A Cardiogenic Shock due to an Acute MI with LCA Arising from the Right Coronary Sinus Successfully Treated with PCI.

Coronary artery anomalies (CAAs) are a diverse group of congenital anomalies with an incidence ranging from 0.17% in autopsy cases to 1.2% in patients undergoing coronary angiography. The left coronary artery (LCA) originating from the right coronary sinus is a very rare CAA with a frequency of 0.03%. We present a very rare case of a cardiogenic shock as a consequence of an acute anterolateral myocardial infarction by a totally occlusive lesion in the long left main stem with a complete LCA arising from the right coronary sinus in an 85-year-old female. This lesion was successfully treated with 2 drug-eluting stents. This is perhaps the first published case about cardiogenic shock due to an acute myocardial infarction associated with this type of coronary anomalies, and it presents a special challenge in the catheter laboratory.

High failure rate after valve-sparing aortic root replacement using the "remodeling technique" in acute type A aortic dissection.

BACKGROUND: Valve-sparing surgery including the replacement of the sinus of valsalvae were initially meant to be promising approaches in the treatment of acute type A aortic dissection. However, the long-term outcome after valve-sparing aortic root replacement in acute type A dissection is currently the subject of intense debate, and the evidence reported in the literature is sparse. Here we report on our experience on valve sparing aortic root replacement inpatients with acute type A dissection. METHODS: From August 1995 to November 2000, 30 patients with acute type A dissection received valve-sparing aortic root replacement. Two different techniques were performed: the "remodeling" technique, first described by Yacoub in 1983 (8 patients) and the "reimplantation" technique, initially described by David and Feindel, in 1992 (22 patients). Endpoints of the study were early and late mortality, as well as aortic valve-related complications and reoperations. RESULTS: The mean follow-up time was 22.6+/-15.4 months. The overall 30 day mortality was 17% (5/29) and the late mortality 4% (1/24). During the observation period, 4 patients had to be reoperated (n=3) for acute aortic valve regurgitation after aortic root remodeling and for acute aortic valve endocarditis (n=1) after aortic root reimplantation. In the 3 patients with acute aortic valve regurgitation, symptoms occurred 44, 24, and 17 months after the initial operation in these patients. Intraoperatively prolapsing aortic leaflets because of commissural detachment was found in all 3 cases. In all other patients the latest echocardiographic follow-up examination revealed freedom from aortic regurgitation higher than grade 1. CONCLUSIONS: The high failure rate of aortic root remodeling inpatients with acute type A aortic dissection is discouraging. Whether this technique should be applied in acute type A aortic dissection is questionable. In contrast, aortic root reimplantation lead to favorable midterm outcome. Thus, we recommend consideration of this technique for surgical treatment of patients with acute type A aortic dissection.

No association between transmembrane protein-tyrosine phosphatase receptor type C (CD45) exon A point mutation (77C>G) and idiopathic dilated cardiomyopathy.

To investigate whether a 77C>G polymorphism in exon A of the CD45 gene causing a variant CD45RA expression pattern is associated with the development of idiopathic dilated cardiomyopathy (DCM), we studied a total of 414 individuals (104 patients and 310 controls). CD45RA expression pattern on lymphocytes was examined by flow cytometric analysis and subsequently the CD45 77C>G polymorphism was genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA). We found 5 patients and 8 control individuals displaying the variant CD45RA expression pattern. All identified individuals carried the heterozygous CD45 77C>G polymorphism. The frequency of the 77G allele in the patient group was 2.4%, which was not significantly different from 1.3% found in the control group (p=0.327). In conclusion, the data of this preliminary study could not reveal any association between the CD45 77C>G polymorphism and susceptibility to idiopathic DCM in a German population.

Time course of physical reconditioning during exercise rehabilitation late after heart transplantation.

