patients. All echocardiographic 2D and 3D volumetric function parameters correlated with CMR data, whereas a correlation was not seen with any of the longitudinal function parameters. NT-proBNP correlated with tricuspid annular plane systolic excursion (r = -0.43, p = 0.02) and CMR ejection fraction (EF) (r = -0.62, p = 0.003). CONCLUSION: Systematic evaluation of sysRV is complex and should include not only volumetric parameters but also parameters of longitudinal function in addition to measurement of NT-proBNP. In patients with good image quality, 3D-echocardiography can be used to assess volumes and EF.

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.

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.

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.

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.

Effects of radial stretch on target lesion revascularization after percutaneous coronary intervention: an intravascular ultrasound study.

OBJECTIVE: To analyze possible associations between radial stretch during coronary angioplasty and the incidence of target lesion revascularization (TLR). PATIENTS AND METHODS: Intravascular ultrasound images were obtained before and after revascularization in 182 native coronary lesions. The quantitative intravascular ultrasound parameters (external elastic membrane cross-sectional area [EEM-A], lumen areas [LA], plaque area [PA], calculated as EEM-A-LA, and changes between pre- and postinterventional LA [DLA], EEM-A [DEEM-A] and PA [DPA]) were correlated with the incidence of TLR. RESULTS: TLR was performed in 60 (33%) patients, while 122 (67%) patients remained event free. Postinterventional PA remained significantly larger in the TLR group than in the event-free group (9.2 +/- 3.3 mm2 versus 7.9 +/- 3.3 mm2; P=0.02). The radial stretch during intervention, expressed as DEEM-A, and the balloon to artery ratio was significantly larger in the TLR group (DEEM-A: 1.9 +/- 2.1 mm2 versus 1.3 +/- 2.0 mm2; P=0.03; balloon to artery ratio: 1.3 +/- 0.2 versus 1.0 +/- 0.5; P=0.04). Multivariate analysis revealed DEEM-A (P=0.01), DPA (P=0.03), diabetes (P=0.001, odds ratio 5.2, 95% CI 4.9 to 6.5) and adaptive remodelling (P<0.001, odds ratio 4.1, 95% CI 3.5 to 6.4) as independent predictors for TLR. CONCLUSION: Whereas patients in whom lumen gain is achieved primarily by plaque reduction with less wall stretch tend to remain event free, patients with significant radial stretch (ie, less reduction of the PA, but a radial outward shift of the plaque mass) experience a higher incidence of TLR.

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.

Prevention of stent thrombosis following brachytherapy and implantation of drug-eluting stents.

The implementation of coronary brachytherapy and especially the application of drug-eluting stents for the prevention of in-stent restenosis are of vital importance in the field of interventional cardiology. Despite undeniable benefits of these new methods a potential increased risk for the occurrence of stent thrombosis as a result of the mode of action of these new methods has to be taken into consideration. The prevention of stent thrombosis following coronary brachytherapy and implantation of drug-eluting stents is therefore of particular importance to assure the success of these forward-looking technologies. This article provides an overview of current data regarding the incidence of stent thrombosis following brachytherapy and implantation of drug-eluting stents and it's implication for clinical practice.

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

BACKGROUND: Diabetic 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. DESIGN: This study analyses the mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients with intravascular ultrasound (IVUS). METHODS: IVUS 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 (deltaLA), EEM (deltaEEM) and PA (deltaPA) were calculated. RESULTS: Pre-interventional PA (diabetic patients: 12.4 +/- 4.4 mm2 compared with non-diabetic patients: 10.7 +/- 3.6 mm2, = 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 = 0.04), deltaEEM (0.9 +/- 1.8 mm2 compared with 1.8 +/- 1.8 mm2 P = 0.04) and deltaLA (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). CONCLUSION: Diabetic 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.

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length.

OBJECTIVE: The goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BACKGROUND: Underdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. METHODS: Baseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation ((192)Ir: Checkmate, Cordis, Miami, Florida; (32)P: Gallileo, Guidant, Houston, Texas; (90)Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of "reference isodose length" (RIL), defined as a segment with >/=90% of reference dose at 1 mm vessel wall depth, were measured. "Safety margin" was defined as the distance between the outermost injury and outermost end of the RIL, "geographical miss" (GM) as a complete injured segment not being covered by the RIL, and "restenosis" as the percent diameter stenosis >50%. RESULTS: Baseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. CONCLUSIONS: Geographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

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.