"Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it is the only thing that ever has."

Margaret Mead
Original article
peer-reviewed

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model



Abstract

Objectives: This porcine pre-clinical investigation sought to demonstrate a new and novel application for radiosurgery, the ablation of cardiac arrhythmias. Pre-clinical studies in the porcine animal model were used to investigate the accuracy with which the pathological region in the heart that is routinely treated for atrial fibrillation could be targeted with radiosurgery. Pathologic and electrophysiologic (EP) changes resulting from radiosurgical ablation were used as primary study endpoints.

Methods: Two Hanford mini-swine (approximately 35 kg) were studied. A cardiac-gated CT study was performed. Isocentric treatments were delivered with the CyberKnife® (Accuray Inc, Sunnyvale, CA) in a single fraction at prescribed doses of 25 Gy (N=1) and 35 Gy (N=1). The treatment volume was selected to create electrical isolation of two pulmonary veins (the source of atrial aberrant tachycardias, such as atrial fibrillation) from the body (antrum) of the left atrium, as has been proven successful with thermal catheter ablation procedures. Animals were followed for six months, and then underwent electrophysiologic (EP) testing in the cardiac catheterization lab to test for electrical isolation of the pulmonary veins. Trans esophageal echocardiography was carried out to examine cardiac function post-radiosurgery. Finally, the hearts of the treated animals were submitted for pathologic analysis.

Results: Long-term follow-up after left atrial radiosurgery demonstrated transmural, circumferential fibrosis that correlated to electrical isolation, similar to that found in catheter ablation. The EP study documented intended pulmonary vein isolation (electrical block), using a decapolar Lasso catheter (Biosense Webster, Diamond Bar, CA). Histologic analysis showed transmural fibrosis and contiguity (desired) of the ablation scar within the target. Echocardiographic monitoring of atrial and ventricular function six months post radiosurgery demonstrated normal cardiac function. Both animals met the survival endpoint with no adverse events.

Conclusions: Cardiac radiosurgery for the treatment of atrial fibrillation can be safely performed in the porcine animal model using appropriate treatment planning, taking into account cardiac anatomy, motion and targeting concerns. Electrophysiologic and pathologic assessment correlated radiation-induced tissue effect to the target tissue. Proof of concept is therefore confirmed. This technique has the potential to provide a significant advancement in the treatment of atrial fibrillation and other cardiac arrhythmias, especially for those patients who have failed drug therapy and are not candidates for intra-cardiac catheter ablation. Clinical studies are needed to prove safety and efficacy.



Want to read more?

Create a free account to continue reading this article.

Already a member? Login.



Original article
peer-reviewed

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model


Author Information

Edward Gardner

CyberHeart, Inc., Portola Valley, CA 94028

Alice B. Jack

CyberHeart Inc

Paul Zei

Department of Cardiology, Stanford University School of Medicine

Amin Al-Ahmad

Department of Cardiology, Stanford University School of Medicine

Elena Ladich

CV Path Institute, Gaithersburg, MD

Patricia Takeda

Sutter Memorial Hospital, Sacramento, CA


Ethics Statement and Conflict of Interest Disclosures

Human subjects: This study did not involve human participants or tissue. Animal subjects: The Sutter Institute for Medical Research in Sacramento, CA Issued protocol number N/A. Conflicts of interest: The authors have declared the following conflicts of interest: Other relationships: All animals were treated with care in accordance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and approved by the local animal care committee. Financial relationships: Patrick Maguire declare(s) an alternate financial activity from Cyberheart, Inc. President and CEO. Alice Jack declare(s) an alternate financial activity from Cyberheart, Inc. Executive Vice President. Edward Gardner, Luis Fajardo, Amin Al-Ahmad, Paul Zei, Patricia Takeda, and Elena Ladich declare(s) an alternate financial activity from Cyberheart, Inc. Consultants. Intellectual property info: There are provisional patents owned by CyberHeart Inc. The authors have no patents.

Acknowledgements

The authors wish to acknowledge the expertise and support provided by the research team at the Sutter Institute for Medical Research.


Original article
peer-reviewed

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model


Figures etc.

Share
Original article
peer-reviewed

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model

  • Author Information
    Patrick J. Maguire Corresponding Author

    CyberHeart Inc.