BACKGROUND: Exercise rehabilitation improves physical capacity in heart transplant recipients. The time course of physical reconditioning and skeletal muscle adaptation late after transplantation are unknown. METHODS: Twenty-one heart transplant recipients, at 5.2 +/- 2.1 years after transplantation, completed 1 year of an individually tailored home ergometer-training program (2.1 +/- 0.7 sessions weekly with matched heart rates, intensity at 10% below anaerobic threshold). We analyzed time course of physical reconditioning data for each home-training session (n = 2,396). Constant-load tests with consistent blood lactate concentrations were performed quarterly (n = 105) to estimate the time course of skeletal muscle adaptation. Nine heart transplant recipients served as a control group (CG). RESULTS: After 12 months, exercise capacity for matched heart rates (112 +/- 11 beats/min; CG, 114 +/- 8 beats/min) increased by 35% +/- 19% (from 43 +/- 14 to 58 +/- 18 W; p < 0.001; CG, 53 +/- 18 to 54 +/- 18 W); 24% of the increase was caused by improved skeletal muscle function and 11% by central functioning. Physical reconditioning showed its greatest increase within the first 3 months (+18%; p < 0.001); 50% of the increase consisted of better skeletal muscle or central functioning. Between the 4(th) and 12(th) months, exercise capacity increased continuously (+15%; p < 0.001), mainly because of better skeletal muscle functioning. CONCLUSIONS: The persistent improvement in exercise capacity along with consistent lactate concentrations during 12 months of training indicates that exercise training could counteract the negative side effects of immunosuppressive treatment on skeletal muscles. Even late after heart transplantation, physical training should be performed regularly to prevent the accelerated decrease in exercise capacity and in skeletal muscle function.

Longitudinal analysis of Epstein-Barr viral load in plasma and peripheral blood mononuclear cells of transplanted patients by real-time polymerase chain reaction.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a significant cause of morbidity and mortality in transplant recipients and is caused by iatrogenic suppression of T cell function. Elevations in the Epstein-Barr viral (EBV) load in plasma (>1000 EBV copies/100 microL plasma) or peripheral blood mononuclear cells (PBMC) (>5000 EBV copies/microg PBMC DNA) as determined by real-time quantitative polymerase chain reaction (RQ-PCR) have been shown to be sensitive indicators for the development of PTLD in patients. METHODS: The diagnostic value of frequent monitoring of EB viral load in peripheral blood from 46 patients after heart transplantation was investigated compared with 21 healthy controls in a prospective longitudinal study. EB viral load was detected in PBMC and plasma using real-time quantitative (RQ)- polymerase chain reaction (PCR)-based assays and compared with serological parameters of EBV infection or with the occurrence of CMV reactivations. RESULTS: EB viral load was significantly increased in PBMC and in plasma from transplanted patients compared with healthy controls. Regarding levels and fluctuations of EB viral load in PBMC, patients were grouped in three distinct categories with high, intermediate, or low EB viral load. Although in one patient without PTLD, the EB viral load exceeded the threshold value for PTLD of 5000 EBV copies/microg PBMC DNA, all patients had an EB viral load in plasma of less than 1000 EBV copies/100 microL plasma. No correlation was found between the level of EB viral load and serological parameters of EBV reactivations in patients or in healthy control individuals. EBV and cytomegalovirus reactivations occurred independently in the majority of patients. CONCLUSIONS: EB viral load measurements in plasma and PBMC of patients using RQ-PCR are superior to serology and are a powerful tool for monitoring transplanted patients.

Inhibition of aortic allograft vasculopathy by local delivery of platelet-derived growth factor receptor tyrosine-kinase blocker AG-1295.

BACKGROUND: Signal transduction through the platelet-derived growth factor (PDGF)/PDGF-receptor (PDGFR) system has been linked to vascular smooth muscle cell migration and proliferation leading to allograft vasculopathy. This study describes the effect of the tyrphostin AG-1295, a specific PDGFR tyrosine-kinase inhibitor, on neointimal formation in this disease. METHODS AND RESULTS: Rat aortic allografts transplanted from dark agouti (RT1 ) donors to Wistar-Furth (RT1 ) recipients were assessed in a new treatment model for local drug delivery from polymeric carrier matrices precoated with AG-1295. Matrices were wrapped around the graft immediately after transplantation. The recipients received no background immunosuppression. At day 80 posttransplantation, intimal thickness in AG-1295-treated grafts was reduced when compared to controls (11.8+/-9.1% intimal thickness vs. 23.7+/-6.4% intimal thickness; P=0.042). This finding corresponded to inhibition of intimal PDGFR-beta expression in AG-1295-treated grafts at day 20 posttransplantation (P =0.029 vs. allogeneic controls). CONCLUSIONS: The tyrphostin AG-1295 reduces neointimal formation in aortic allograft vasculopathy by inhibition of PDGFR-beta-triggered tyrosine phosphorylation. Local drug release of specific tyrosine-kinase inhibitors from perivascularly co-implanted polymeric carrier matrices is effective in the prophylaxis of allograft vasculopathy under selected experimental conditions.

