ALTERNATIVE APPROACH FOR END-STAGED ISCHEMIC CARDIOMYOPATHY WITH LV ANEURYSM COMBINING SURGICAL AND CELL THERAPY THESSALONIKI, 2018

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1 ALTERNATIVE APPROACH FOR END-STAGED ISCHEMIC CARDIOMYOPATHY WITH LV ANEURYSM COMBINING SURGICAL AND CELL THERAPY THESSALONIKI, 2018 Kostas Katsavrias Sotirios N. Prapas A Cardiac Surgery Dpt Henry Dunant Hospital, Athens, Greece

2 How we Approach the Ischemic Heart Disease Isolated ischemic disease: Π-circuit Ischemic disease and poor LV: Π-circuit External reshaping of LV (off-pump) Stem cells implantation

3 2005

4 Thanks to Federico BENETTI Under the tree of Hippocrates KOS-GREECE, 2002 EPIDAVROS- GREECE, 2005 S. Prapas, F. Benetti

5 THE FIRST PATIENT Postop TL-201

6 THE PHILOSOPHY OF NATURAL CORONARY REVASCULARIZATION Creation of a secondary arterial circuit attached to the diseased coronary one BRAIN HAND HEART Annals,2002

7 THE PHILOSOPHY OF EXTERNAL RESHAPING OF THE LEFT VENTRICLE In the era of thrombolysis and primary PCI, large aneurysmatic segments of the ventricular wall are rarely seen. However, dyskinetic areas of the ventricular myocardium, due to myocardial infarction remain a common finding encountered in clinical practice and must be treated restoring the geometry of LV.

8 INOVATIONS,2006

9 EXTERNAL RESHAPING OF INFERIOLATERAL WALL

10 External Reshaping of LV Reshaping of Anterioseptal Wall Pre Op Post Op

11 External Reshaping of LV Reshaping of Anteriolateral Wall

12 THE PHILOSOPHY OF STEM CELL IMPLANTATION In patients with myocardial infarction, autologous stem cell therapy has been shown to stimulate angiogenesis, repair local cardiac tissue and improve cardiac function. In patients with ischemic HF, this therapy has been demonstrated to improve ejection fraction, heart pumping action, quality of life, NYHA class and exercise capacity.

13 Evidence for cardiomyocyte renewal in humans Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J. Department of Cell and Molecular Biology, Karolinska Institutet, SE Stockholm, Sweden. Comment in: Science Apr 3;324(5923):47-8. It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies. PMID: [PubMed - indexed for MEDLINE]

14 Evidence for cardiomyocyte renewal in humans cells refurbishing in humans Bergmann et al, Science 2009; 324: 98

15 Clinical Studies Intracardiac progenitor cell therapy and coronary bypass surgery Paris (Menasche et al. 2001) Rostock (Stamm et al. 2003) Milano (Pompilio et al. 2004) Leicester (Galinanes et al. 2004) Pittsburgh (Patel et al. 2005) USA multicenter (Dib et al. 2005) Düsseldorf (Klein et al. 2005) etc. Skeletal myoblasts & CABG intracardiac BMSC (CD 133+) & CABG intracardiac BMSC (CD 133+) & CABG BMNC & CABG intracardiac BMSC (CD 34+) & CABG Skeletal Myoblasts & CABG intracardiac BMSC (CD 133+) & CABG

16 Stem Cell Harvest & Separation Prior stem cell separation techniques utilized time con- suming chemical (Ficoll), cell filtering (Clinimac, FALCON, Baxter) or cell culture methodologies which made point of care clinical applications impractical. Current techniques require smaller autologous bone marrow aspirates ( ml) from the patients iliac crest with rapid (15 min), point of care separation of bone marrow MNC using gradient centrifugation. 15 minutes

17 MATERIALS Preop IABP was used in most patients.

18 THE METHOD Implantation

19 THE PHILOSOPHY OF STEM CELL IMPLANTATION The ANATOLIAN JOURNAL OF CARDIOLOGY,2008

20 MATERIALS & METHODS Between July 2005 March 2013, 92 patients, (mean age 58±8.9y), NYHA III IV (4 were transplantation candidates, 1 was rejected because of severe respiratory dysfunction). Preoperatively: EF: 23.5±7.4% LVEDD: 64.1±4.9mm Mapping of areas of reversible and non-reversible ischemia

21 PREOPERATIVE INVESTIGATIONS & MANAGEMENT Recording of medications Dipyridamole thallium scanning TTE MRI Hematologic assessment Pulmonary function tests IABP and/or Levosimendan support if needed

22 DESCRIPTIVE ANALYSIS Heart Failure: 92 pts OPCAB+BMC s: 31 pts OPCAB+Ext.Reshaping+BMC s: 36 pts CABG+Ext.Reshaping+MVrepair+BMC s: 11 pts CABG+Ext.Reshaping+MVrepair+Ablation+BMC s: 1 pt CABG+Int.Reshaping+BMC s: 3 pts CABG+BMC s (Beating Heart): 1 pt Heart Failure + Diffuse coronary disease: 9 pts OPCAB+BMLR (TMR+BMC s): 9 pts

23 70 y.o. male CASE REPORT Shortness of breath on small exertion weakness Hx: CAD, multiple MIs, dyslipidemia, smoking Preop meds: Enalapril 10mg Carvedilol 6.25mg Spironolactone 25mg Furosemide 40mg

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25 THE METHOD

26 THE METHOD

27 WHAT WE HAVE OBSERVED Increase of EF Decrease of NYHA class Better QOL

28 WHAT WE HAVE OBSERVED Pre-Op 6 months Post-Op

29 WHAT WE HAVE OBSERVED Pre-Op EF: 25% 6 months Post-Op EF: 36%

30 WHAT WE HAVE OBSERVED 6 months Post-Op Pre-Op

31 IN-HOSPITAL MORTALITY 6/92 pts (6,5%) According to urgency N Mortality % Urgent Elective ,5

32 MID-TERM MORTALITY 1-96 months 10 deaths / 86 pts (6 cardiac and 4 non cardiac deaths in 12 to 87 months) (11,6%)

33 MORTALITY IN RELATION TO EF Mortality EF < 25% EF 25-35% EF 35-45% No: 41 pts No: 35 pts No: 16 pts Perioperative-30 d 5 / 41 ( 12,2 % ) 1 / 35 ( 2,8 % ) 0 / 16 ( 0 % ) Mid Term Cardiac 3 / 36 ( 8,3 % ) 2 / 34 ( 5,9 % ) 1 / 16 ( 6,2 % ) Mid Term NON Cardiac 1 / 36 ( 2,8 % ) 3 / 34 ( 8,8 % ) _ Mid Term Total 4 / 36 ( 11,1 % ) 5 / 34 ( 14,7 % ) 1 / 16 ( 6,2 % ) TOTAL 9 / 41 ( 21,9 % ) 6 / 35 ( 17,1 % ) 1 / 16 ( 6,2 % )

34 MID TERM MORTALITY IN RELATION TO CAUSE 1 ARREST 2 ARREST 3 ARREST 4 ARREST 5 ARREST 6 PULM.OEDEMA 7 CA 8 CA 9 HAEMORRAGE 10 ACCIDENT

35 POST-MI VSD

36 POST-MI VSD Left Right Left

37 POST-MI VSD

38 POST-MI VSD

39 Thank you