    Edward Gardner

    CyberHeart, Inc., Portola Valley, CA 94028

    Alice B. Jack

    CyberHeart Inc

    Paul Zei

    Department of Cardiology, Stanford University School of Medicine

    Amin Al-Ahmad

    Department of Cardiology, Stanford University School of Medicine

    Luis Fajardo
    Elena Ladich

    CV Path Institute, Gaithersburg, MD

    Patricia Takeda

    Sutter Memorial Hospital, Sacramento, CA


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: This study did not involve human participants or tissue. Animal subjects: The Sutter Institute for Medical Research in Sacramento, CA Issued protocol number N/A. Conflicts of interest: The authors have declared the following conflicts of interest: Other relationships: All animals were treated with care in accordance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and approved by the local animal care committee. Financial relationships: Patrick Maguire declare(s) an alternate financial activity from Cyberheart, Inc. President and CEO. Alice Jack declare(s) an alternate financial activity from Cyberheart, Inc. Executive Vice President. Edward Gardner, Luis Fajardo, Amin Al-Ahmad, Paul Zei, Patricia Takeda, and Elena Ladich declare(s) an alternate financial activity from Cyberheart, Inc. Consultants. Intellectual property info: There are provisional patents owned by CyberHeart Inc. The authors have no patents.

    Acknowledgements

    The authors wish to acknowledge the expertise and support provided by the research team at the Sutter Institute for Medical Research.


    Article Information

    Published: August 02, 2011

    DOI

    10.7759/cureus.32

    Cite this article as:

    Maguire P J, Gardner E, Jack A B, et al. (August 02, 2011) Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model. Cureus 3(8): e32. doi:10.7759/cureus.32

    Publication history

    Published: August 02, 2011

    Copyright

    © Copyright 2011
    Maguire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objectives: This porcine pre-clinical investigation sought to demonstrate a new and novel application for radiosurgery, the ablation of cardiac arrhythmias. Pre-clinical studies in the porcine animal model were used to investigate the accuracy with which the pathological region in the heart that is routinely treated for atrial fibrillation could be targeted with radiosurgery. Pathologic and electrophysiologic (EP) changes resulting from radiosurgical ablation were used as primary study endpoints.

Methods: Two Hanford mini-swine (approximately 35 kg) were studied. A cardiac-gated CT study was performed. Isocentric treatments were delivered with the CyberKnife® (Accuray Inc, Sunnyvale, CA) in a single fraction at prescribed doses of 25 Gy (N=1) and 35 Gy (N=1). The treatment volume was selected to create electrical isolation of two pulmonary veins (the source of atrial aberrant tachycardias, such as atrial fibrillation) from the body (antrum) of the left atrium, as has been proven successful with thermal catheter ablation procedures. Animals were followed for six months, and then underwent electrophysiologic (EP) testing in the cardiac catheterization lab to test for electrical isolation of the pulmonary veins. Trans esophageal echocardiography was carried out to examine cardiac function post-radiosurgery. Finally, the hearts of the treated animals were submitted for pathologic analysis.

Results: Long-term follow-up after left atrial radiosurgery demonstrated transmural, circumferential fibrosis that correlated to electrical isolation, similar to that found in catheter ablation. The EP study documented intended pulmonary vein isolation (electrical block), using a decapolar Lasso catheter (Biosense Webster, Diamond Bar, CA). Histologic analysis showed transmural fibrosis and contiguity (desired) of the ablation scar within the target. Echocardiographic monitoring of atrial and ventricular function six months post radiosurgery demonstrated normal cardiac function. Both animals met the survival endpoint with no adverse events.

Conclusions: Cardiac radiosurgery for the treatment of atrial fibrillation can be safely performed in the porcine animal model using appropriate treatment planning, taking into account cardiac anatomy, motion and targeting concerns. Electrophysiologic and pathologic assessment correlated radiation-induced tissue effect to the target tissue. Proof of concept is therefore confirmed. This technique has the potential to provide a significant advancement in the treatment of atrial fibrillation and other cardiac arrhythmias, especially for those patients who have failed drug therapy and are not candidates for intra-cardiac catheter ablation. Clinical studies are needed to prove safety and efficacy.



Want to read more?

Create a free account to continue reading this article.

Already a member? Login.



Patrick J. Maguire, M.D.

CyberHeart Inc.

For correspondence:
pmaguire@cyberheartinc.com

Edward Gardner, None

CyberHeart, Inc., Portola Valley, CA 94028

Alice B. Jack, None

CyberHeart Inc

Paul Zei, None

Department of Cardiology, Stanford University School of Medicine

Amin Al-Ahmad, None

Department of Cardiology, Stanford University School of Medicine

Luis Fajardo, None

Elena Ladich, None

CV Path Institute, Gaithersburg, MD

Patricia Takeda, None

Sutter Memorial Hospital, Sacramento, CA

Patrick J. Maguire, M.D.

CyberHeart Inc.

For correspondence:
pmaguire@cyberheartinc.com

Edward Gardner, None

CyberHeart, Inc., Portola Valley, CA 94028

Alice B. Jack, None

CyberHeart Inc

Paul Zei, None

Department of Cardiology, Stanford University School of Medicine

Amin Al-Ahmad, None

Department of Cardiology, Stanford University School of Medicine

Luis Fajardo, None

Elena Ladich, None

CV Path Institute, Gaithersburg, MD

Patricia Takeda, None

Sutter Memorial Hospital, Sacramento, CA