Increased plasma homocysteine concentrations accelerate cardiac allograft vasculopathy.

BACKGROUND: A toxic and pro-oxidative effect of homocysteine on the coronary endothelium may accelerate cardiac allograft vascular disease (CAVD). In this study, we evaluated the influence of hyperhomocysteinemia on the course of CAVD. METHODS: We investigated plasma homocysteine (tHCY) concentrations in 183 consecutive heart transplant recipients (158 men and 25 women, mean aged 53.1 +/- 10.0 years, at 6.7 +/- 3.2 years after transplantation) to evaluate the course of CAVD. We used serial coronary angiography to assess coronary status and graded the severity of CAVD based on the extent of luminal obstruction in the main coronary arteries (graded as 1-4). We defined progression as increased focal stenosis of >/=30% or as detection of a new coronary lesion after a mean observation period of 2.8 +/- 1.0 years. A multivariate analysis (backward logistic regression) was performed that included potential risk factors for CAVD. We excluded patients undergoing dialysis. RESULTS: Initially, tHCY concentrations were increased in the entire cohort (mean, 18.6 +/- 7.6 mumol/liter) and ranged from 6.6 to 46.9 mumol/liter. A total of 105 patients (57.0%) had CAVD at first angiography, and progression was detected in 52 transplant recipients (28.0%). Patients with progressive CAVD had significantly greater tHCY concentrations (21.6 +/- 6.2 mumol/liter) at baseline investigation compared with patients who had stable courses (17.4 +/- 7.7 mumol/liter; p < 0.001). These results were independent of parameters such as sex, age, dyslipoproteinemia, cyclosporine blood concentrations, and indication for transplantation. CONCLUSIONS: Progression of CAVD is strongly associated with increased tHCY concentrations. The intervals between routine surveillance angiography should be shortened in patients with hyperhomocysteinemia, and routine medical treatment to decrease homocysteine concentrations should be considered.

Mycophenolate mofetil for secondary prevention of cardiac allograft vasculopathy: influence on inflammation and progression of intimal hyperplasia.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the single most important complication impairing long-term survival after heart transplantation (HTx). Intimal hyperplasia as a response to immunologic and non-immunologic injury is involved in the pathogenesis. Because improved immunosuppressive properties with mycophenolate mofetil (MMF) have been shown within the first year, beneficial effects on intimal hyperplasia and systemic inflammation might be found late after HTx as well. METHODS: After a baseline examination with intravascular ultrasound (IVUS, volumetric assessment) 30 patients (2.0 +/- 1.1 years post-HTx) were prospectively randomized to receive either MMF (2 g/day) or to continue with azathioprine (AZA) as part of a triple immunosuppression protocol with cyclosporine and prednisolone. Markers of systemic inflammation and changes in vascular geometry were evaluated by IVUS after 1 year of follow-up. RESULTS: With regard to inflammation, significantly lower values were found for high-sensitive C-reactive protein (CRP) in the MMF group (AZA 1.8 +/- 1.2 mg/liter. vs MMF 1.0 +/- 4.1 mg/liter, p = 0.02). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-beta did not differ between the groups. IVUS revealed no significant differences between groups. There was a weak trend toward a larger increase in plaque volume (AZA 13 +/- 43 mm(3) vs MMF 27 +/- 41 mm(3), p = 0.33), whereas MMF-treated patients tended to show a small increase in vessel dimensions (AZA +10 +/- 63 mm(3) vs MMF +50 +/- 87 mm(3), p = 0.17). CONCLUSIONS: Changing immunosuppression from a standard AZA-based regimen to MMF resulted in a decrease in systemic inflammatory activity as indicated by levels of high-sensitive CRP. However, progression of intimal hyperplasia did not differ significantly, and the weak trend toward vascular enlargement could indicate some influence on vascular geometry.

