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The angiotensin blocker (ARB) eprosartan (600 mg once daily) and the calcium antagonist diltiazem (90 mg twice daily) were studied in a 24-month prospective, randomized, double-blind trial involving 53 heart transplant patients. The study compared their effects on the development of post-transplant cardiac allograft vasculopathy, a condition that frequently impairs long-term post-transplantation survival and where angiotensin blockers might be expected to play a preventive role. From baseline to month 12, the mean plaque volume increased by 7.7 mm3 for eprosartan-treated patients and by 34.4 mm3 for diltiazem-treated patients, but the eprosartan-related trend for reduced myointimal hyperplasia was not statistically significant. The trend in favour of eprosartan for secondary parameters (mean intimal index, vessel volume, lumen volume and coronary flow reserve) also failed to reach significance. The lack of effect might be due to a lower than planned sample size and observation periods due to recruitment difficulties. A larger study is required to confirm these preliminary findings.

Predominantly elderly and multimorbide patients require frequently intensive care observation and treatment due to acute gastrointestinal and renal disease. Manifest circulatory and rhythm instability, acute heart failure and severe metabolic or electrolyte derangements present indications for submission to a critical care unit. Stabilization of vital functions, control of specific therapeutic procedures (e. g. renal replacement therapy), and early recognition of secondary complications belong to the tasks of intensive care. Beyond a baseline monitoring available procedures comprises a broad spectrum from pulseoxymetrie to pulmonary artery catheter monitoring depending of the need of the individual patient.

Quality of life in lung transplant recipients (LTR) is reported to be comparable with that of the general population. However, previous studies have shown that exercise capacity was reduced to 30 - 40 % of normal values. The purpose of this study was to investigate the gap between good self-reported quality of life and reduced exercise capacity in LTR, to describe possible correlations and to compare the results with those of a control group (CG).27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11 female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) % 75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/- 4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic disease" self-rating questionnaire.Significant differences were shown in objective exercise related variables (peak oxygen consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p0.01); percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p0.01). The rating of subjective quality of life in physical, psychological and social domains of LTR did not differ from values of the CG or of the general population (n = 1143). The quality of life in the physical domain correlated significantly with peak exercise capacity (LTR r = 0.44, p0.05; CG r = 0.37; p0.05).Patients 7 months after lung transplantation described their physical, social and psychological quality of life as equally good as the healthy control group. However, peak exercise capacity and oxygen consumption were markedly reduced. To improve physical capacity in the range of daily activities, an exercise training program should be offered to patients after lung transplantation.

Longterm treatment after heart transplantation (HTX) improves survival, although the quality of life and exercise tolerance decreased continuously between one and ten years after transplantation. The role of physical exercise and psychological support in longterm treatment after HTX has not been determined. We analyzed the effects of a one year outpatient rehabilitation program in combination with a home based, computer assisted training program on exercise capacity, coronary risk factors and quality of life.20 heart transplant recipients in an intervention group and 12 patients after HTX in a control group participated in the study (IG (CG); 5.1+/-2.2 (4.5+/-2.3) years after HTX; age: 55+/-7 (54+/-8) years; body mass index: 28.3+/-1.0 (28.7+/-0.9) kg.m(-2)). Before and after the intervention, maximum and constant load exercise capacity, and self-reported quality of life were evaluated. The 12 month intervention period included 10 days of exercise testing as well as medical and psychological support. Furthermore, the IG group performed a computer-assisted and controlled home ergometer training every second day.After one year with 114+/-18 exercise training sessions, maximum oxygen consumption increased in the IG from 18.8+/-4.2 to 20.1+/-4.2 ml.min(-1).kg(-1) (p0.05; CG 19.3+/- 4.5 to 18.5+/-2.8 ml.min(- 1).kg(-1); p0.01 IG vs CG). In the IG, lower back pain, body fat, and blood pressure were all reduced, while the self-reported quality of life, endurance exercise capacity and HDL cholesterol were increased. No significant changes occurred in the control group.When initiated years after heart transplantation, longterm rehabilitation reduced coronary risk factors and significantly improved both the subjects' quality of life, as well as a near to normal capacity for physical work.

