The Future of Mechanical Circulatory Support

Early Goals of Life, and then Life Outside the Hospital

The pioneering, clinical experience with durable, implantable blood pumps began in earnest in the late 1980s. In that early era, it was a remarkable breakthrough to offer hope of life to patients declining while awaiting heart transplantation and then, ultimately, offer hope for quality of life .

The first device to complete a controlled, clinical trial culminating in US Food and Drug Administration (FDA) approval in 1994 for bridging to transplantation was the HeartMate IP (Thermo CardioSystems, Boston, MA), an implantable, pulsatile left ventricular assist device (LVAD) powered pneumatically by a 90-pound external console. Patients received a survival benefit but remained hospital bound. A portable, 25-pound, pneumatic driver subsequently offered patients greater mobility and early experience with discharge. Electrically powered blood pumps, emerging with the next-generation HeartMate series, the VE and XVE LVADs, were the next to receive FDA approval. This opened the era of outpatient LVAD support and improved quality of life with patients engaging in light recreation and with some returning to their occupations.

That first-generation implantable technology was limited by durability , with mechanical bearing and tissue valve failures occurring on average at 1.5 years. Infections were problematic, especially with the early, large, rigid percutaneous leads. However, an advantage of that technology that has yet to be reproduced is freedom from anticoagulation more than aspirin.

Exploring Long-Term Life with ‘Destination Therapy’

A decade later, in the late 1990s, the field began the transition to long-term implantation, introducing the era of so-called destination therapy (DT), moving beyond bridging to transplantation. The National Institutes of Health (NIH)-supported Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial became the setting for the first randomized controlled trial of LVAD therapy with the HeartMate XVE compared to optimum medical management over a 2-year period of observation.

Patients receiving an LVAD lived longer, demonstrating a survival benefit greater than any other heart failure therapy previously studied. The hoped-for improvement in quality of life appeared believable. However, mortality (23% survival at 2 years) and morbidity (especially with pump failures and infections) were still considerable, well behind outcomes with heart transplantation. That was not too surprising considering that the population studied had the most advanced level of heart failure ever studied up to that time.

The REMATCH trial served as an early catalyst to the field, opening the door to the long sought-after goal of life-long therapy. Data from that trial were used to secure Medicare approvals for reimbursement at levels that permitted cautious growth of the field. And, clinical teams began forming, with the important, high-profile entry of heart failure cardiologists joining the efforts of the heart surgeons whose leadership had been instrumental during the early startup stages of the MCS field.

The Pathway to Improvement

The pioneering efforts of the late 1980s through the 1990s were leveraged into an era of progressive improvement throughout the decade of the 2000s. Blood pump therapy had to improve substantially to begin approaching heart transplantation, the ‘gold-standard’ for end-stage heart failure at that time. It would have to follow the precedent observed with heart transplantation in which humble beginnings during the initial pioneering stages gave way to progressively improving outcomes.

Three areas of improvement would be necessary:

• 1.

  Technology , including a new-generation of blood pumps;

• 2.

  Management , of both the patients and devices; and

• 3.

  Patient selection , based on new insight into patient risk factors.

The course to be followed for outcomes improvement, throughout that next era and into the future, is illustrated in Fig. 22.1 . The survival outcomes for the pioneering phase of MCS, represented by the 2-year survival curve with LVADs observed during the REMATCH trial, are superimposed on the 17-year survival curve for heart transplantation in the current era. Improving outcomes with MCS would be driven by the three factors most responsible: technology, management, and patient selection.

PATIENT Selection and Risk Mitigation

Early in the history of the MCS field, patients implanted with devices were extremely high-risk patients, literally on death’s door. Moving to earlier-stage patients would be expected to improve outcomes through lower exposure to perioperative risk. If pushed prematurely, however, the benefits of device therapy could be outweighed by the risks associated with good, but less-than-perfect, technology. The search for appropriate ‘equipoise’ balancing risk versus benefit at a given time with a given technology, has been a subject of considerable discussion.

The US national Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) has afforded guidance with patient risk factor characterization and relevant outcomes data. Fig. 22.2 illustrates the breakdown of New York Heart Association (NYHA) class IV patients into six categories from highest severity of illness (IM 1) to lowest (IM 6), followed by NYHA class III (IM 7). The INTERMACS data confirm a lower likelihood of survival in the higher-acuity categories (lower IM levels), indicating the importance of careful patient selection. Preoperative optimization to reduce risk has been recognized as essential.

The Era of Improving Survival

A review of survival with LVADs throughout multiple clinical trials starting with the REMATCH trial demonstrates progressive improvement, now approaching that of heart transplantation, at least within the first 3 to 5 years. This is illustrated in Fig. 22.3 , demonstrating progressive improvement in survival from early clinical trials to more recent ones.

Real-world experiences have supported this trend. Individual center and small group experiences have excelled, approaching equivalence to survival with heart transplantation.

RECOGNIZING the OPPORTUNITIES

The most important prospect in the near-term to improve the MCS field is to address the ominous challenge of adverse events (AEs). Data from the INTERMACS illustrates this and serves as a wake-up call. By 12 months after implantation with current-generation ventricular assist devices (VADs), 70% of patients will have experienced one major AE, whether it be bleeding, stroke, device thrombosis/malfunction, infection, or death. This is illustrated in Fig. 22.4 , which graphically displays the sobering magnitude of the AE challenge and summarizes the estimated rates of occurrence of the most troublesome AEs. The cumulative impact of the AEs year after year is considered the most significant impediment to responsible growth of the MCS field, whether that be through limiting the number of patients served or slowing expansion into earlier-stage heart failure.

In addition to the substantial clinical impact of AEs, the economic challenge created by the AEs is enormous. Underlying this is the high frequency of re-hospitalizations. The costs of device replacement, rehospitalizations, diagnostic workups, and therapeutic interventions quickly add up. While the initial implantation costs remain high, it is the long-term costs that represent the greatest challenge. While there are encouraging trends with the most recent clinical experience, this opportunity for improving cost-effectiveness through improving AEs cannot be ignored.

MAPPING the Pathway to OPTIMIZATION

As was noted throughout the history of the MCS field, ongoing improvements with technology, management, and patient selection will be fundamental to overcoming the challenges. While requests abound for better technology, it is clear that outcomes can be improved even with existing technology by improving management and patient selection.

Insight into this is garnered from observations of large differences in outcomes, varying from center to center even with the same devices. For example, wide differences in rates of pump thrombosis have been noted even with the same LVAD. Stroke rates have varied considerably between centers and across eras even with the same device.

Evidence exists to support the idea that improvements in thrombosis with HeartMate II LVADs can be achieved as a result of minimizing variation in management by standardization around best practices, either evidence based or through consensus. Improvements in stroke rates with HVAD LVADs have been noted with better management of blood pressure. Certainly, patient factors contribute varying degrees of risk for the occurrence of AEs—either through a state of compromise and deterioration induced by progressive heart failure—or through inherent biologic or genetically induced conditions that may predispose a particular patient to specific risks.

Optimizing TECHNOLOGY

A wish list of technological improvements is presented in Fig. 22.5 . These improvements are broadly categorized into those for safety, for performance, and for utility. Safety is the highest priority given that the greatest challenge in MCS is the AE issue.