Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2016 Jun 1;37(21):1659-66.
doi: 10.1093/eurheartj/ehv559. Epub 2015 Oct 29.

Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT

Birgit Assmus  1 , Samer Alakmeh  2 , Salvatore De Rosa  2 , Halvard Bönig  3 , Eva Hermann  4 , Wayne C Levy  5 , Stefanie Dimmeler  6 , Andreas M Zeiher  7
Affiliations
Randomized Controlled Trial

Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT

Birgit Assmus et al. Eur Heart J. .

Abstract

Aims: Regenerative therapies have evolved as a promising new option in the treatment of post-infarction heart failure. A major limitation of intracoronary application of autologous bone marrow-derived mononuclear cells (BM-MNCs) is that homing of the applied cells is profoundly reduced in patients with post-infarction heart failure compared with patients with acute myocardial infarction. However, early pilot and also randomized controlled trials have demonstrated significant improvements in overall cardiac function. The aim of the present analysis was to quantify a potential mortality risk reduction and reduced hospitalization in order to provide data for a prospective outcome trial.

Methods and results: The results of an ongoing single-centre registry including 297 post-infarction heart failure patients suggest that repeated intracoronary application of autologous bone marrow-derived cells is associated with a significant better 2-year survival compared with a single BM-MNC application (2-year survival 93.6 vs. 84.0%, P = 0.03). Likewise, mortality is significantly lower at 2-year follow-up compared with the mortality estimated by the use of the Seattle Heart Failure Model (SHFM) in patients receiving repeated BM-MNC application (observed mortality 6.4%, predicted mortality 16.2%, P = 0.02). Although the trend persisted at 3-year follow-up, the mortality reduction was no longer statistically significant between single and repeated treatment (mortality 21.9 vs. 13.7%, P = 0.06).

Conclusion: Repeated intracoronary administration of BM-MNC appears to be associated with improved clinical outcome compared with single treatment at 2 years. This registry provides the rationale for the design of the multicentre randomized, controlled, open-label REPEAT trial, which prospectively compares the effects of single vs. repeated intracoronary application of autologous BM-MNC on total and SHFM-predicted mortality in patients with chronic post-infarction heart failure.

Keywords: Cell therapy; Chronic heart failure; Ischaemic cardiomyopathy; Outcome trial.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Seattle Heart Failure Model-predicted mortality (black) and observed mortality (blue) of the total study cohort. (B) Seattle Heart Failure Model-predicted mortality (grey) and observed mortality (black), separated by single and repeated treatment. Standard errors were derived from Kaplan–Meier analysis.
Figure 2
Figure 2
(A) Cox regression analysis for total mortality, adjusted for the Seattle Heart Failure Model score, in the entire study cohort (left) and the landmark analysis (right). Note that the reference time (90 days) for the landmark analysis is marked by a vertical line. (B) Cox regression analysis for the combined endpoint mortality and rehospitalization for heart failure, adjusted for the Seattle Heart Failure Model score, in the entire study cohort (left) and the landmark analysis (right). The reference time (90 days) for the landmark analysis is marked by a vertical line.
See this image and copyright information in PMC

Comment in

  • Repetition rescues regenerative reserve.
    Behfar A, Gersh B, Terzic A. Behfar A, et al. Eur Heart J. 2016 Jun 1;37(21):1667-70. doi: 10.1093/eurheartj/ehv596. Epub 2015 Dec 5. Eur Heart J. 2016. PMID: 26637833 No abstract available.

References

    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. Heart disease and stroke statistics-2015 update: a report from the American heart association. Circulation 2015;131:e29–e322. - PubMed
    1. Shafazand M, Schaufelberger M, Lappas G, Swedberg K, Rosengren A. Survival trends in men and women with heart failure of ischaemic and non-ischaemic origin: data for the period 1987-2003 from the Swedish Hospital Discharge Registry. Eur Heart J 2009;30:671–678. - PubMed
    1. Malliaras K, Marban E. Cardiac cell therapy: where we've been, where we are, and where we should be headed. Br Med Bull 2011;98:161–185. - PMC - PubMed
    1. Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med 2014;20:857–869. - PubMed
    1. Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation 2012;126:551–568. - PMC - PubMed

Publication types