Quality of life late after heart transplantation is reported to be comparable with that of the general population. However, peak exercise capacity remained approximately 60% of what was normal between 1 and 10 years after transplantation. The gap between patients' good quality of life and their impaired exercise tolerance is not yet explained. The purpose of our study was to examine the relation between quality of life and exercise- related variables in heart transplant recipients (HTR). Then, the results of these examinations were compared with those of patients having congestive heart failure (CHF), with the use of controls (C), respectively.(Mean values+/-SD) 29 HTR 4.4 +/- 2.1 years after transplantation, 29 CHF (NYHA II n = 22, III n = 7) and 29 C (age 54 +/- 9, 61 +/- 10, 56 +/- 10 years, body mass index 28 +/- 3, 29 +/- 5, 28 +/- 4 kg x m(-2), body fat 25 +/- 4, 27 +/- 6, 26 +/- 5%, respectively) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic diseases" questionnaire.Peak oxygen consumption was impaired in HTR and in CHF compared with C (19.0 +/- 4.5, 18.6 +/- 4.3, and 30.2 +/- 6.6 ml x min x kg(-1), respectively; p0.01 vs. C each). HTR and CHF patients' quality of life in the physical scores were both impaired (p0.05 or p0.01 vs. C, respectively), but HTRs have reported better scores than CHF (p0.05). In the psychological role, CHF was impaired against C (p0.05), and HTR scores were comparable with C. In social functioning HTR and CHF patients both showed reduced quality of life dimensions. The Pearson correlation analysis showed that quality of life in physical functioning was related to peak oxygen consumption (p0.001) and percentage of predicted workload (p0.001). Quality of life in the social and psychological domains showed no association to exercise-related values.In HTR and in CHF, exercise testing variables were dominant predictors among the physical scales in quality of life, but not among social or psychological scales. Therefore, even late after heart transplantation, improving physical capacity should be a therapeutic goal with the intention of further increasing the quality of life.

With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines.Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed.Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities.Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.

Due to an improvement of results after heart transplantation, there is a continuously growing number of long-term surviving patients. Aimed at a characterization of established diagnostic and therapeutic protocols, the Working Group of Thoracic Organ Transplantation within the German Society of Cardiology performed a survey among all German heart transplantation centers. Based on the experience of 1,500 patients, the clinical relevance as well as approaches for prevention and treatment of rejection, infection, cardiac allograft vasculopathy, malignancy, hypertension, renal insufficiency, and quality of life were assessed by a questionnaire. As a result, a time dependency of expected complications could clearly be shown. While early after HTX acute rejection and infection episodes were judged as clinically important, later on cardiac allograft vasculopathy, malignancy, and renal insufficiency predominate as relevant complications. This spectrum was reflected by a differentiated diagnostic protocol (early after HTX more frequent diagnostic procedures for rejection and infection, later intensified examinations to identify cardiac allograft vascular disease and malignancy) as well as by different intensities of immunosuppression and concomittant medication. Regarding further improvement of survival rates and quality of life, future clinical and scientific activities should be focused on the prevention of late complications after heart transplantation.

Recently, homocysteine (HCY) levels have been suggested to be a risk factor in cardiac allograft vascular disease (CAVD). As plasma levels are partially under genetic control, we investigated the influence of the methylenetetrahydrofolate reductase (MTHFR) polymorphism on HCY levels and development of CAVD in heart transplant (HTX) recipients.Genotyping and assessment of fasting HCY levels were performed in a cohort of 146 HTX recipients and correlated to the onset and progression of CAVD, assessed by serial angiography.Actuarial freedom from CAVD did not differ significantly between the genotypes. However, patients positive for CAVD presented with higher HCY levels than CAVD-negative individuals (21.0+/-9.4 vs. 18.2+/-6.6 micromol/L, P=0.046).There is some evidence that plasma HCY might be involved in development of CAVD. However, polymorphism of the MTHFR gene could not be shown to be related to severity of allograft vascular disease.

Hepatitis B may take a rapid and aggressive course in patients under immunosuppression. Nucleoside analogues have been shown to suppress viral replication effectively. To investigate the effect of famciclovir in immunosuppressed patients, 21 heart transplant recipients with chronic hepatitis B infection were included in a prospective study.Patients have been treated with Famciclovir for a median of 14 months. Hepatitis B virus replication and biochemical parameters were regularly tested and liver biopsies were taken before treatment and after a median time of 7 months. HBV-polymerase was sequenced in all patients before therapy and in those patients who experienced virological breakthrough.Nineteen patients were treated for at least 6 months. Hepatitis B virus-DNA levels declined in all patients and became negative in 8 patients. Mean hepatitis B virus-DNA levels decreased from 199+/-269 to 34+/-53 pg/ml after 24 weeks (P=0.003). During treatment HBeAg became negative in five patients. Mean alanine aminotransferase decreased from 42+/-26 to 24+/-10 U/L (P=0.006). Histological analysis revealed improved inflammatory activity according to the Ishak-score in 11/16 (69%) patients. Total inflammatory activity scores decreased from 8 to 6 (median, NS), but interface hepatitis score (P=0.02) and lobular inflammation score (P=0.006) improved significantly. Median fibrosis scores fell from 5 to 3 (P=0.002). Three patients developed virological breakthrough on famciclovir after 7, 8, and 26 months of treatment showing HBV-polymerase amino acid changes L528 M, S567A, and I581K, respectively.Famciclovir improves not only biochemical and virological features but also hepatic inflammation and liver fibrosis in patients with chronic hepatitis B under heavy immunosuppression. Virological breakthrough may develop and requires close monitoring.

