Impact of myocardial injury after coronary artery bypass grafting on long-term prognosis.

AIMS: The most appropriate definition of perioperative myocardial infarction (pMI) after coronary artery bypass grafting (CABG) and its impact on clinically relevant long-term events is controversial. We aimed to (i) analyse the incidence of pMI depending on various current definitions in a 'real-life' setting of CABG surgery and (ii) determine the long-term prognosis of patients with pMI depending on current definitions. METHODS AND RESULTS: A consecutive cohort of 2829 coronary artery disease patients undergoing CABG from two tertiary university centres with the presence of serial perioperative cardiac biomarker measurements (cardiac troponin and creatine kinase-myocardial band) were retrospectively analysed. The incidence and prognostic impact of pMI were assessed according to (i) the 4th Universal Definition of Myocardial Infarction (4UD), (ii) the definition of the Society for Cardiovascular Angiography and Interventions (SCAI), and (iii) the Academic Research Consortium (ARC). The primary endpoint of this study was a composite of myocardial infarction, all-cause death, and repeat revascularization; secondary endpoints were mortality at 30 days and during 5-year follow-up. There was a significant difference in the occurrence of pMI (49.5% SCAI vs. 2.9% 4UD vs. 2.6% ARC). The 4th Universal Definition of Myocardial Infarction and ARC criteria remained strong independent predictors of all-cause mortality at 30 days [4UD: odds ratio (OR) 12.18; 95% confidence interval (CI) 5.00-29.67; P < 0.001; ARC: OR 13.16; 95% CI 5.41-32.00; P < 0.001] and 5 years [4UD: hazard ratio (HR) 2.13; 95% CI 1.19-3.81; P = 0.011; ARC: HR 2.23; 95% CI 1.21-4.09; P = 0.010]. Moreover, the occurrence of new perioperative electrocardiographic changes was prognostic of both primary and secondary endpoints. CONCLUSION: Incidence and prognosis of pMI differ markedly depending on the underlying definition of myocardial infarction for patients undergoing CABG. Isolated biomarker release-based definitions (such as troponin) were not associated with pMI relevant to prognosis. Additional signs of ischaemia detected by new electrocardiographic abnormalities, regional wall motion abnormalities, or coronary angiography should result in rapid action in everyday clinical practice.

Elevated Wall Shear Stress in Aortic Type B Dissection May Relate to Retrograde Aortic Type A Dissection: A Computational Fluid Dynamics Pilot Study.

OBJECTIVE: Retrograde aortic type A dissection (RTAD) is a known complication in patients with aortic type B dissection. The purpose of this computational fluid dynamics (CFD) study was to identify haemodynamic risk factors for the occurrence of RTAD. METHODS: Computed tomographic angiography (CTA) images of 10 patients with type B dissections, who subsequently developed a RTAD, were retrospectively analysed together with patients constituting a control group (n = 10) where no further vascular events after the initial type B dissection occurred. CFD simulations were conducted based on 3D surface models of the aortic lumen derived from CTA datasets. For both groups, pressures, velocity magnitudes and wall shear stress (WSS) were compared at the site of the future RTAD entry tear and the surrounding aortic wall. RESULTS: WSS at the site of the future entry tear was significantly elevated compared with the surrounding wall (15.10 Pa vs. 5.15 Pa, p < .001) and was significantly higher in the RTAD group than in the control group (6.05 Pa, p < .002). Pressures and velocity magnitudes were not significantly elevated at the entry tear (3825.8 Pa, 0.63 m/s) compared with the aortic arch (3549.8 Pa, 0.50 m/s) or control group (3501.7 Pa, 0.62 m/s). CONCLUSIONS: Increased WSS accompanies the occurrence of RTAD. The results merit the design for a prospective study to confirm whether WSS is a risk factor for the occurrence of RTAD.

Heart transplantation as salvage therapy for progressive prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE).

BACKGROUND: Prosthetic valve endocarditis (PVE) has the highest in-hospital mortality among all cases of infective endocarditis (IE), it is estimated at about 40 %. Orthotopic heart transplantation (OHT) as a measure of last resort, may be considered in selected cases where repeated surgical procedures and conservative efforts have failed to eradicate persistent or recurrent IE. Only few clinical data are available regarding this rare indication for OHT, since active IE has traditionally been considered as a contraindication for OHT. CASE PRESENTATION: We report on a 55 year old male patient who underwent prosthetic valve replacement with a mechanical valved conduit ten years ago and developed now persistent PVE with severe complications due to methicillin-resistant Staphylococcus epidermidis (MRSE). Repeated surgical procedures and conservative efforts have failed to eradicate the pathogen. Regarding the lack of curative options, salvage OHT was discussed as a measure of last resort. 28 months after the first diagnosis of PVE, the patient was successfully transplanted and is now doing well under close follow-up (6 months post-OHT). CONCLUSIONS: PVE remains a challenging condition regarding diagnosis and treatment. The presented case underscores the urgent need for an integrated and multidisciplinary approach to patients with suspected and definitive IE - especially in PVE. OHT might be a feasible measure of last resort in selected patients with IE. Our case report adds published clinical experience to this rarely performed procedure and consolidates previous findings.

