Recent advances in porcine cardiac xenotransplantation: from aortic valve replacement to heart transplantation

ABSTRACT

Introduction

Cardiac xenotransplantation presents significant potential to the field of heart failure by addressing the high demand for donor organs. The availability of xenograft hearts would substantially augment the number of life-saving organs available to patients and may ultimately liberalize eligibility criteria for transplantation.

Areas Covered

In this review, we will discuss the need for cardiac xenotransplantation and the history of research and clinical practice in this field. Specifically, we address immunologic concepts and clinical lessons learned from heart valve replacement using xenogeneic tissues, the advancement of xenotransplantation using organs from genetically modified animals, and the progression of this research to the first-in-man pig-to-human heart transplantation.

Expert Opinion

Cardiac xenotransplantation holds tremendous promise, but the indications for this new treatment in adults will need to be clearly defined because mechanical support with ventricular assist devices and total artificial hearts are increasingly successful alternatives in heart failure. Cardiac xenotransplantation will also serve as temporary bridge to allotransplantation in babies with complex congenital heart disease who are too small for the currently available mechanical assist devices and total artificial hearts. Moreover, xenotransplantation of the part of the heart containing a heart valve could deliver growing heart valve implants for babies with severe heart valve dysfunction.

KEYWORDS:

• Xenotransplantation
• aortic valve replacement
• heart transplantation
• partial heart transplantation

Article highlights

• Bioprosthetic valves from porcine donors have been in clinical use for decades. These valves do not have viable cells, and are specially treated to mask the xenoantigens.

• Previous attempts at cardiac xenotransplantation using wildtype donors have failed.

• Recent progress in biotechnology resulted in humanized pig donors through genetic engineering.

• Such genetically engineered pig donors have turned xenotransplantation into reality.

Declaration of interest

Dr. Mohiuddin reports non-financial support from United Therapeutics, Inc (Revivicor is a subsidiary). The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript is an employee of XTransplant, Germany. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.