Despite considerable progress in the knowledge about pathophysiology of cardiac allograft vascular disease (CAVD), only few systematic studies are available, characterizing the natural course during long-term follow-up after heart transplantation (HTX). Therefore, we analyzed in 354 heart transplant recipients (305 male, 45.9 +/- 11.2 years, mean observation period 5.8 +/- 3.0 years, range 0.9-12.4 years) the results of 1129 coronary angiograms under the aspects of development, severity, localization, and progression of disease related to the prognosis of patients. As expected an increasing prevalence was found over time with a luminal obstructionor = 30% in 83% of all patients more than 10 years after HTX. Coronary artery stenosis (or = 50%) at initial diagnosis was predominantly localized in the LAD (46%) followed by RCX (31%) and RCA (23%). Angiographic risk profiles with an impaired prognosis could be identified in the form of an early development (4 years post HTX) of disease (p = 0.03), luminal obstruction50% (p = 0.001), and multivessel appearance at first diagnosis (p = 0.02) as well as in progressive forms of CAVD (p = 0.001). Summarizing, CAVD is a frequent finding in HTX recipients. Especially in patients with early onset, progressive, and advanced stages of disease it represents a prognostically limiting complication following HTX. Identification of the natural course is of major importance defining the need and efficacy of future palliative therapeutical approaches.

Minimally invasive direct coronary artery bypass (MIDCAB) grafting without cardiopulmonary bypass (CPB) through an anterolateral minithoracotomy has become a promising therapeutical option especially in multimorbid, elderly and reoperative patients with single vessel disease. However, this procedure precludes complete revascularization in multivessel disease because the minithoracotomy limits the surgical access either to anterior or lateral or posterior vessels of the beating heart. To expand the benefits of the MIDCAB concept to patients with multivessel disease, new interdisciplinary approaches have recently been introduced.Since December 1996, 26 patients (21 male, 5 female, mean age 56.6 +/- 18.8 years) underwent a "hybrid" revascularization performed as a primary MIDCAB procedure for grafting of the left anterior descending artery (LAD) with the left internal mammary artery (LIMA) followed by staged angioplasty and stenting of additional coronary lesions.After MIDCAB grafting, the postoperative course was uneventful in all patients. Coronary re-angiography after a median of 7 days revealed patent and functioning LIMA grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty (PTCA) and occasional stenting (n = 8), a total of 31 lesions were treated successfully. Procedure related complications did not occur. All patients remained angina-free and no stress electrocardiographic changes were recorded.Our preliminary results of a "hybrid" approach to myocardial revascularization suggest that this concept is a safe and effective approach of complete revascularization for selected patients with multivessel involvement. Especially elderly and reoperative patients with significant comorbidity may benefit from hybrid procedures avoiding cardiopulmonary bypass and midsternotomy.

The aim of this study was to characterize progression of cardiac allograft vasculopathy (CAV) with special respect to coronary artery geometry.As previously shown by intravascular ultrasound (IVUS), CAV is characterized by a multifocal intimal hyperplasia. Little is known, however, about vascular remodeling processes influencing vessel geometry and luminal narrowing.In 30 heart transplant recipients serial IVUS studies were performed at baseline (BL) and after a mean follow-up period of 12.5+/-2.5 months. Changes in plaque, lumen and vessel volume were assessed in the proximal left anterior descending artery. Pattern of remodeling was analyzed in patients "early" (n = 15, BL study 1.4+/-0.7 months after heart transplantation [HTX]) compared with "late" after HTX (n = 15, BL 46.1+/-29.1 months).Plaque volume was found to increase by a mean of 23.8+/-25.9 mm3, not significantly different within and beyond the 1st year after HTX. Significant differences, however, were observed in changes in vessel volume with a mean decrease of -52.8+/-70.9 mm3 in the early group, whereas late follow-up group presented with an enlargement of 32.3+/-46.0 mm3. Based on these changes, lumen volume decreased by -73.2+/-69.8 mm3 early, in contrast to a slight increase of 5.2+/-32.6 mm3 in the late group.Progression of CAV is a complex process, modified by changes in the vascular geometry. Especially within the 1st year after HTX, luminal loss is influenced not only by an increase in plaque area but by a decrease in total vessel volume as well.

