Impact of estradiol, testosterone and their ratio on left and right auricular myofilament function in male and female patients undergoing coronary artery bypass grafting.

BACKGROUND: The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. METHODS: 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. RESULTS: Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). CONCLUSIONS: This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.

Clinically inapparent right heart dysfunction is associated with reduced myofilament force development in coronary artery disease.

BACKGROUND: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. METHODS: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. RESULTS: Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34%, p = 0.018), preoperative AFib (43 vs. 16%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m2, p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm2, p = 0.005) and reduced LVEF (50 vs. 55%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75-6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12-5.73, Euro Score II (OR 1.34, CI 1.02-1.78), preoperative AF (OR 4.86, CI 2.06-11.47), GFR (OR 7.72, CI 1.87-31.96), albumin (OR 1.56, CI 0.52-2.60), Pentraxin-3 (OR 19.68, CI 14.13-25.24), depressed LVEF (OR 8.61, CI 6.37-10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40-4.29 and pCa 5.2; OR 2.00, CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. CONCLUSIONS: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.

Factors associated with smoking cessation in patients with coronary heart disease: a cohort analysis of the German subset of EuroAspire IV survey.

BACKGROUND: Tobacco smoking is one of the most important risk factors of coronary heart disease (CHD). Hence, smoking cessation is considered pivotal in the prevention of CHD. The current study aimed to evaluate smoking cessation patterns and determine factors associated with smoking cessation in patients with established CHD. METHODS: The fourth European Survey of Cardiovascular Disease Prevention and Diabetes investigated quality of CHD care in 24 countries across Europe in 2012/13. In the German subset, smoking cessation patterns and clinical characteristics were repetitively assessed a) during index event due to CHD by medical record abstraction, b) as part of a face-to-face interview 6 to 36 months after the index event (i.e. baseline visit), and c) by telephone-based follow-up interview two years after the baseline visit. Logistic regression analysis was performed to search for factors determining smoking status at the time of the telephone interview. RESULTS: Out of 469 participants available for follow-up, 104 (22.2%) had been classified as current smokers at the index event. Of those, 65 patients (62.5%) had quit smoking at the time of the telephone interview, i.e., after a median observation period of 3.5 years (quartiles 3.0, 4.1). Depressed mood at baseline visit and higher education level were less prevalent amongst quitters vs non-quitters (17.2% vs 35.9%, p = 0.03 and 15.4% vs 33.3%, p = 0.03), cardiac rehabilitation programs were more frequently attended by quitters (83.1% vs 48.7%, p < 0.001), and there was a trend for a higher prevalence of diabetes at baseline visit in quitters (37.5% vs 20.5%, p = 0.07). In the final multivariable model, cardiac rehabilitation was associated with smoking cessation (OR 5.19; 95%CI 1.87 to 14.46; p = 0.002). DISCUSSION: Attending a cardiac rehabilitation program after a cardiovascular event was associated with smoking cessation supporting its use as a platform for smoking cessation counseling and relapse prevention.

Sex differences in volume overload in skinned fibers.

BACKGROUND: The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. METHODS: In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5-4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. RESULTS: The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. CONCLUSION: This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more "energy efficient".

[Venoarterial extracorporeal membrane oxygenation in an awake patient : Use of the mobile ECMO team for fulminant pulmonary embolism]. / Venoarterielle extrakorporale Membranoxygenierung am wachen Patienten : Einsatz des mobilen ECMO-Teams bei fulminanter Lungenarterienembolie.

The current report highlights the use of venoarterial extracorporeal membrane oxygenation (va-ECMO) in a case of pulmonary embolism complicated by right ventricular failure. A 38-year-old woman was admitted to a secondary care hospital with dyspnea and systemic hypotension. Diagnostic testing revealed a massive pulmonary embolism. Thrombolytic therapy was unsuccessful necessitating thromboendarterectomy in the presence of cardiogenic shock. To allow the necessary transport of the highly unstable patient to a tertiary care center a mobile ECMO team was called in. The team immediately initiated awake va-ECMO as a bridge to therapy. Extracorporeal support subsequently allowed a safe transportation and successful completion of the surgical procedure with complete recovery.

Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys.

BACKGROUND: Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012-13; and EA-V, 2016-17) in Germany. METHODS: The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V). RESULTS: 384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%). CONCLUSION: Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

Variations in cardiovascular risk factors in people with and without migration background in Germany - Results from the STAAB cohort study.

BACKGROUND: About 20% of the German population have a migration background which might influence prevalence of preventable cardiovascular risk factors (CVRF). METHODS: We report data of the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of inhabitants of the City of Würzburg, Germany, aged 30 to 79 years. Individuals without migration background were defined as follows: German as native language, no other native language, and/or born in Germany. All other participants were defined as individuals with migration background. RESULTS: Of 2473 subjects (51% female, mean age 54 ±â€¯12 years), 291 (12%) reported a migration background: n = 107 (37%) from a country within the EU, n = 117 (40%) from Russia, and n = 67 (23%) from other countries. Prevalence of hypertension, atherosclerotic disease, and diabetes mellitus was similar in individuals with and without migration background. By contrast, prevalence of obesity and metabolic syndrome was significantly higher in individuals with migration background, with the least favourable profile apparent in individuals from Russia (individuals without vs. with migration background: obesity 19 vs. 24%, p < 0.05; odds ratio: EU: 1.6, Russia: 2.2*, other countries: 0.6; metabolic syndrome 18 vs. 21%, p < 0.05; odds ratio: EU: 1.2, Russia: 1.7*, other countries: 1.5; *p < 0.05). CONCLUSION: Individuals with migration background in Germany might exhibit a higher CVRF burden due to a higher prevalence of obesity and metabolic syndrome. Strategies for primary prevention of heart failure may benefit from deliberately considering the migration background.

A multilayered electrospun graft as vascular access for hemodialysis.

Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access-an autogenous arteriovenous fistula-is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts.

[End-of-life decisions and practices in critically ill patients in the cardiac intensive care unit. A nationwide survey]. / Begrenzung und Abbruch lebenserhaltender Maßnahmen bei kritisch kranken kardiochirurgischen Patienten. Ergebnisse einer bundesweiten Umfrageaktion.

BACKGROUND: Ethical and medical criteria in the decision-making process of withholding or withdrawal of life support therapy in critically ill patients present a great challenge in intensive care medicine. OBJECTIVES: The purpose of this work was to assess medical and ethical criteria that influence the decision-making process for changing the aim of therapy in critically ill cardiac surgery patients. MATERIALS AND METHODS: A questionnaire was distributed to all German cardiac surgery centers (n = 79). All clinical directors, intensive care unit (ICU) consultants and ICU head nurses were asked to complete questionnaires (n = 237). RESULTS: In all, 86 of 237 (36.3 %) questionnaires were returned. Medical reasons which influence the decision-making process for changing the aim of therapy were cranial computed tomography (cCT) with poor prognosis (91.9 %), multi-organ failure (70.9 %), and failure of assist device therapy (69.8 %). Concerning ethical reasons, poor expected quality of life (48.8 %) and the presumed patient's wishes (40.7 %) were reported. There was a significant difference regarding the perception of the three different professional groups concerning medical and ethical criteria as well as the involvement in the decision-making process. CONCLUSION: In critically ill cardiac surgery patients, medical reasons which influence the decision-making process for changing the aim of therapy included cCT with poor prognosis, multi-organ failure, and failure of assist device therapy. Further studies are mandatory in order to be able to provide adequate answers to this difficult topic.

Opening and closing characteristics of the aortic valve after different types of valve-preserving surgery.

