Administration of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: the SCIPIO Trial: Surgical Aspects and Interim Analysis of Myocardial Function and Viability by Magnetic Resonance

Overview

Journal Circulation

Specialty Cardiology & Vascular Diseases

Date 2012 Sep 12

PMID 22965994

Citations 211

Authors

Atul R Chugh

Garth M Beache

John H Loughran

Nathan Mewton

Julius B Elmore

Jan Kajstura

Patroklos Pappas

Antone Tatooles

Marcus F Stoddard

Joao A C Lima

Mark S Slaughter

Piero Anversa

Roberto Bolli

Affiliations

Soon will be listed here.

Abstract

Background: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

Methods And Results: A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4% [P=0.004, n=8] and 41.2 ± 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]).

Conclusions: Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.

Clinical Trial Registration: This study is registered with clinicaltrials.gov, trial number NCT00474461.

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References

Dill T, Schachinger V, Rolf A, Mollmann S, Thiele H, Tillmanns H . Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: results of the Reinfusion of Enriched.... Am Heart J. 2009; 157(3):541-7. DOI: 10.1016/j.ahj.2008.11.011. View

Kim R, Wu E, Rafael A, Chen E, Parker M, Simonetti O . The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000; 343(20):1445-53. DOI: 10.1056/NEJM200011163432003. View

Abdel-Latif A, Bolli R, Tleyjeh I, Montori V, Perin E, Hornung C . Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007; 167(10):989-97. DOI: 10.1001/archinte.167.10.989. View

Heusch G . SCIPIO brings new momentum to cardiac cell therapy. Lancet. 2011; 378(9806):1827-8. DOI: 10.1016/S0140-6736(11)61648-6. View

Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M . Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J. 2002; 143(3):398-405. DOI: 10.1067/mhj.2002.121264. View

Wu E, Judd R, Vargas J, Klocke F, Bonow R, Kim R . Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet. 2001; 357(9249):21-8. DOI: 10.1016/S0140-6736(00)03567-4. View

Beltrami C, Finato N, Rocco M, Feruglio G, Puricelli C, Cigola E . Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation. 1994; 89(1):151-63. DOI: 10.1161/01.cir.89.1.151. View

Strauer B, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C . Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol. 2005; 46(9):1651-8. DOI: 10.1016/j.jacc.2005.01.069. View

Shivalkar B, Maes A, Borgers M, Ausma J, Scheys I, Nuyts J . Only hibernating myocardium invariably shows early recovery after coronary revascularization. Circulation. 1996; 94(3):308-15. DOI: 10.1161/01.cir.94.3.308. View

10.

Grothues F, Smith G, Moon J, Bellenger N, Collins P, Klein H . Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002; 90(1):29-34. DOI: 10.1016/s0002-9149(02)02381-0. View

11.

Roger V, Go A, Lloyd-Jones D, Adams R, Berry J, Brown T . Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2010; 123(4):e18-e209. PMC: 4418670. DOI: 10.1161/CIR.0b013e3182009701. View

12.

Hsu L, Natanzon A, Kellman P, Hirsch G, Aletras A, Arai A . Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006; 23(3):298-308. DOI: 10.1002/jmri.20496. View

13.

Vanoverschelde J, Depre C, Gerber B, Borgers M, Wijns W, Robert A . Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction. Am J Cardiol. 2000; 85(12):1432-9. DOI: 10.1016/s0002-9149(00)00790-6. View

14.

Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A . Human cardiac stem cells. Proc Natl Acad Sci U S A. 2007; 104(35):14068-73. PMC: 1955818. DOI: 10.1073/pnas.0706760104. View

15.

Nacif M, Chugh A, Lima J, Bluemke D . How should infarct size be measured on LGE sequences? A call for a change in the guidelines. JACC Cardiovasc Imaging. 2011; 4(11):1223. DOI: 10.1016/j.jcmg.2011.08.010. View

16.

He J, Ogden L, Bazzano L, Vupputuri S, Loria C, Whelton P . Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med. 2001; 161(7):996-1002. DOI: 10.1001/archinte.161.7.996. View

17.

Soliman O, Kirschbaum S, van Dalen B, der Zwaan H, Mahdavian Delavary B, Vletter W . Accuracy and reproducibility of quantitation of left ventricular function by real-time three-dimensional echocardiography versus cardiac magnetic resonance. Am J Cardiol. 2008; 102(6):778-83. DOI: 10.1016/j.amjcard.2008.04.062. View

18.

Dawn B, Stein A, Urbanek K, Rota M, Whang B, Rastaldo R . Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A. 2005; 102(10):3766-71. PMC: 553298. DOI: 10.1073/pnas.0405957102. View

19.

DAmario D, Cabral-da-Silva M, Zheng H, Fiorini C, Goichberg P, Steadman E . Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circ Res. 2011; 108(12):1467-81. PMC: 3299060. DOI: 10.1161/CIRCRESAHA.111.240648. View

20.

Mintz L, Ingels Jr N, Daughters 2nd G, Stinson E, Alderman E . Sequential studies of left ventricular function and wall motion after coronary arterial bypass surgery. Am J Cardiol. 1980; 45(2):210-6. DOI: 10.1016/0002-9149(80)90637-2. View