Changes in geometry of the aortic root, especially a dilatation of the sinotubular junction, are the major causes of aortic valve regurgitation in ascending aortic aneurysm. In valves without structural defect, a valve sparing aortic root reconstruction may be a therapeutic option. Aim of this study was the assessment of functional results, in the early postoperative, and during follow-up, in a large patient cohort from one centre.Between July 1993 and March 1998, a total of 48 valve sparing operations were performed at Hannover Medical School. Mean age of patients (34 males, 14 females) was 47.4 +/- 19 years. In a prospective design clinical, and echocardiographic examinations were performed pre-, intra and early postoperatively as well as 3.6 and then every 12 months during follow-up. Structural valve changes, systolic pressure gradients as well as the degree of diastolic regurgitation were evaluated.Aortic root reconstruction was successful in all patients; none died perioperatively. Extension of the underlying disease to the aortic arch was present in eleven, acute and chronic dissection of the ascending aorta (type A) in two and three patients, respectively. Echocardiographic follow-up over a mean period of 25.1 +/- 18.3 months (cumulatively 1204 months) revealed stable valve function in 41 patients without (n = 30) or with a minimal (n = 11) regurgitation. In three patients moderate valve regurgitation (grade 2) was observed, three patients (6.3%) had to be reoperated because of a progressive valve failure. Thromboembolic or bleeding complications were not observed.Valve sparing aortic root reconstruction is a promising alternative to the composite replacement of the ascending aorta. Low perioperative morbidity and mortality rates as well as favourable functional results were demonstrated. Long-term anticoagulation can be avoided. Long-term follow-up will be necessary to assess the definitive role of this new surgical approach.

Despite increasing knowledge about degree and distribution pattern of intimal hyperplasia in cardiac allograft vasculopathy, coronary artery remodeling is only poorly understood in this disease.To evaluate vascular geometry, intravascular ultrasound was used to characterize 57 advanced lesions in 35 consecutive transplant recipients. Lumen, plaque, and vessel area in these target lesions were compared with proximal and distal reference sites.Vascular remodeling by compensatory local vessel enlargement (positive remodeling) and circumscript vascular constriction (negative remodeling) could be demonstrated. Plaque area in stenotic lesions was significantly increased compared with the mean reference site (5.6+/-3.0 mm2 versus 2.8+/-1.5 mm2, p0.001); however, inadequate compensatory enlargement rather than intimal hyperplasia was shown to be the most important predictor of luminal obstruction (r = 0.77, p0.001).

The authors retrospectively analyzed early and late results of surgical treatment for 79 Marfan patients with aneurysms and dissection of the proximal aorta.From September 1979 to February 1996, 79 patients with Marfan syndrome underwent aortic root replacement using composite grafts (n=68, Bentall-technique 63, button-technique 5), and ascending aortic replacement with a valve-sparing procedure (n=11). There were 12 patients (15.2%) who simultaneously received partial or total arch replacement. 55 patients (69.6%) were male, and 24 female (30.4%). The average age was 33.8 years. Forty-one patient (51.9%) had non-dissecting aneurysms while the remaining 38 patients suffered from either acute (24.0%) or chronic aortic dissection (24.0%). The aortic valve was involved in 97.5% of all cases.The total early mortality (or =30 days) was 3.8%, 10.5% for acute aortic dissection and 2.4% for non-dissecting aneurysms. There were no early postoperative deaths in patients after valve-sparing operation and in those with chronic aortic dissection. The follow-up rate was 98.7%. During a mean follow-up of 68+/-25 months 10 patients (13.3%) died and cardiac complications were a common cause of the late deaths. There was no late mortality in the valve-sparing operations during a mean follow-up period of 8+/-6 months, however, 1 required valve replacement. 19 (25.3%) of the 75 patients surviving late have undergone 25 secondary operations on the cardiovascular system. Reoperations at aortic sites distant from the original were much more frequent after primary repair for acute and chronic dissection when compared to non-dissecting aneurysms (p0.005). Actuarial survival rate of all patients with composite graft replacement including early deaths was 91.2% at 1 year, 84.4% at 5 years and 75.2% at 10 years.Composite graft insertion has become the gold standard for treating Marfan-patients with non-dissecting and dissecting aneurysms of the aortic root. Our early experience in 11 patients with valve-sparing procedures indicated that this,variant may be the better choice in selected patients.

