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  • Letter to the Editor
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‘Recirculating cardiac delivery’ method of gene delivery should be called ‘non-recirculating’ method

Gene Therapy volume 16, pages 939–940 (2009)Cite this article

I am writing to you regarding a paper entitled ‘Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals’, which was recently published in Gene Therapy.1 The authors use a ‘recently established cardiac-directed recirculating method of gene delivery’ to administer three different doses (low, medium and high) of AAV2/1SERCA2a to sheep with pacing-induced heart failure. The control animals received no vector. Pacing was resumed after gene (or control=no gene) delivery for an additional 4–6 weeks. Echocardiographic and LV pressure measurements were carried out at the termination of the study.

In this largely negative study, the results were presented in a manner making evaluation of the significance of the findings difficult. For example, in the abstract, it is stated that gene therapy ‘elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis (+dP/dtmax; low dose −220±70, P>0.05; medium dose 125±53, P<0.05, high dose 287±104, P<0.05).’ Yet, the authors do not provide the absolute values for dP/dt after gene therapy to allow the reader to evaluate the relative magnitude of the final values of dP/dt in each group. Given that there were baseline differences in dP/dt of over 200 mmHg among the groups in some cases (control dP/dt 814±121 mmHg vs high-dose dP/dt 615±98.6 mm Hg, Table 1), if one compared absolute values of the actual dP/dt in these groups (rather than the delta values), one would likely find that there was in fact no significant difference in the positive dP/dt between the controls and the high-dose group at the time of killing. Similarly, given that the baseline EF was 37% in the control group and 25% in the high-dose group (Table 1, Figure 2), showing a positive improvement in EF in the high-dose group, averaging approximately 10%, and a negative change in EF of 4% in the control group, indicates that there was likely no significant difference in the ejection fraction in the high-dose group compared with that in the control group at the end of the study.

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References

  1. Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM . Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Therapy 2008; 15: 1550–1557.

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  2. Kaye DM, Preovolos A, Marshall T, Byrne M, Hoshijima M, Hajjar R et al. Percutaneous cardiac recirculation-mediated gene transfer o of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J Am Coll Cardiol 2007; 50: 253–260.

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  3. Bridges CR, Burkman JM, Malekan R, Konig SK, Chen H, Yarnall CB et al. Global cardiac-specific transgene expression using cardio-pulmonary bypass with cardiac isolation. Ann Thorac Surg 2002; 73: 1939–1946.

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  4. Bridges CR, Gopal K, Holt DE, Yarnall C, Cole S, Anderson RB et al. Efficient myocyte gene delivery using complete cardiac surgical isolation in situ. J Thorac Cardiovasc Surg 2005; 130: 1364–1370.

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  1. Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania, Philadelphia, PA, USA

    C R Bridges

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  1. C R Bridges
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Bridges, C. ‘Recirculating cardiac delivery’ method of gene delivery should be called ‘non-recirculating’ method. Gene Ther 16, 939–940 (2009). https://doi.org/10.1038/gt.2009.35

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