Marcus Franz

Transcatheter treatment of tricuspid regurgitation by caval valve implantation—experimental evaluation of decellularized tissue valves in central venous position

BACKGROUND: Caval valve implantation has been suggested for transcatheter treatment of severe tricuspid regurgitation (TR). Combining the interventional technique with the promising surgical experience with decellularized valves, we sought to evaluate the functional and structural outcome of decellularized pericardial tissue valves (dTVs) in the low‐pressure venous circulation in a chronic model of TR. METHODS AND RESULTS: Sixteen pericardial tissue valves were heterotopically implanted in the inferior and superior vena cava in a sheep model (54–98 kg; median 74.5 kg, n = 8) of severe TR. The devices were assembled using self‐expanding nitinol stents and bovine pericardia decellularized by a detergent‐based protocol (group dTV; n = 8). Glutaraldehyde‐fixed pericardial tissue valves served as control (GaTV, n = 8). After 6 months, device function and structural maturation were analyzed using echocardiographic, histologic, immunohistologic, and electron microscopic approaches. After implantation, cardiac output increased significantly from 3.7 ± 1.1 l/min to 4.8 ± 1.1 l/min (P < 0.05) and competent valve function was verified by angiography. At 6 months, angiographic and echocardiographic evaluation revealed moderate to severe regurgitation in all GaTV. In contrast, five of the eight dTVs functioned well with only minor regurgitation. In these animals, autopsy revealed preserved valve structure with tender leaflets without signs of thrombosis or calcification. Conversely, GaTV showed severe degeneration with large calcification areas. Microscopic and histologic analysis confirmed endothelial repopulation in both valve types. However, additional interstitial reseeding was observed in decellularized valves. CONCLUSIONS: In the venous circulation in severe TR, decellularized valves show superior functional performance compared to Ga‐fixed tissue valves. Macroscopic and microscopic analyses suggest preserved structural integrity and advanced endothelial and interstitial repopulation with evidence of less degradation in dTV.

Increased levels of circulating arginase I in overweight compared to normal weight adolescents

Overweight and the metabolic syndrome have become major problems, especially in children and adolescents. Obesity at a young age increases the risk for cardiovascular diseases and diabetes mellitus later in life. An early event in the development of cardiovascular disease is endothelial dysfunction which is found in obese young individuals. Increased activity of the enzyme arginase has been described as a central mechanism for endothelial dysfunction, especially in patients with diabetes mellitus. The aim of the study was to determine plasma levels of arginase in overweight adolescents.

Positive effect of eplerenone treatment on endothelial progenitor cells in patients with chronic heart failure

Background: Endothelial progenitor cells (EPCs) are known to play a significant role in reendothelialization and vascular repair. Recently, a mineralocorticoid receptor was demonstrated to be expressed by EPCs. The study aimed to evaluate a potential influence of eplerenone treatment on the total number of EPCs in patients with chronic heart failure. Methods: Eighty-seven male patients with chronic heart failure were included (age: 23–83 years; body mass index 29.1 ± 5.1 kg/m2; New York Heart failure classification (NYHA) I: 29 patients, NYHA II: 32 patients, NYHA III: 26 patients). Numbers of circulating EPCs were quantified immediately using flow cytometry. Twenty-eight patients received therapy with eplerenone. Patients were further characterized by echocardiography, spirometry and laboratory markers. Results: Patients with ongoing eplerenone administration showed higher levels of circulating cells expressing CD34+ (p<0.05) and CD34+KDR+ (p<0.05) and CD34+CD133+KDR+ cells (p<0.05). The effects of eplerenone treatment could be shown to be independent of NYHA status, genesis of the underlying cardiovascular morbidity, left ventricular function and co-medication. Conclusion: Patients with chronic heart failure treated with eplerenone show higher numbers of EPCs. The clinical benefit for treatment with eplerenone has been demonstrated even for patients with mild heart failure and might be partially mediated by EPCs.

MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation

Background: Heart failure leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. It is interesting to note that unique cardiac and systemic microRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium. Methods: Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and acetylation levels in rodent models of SIRT3–/–and transgenic microRNA-195 (miR-195) overexpression were compared with wild type. Luciferase assays, Western blotting, immunoprecipitation assays, and echocardiographic analysis were performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase were measured. Results: In failing human myocardium, we observed induction of miR-195 along with decreased expression of the mitochondrial deacetylase SIRT3 that was associated with increased global protein acetylation. We further investigated the role of miR-195 in SIRT3-mediated metabolic processes and its impact on regulating enzymes involved in deacetylation. Proteomic analysis of the total acetylome showed increased overall acetylation, and specific lysine acetylation of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR-195 downregulates SIRT3 expression through direct 3′-untranslated region targeting. Treatments with either sirtuin inhibitor nicotinamide, small interfering RNA–mediated SIRT3 knockdown or miR-195 overexpression enhanced acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP synthase activity and impaired mitochondrial respiration.SIRT3–/– and miR-195 transgenic mice consistently showed enhanced global protein acetylation, including PDH complex and ATP synthase, associated with decreased enzymatic activity. Conclusions: Altogether, these data suggest that increased levels of miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3 suppression and enzymatic inhibition via increased acetylation of PDH and ATP synthase that are essential for cardiac energy metabolism.

Effect of endothelin‐1 and endothelin receptor blockade on the release of microparticles

Increased levels of endothelial cell microparticles (EMP) are known to reflect endothelial dysfunction (ED). In diabetes mellitus type 2 (T2DM), the expression of endothelin (ET)‐1 is increased. As treatment with an ET‐1 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with ET‐1 antagonists affects EMP levels in vitro and in vivo in patients with T2DM.

Insulin like growth factor binding protein 2 (IGFBP-2) for risk prediction in patients with severe aortic stenosis undergoing Transcatheter Aortic Valve Implantation (TAVI)

INTRODUCTION Severe aortic stenosis (AS) caused by degenerative calcification is the most frequent acquired valvular heart disease worldwide and mortality rates are considerably high. Transcatheter Aortic Valve Implantation (TAVI) is a well-established method for valve replacement in high risk patients with AS. However, there is a lack of reliable predictors for patients undergoing TAVI since commonly used scores were developed for surgical populations. MATERIALS AND METHODS 208 patients subjected to TAVI were included in this study. Plasma samples were obtained before TAVI and were evaluated for IGFBP-2 using commercially available ELISA kits. IGFBP-2 levels were analyzed for their ability for risk prediction after TAVI. RESULTS IGFBP-2 levels measured before TAVI correlated significantly with left ventricular ejection fraction, EUROSCORE and other functional and prognostic parameters like the 6-minute walking test. When patients were retrospectively divided in two groups with a cut-off of serum IGFBP-2 levels of 275 ng/ml, IGFBP-2 was a strong predictor for 30-day and one-year mortality (3% vs. 11%, p = 0.05 and 18.2% vs. 46.2%; p < 0.001 respectively). Compared to an EUROSCORE above 20 or an STS score cut-off above 8, IGFBP-2 plasma levels above 275 ng/ml outperformed the established risk score for prediction of one-year mortality as assessed by NRI (0.65 95% CI 0.37-0.94; p < 0.001 and 0.54 95% CI 0.25-0.82; p < 0.001, respectively). CONCLUSIONS Our results indicate that IGFBP-2 could serve as new outcome predictor for patients undergoing TAVI procedure. By providing additional information to the commonly used EUROSCORE, IGFPB-2 analysis could further assist Heart Team decision making.

Psoriatic arthritis is associated with bone loss of the metacarpals.

BackgroundBoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring methods.MethodsThe study includes 104 patients with verified PsA. The BX method was used to measure the Metacarpal Index (MCI) at the metacarpal bones (II–IV). Additionally, the T-score of the MCI (T-scoreMCI) was calculated. Radiographic severity was determined by the Psoriatic Arthritis Ratingen Score (Proliferation Score and Destruction Score) as published by Wassenberg et al. and the Psoriatic Arthritis modified van der Heijde Sharp Score (Joint Space Narrowing Score and Erosion Score).ResultsFor the total PsA study cohort, the T-scoreMCI was significantly reduced by −1.289 ± 1.313 SD. The MCI negatively correlated with the Proliferation Score (r = −0.732; p < 0.001) and the Destruction Score (r = −0.771; p < 0.001) of the Psoriatic Arthritis Ratingen Score. Lower coefficients of correlations were observed for the Psoriatic Arthritis modified van der Heijde Sharp Score. In this context, a severity-dependent and PsA-related periarticular demineralisation as measured by the MCI was quantified. The strongest reduction of −30.8 % (p < 0.01) was observed for the MCI in the Destruction Score.ConclusionsThe BX MCI score showed periarticular demineralisation and severity-dependent bone loss in patients with PsA. The measurements of the BX technique were able to sensitively differentiate between the different stages of disease manifestation affecting bone integrity and thereby seem to achieve the potential to be a surrogate marker of radiographic progression in PsA.

Effect of a weight loss program in obese adolescents; a long-term follow-up

OBJECTIVES Obesity during adolescence is an increasing health problem in industrial countries. The co-morbidities associated with obesity include important metabolic diseases. METHODS To analyze the effect of a weight-loss program, we recruited 12 obese, male adolescents before entering this program. We determined body weight measures at baseline, 6-week and 36-month follow-up. Also, the long-term changes of blood pressure, HbA1c, and CRP were evaluated. Twenty healthy age-matched adolescents served as controls. RESULTS Within the intervention group ((body mass index [BMI, kg/m2] > 95th percentile for age and sex, age 13-17 years) the BMI and BMI-standard deviation score [SDS] were significantly reduced in the 6-week follow-up after completing the weight loss program. However, the significant weight-reduction effect was not persistent until the 36-month follow-up. CONCLUSION The 6-week weight-loss program had beneficial short-term effects on body weight, BMI, and BMI-SDS in obese adolescents, but these effects could not be maintained until the 36-month follow-up.

