Candidate Selection and Decision Making in Mechanical Circulatory Support

Bridge to Transplant

Policies from the United Network for Organ Sharing (UNOS) and others have increasingly prioritized the use of donors for the sickest patients. This has had a significant impact on the use of LVADs for BTT. With the ability to stabilize transplant-eligible patients with durable LVAD, thereby resulting in a higher transplant priority status for those MCS patients going forward, the remaining non-MCS patients at the lowest status now rarely undergo transplantation. This change toward performing transplantation on the sickest patients and continual increases in waiting time for non-MCS patients has contributed to pretransplant use of LVADs, now with more than half of patients having LVADs at the time of heart transplantation. Further changes to the UNOS allocation system in 2018 promise to further increase the use of MCS prior to transplantation, although further prioritization of the sickest patients may shift BTT MCS from durable LVAD to temporary forms of support. Despite this growth in BTT MCS over time, the relatively fixed donor pool limits the number of transplants per year (~ 3000 annually in the United States) and caps the number of possible BTT LVADs.

Destination Therapy

Given the limited heart donor pool and complications related to transplantation, MCS has always been seen as a permanent alternative to transplantation, i.e., DT. However, not until the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study in 2001 were MCS technologies and techniques advanced enough to consider LVAD as permanent therapy for large numbers of patients. Since REMATCH, and primarily driven by the increased durability of continuous-flow devices, DT LVAD outcomes have improved, and DT LVAD use has increased. While BTT and DT LVADs tend to look essentially the same in terms of the devices and procedures involved, there are important differences. Patients considering DT have reasons they are not BTT candidates—e.g., advanced age, multiple comorbidities, or suboptimal social determinants of health—and these reasons can make living with the device more difficult, as well as worsen postimplantation survival and quality of life (QoL). Furthermore, the framework for decision making may be different, as DT LVAD patients do not have a “bail out option in the event of complications (e.g. recurrent gastrointestinal bleeding or infection) or dissatisfaction with the device.

Non-MCS Alternatives

Indications for MCS are framed by other available treatment options. There are relatively few alternative strategies to MCS for candidates who progress into irreversible cardiogenic shock. Intravenous inotropes can be used effectively in the short term for some patients awaiting transplant (either in hospital or at home). However, data from several studies have shown that the long-term outcome with LVAD is significantly better than continued use of intravenous inotropes. Contemporary use of inotropes has seen improved outcomes, perhaps because of better patient selection. Ongoing medical management with a shift to palliation is also an alternative and remains the most common approach for the vast majority of patients dying from HF. Therefore, decisions about how to proceed with patients slipping into INTERMACS category 3 remain challenging and dependent on multiple patient factors. Recent evidence has also shown that both patient and physician perceptions of illness severity, risk of death, and need for advanced therapies in non–inotrope-dependent patients are likely underestimated.

Timing

The most frequent question debated by MCS experts and industry is based on defining “ideal timing” for MCS therapy. Recent data suggest that there is a relatively narrow window for MCS. Clinical events can be useful as milestones marking the transition to end-stage disease and, thus, triggers for consideration of MCS (see the I-NEED-HELP mnemonic in Table 4.1 ). That said, earlier LVAD implantation in patients not yet showing frank end-organ dysfunction while on oral therapies has not appeared to markedly improve post-LVAD survival compared with patients who continued with medical therapy with the potential for delayed LVAD implantation and exposes patients earlier to the operative and longer-term risks of LVAD. Thus, until patients have irreversible disease severity that markedly reduces quantity or quality of life, durable LVAD is generally delayed. This must be tailored to each patient; often, objective measures (6-minute walk and peak oxygen consumption) may meet MCS criteria, but the patient feels that his/her QoL is acceptable and must be balanced with the total burden of MCS. INTERMACS 4 patients, but usually not INTERMACS 5–7 patients, are more likely to have significant improvements in QoL with LVAD ( Fig. 4.2 ).

Conversely, LVAD implantation too late puts cardiogenic shock patients at higher risk for postoperative complications and prolonged recovery. Even if such patients survive surgery, prolonged exposure to deranged hemodynamics may leave them with permanently impaired renal function, pulmonary hypertension, cardiac cirrhosis, and a very unsatisfactory post-MCS outcome.