Constrictive Pericarditis in the Presence of Remaining Remnants of a Left Ventricular Assist Device in a Heart Transplanted Patient.

Constrictive pericarditis (CP) is a severe subform of pericarditis with various causes and clinical findings. Here, we present the unique case of CP in the presence of remaining remnants of a left ventricular assist device (LVAD) in a heart transplanted patient. A 63-year-old man presented at the Heidelberg Heart Center outpatient clinic with progressive dyspnea, fatigue, and loss of physical capacity. Heart transplantation (HTX) was performed at another heart center four years ago and postoperative clinical course was unremarkable so far. Pharmacological cardiac magnetic resonance imaging (MRI) stress test was performed to exclude coronary ischemia. The test was negative but, accidentally, a foreign body located in the epicardial adipose tissue was found. The foreign body was identified as the inflow pump connection of an LVAD which was left behind after HTX. Echocardiography and cardiac catheterization confirmed the diagnosis of CP. Surgical removal was performed and the epicardial tubular structure with a diameter of 30 mm was carefully removed accompanied by pericardiectomy. No postoperative complications occurred and the patient recovered uneventfully with a rapid improvement of symptoms. On follow-up 3 and 6 months later, the patient reported about a stable clinical course with improved physical capacity and absence of dyspnea.

Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction.

OBJECTIVE: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. METHODS: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. RESULTS: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. CONCLUSIONS: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

[In vivo detection of integration of grafted cells after myocardial transplantation]. / Bildgebende Verfahren zum In-vivo-Nachweis der Integration transplantierter Zellen im Myokard.

Myocardial transplantation of myocytes and bone marrow derived cells is currently under clinical evaluation as an alternative therapy of heart failure. One of the main problems of all clinical studies performed so far is the inability to track the fate of the transplanted cells. The aim of our study was the development of a potentially clinically applicable approach, which allows for detection of the transplanted cells without need for collection of tissue samples. Fetal canine cardiomyocytes were labelled with the non-toxic fluorescent membrane dye Vybrant CM-DiI and delivered into the free wall of the left ventricle of adult mongrel dogs. For subsequent tracking of the cellular graft, the dogs underwent a second operation in which an intra-vital microscope was mounted above the exposed heart within the thorax. A special computer software eliminated artefacts caused by myocardial contraction. Two months after transplantation, the fluorescent graft was macroscopically visible by intra-vital microscopy using a 10x magnification. Histological studies served as microscopic control and confirmed the existence of DiI-labelled cells at the site of injection. Connexin 43 immunoreactivity was visible at junctional complexes between donor and recipient cells, suggesting morphologic and functional coupling as a result of gap junction formation. Our results demonstrate that in vivo detection of transplanted cells in the heart is feasible. Further technical adjustments should allow for thoracoscopic/endoscopic application of this method, making it appropriate for use in other organs and in clinical studies.

Clinically applicable 7-Tesla magnetic resonance visualization of transplanted human adult stem cells labeled with CliniMACS nanoparticles.

BACKGROUND: Intra-myocardial transplantation of bone marrow derived cells is currently under clinical evaluation as a therapy for heart failure. A major limitation of all clinical studies for myocardial restoration through cell transfer is the inability to track the fate of the transplanted cells. We present a clinically applicable technique using advanced ultra high-field 7-Tesla (7T) magnetic resonance imaging (MRI) of nanoparticle-labeled transplanted human EPCs in porcine ischemic hearts. METHODS: CD133 positive cells were isolated from bone marrow by magnetic bead selection. Positive cells (5 - 8 x 10 (6) cells) were transplanted into porcine ischemic myocardium (n = 8). Control animals (n = 3) received a medium injection. MRI on a 7T scanner was performed to demonstrate the distribution of the EPCs. RESULTS: CD133+ cells were identified on gradient echo images (T(1)-weighted) within the myocardium 4 weeks after transplantation. CONCLUSIONS: Magnetically labeled EPCs transplanted for therapeutic neovascularization or reduction of infarct size in myocardial ischemia can be visualized by MRI at high-field strengths.

Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy.

We report the case of a 58-year-old man with end-stage non-ischemic cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic function. He underwent autologous CD133+ BM-derived cell transplantation through a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells were injected by the transepimyocardial route. Six months after the operation TTE and cMRI showed a clear improvement in left ventricular contractility.

Clinically established hemostatic scaffold (tissue fleece) as biomatrix in tissue- and organ-engineering research.

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.

[Anticoagulation in pregnant women after artificial heart valve replacement: is low-molecular-weight heparin an alternative?]. / Antikoagulation bei schwangeren Frauen nach künstlichem Herzklappenersatz: Ist niedermolekulares Heparin eine Alternative?

We report on the case of a 24-year-old pregnant woman with acute mechanical mitral valve thrombosis due to a treatment failure of low molecular weight heparin (LMWH) for permanent anticoagulation following mechanical valve replacement. Initially, our patient was put on oral warfarin for anticoagulation, but when her pregnancy was perceived the anticoagulation regimen was switched to daily subcutaneous administration of LMWH in order to minimize the risk of warfarin-induced embryopathy. During her 24th week of gestation she developed acute life-threatening pulmonary edema and hemodynamic instability, which was caused by an acute thrombosis of her artificial mitral valve. In an emergency operation the thrombozed valve was replaced by a porcine biological heart valve. The patient recovered uneventfully and gave birth to a healthy child in her 35th gestational week by cesarean section. In addition we discuss the rationale of different anticoagulation regimens with regard to maternal and fetal outcome with special consideration of LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.

Minimally invasive removal of a dislocated stent from the right atrium after previous CABG.

Repeat sternotomy after previous open heart operations constitutes a serious risk factor for cardiac injury, particularly in the presence of a patent internal thoracic artery. We report a case of successful minimally invasive removal of a dislocated subclavian vein stent entangled in the tricuspid valve in a patient 5 years after coronary artery bypass surgery.

Off-bypass coronary bypass grafting via minithoracotomy using mechanical epicardial stabilization.

BACKGROUND: Minimally or less invasive surgical coronary revascularization has gained increasing interest along with new techniques and devices designed for easier and safer procedures. Until recently, it appeared questionable whether grafting techniques with avoidance of cardiopulmonary bypass techniques would allow adequate results compared with conventional techniques using cardioplegic arrest. METHODS: Since June 1996, minimally invasive direct coronary artery bypass grafting procedures without cardiopulmonary bypass were intended in 24 patients (19 male, 5 female; age, 60.5 +/- 10.5 years) applying a special system (CardioThoracic Systems, Inc) for internal mammary artery access and epicardial surface stabilization approaching through an anterolateral minithoracotomy. Neither video-assisted preparation nor additional pharmacologic stabilization was applied. Concomitant risk factors and associated comorbidity were frequent. RESULTS: The procedure was completed in 23 patients, grafting the left anterior descending coronary artery (n = 21) or diagonal branches (n = 3, 1 sequential) as scheduled. In 1 case with internal mammary artery dissection, cardiopulmonary bypass and sternotomy became necessary. Simultaneous carotid endarterectomy was performed in 1 patient. There were two episodes of intraoperative ventricular fibrillation; no other major complications occurred. Postoperative evaluation was obtained in 16 patients (15 by angiography, 1 by Doppler echocardiography) so far and revealed adequate graft function and patency. CONCLUSIONS: Using specially designed instruments for internal mammary artery access and epicardial surface stabilization, minimally invasive direct coronary artery bypass grafting procedures via a minithoracotomy avoiding cardiopulmonary bypass techniques may be applied safely and successfully, even in increased risk constellations.

[Mechanical circulatory support. 1: Intra-aortic balloon counterpulsation (IABP)]. / Mechanische Kreislaufunterstützung. Teil 1: Intraaortale Ballongegenpulsation (IABP).

In cardiac surgery mechanical circulatory support with intra-aortic balloon counterpulsation (IABP) is an established measure for the therapy of perioperative low-output-syndrome and refractory cardiogenic shock. The favourable influence on the myocardial oxygen supply and demand-relationship with an improvement of the energetic balance guarantees the functional and ultrastructural recovery of reversibly damaged ischemic myocardium. The efficacy of IABP is uncontradicted and verified by high survival rates even in patients with severe impairment of the ventricular function. The system is easy to applicate by standardized surgical techniques of im- and explantation, safely to handle due to improvements of the technical equipment and can be applied at a low risk.