BACKGROUND: The surgical approach to aortic root aneurysm and/or dissection remains controversial. The use of valve-sparing operations, which are thought to have many advantages, is increasing. We hypothesized that the particular technique and type of surgery could influence valve motion characteristics and function. Therefore, we studied the instantaneous opening and closing characteristics of the aortic valve after the main 2 types of valve-sparing surgery. METHODS AND RESULTS: In 20 patients (10 with tube replacement of the aortic root, group A; and 10 with separate replacement of the sinuses of Valsalva, group B) and 10 controls (group C), transthoracic and transesophageal studies on aortic valve dynamics were performed. Three distinct phases of aortic valve motion were identified. They were as follows: (1) a rapid opening, with a velocity of 20.9+/-4.2 cm/s in group C, 27.1+/-10.9 cm/s in group B (P=NS), and 58.3+/-18.4 cm/s in group A (group A versus group C, P<0. 001; group A versus group B, P=0.001); (2) a slow systolic closure, with 12.5+/-6.6% and 10.8+/-2.2% of maximal opening in groups C and B, respectively (P=NS), and 3.8+/-1.6% in group A (group A versus group C, P=0.001; group A versus group B, P<0.001); and (3) a rapid closing movement, with a velocity of 26.3+/-5.6 cm/s in group C, 32. 4+/-11.4 cm/s in group B (P=NS), and 21.8+/-3.5 cm/s in group A (group A versus group C, P=NS; group A versus group B, P=0.008). The pressure strain of the elastic modulus was different in groups C and B only at the commissures (682+/-145 g/cm(2) versus 1896+/-726 g/cm(2), respectively; P<0.001). At all root levels, the distensibility was reduced in group A (P<0.001). Systolic contact of aortic cusps and wall occurred only in group A. CONCLUSIONS: Near-normal opening and closing characteristics can be achieved by a technique that preserves the shape and independent mobility of the sinuses of Valsalva.

Impact of preoperative aortic root diameter on long-term aortic valve function after valve sparing aortic root reimplantation.

BACKGROUND: Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. METHODS AND RESULTS: From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43+/-26 months, group B 40+/-25 months, group C 23+/-19 months; group C versus group A, P=0.005; group C versus group B, P=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98+/-2%, for group B 96+/-3%, and for group C 100+/-0% (P=ns). Freedom from reoperation for group A was 98+/-2%, for group B 96+/-3%, and for group C 88+/-8% (P=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100+/-0%, for group B 88+/-8%, and for group C 94+/-5% (P=ns). During follow-up no thromboembolic or bleeding events were noticed. CONCLUSIONS: Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.

Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease.

BACKGROUND: Chemotherapeutic treatment for patients with symptomatic coronary artery disease to reduce cardiovascular events may be initiated in response to elevated antibody titers against Chlamydia pneumoniae or cytomegalovirus. How antibody titers are associated with the endovascular presence of these microorganisms is still unclear. METHODS AND RESULTS: Antibody titers against C pneumoniae (microimmunofluorescence) and cytomegalovirus (ELISA) in patients undergoing primary (coronary desobliterates, n=80) or repeated CABG (occluded vein grafts, n=45) were correlated with the endovascular presence of the 2 microorganisms. C pneumoniae was detected by means of a nested polymerase chain reaction (PCR) and by culturing. Both conventional PCR and quantitative PCR were applied for detection of cytomegalovirus. C pneumoniae (PCR/culture) was detected in 19/9% (15/80 and 7/80) of coronary desobliterates and in 18/11% (8/45 and 5/45) of occluded vein grafts. There was no statistical evidence that IgG values differed between patients with or without C pneumoniae detection who were undergoing primary CABG. In contrast, repeated-CABG patients with a positive PCR (P=0.0027) or C pneumoniae culture (P=0.0018) had distinctly elevated IgG titers compared with patients in whom C pneumoniae was not detected. Cytomegalovirus could not be detected in the examined specimens. CONCLUSIONS: Cytomegalovirus infection does not seem to be associated with advanced coronary artery lesions. C pneumoniae antibody titers are not associated with the endovascular presence of C pneumoniae in patients with coronary artery disease. The observed strong association between elevated IgG titers and the detection of C pneumoniae in occluded vein grafts warrants further investigation.