Using intravascular ultrasound, we demonstrated plaque-induced compensatory enlargement of coronary arteries in cardiac allograft vasculopathy. Besides intimal hyperplasia, adaptive remodeling processes of vessel and luminal geometry have physiologic and prognostic importance.

Due to improved hemodynamic properties stentless bioprostheses represent a new therapeutic option in the surgical treatment of aortic valve disease.Between February 1993 and June 1995 22 patients with a small aortic root regarded as suboptimal for a stented bioprosthesis (diameteror = 23 mm, mean 21.6 +/- 1.9 mm) underwent aortic valve replacement with a Biocor stentless prosthesis. Mean age was 63.9 +/- 15.4 years (17-85 years). Valve size ranged from 21 to 27 mm (mean 25 mm) and exceeded the root diameter by 4 mm. As compared to a control group of patients with root enlargement (n = 10) total bypass time and cross-clamp time in the stentless group were significantly shorter (83.3 +/- 12.7 and 60.9 +/- 9.2 min versus 95.8 +/- 27.1 and 69.5 +/- 16.5 min, p = 0.054 and p0.05), respectively.Three patients died postoperatively unrelated to the choice of valve. There were no late deaths. No thromboembolic or bleeding events were observed. Follow up data are available over a period of 1-25 months (mean 12.5 months, median 16 months). Echocardiographic evaluation revealed no aortic regurgitation; mean valve gradients were 9.9 +/- 4.1 mmHg (peak 19.2 +/- 6.0 mmHg). For specific root diameters these gradients were compared to established data for Hancock bioprostheses demonstrating significant differences in transvalvular gradients between the two valve designs for given root diameters. Unloading the left ventricle resulted in regression of left ventricular hypertrophy (decrease in wall thickness from 13.6 +/- 1.7 mm to 11.2 +/- 2.0 mm). Exercise capacity improved from NYHA III-IV preoperative to I-II postoperative.In patients with a small aortic root stentless valves represent a new option. Compared to root enlargement with standard bioprosthesis myocardial ischemia is shorter and implantation of larger valve sizes results in superior hemodynamics.

Aortic valve regurgitation in conjunction with ectasia of the proximal aorta is a common finding. The pathologic mechanism of valve insufficiency is mainly caused by dilatation of the aortic root at the level of the sino-tubular and the aorto-ventricular junction. Total replacement of the proximal aorta with resuspension of the aortic valve within the graft is a new alternative approach. Between July 1993 and March 1995, 17 patients were treated for root ectasia using this approach. The age ranged from 15 to 70 years. Aortic insufficiency (mean grade 3) was present in all patients. The operation consisted of total replacement of the proximal aorta with resuspension of the native valve within the graft. In five patients the aortic arch was replaced as well, one patient underwent mitral reconstruction for severe mitral regurgitation. There was no mortality; postoperative aortic regurgitation was reduced to a mean of 0.7. Aortic valve function has been stabled in 16 instances, in one patient a mild increase in regurgitation was seen. Aortic valve reconstruction in conjunction with total tubular graft replacement of the proximal aorta is a new alternative approach for patients with root ectasia. The disadvantages of mechanical heart valve replacement can be avoided.

Tricuspid regurgitation following heart transplantation can become a severe problem in a subset of patients, where medical therapy fails. Operative findings are described and results of subsequent results with surgical intervention including repair and replacement are analysed. Although follow-up is short, tricuspid replacement seems superior to reconstruction following heart transplantation. Best results are obtained, if replacement is performed, before right ventricular function deteriorates.

A case report is given of a 37-year-old patient suffering from rigid spine syndrome and hypertrophic non-obstructive cardiomyopathy. Clinical-cardiological and neurological findings are discussed. This is the first description of such a case in the German-language region; only two other similar publications are found in the whole literature. Follow-up is documented over a period of 10 years; apart from the early dominating neuro-muscular deficit, we saw only a mild progression of symptoms. Signs of an increasing diastolic dysfunction of the left ventricle without clinical complaints were the main cardiological findings. Because of substantial progress in elucidating the genetics of hypertrophic cardiomyopathies over recent years, case reports about the association of two different type of muscular disorders are thought to be of special interest in terms of a common etiological basis.