Therapy for Heart Failure: The Leipzig Approach

Introduction

Heart failure is the “Achilles heel” of cardiac surgical therapy. Being aware of this problem Prof. Mohr focused on therapeutic options and the possibilities when cardiac surgical therapy could be of benefit for our patients. He had this specific interest already during his early surgical career when he successfully established a new heart transplantation program in Göttingen in the years 1990 until 1994. During this time a frequent collaboration with Germany's largest transplantation center, the Heart and Diabetes Center in Bad Oeynhausen, Germany was established. In the consecutive years, several teams from Göttingen and later from Leipzig visited Bad Oeynhausen and learned from the large experience there. Based on this training a very successful patient support group was also formed at that time.

Prof. Mohr was one of the first leaders who taught his fellows and residents to collaborate with other medical specialties, to team up with cardiologists and thus to form a true interdisciplinary team. Especially close collaborations with the pharmacology,[1] the cardiology, and the pathology departments should be mentioned in this context. This concept as an expression of Prof. Mohr's extraordinary leadership was certainly the base for a successful surgical heart failure program at the Leipzig Heart Center.

Besides thoracic organ transplantation and mechanical circulatory support, guided by Prof. Mohr, the interest of our group focused on evaluating further surgical therapeutic options to treat heart failure. We concentrated on conventional surgical therapies in patients with heart failure and on exploring new technologies. Therapeutic options of the cardiac surgeons for patients with heart failure include therapy of underlying conditions, such as coronary artery disease or valve disease (mostly mitral valve disease), reconstruction of left ventricular size and dimensions, additional new techniques such as ventricular reshaping using splints or external meshes, or resynchronization therapy. Also, therapeutic options such as assist device implantation and heart transplantation have to be considered.