Aortic valve reimplantation in ascending aortic aneurysm: risk factors for early valve failure.

BACKGROUND: Aortic root reconstruction by reimplantation of the native valve represents a new therapeutic option for ascending aortic aneurysms. Information about long-term follow-up is limited, and possible predictors for failure of reconstruction have not been evaluated so far. METHODS: After aortic valve reimplantation 101 patients were followed in a prospective observational study. From this cohort the first 75 consecutive patients with a complete 1-year follow-up were chosen for further analysis. Clinical and echocardiographic data were obtained preoperatively, intraoperatively, and early postoperatively, as well as after 1 year of follow-up. RESULTS: No mortality was observed within the first 30 days. There were 52 male patients, mean age was 49.1+/-20.6 years, observation period was 35.6+/-20.6 months, and Marfan's syndrome was present in 22 patients. Although in 67 patients a stable valve function could be demonstrated, 5 patients presented with mild aortic insufficiency or had to be operated on again for secondary valve failure (n = 3). Analyzing possible demographic, disease-related, and procedure-related risk factors in a multivariable approach, only level of coaptation within the graft (as assessed by echocardiography) could be identified as being related to the subsequent development of aortic insufficiency. Coaptation level within the tube graft (type A) resulted in a mean aortic regurgitation grade of 0.3+/-0.5 as compared with a mean grade of 2.5+/-0.6 for a coaptation type C (below the prosthesis; p < 0.001). CONCLUSIONS: Aortic valve reimplantation is a promising alternative to alloprosthetic composite replacement. A level of coaptation within the tube graft is essential to achieve valve competence.

Heart transplantation: echocardiographic assessment of morphology and function after more than 10 years of follow-up.

BACKGROUND: Over recent years, heart transplantation (HTX) developed into a successful option for long-term treatment of end-stage heart failure. Ten-year survival ranges between 40% and 50%. Little is known, however, about function and morphology of transplanted hearts during follow-up of more than 10 years. METHODS: In a consecutive cohort of 65 patients (55 male, 54.6 +/- 12.1 years at the time of transplantation), graft function was assessed by color Doppler echocardiography 12.5 +/- 1.4 years after heart transplantation (10 to 15 years). RESULTS: Left atrial and ventricular dimensions were found in a normal range (LA 37.7 +/- 8.9 mm, LV enddiastolic 45.6 +/- 6.4 mm, 30 to 71 mm). Ejection fraction (EF) of 71 +/- 11.7% and a fractional shortening of 35.3 +/- 10.3% presented with normal values. Left ventricular mass (male 263.8 +/- 111.4 g, female 373.0 +/- 181.1 g) was slightly increased resulting in mild hypertrophy in women. Focused on right ventricular morphology, enlargement of both the right atrium and the right ventricle (RA 40.7 +/- 11.8 mm, RV 37.4 +/- 8.3 mm) was observed in the majority of the patients. Tricuspid valve insufficiency (> grade II) was present in 46 of 65 patients; 5 patients had previously undergone tricuspid valve replacement. Atrial filling waves were detectable in only 47 of 65 patients, thus, 28% of patients showed signs of LA-dysfunction. CONCLUSIONS: More than 10 years post-HTX, cardiac grafts were characterized by normal left ventricular dimensions and ejection fraction. LA-dysfunction and RV-enlargement associated with tricuspid insufficiency were frequent findings, however, not associated with clinical signs of congestive heart failure in the majority of patients.

Results of valve-sparing aortic root reconstruction in 158 consecutive patients.