Surgical therapy of infective endocarditis. General aspects and case report

ZusammenfassungHintergrund:Die infektiöse Endokarditis durch Viridans-Streptokokken ist mit einer Letalität von 5–10% assoziiert und stellt bis heute eine Herausforderung bezüglich frühzeitiger Diagnose, Selektion der Antibiotika sowie Wahl des richtigen Zeitpunkts für eine chirurgische Intervention dar.Fallbeschreibung:Bei einem 37-jährigen Patienten fielen im Rahmen einer Anämiediagnostik bei körperlicher Schwäche ein Systolikum sowie ein Fieberanstieg auf. In der Blutkultur konnte Streptococcus mitis, echokardiographisch eine Endokarditis von Aorten- und Mitralklappe mit Insuffizienzen sowie eine hypertrophe obstruktive Kardiomyopathie (HOCM) nachgewiesen werden. Bei hämodynamischer Stabilität wurde der Patient resistenzgerecht mit Penicillin G und Gentamicin sowie Verapamil behandelt. Aufgrund einer Größenprogredienz der Endokarditisvegetationen und einer Verschlechterung der hämodynamischen Situation mit Sepsis erfolgten der operative Ersatz von Aorten- und Mitralklappe sowie die septale Myektomie. Postoperativ kam es zum Bild einer schweren Sepsis, welches eine Behandlung mit Katecholaminen erforderte und von einer respiratorischen Insuffizienz mit Beatmungspflichtigkeit begleitet wurde. Schließlich konnte der Patient in die postprimäre Frührehabilitation entlassen werden.Schlussfolgerung:Die Indikation zur chirurgischen Therapie bei Doppelklappenendokarditis und HOCM stellt in ihrer Entscheidungsfindung im Hinblick auf Patientenalter, Zielsetzung der konservativen Therapie sowie Risiko und Tragweite der komplexen Operation eine hohe interdisziplinäre Herausforderung dar und ist bei Hinweisen auf einen Progress des Geschehens unter resistenzgerechter Antibiose zügig zu stellen.AbstractBackground:Infective endocarditis due to viridans streptococci is associated with a mortality of 5–10%. Even today, it remains difficult to diagnose it at an early stage, to select a sufficient antibiotic therapy and to choose the right time for surgical intervention.Case Report:A 37-year-old male patient presented with anemia, fever, adynamia and a loud systolic murmur over the base of the heart. Blood culture data were positive for Streptococcus mitis. Transthoracic echocardiography revealed an endocarditis of the aortic and mitral valve with regurgitations as well as a hypertrophic obstructive cardiomyopathy. The hemodynamically stable patient was treated with penicillin G, gentamicin and verapamil. Because of an extension of valve vegetations and a decline in the hemodynamic situation with an incipient sepsis, the patient was surgically treated urgently by replacement of the aortic and mitral valve as well as a Morrow septal myectomy. A postoperative sepsis required the application of high catecholamine doses. Because of a respiratory insufficiency, a prolonged mechanical ventilation was required. Finally, the patient could be discharged for in-hospital rehabilitation.Conclusion:The indication for surgical therapy in patients with endocarditis of the aortic and mitral valve as well as hypertrophic obstructive cardiomyopathy should be critically discussed with regard to the patients age, the aims of conservative therapy, and the consequences of a surgical intervention. If there are any indices of a disease progress in spite of antibiotic therapy, patients should be subjected to cardiac surgery immediately.BACKGROUND Infective endocarditis due to viridans streptococci is associated with a mortality of 5-10%. Even today, it remains difficult to diagnose it at an early stage, to select a sufficient antibiotic therapy and to choose the right time for surgical intervention. CASE REPORT A 37-year-old male patient presented with anemia, fever, adynamia and a loud systolic murmur over the base of the heart. Blood culture data were positive for Streptococcus mitis. Transthoracic echocardiography revealed an endocarditis of the aortic and mitral valve with regurgitations as well as a hypertrophic obstructive cardiomyopathy. The hemodynamically stable patient was treated with penicillin G, gentamicin and verapamil. Because of an extension of valve vegetations and a decline in the hemodynamic situation with an incipient sepsis, the patient was surgically treated urgently by replacement of the aortic and mitral valve as well as a Morrow septal myectomy. A postoperative sepsis required the application of high catecholamine doses. Because of a respiratory insufficiency, a prolonged mechanical ventilation was required. Finally, the patient could be discharged for in-hospital rehabilitation. CONCLUSION The indication for surgical therapy in patients with endocarditis of the aortic and mitral valve as well as hypertrophic obstructive cardiomyopathy should be critically discussed with regard to the patients age, the aims of conservative therapy, and the consequences of a surgical intervention. If there are any indices of a disease progress in spite of antibiotic therapy, patients should be subjected to cardiac surgery immediately.

Coronary Artery Bypass Grafting using Bilateral Internal Thoracic Arteries through a Left-Sided Minithoracotomy: A Single-Center Starting Experience

OBJECTIVE  Coronary artery bypass grafting (CABG) using bilateral internal thoracic artery (BITA) is associated with the best long-term survival. However, using BITA increases the risk of sternal wound infections with conventional sternotomy. We describe here our initial results of minimally invasive CABG (MICS-CABG) using BITA. METHODS  Patients were operated through an incision similar to that of standard minimally invasive direct CABG. All operations were performed off-pump. We evaluated patients quality of life (QoL) using the Medical Outcomes trust, 36-Item Short Form Health Survey (SF-36). RESULTS  Between February 2016 and August 2017, we performed 21 cases of MICS-CABG using BITA. There was no intraoperative complication and no conversion to sternotomy or to on-pump. Two patients required reexploration through the same minithoracotomy for postoperative bleeding. Two cases of early postoperative graft failure were identified. There was no stroke or in-hospital mortality. The median duration of follow-up was 13 months, with a maximum of 19 months. Relief of angina was achieved in all patients. There was one readmission for superficial wound infection, which was conservatively treated. An 84-year-old man died 4 months after the operation. The remaining 20 patients attested good QoL with the SF-36 questionnaire. CONCLUSIONS  Myocardial revascularization using BITA can be safely achieved off-pump through a left-sided minithoracotomy with good postoperative and short-term outcomes.