Atrial natriuretic peptide release at rest and with exercise after cardiac transplantation with bicaval anastomoses.

Bicaval anastomoses in orthotopic cardiac transplantation offer the advantage of preserving the right atrial geometry. To elucidate the impact of this anastomotic technique on atrial natriuretic peptide plasma levels at rest and with exercise, nine patients were submitted to a symptom-limited supine exercise test. Atrial natriuretic peptide plasma levels in samples obtained from the right atrium were elevated at rest (274.4 +/- 60.4 pg/ml), at peak exercise (438.1 +/- 71.7 pg/ml), and thereafter (328.1 +/- 71.2 pg/ml) with respect to normal reference values of 21 +/- 1 pg/ml at rest and 92 +/- 14 at peak exercise. Renin, angiotensin, and aldosterone plasma levels were almost normal and did not indicate any pathologic processes in volume homeoostasis. Right-sided hemodynamic parameters were not correlated with atrial natriuretic peptide secretion. An adverse relationship between cold ischemic time of the donor organ and atrial natriuretic peptide release was found (r = 0.88, p < 0.0008), indicating that endocrine cardiocytes are sensitive to prolonged ischemia. Atrial natriuretic peptide release may thus be independent of the surgical approach, and other unique characteristics of the transplanted heart, such as denervation, are more likely to be responsible for elevated atrial natriuretic peptide plasma concentrations after orthotopic heart transplantation.

Time course of dimension and function of the autologous pulmonary root in the aortic position.

Although the autologous, fully vital, and compatible pulmonary root theoretically offers the prospect of an ideal aortic valve substitute, this type of replacement is performed in only a few centers. Major concern relates to the fate of root dimension and function in the systemic circulation and is largely unknown. To investigate the fate of the aortic root, we conducted echocardiographic examinations of eight freestanding pulmonary roots used for aortic valve replacement in adults. The studies were performed at discharge from the hospital and up to 21 months (mean 12.5 +/- 6.6 months) after the operation, as well as in 26 matched control subjects. There were no significant differences between the first and second postoperative studies regarding the root diameter (mean 26.6 +/- 2.1 mm and 27.6 +/- 2.6 mm, respectively), which was within control limits, the maximum transvalvular pressure gradient (mean 4.6 +/- 1.2 mm Hg and 6.6 +/- 2.1 mm Hg, respectively), the maximum leaflet separation (mean 22.1 +/- 1.4 mm and 22.1 +/- 1.8 mm, respectively), and the degree of insufficiency. At the first study, grade I aortic regurgitation was found in four patients and grade I-II in one patient. Regurgitation increased slightly in one patient with an abnormal leaflet. In three patients primary grade I regurgitation disappeared. These data suggest that the pulmonary root in the aortic position can withstand systemic circulation without changes in dimension and function for up to 21 months. Furthermore, some evidence is provided to indicate that in certain cases the viable autograft may adapt to systemic pressure, as indicated by the disappearance of primary regurgitation.

Acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus.

OBJECTIVE: Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. METHODS: Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. RESULTS: Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. CONCLUSION: Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.

Performance of a stentless xenograft aortic bioprosthesis up to four years after implantation.

Conventional biologic and mechanical prostheses have important limitations with regard to their hemodynamic characteristics and long-term durability. We evaluated the hemodynamic function of a stentless porcine aortic prosthesis in 10 patients by invasive pressure measurements and angiography with videodensitometry 8 +/- 4 days after operation, as well as by Doppler echocardiography 35 +/- 15 months after valve replacement. The early postoperative invasive study revealed a mean gradient of 8 +/- 6 mm Hg across the prosthesis, no regurgitation in eight patients, and mild regurgitation, defined as less than 20% regurgitant fraction, in the remaining two patients. The late postoperative Doppler echocardiographic study revealed a mean gradient across the aortic prosthesis of 6 +/- 3 mm Hg, mean Doppler-derived valve orifice area of 1.8 +/- 0.6 cm2, and color Doppler flow velocity mapping suggested no regurgitation in eight patients and mild regurgitation in two patients corresponding to early postoperative angiography. None of the 10 patients received anticoagulation therapy. The clinical course of all patients was without incident. This stentless aortic bioprosthesis may offer hemodynamic advantage; however, further studies are needed to allow comparison with conventional mechanical and biologic prostheses.

