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Long-Term Mechanical Circulatory Support and TAH
Mechanical Circulatory Support
Heart failure remains a leading cause of death in the United States with over 250,000 attributable deaths annually . Despite improvements in medical care, time to coronary revascularization, and electrophysiological interventions such as cardiac resynchronization therapy and automated implantable cardioverter-defibrillators, decompensated heart failure carries significant morbidity and mortality. In the United States and around the world, heart transplantation, the definitive therapy for advanced heart failure, is limited by scarcity of donor organs.
To combat the rising need for advanced cardiopulmonary support, mechanical circulatory support (MCS) devices including left ventricular assist devices (LVADs) emerged to fill the void. In the 1960s, Dr.’s Debakey, Spencer, and Dennis described temporary ventricular support in the form of extended postoperative cardiopulmonary bypass in patients unable to wean from the pump after cardiac surgery. However, the cardiopulmonary bypass circuit was not a durable form of support. In 1963, the Baylor College of Medicine in Houston, TX developed the first implantable LVAD. Several years later in 1966, this same technology was used to support a patient suffering from decompensated heart failure for 10 days, the first documented survival associated with MCS.
Dr. Debakey was a pioneer in the evolution of MCS and was quick to note several shortcomings of the early devices used to provide long-term support. In his 1971 article reviewing his experience with LVAD support, Debakey highlighted the lack of a portable power source and control mechanism, the high cost of implantation and maintenance, the lack of an atraumatic blood-biomaterial interface, and the invasive implantation as several key factors limiting widespread use of LVAD support . Several of these barriers remain today.
First generation LVADs, including the Heartmate (HM) I XVE (Thoratec Corp.), Thoratec paracorporeal ventricular assist device (PVAD), and Novacor LVAD (World Heart Corporation, CA, USA) were pulsatile, positive displacement devices. The Heartmate I device consisted of a pusher-plate actuator which was driven either electrically or pneumatically. Inflow consisted of a cannula inserted into the left ventricular apex which was connected to a Dacron graft with a porcine valve that traveled back to the pump with the outflow also comprised of a Dacron graft with a porcine valve. The HM I conduit was lined with titanium microspheres and a fibrillar textured inner surface, creating a biologic interface that promoted formation of a pseudointima that was resistant to thrombogenesis. This enabled patients to be managed with aspirin rather than anticoagulation. The Novacor device was a portable, electric dual pusher plate device with the pump composed of a smooth polyurethane sac with gelatin-sealed polyester inflow and outflow grafts and received FDA approval as a bridge-to-transplantation device. In contrast to the Heartmate XVE, patients with Novacor LVADs still required systemic anticoagulation.
While these early devices provided excellent support, long-term durability was limited by the pulsatile nature of the pump. Additionally, the presence of a large external lead rendered patients vulnerable to infection. As a result of the aforementioned shortcomings and patient dissatisfaction with the loud pulsatile pump, only the Thoratec PVAD remains commercially available today.
Indications for Therapy (BTT vs DT, Bridge to decision, bridge to recovery)
While historical indications for LVAD therapy were limited to bridge-to-transplantation and destination therapy, improvements in the cost and ease of implantation have given way to new indications including both bridge-to-recovery and bridge-to-decision. In patients with decompensated heart failure unabated by intraaortic balloon pump counterpulsation therapy and pharmacologic support, LVADs have emerged as a viable alternative to extracorporeal membrane oxygenation (ECMO). Approximately 85% of MCS involves isolated LVAD use whereas the remaining 15% of cases may involve biventricular support in the form of a BiVAD or total artificial heart (TAH). Bridge-to-transplantation (BTT) indicates temporary MCS until a donor heart becomes available.
Currently, both Heartware HVAD and Heartmate II and III devices are available for the BTT indication. Candidates for BTT therapy have worsening Class IIIb (markedly limited physical activity, symptomatic with light exertion) or IV (symptomatic at rest) New York Heart Association (NYHA) heart failure and have often failed conservative management with inotropic support and IABP counterpulsation. These patients may have reversible contraindications to transplantation that are actively being evaluated and corrected. The shortage of donor hearts in the United States has led to a steady rise in the number of candidates requiring BTT with LVAD support. The 2010 report from the ISHLT documented growth in the BTT population from 13.4% from 1992-2001 to 20.1% from 2002-2006 .
Alternatively, destination therapy indicates durable long-term LVAD support without the intention, at least in the short-term, for eventual heart transplantation. In a recent report in the Journal of Heart and Lung Transplantation from 2014, Kirklin et al reported a 1-year survival rate greater than 80% and a 2-year survival greater than 70% in over 10,000 patients in the INTERMACS database who received continuous flow LVADs in the first 8 years of enrollment . As of 2014, 141 centers in the US had received designation from the Center for Medicare and Medicaid Services (CMS) as destination therapy (DT) centers, and the percentage of LVADs implanted as destination therapy has tripled over the last decade from 14.7% in 2006 to 45.7% in 2014. It should be noted that the DT indication does not preclude transplantation in the event of secondary end organ recovery, in fact approximately 10% of DT recipients undergo heart transplantation within the first year of implantation.
Reversible causes of decompensated heart failure in which recovery of native cardiac function is expected may be managed with LVAD support under the bridge-to-recovery indication. In fact, mounting evidence suggests that ventricular loading via LVAD therapy leads to advantageous ventricular remodeling and improves myocardial structure and function. In a recent publication in the Journal of the American College of Cardiology, Drakos and colleagues demonstrated that among 80 patients with both ischemic and non-ischemic cardiomyopathy, implantation of continuous-flow LVADs resulted in a 50% increase in left ventricular ejection fraction (LVEF) in 1/3 of patients after 6 months. Additionally, a 50% reduction in LV end systolic and end diasolic volume and a substantial reduction in LV mass one month after implantation were appreciated . Myocardial recovery with LVAD support is augmented by the timely institution of various pharmacologic agents. Pharmacotherapy, consisting of angiotensin converting enzyme (ACE) inhibitors, beta blockade, and aldosterone antagonists reduces cardiac myocyte hypertrophy and decreases the cellular metabolic burden placed on ventricular myocytes.
Finally, bridge-to-decision implies that transplant eligibility is under consideration and LVAD support as a salvage intervention is necessary until a decision regarding long-term support has been rendered. This often occurs as a result of secondary end organ insufficiency in the setting of decompensated heart failure. Transplant candidacy hinges on recovery of end organ function.
Outcomes of Mechanical Circulatory Support
The growth and development of MCS has spurred several initiatives including the creation of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) in 1999 and subsequently the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) in 2006, both of which are global registries intentioned to evaluate outcomes among adults receiving MCS. MCS has emerged as an invaluable modality in the management of advanced heart failure. While MCS devices have not realized the equivalent long-term gains of heart transplantation, these devices are much more readily available and can serve a larger proportion of the end stage heart failure population, including those not considered for hear transplantation.
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