BACKGROUND: This study assesses the durability and clinical outcome of valve-sparing aortic root reconstruction using the reimplantation technique in a single center cohort. METHODS: From July 1993 to July 2001, 158 patients underwent replacement of the ascending aorta with native valve reimplantation. Mean age of patients was 52 +/- 17 years (9 to 84 years), 103 were men (65%). Thirty-four patients (22%) suffered from Marfan's syndrome. Aortic dissection Stanford type A was present in 29 patients (19%) (22 acute, 7 chronic), and concomitant partial or total arch replacement was necessary in 57 patients (36%). One or more additional procedures were performed in 28 patients (18%). Mean follow-up was 36 +/- 25 months (0.4 to 96 months). RESULTS: Thirty-day mortality was 3.8% (6 patients), but only 2.2% in elective patients. Mean bypass time was 169 +/- 50 minutes (99 to 440 minutes), aortic cross-clamp time was 129 +/- 31 minutes (79 to 205 minutes). In patients undergoing arch replacement, circulatory arrest was 26 +/- 18 minutes (7 to 99 minutes). During follow-up, there were 5 (3.3%) cardiac-related late deaths. Grade of aortic insufficiency (AI) decreased from 2.3 +/- 1.1 (0 to 4) preoperatively to 0.23 +/- 0.44 (0 to 2) postoperatively (p < 0.0001). Six patients required aortic valve replacement, 4 of those due to progressive AI. Average grade of AI increased significantly to 0.42 +/- 0.61 (0 to 3) at latest evaluation (p = 0.002). Two patients experienced a transient ischemic attack within the first postoperative week. No further thromboembolic complications were noticed. All patients presented with a favorable exercise tolerance. CONCLUSIONS: The aortic valve reimplantation technique achieves excellent clinical outcome with few complications even in complex pathologies. Lack of anticoagulation and favorable durability encourage wider and earlier use of this technique.

A novel small-animal model for accelerated investigation of tissue-engineered aortic valve conduits.

The objective of the study was to describe a novel small-animal model of tissue-engineered aortic valve conduits and to investigate biological processes in an accelerated and inexpensive fashion. An isogenic Lewis-to-Lewis rat model was used to exclude immunological factors of graft deterioration. U-shaped aortic valvular grafts were decellularized and characterized morphologically. Acellular conduits were repopulated with labeled isogenic cells in a bioreactor under flow conditions. Grafts were anastomosed to the recipient's abdominal aorta in an end-to-side manner (n = 7). Native rat aortas were implanted as a control group (n = 7). Grafts were explanted after 28 days and characterized. After treatment with trypsin-ethylenediaminetetraacetic acid, no residual cells were visualized in the scaffold. Mean DNA content decreased from 0.347 to 0 microg/mg of DNA/tissue, and the content of collagenous connective tissue and proteoglycans appeared slightly reduced. Isolated aortic rat endothelial cells and myofibroblasts were repopulated on the acellularized scaffold, and fluorescent-labeled myofibroblasts were identified in the meshwork. Endothelial cells formed a monolayer on the luminal surface. Reseeded cells were viable as ascertained using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. After implantation, Doppler and M-mode echography proved pulsatile cusp movement. All conduits were patent after 28 days. Examination of tissue-engineered explants revealed thickened aortic walls and incompetent valve function. Microscopically, aortic intima and media appeared normal, whereas the adventitia showed hyperproliferation of fibroblasts. Our new model leads to accelerated and reproducible results, suited to investigation of biological patterns of tissue engineering. The observed adventitial fibrosis emphasized the importance of careful selection of optimal cell types for repopulation in tissue-engineered constructs.

Removal of a left atrial thrombus adherent to a patent foramen ovale occluder.

A 62-year-old man presented with bilateral thromboembolic occlusion of the lower leg arteries 8 months after closure of a patent foramen ovale with an Amplatzer patent-foramen-ovale occluder (AGA Medical Corporation, Plymouth, MN). Then he developed an acute myocardial ischemia. A left heart catheter revealed thromboembolic occlusion of the right coronary artery, and echocardiography demonstrated a thrombus attached to the device within the left atrium. Cerebral computer tomography showed a new ischemic lesion. In an emergency procedure, the device and the left atrial thrombus were removed, the septal defect was closed, and a coronary artery bypass grafting was performed. The patient was discharged from the hospital in stable condition.

LMNA mutations in cardiac transplant recipients.

