Transplantation and Long-Term Implantable Mechanical Circulatory Support



Transplantation and Long-Term Implantable Mechanical Circulatory Support


Ryan J. Vela

Matthias Peltz



INTRODUCTION

Over 250,000 patients suffer from advanced heart failure (HF) in the United States.1 These patients are either severely symptomatic on or failing guideline-directed heart failure medical therapy (GDMT) and merit consideration for advanced heart failure therapies—a term that refers to fully implantable mechanical circulatory support devices and cardiac transplantation. Prognosis in this patient population is poor, with an estimated 5-year survival of 20%.2 Outcomes for patients on inotropes are particularly dismal, ranging from 6% to 50% survival at 1 year.3,4

Since Alexis Carrel first developed the surgical techniques essential for cardiac transplantation and performed the first heterotopic heart transplant in a dog in 1905,5 progress in cardiac transplantation and mechanical circulatory support of the failing heart have often proceeded in parallel, in part because circulatory support is considered essential for both procedures. Whereas Carrel and Lindbergh received much of the early recognition, largely unknown in the West, Demikhov in 1937 described the first use of a total artificial heart to support the canine circulation and later, in 1951, the first orthotopic heart transplantation in the same animal model.6,7 In the United States, Shumway and Lower developed the surgical technique and explored the immunologic mechanisms that laid the foundation for human heart transplantation.8 It was left to Christiaan Barnard to perform the first human heart transplant on Louis Washkansky on December 3, 1967.9 Despite early enthusiasm, initial outcomes were dismal, with only 20% of patients surviving 1 year. It became apparent that, although a number of skilled surgeons could perform the technical aspects of cardiac transplantation, the understanding of immunobiology and rejection was limited, leading to the demise of many recipients. For the next decade, transplantation was performed only at a handful of specialty centers where outcomes gradually improved. It was the discovery of cyclosporine and steroid-sparing immunosuppression protocols that led to more widespread adoption of cardiac transplantation and established it as the gold standard therapy for patients with end-stage cardiac disease.10

Even before the first human heart transplant, the development of cardiopulmonary bypass established the basis for cardiac support devices. The first ventricular assist device (VAD) for human use was created by Domingo Liotta in 1962. This paracorporeal device was implanted in 1963 to support a patient in cardiogenic shock following a complicated aortic valve replacement. Unfortunately, the patient did not survive.11 Undeterred, Liotta and DeBakey in 1966 were able to successfully support a patient while awaiting cardiac recovery after the patient failed to wean off cardiopulmonary bypass during a mitral valve operation.12 The first human total artificial heart implant was performed by Liotta and Denton Cooley in 1969 to support a patient while awaiting a donor heart.13

Technologies continued to evolve and by the 1980s, multiple left ventricular assist device (LVAD) platforms were available to bridge patients to cardiac transplantation.14 In 1994, the implantable HeartMate VE LVASTM by Thoratec Corporation (Pleasanton, CA) gained U.S. Food and Drug Administration (FDA) approval as a bridge to transplantation device (www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P920014). Although early VADs were initially intended to support patients while waiting for a donor organ, it became apparent that as technology continued to improve and systems became fully implantable, VADs could potentially also be considered as therapy for patients ineligible for transplantation, so-called destination therapy. This benefit was demonstrated in the landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial comparing the HeartMate XVETM LVAD by Thoratec to inotrope therapy.15 Improved outcomes in the device group led to FDA approval in 2002 and Centers for Medicare & Medicaid Services (CMS) approval in 2003 for patients who were otherwise ineligible for transplantation, ushering in the modern era of advanced therapies for the failing heart. This pneumatic pump device was placed intra-abdominally and typically failed by 18 to 24 months, needing replacement. It was not until the introduction of continuous flow devices that potential indefinite support of patients became a possibility. The HeartMate IITM device by then Thoratec, Inc. (now Abbott, Abbott Park, IL), an axillary flow pump, proved to be vastly superior to its predecessor16 and to this day remains the most frequently implanted device. Although smaller than the Heart-Mate XVE, it still required the development of a preperitoneal
pocket to place the pump. Device technology has continued to evolve and the two most frequently implanted devices, the HeartWareTM HVADTM (Medtronic, Minneapolis, MN) and HeartMate 3TM (Abbott, Abbott Park, IL), are both placed intrapericardially. These centrifugal flow devices also no longer have any contact surfaces between the impeller and the device housing, and blood is propelled in a near frictionless manner. The HVAD impeller is levitated by hydrostatic forces and magnetically powered whereas the HeartMate 3 is fully magnetically levitated.17,18 As VAD technology and clinical experience managing these patients have evolved, outcomes have improved. However, Medtronic recently stopped the global sale and distribution of the HeartWareTM HVADTM system because of an increased risk of neurologic adverse events and mortality associated with the internal pump and the potential for the internal pump to stop, with delay or failure to restart. See Table 92.1 for outcomes from selected LVAD-related clinical studies.


May 8, 2022 | Posted by in CARDIOLOGY | Comments Off on Transplantation and Long-Term Implantable Mechanical Circulatory Support

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