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.




INDICATIONS

The decision to pursue either transplantation or VADs is complex and depends on the disease etiology, symptoms, prognosis, overall candidacy, and availability of other treatment options. Although consideration of support in the setting of cardiogenic shock—characterized by failure to wean off inotropic support or need for temporary mechanical support—seems obvious, indications for their use in the ambulatory setting are frequently not considered even though guidelines for referral to an HF program are well established. These criteria include recurrent admissions for decompensated HF or intolerance of GDMT.4 HF risk models, such as the Seattle Heart Failure Model, provide additional guidance for decision-making.19 Evaluations for advanced HF therapies require a multidisciplinary approach with consideration of the candidate’s comorbidities, social and financial support. These are discussed in detail in chapter 65.








Some patients with ischemic, valvular, congenital, or other structural heart diseases may be candidates for conventional high-risk cardiac surgery or transcatheter therapies. Expected procedural and long-term survival from these procedures is important for guidance in patients that may be candidates for multiple therapeutic options. Predictive models may be important tools to determine the optimal therapy for these patients as suggested by Yoon et al in their ischemic cardiomyopathy population.20 Perioperative mortality for heart transplantation and LVADs is <5% for most cases and long-term median survival after cardiac transplantation exceeds 10 years for the majority of patients.21 Long-term outcomes after LVAD implantation continue to improve, and although these remain inferior to transplantation, intermediate-term results are approaching survival after transplantation.22 A reasonable approach to these patients is to consider advanced HF therapies when the predicted operative risk and 1-year survival of other interventions are worse than the expected outcomes from advanced therapies. At our program, we frequently perform at least a limited evaluation for cardiac transplantation and LVAD to be available as rescue therapy if cardiac complications from high-risk surgery or transcatheter interventions arise. See Algorithm 92.1.

Advanced HF therapies are typically considered only for patients with severe HF symptoms, New York Heart
Association (NYHA) classes IIIB or IV. With the advent of durable VADs, advanced HF categories have been subdivided further by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Classification (see Table 92.2). The vast majority of patients treated with advanced HF therapies fall into categories 1 to 4 whereas the benefits of either cardiac transplantation or LVADs are less well established for higher INTERMACS classifications. The recent, nonrandomized Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management (ROADMAP) study compared the HeartMate 2TM to optimal medical management in INTERMACS class 4 to 7 patients.23 Although symptom control and HF admissions were improved with device therapy, complications were increased and survival was not different in the intention-to-treat analysis.






Candidacy for device therapy involves an extensive multi-disciplinary approach. This includes not only a thorough medical evaluation but also determination of adequate financial and social support to ensure long-term success of these interventions. Current decision-making for advanced therapy candidates is dependent on whether patients are eligible for cardiac transplantation or not. Transplantation is inherently limited by the availability of acceptable donor organs, and listing is reserved for the most suitable candidates.

Many other patients may be reasonable VAD candidates even if they are declined for cardiac transplantation. The
majority of patients are implanted as destination therapy, with that number increasing in the United States with the introduction of the new heart allocation system that has deprioritized bridge to transplantation VAD.22 A small percentage of LVADs are placed as a bridge to recovery, usually in patients with more recent onset of symptoms. Although uncommon, excellent results have been obtained at some centers with this strategy.24







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

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