Lamin A and C are components of the nuclear envelope, located at the nucleoplasmatic surface of the inner nuclear membrane within cells. Recently, mutations within LMNA encoding lamin A/C have been associated with various disease entities including cardiomyopathy. We screened heart transplant recipients suffering from dilated cardiomyopathy (DCM) with a positive family history of LMNA mutations. Four index patients and one relative belonging to four unrelated families carrying LMNA mutations were identified. The mutations p.Q355X and p.S22L have not been reported before, whereas p.R190W has already been reported in other studied DCM cohorts. In the patients of the present study, the mean age at manifestation of heart disease was 37.6 years (range 30-45 years), with progression to end-stage heart failure requiring transplantation at a mean age of 45.8 years (range 35-54 years). Three patients presented initially with atrial fibrillation. These data confirm the involvement of LMNA mutations in patients with DCM and extend the mutational spectrum of LMNA. The p.R190W mutation has been reported in different populations and may therefore be useful for analyzing the impact of a specific LMNA mutation on the phenotype of muscle disease.

Functional endurance capacity and exercise training in long-term treatment after heart transplantation.

OBJECTIVE: The aim of this study was to investigate the influence of cardiac denervation on endurance exercise capacity in heart transplant recipients (HTR) in comparison to patients with coronary artery disease (CAD). METHODS: We performed two successive incremental tests and a 30-min constant load test (CLT) in 20 HTR (55 +/- 7 years old, 4.9 +/- 2.2 years after transplantation) and in 13 patients with CAD (58 +/- 8 years). RESULTS: Maximal workload in HTR was 106 +/- 25 W (163 +/- 41 W; p < 0.01). In CLT at anaerobic threshold of 55 +/- 6 W (97 +/- 34 W; p < 0.01), lactate increased from 0.9 +/- 0.2 (1.0 +/- 0.2) to 2.9 +/- 1.3 (3.3 +/- 1.3) after 10 min and to 3.1 +/- 1.6 (3.4 +/- 1.5; NS) mmol. l(-1) after 30 min, confirming that the anaerobic threshold reflects a steady state. The CLT kinetics of heart rate (+6 beats in HTR and in CAD between 10th and 30th min) and lactate are comparable in HTR and CAD, demonstrating that endurance kinetics are not influenced by cardiac denervation.

Reduction of cyclosporine after introduction of mycophenolate mofetil improves chronic renal dysfunction in heart transplant recipients--the IMPROVED multi-centre study.

AIMS: This comparative prospective multi-centre study evaluated efficacy and safety of cyclosporine A downtitration in heart transplant recipients with chronic renal dysfunction potentially attributable to cyclosporine (n=161). METHODS: In the intervention arm (n=109, recruited from 9 centres), mycophenolate mofetil was introduced de novo or substituting azathioprine, followed by cyclosporine reduction (target trough levels 2-4 microg/ml and 50 ng/ml, respectively). In controls (n=52, recruited from 1 centre), immunosuppression remained unchanged. Renal function was recorded twelve, six, and three months before, and throughout the eight-month study period. RESULTS: At study entry, cyclosporine trough levels and renal function parameters were comparable. At study end, mean+/-SD cyclosporine in the intervention arm was 57+/-24 vs. 116+/-36 ng/ml in controls. During the study, creatinine decreased by 23.3+/-50.7 micromol/l (P<0.0001) in the intervention arm but increased by 7.3+/-46.9 micromol/l (P=0.992) in controls (P=0.0001 for comparison between groups). A creatinine reduction of at least 20% was found in 35% of subjects of the intervention arm but only in 4% in the control arm (P<0.0001 for comparison between groups). Improvement in renal function was not weakened after adjustment for baseline characteristics in multiple regression analysis. Renal function improved in strata of creatinine entry values from 150 to 310 micromol/l, regardless of the presence of diabetes. Myocardial biopsies at target levels for cyclosporine and mycophenolate mofetil showed three reversible subclinical rejection episodes. CONCLUSIONS: Cyclosporine downtitration improved renal dysfunction in diabetic and non-diabetic heart transplant recipients across a wide range of creatinine levels. The long-term benefit of this strategy deserves further study.