Objective Measures of Disease Severity Warranting MCS

The generally accepted criteria for implantation of LVAD are based on parameters that indicate impaired systemic perfusion and end-organ function. These are discussed in detail in Chapter 3 . Functional testing and hemodynamic measures are two of the most commonly employed methods. During cardiopulmonary stress testing, a peak oxygen consumption (VO ₂ ) of < 12–14 mL/kg/min with a respiratory exchange ratio (RER) > 1.05 on optimal pharmacologic therapy suggests marked cardiac dysfunction; in the presence of a submaximal test (lower RER), a ventilation equivalent of carbon dioxide (VE/VCO ₂ ) slope of > 35 is also suggestive of poor prognosis. Similarly, right heart catheterization-derived invasive hemodynamics are useful to define advanced disease (as well as right ventricular [RV] function, discussed further in this chapter). Cardiogenic shock is suggested by the combination of (A) systolic blood pressure < 90 mm Hg, (B) cardiac index less than 1.8 L/min/m ² if the candidate is not supported by inotropes or < 2.0 L/min/m ² if the candidate is supported by at least one inotrope, and (C) pulmonary capillary wedge pressure greater than 15 mm Hg. The inability to improve these numbers without inotropic or mechanical support is a harbinger of severe progressive HF. That said, rarely should a single number be treated. Just as a VO ₂ of < 14 does not necessarily necessitate activation for advanced therapies, neither does a cardiac index < 1.8 L/min/m ² require initiation of inotropic support and movement toward MCS. Without end-organ dysfunction and manageable symptoms, many such patients—under close watch and with careful instructions to seek care for changes in clinical status—can do well for months to years.

Heart Failure Risk Scores

The totality of clinical information about a patient should be integrated to estimate prognosis and, thus, the need for MCS. However, with more than 100 variables known to be associated with mortality and rehospitalization in HF, appropriately prioritizing some information over others is important (see Chapter 3 ). Risk models work to narrow and weight prognostic information. Commonly used multivariable instruments for estimating prognosis in patients with symptomatic HF are the Heart Failure Survival Score, the Seattle Heart Failure Model (SHFM) ( https://depts.washington.edu/shfm/ ), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk calculator ( http://www.heartfailurerisk.org/ ). Because contemporary survival after LVAD implantation in carefully selected patients consistently caps out around 82% at 1 year, patients should generally not be considered for LVAD until their estimated mortality without LVAD meets or exceeds 18% in the coming year. The SHFM and MAGGIC online calculators can provide such tailored estimates for patients. However, application of these scores to individual patients should be interpreted with caution, as their miscalibration can lead to significant underestimation of risk in populations with particularly advanced HF. Furthermore, most prognostic models in HF focus on mortality, whereas symptom relief and QoL also rank high in importance to individual patients. In addition, risk scores should be updated prospectively to account for the most recent clinical data.

Prediction of survival after LVAD implantation is even more difficult than prediction of survival with ongoing medical management of HF. A number of LVAD risk scores have been developed, only to be shown in validation testing to poorly predict whether patients will live well after device implantation. For example, the HeartMate II risk score was found to have a c statistic of 0.64–0.71 in validation, suggesting that, about one-third of the time, a randomly selected patient who survives will have a worse risk score than a randomly selected patient who dies. Calibration of these models has also been problematic when applied to different populations, with significant underestimation of survival when scores derived in largely INTERMACS 3 populations are applied in less sick populations being considered for LVAD. The difficulty in predicting post-LVAD outcomes is likely not driven by failure to measure the right risk factors; post-LVAD mortality appears to be less dependent on preimplantation patient factors and more dependent upon operative and postimplantation events that are not present before surgery and thus cannot be measured before the decision to proceed with LVAD is made.

Despite the limitations of prognostic models, they are generally more accurate than clinical intuition, which is prone to bias. Therefore, clinicians treating patients with severe HF need to learn how to leverage objective risk models, while recognizing their limitations and adapting them based on unique clinical and psychosocial features and serial assessments not generally incorporated into such models. Furthermore, uncertainty should be actively recognized by clinicians in their approach to medical decision making and shared decision making (discussed further in the chapter).