Bicaval versus atrial anastomoses in cardiac transplantation. Right atrial dimension and tricuspid valve function at rest and during exercise up to thirty-six months after transplantation.

Conventional cardiac transplantation with atrial anastomoses alters atrial integrity, geometry, and possibly function. Theoretically, this may also contribute to the development of tricuspid insufficiency that is frequently observed after the operation. Thus more anatomic transplantation techniques using bicaval anastomoses were recently introduced into clinical practice. Knowledge of their efficacy, however, is scarce. Therefore right atrial size and tricuspid valve function were compared in patients with bicaval (group A) and standard atrial (group B) anastomoses in a randomized, prospective study. The results of this echocardiographic study at rest and exercise in 18 patients (bicaval n = 8; atrial n = 10) on the average 28 months after transplantation are presented. The right atrial dimension was comparable between group A patients and control subjects and larger in group B patients (p < 0.05). The incidence of tricuspid regurgitation was not different between the two groups at rest, but it was at exercise (50 watts of workload) (p < 0.05). This study suggests that up to 36 months after cardiac transplantation the technique of bicaval in contrast to atrial anastomoses preserves right atrial size and reduces tricuspid regurgitation during exercise. Whether this leads to improved hemodynamics and increased exercise capacity remains to be evaluated in a larger series of patients.

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.

Time course of lung function and exercise performance after heart transplantation.

To study the time course of exercise performance and the diffusion capacity after heart transplantation, we submitted two groups of patients to graded symptom-limited supine exercise. Patients in group 1 (n = 11) underwent operation 12.9 +/- 7.0 months before the study; those in group 2 (n = 10) underwent operation 53.9 +/- 14.8 months before the study. Respiratory and cardiovascular parameters were evaluated noninvasively at rest, at individual peak exercise, and 10 minutes later with a commercially available Sensormedics MMC 4400 metabolic measurement chart. Short-term survivors exhibited a lower maximum work capacity compared with that of long-term survivors (63.6 +/- 25.9 versus 100 +/- 50 W, p < 0.05), with a concomitant lower terminal heart rate (123 +/- 19 versus 137 +/- 17 beats/min, p < 0.05) that accounts for the lower cardiac output in this group, but statistical significance was not achieved (13.0 +/- 4.6 versus 17.5 +/- 6.3 L/min, not significant). Interestingly, significant differences were also observed for diffusion capacity before exercise (11.9 +/- 4.8 versus 19.3 +/- 7.3 ml/min/mm Hg, p < 0.05). The improvement of the diffusion capacity may be associated with a time-dependent change in the diffusion characteristics of the alveolocapillary membrane.

Adjuvant treatment of deep sternal wound infection with collagenous gentamycin.

BACKGROUND: The treatment of deep sternal wound infections remains controversial. Currently advocated procedures carry the risk of reinfections. The significance of local antibiotic-releasing systems as an adjuvant therapy to avoid reinfections is the subject of the presented study. METHODS: Forty-two patients with deep sternal wound complication were treated with radical wound debridement, sternal refixation, retrosternal suction drainage, bilateral pectoralis major muscle flaps, and placement of collagenous drug carrier loaded with gentamycin (Sulmycin Implant) underneath, above, and between the sternal edges. RESULTS: No treatment failure and death were observed in our patients. Side effects after adjuvant treatment with collagenous gentamycin were not detected. CONCLUSIONS: The preliminary results of adjuvant therapy with collagenous gentamycin in combination with surgical debridement leads to excellent results in the treatment of early deep sternal wound infections with no death and no primary treatment failures. This technique is easy to perform, reliable, and safe. For final judgment controlled randomized trials are mandatory.