• References

• 1 Schütz E, Gummert J, Mohr F, Oellerich M. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993; 341 (8842): 436
• 2 Gummert JF, Rahmel A, Bucerius J , et al. Mitral valve repair in patients with end stage cardiomyopathy: who benefits?. Eur J Cardiothorac Surg 2003; 23 (6) 1017-1022 , discussion 1022
• 3 Doll N, Opfermann UT, Rastan AJ , et al. Facilitated minimally invasive left ventricular epicardial lead placement. Ann Thorac Surg 2005; 79 (3) 1023-1025 , discussion 1025
• 4 Gummert JF, Doll N, Rahmel A, Richter M, Bossert T, Mohr FW. Surgical strategies for the treatment of heart failure [in German]. Z Arztl Fortbild Qualitatssich 2003; 97 (2) 121-126
• 5 Oz MC, Konertz WF, Kleber FX , et al. Global surgical experience with the Acorn cardiac support device. J Thorac Cardiovasc Surg 2003; 126 (4) 983-991
• 6 Gummert JF, Schneider J, Bossert T, Krakor R, Mohr FW. The acorn cardiac support device (CD) randomized trial: Perioperative results and early follow-up in 26 patients—A single center experience. J Heart Lung Transplant 2002; 21 (1) 126-127
• 7 Gummert JF, Rahmel A, Bossert T, Mohr FW. Socks for the dilated heart. Does passive cardiomyoplasty have a role in long-term care for heart failure patients?. Z Kardiol 2004; 93 (11) 849-854
• 8 Bossert T, Bittner HB, Richter M , et al. Successful management of two heart transplant recipients with mycobacterial pulmonary infections. Ann Thorac Surg 2005; 80 (2) 719-721
• 9 Gummert JF, Falk V, Walther T , et al. Tonsillar carcinoma in the early postoperative course following heart transplantation. Thorac Cardiovasc Surg 1995; 43 (6) 355-357
• 10 Aupperle H, Garbade J, Ullmann C , et al. Ultrastructural findings in porcine hearts after extracorporeal long-term preservation with a modified Langendorff perfusion system. J Vet Med A Physiol Pathol Clin Med 2007; 54 (5) 230-237
• 11 Aupperle H, Garbade J, Ullmann C , et al. Comparing the ultrastructural effects of two different cardiac preparation- and perfusion-techniques in a porcine model of extracorporal long-term preservation. Eur J Cardiothorac Surg 2007; 31 (2) 214-221
• 12 Garbade J, Krautz C, Aupperle H , et al. Functional, metabolic, and morphological aspects of continuous, normothermic heart preservation: effects of different preparation and perfusion techniques. Tissue Eng Part C Methods 2009; 15 (2) 275-283
• 13 Gummert JF, Schütz E, Oellerich M, Mohr FW, Dalichau H. Monitoring of TPMT in heart transplant recipients under immunosuppressive therapy with azathioprine. Artif Organs 1995; 19 (9) 918-920
• 14 Schütz E, Gummert J, Mohr FW, Armstrong VW, Oellerich M. Azathioprine myelotoxicity related to elevated 6-thioguanine nucleotides in heart transplantation. Transplant Proc 1995; 27 (1) 1298-1300
• 15 Schütz E, Gummert J, Armstrong VW, Mohr FW, Oellerich M. Azathioprine pharmacogenetics: the relationship between 6-thioguanine nucleotides and thiopurine methyltransferase in patients after heart and kidney transplantation. Eur J Clin Chem Clin Biochem 1996; 34 (3) 199-205
• 16 Schütz E, Gummert J, Mohr FW, Armstrong VW, Oellerich M. Should 6-thioguanine nucleotides be monitored in heart transplant recipients given azathioprine?. Ther Drug Monit 1996; 18 (3) 228-233
• 17 Richter MH, Richter H, Barten M , et al. Angiotensin II type 1 receptor blockade after cardiac transplantation reduced the incidence and severity of transplant vasculopathy in an animal-based study. Transplant Proc 2002; 34 (5) 1484-1485
• 18 Richter MH, Richter H, Barten M , et al. Cyclosporin A does not enhance the development of transplant vasculopathy: experimental study in a rat cardiac transplant model. Transplant Proc 2002; 34 (5) 1479-1480
• 19 Barten MJ, Dhein S, Chang H , et al. Assessment of immunosuppressive drug interactions: inhibition of lymphocyte function in peripheral human blood. J Immunol Methods 2003; 283 (1-2): 99-114
• 20 Barten MJ, Streit F, Boeger M , et al. Synergistic effects of sirolimus with cyclosporine and tacrolimus: analysis of immunosuppression on lymphocyte proliferation and activation in rat whole blood. Transplantation 2004; 77 (8) 1154-1162
• 21 Barten MJ, Rahmel A, Garbade J , et al. Pharmacodynamic monitoring of the conversion of cyclosporine to tacrolimus in heart and lung transplant recipients. Transplant Proc 2005; 37 (10) 4532-4534
• 22 Barten MJ, Rahmel A, Garbade J , et al. C0h/C2h monitoring of the pharmacodynamics of cyclosporin plus mycophenolate mofetil in human heart transplant recipients. Transplant Proc 2005; 37 (2) 1360-1361
• 23 Barten MJ, Shipkova M, Bartsch P , et al. Mycophenolic acid interaction with cyclosporine and tacrolimus in vitro and in vivo: evaluation of additive effects on rat blood lymphocyte function. Ther Drug Monit 2005; 27 (2) 123-131
• 24 Barten MJ, Garbade J, Bittner HB , et al. Affects of immunosuppression on circulating dendritic cells: an adjunct to therapeutic drug monitoring after heart transplantation. Int Immunopharmacol 2006; 6 (13-14): 2011-2017
• 25 Barten MJ, Rahmel A, Bocsi J , et al. Cytokine analysis to predict immunosuppression. Cytometry A 2006; 69 (3) 155-157
• 26 Boldt A, Barten MJ, Sagner A , et al. The influence of immunosuppressive drugs on T- and B-cell apoptosis via p53-mediated pathway in vitro and in vivo. Transplantation 2006; 82 (3) 422-427
• 27 Boldt A, Barten MJ, Weiss C, Sagner A, Mohr FW, Gummert JF. Novel apoptosis assay to analyze immunosuppression. Cytometry A 2006; 69 (3) 158-160
• 28 Barten MJ, Rahmel A, Boldt A , et al. Pharmacodynamic monitoring of the immunosuppressive therapy in patients after heart transplantation: whole blood flow cytometric analysis of lymphocyte function. Comput Biol Med 2007; 37 (10) 1367-1373
• 29 Barten MJ, Tarnok A, Garbade J , et al. Pharmacodynamics of T-cell function for monitoring immunosuppression. Cell Prolif 2007; 40 (1) 50-63
• 30 Gummert JF, Barten MJ, Bartsch P , et al. Pharmacodynamic (PD) measurements of the immunosuppressive effects of the combination of cyclosporine (CY) and mycophenolate mofetil (MMF): correlation between drug dose and lymphocyte function. J Heart Lung Transplant 2001; 20 (2) 163
• 31 Barten MJ, Rahmel A, Boeger M , et al. Pharmacodynamics of sirolimus and cyclosporine combination therapy. Transplant Proc 2002; 34 (7) 2878
• 32 Barten MJ, Rahmel A, Chang H , et al. Assessment of immunosuppression by lymphocyte functions in human blood. Transplant Proc 2002; 34 (7) 2876-2877
• 33 Barten MJ, Rahmel A, Richter M , et al. Pharmacodynamics of the immunosuppressive effects of the combination of tacrolimus with mycophenolate mofetil. Transplant Proc 2002; 34 (6) 2372-2373