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 ).

Algorithm to guide decisions on non–inotrope dependent patients with advanced heart failure (INTERMACS 4–7). 6MWD , 6-minute walk distance; FDA , Food and Drug Administration; INTERMACS , Interagency Registry for Mechanically Assisted Circulatory Support; LVAD , left ventricular assist device; NYHA , New York Heart Association; OMM , optimal medical management; QoL , quality of life.

(From Estep JD, Starling RC, Horstmanshof DA, et al; ROADMAP Study Investigators. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: results from the ROADMAP study. J Am Coll Cardiol. 2015;66:1747–1761.)

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).

Right Ventricular Dysfunction

RV failure is one of the most important causes of mortality or morbidity after LVAD placement because contemporary durable MCS has evolved to devices implanted into the left ventricle (LV). Not only can RV failure leave patients with significant symptoms of HF that LVAD was supposed to treat (e.g., edema, fatigue, and orthostasis), but also RV failure contributes to bleeding, thrombosis, and renal failure. RV failure requiring prolonged inotropic support or RV mechanical support occurs in about 20% of patients undergoing LVAD placement. While some patients with limited pulmonary hypertension can get by for short periods of time on LVAD support alone (quasi-Fontan physiology), LVAD support alone does not produce adequate hemodynamic support in most patients absent significant RV function. Despite the development of numerous risk scores to predict RV failure post-LVAD, expert clinicians will need to synthesize important clinical information and use judgment to decide if RV function is appropriate for LVAD support. Another inherent vexing challenge is that RV function may deteriorate intraoperatively; hence, a “good” preoperative RV becomes prohibitively dysfunctional during surgery. Device selection and types, including total artificial heart (TAH) and biventricular support, are addressed in Chapter 10 .

Various information can be used to anticipate RV failure. RV failure after LVAD is most commonly due to preexisting RV failure. Patients with RV-predominant disease (e.g., arrhythmogenic RV cardiomyopathy or Ebstein anomaly) are obviously not candidates for LVAD. Patients with nonischemic etiology are more likely to present with biventricular failure and thus have a threefold to fourfold increased risk of needing RV support. Not surprisingly, patients with a chemotherapy-induced cardiomyopathy also experience increased RV failure post-MCS. While a properly functioning LVAD tends to lower pulmonary venous pressures and thus improve RV afterload, LVADs can also cause the interventricular septum to shift leftward, potentially causing disadvantageous geometric changes in the right ventricle that reduce septal contribution to RV stroke volume and exacerbate tricuspid regurgitation.

Building on the risk model discussion from earlier, statistically derived models for the prediction of RV failure after LVAD implantation have been reported. Dominant variables tend to include the inability of the RV to generate high pulmonary-artery pressures (e.g., RV stroke work index less than 300 mm Hg × mL/m ² ) and maintain low central venous pressure (e.g., right atrial to post–capillary wedge pressure ratio > 0.63 and elevated blood urea nitrogen > 39 mg/dL), as well as lung disease at the time of surgery that is likely to create ongoing RV strain after implantation (e.g., preimplantation mechanical ventilator support). Predictive measurements made on echocardiogram before implantation include RV dimension, tricuspid annual plane systolic excursion, RV strain, and severe tricuspid regurgitation. Some surgeons have advocated repair of tricuspid regurgitation at the time of LVAD implantation, but this added procedure increases cardiopulmonary bypass time and has not been clearly associated with reduced risks of RV failure.

Pulmonary hypertension is generally not a contraindication to LVAD, in contrast to its relationship to heart transplant. The ability of the RV to generate high pulmonary-artery systolic pressures pre-LVAD is related to a high RV stroke work index and generally predicts a functioning RV. Because much pulmonary hypertension in patients being considered for LVAD is World Health Organization (WHO) group 2 (i.e., related to chronically elevated pulmonary venous pressures from LV dysfunction), these patients with higher pulmonary artery systolic pressures not only are at a lower risk of acute RV failure but also tend to see their pulmonary hypertension partially improve or reverse in the months after LVAD implantation.

Ventricular Arrhythmia

Electrical abnormalities that affect RV function can also lead to poor outcome with LVAD. Therefore, patients with ventricular tachycardia and ventricular fibrillation that cannot be controlled are not candidates for LVAD; this is further complicated because intravenous inotropic support may also be contraindicated if it worsens the ventricular arrhythmia, leaving biventricular assist devices (BiVAD), veno-arterial ECMO, or TAH support to transplant as the only alternative to palliation and death in refractory cases. While some ventricular arrhythmias are driven by cardiac decompensation and can resolve with improved hemodynamic support, ventricular arrhythmias in patients being considered for LVAD support may be substrate/scar mediated and do not generally disappear postimplantation. Therefore, demonstration of rhythm control with antiarrhythmic or ablation preimplantation may be indicated prior to LVAD implantation. Concomitant intraoperative ventricular arrhythmia ablation at the time of LVAD surgery may be facilitated by epicardial access, but concerns about increased postoperative complications including LVAD thrombosis have been raised. Post-LVAD implantation ablation may also be facilitated by LVAD hemodynamic support, but again may raise concerns about anticoagulation and thrombosis. Pre-MCS patients with complex ventricular arrhythmias require a collaborative management strategy developed by the electrophysiologist, HF cardiologist, and cardiac surgeon.

Cardiac Anatomy, Prior Surgery, and Valve Disease

Not all LV cardiac anatomy is amenable to LVAD (Special Populations, Chapter 17 ). The inflow cannula needs space in the left ventricle to avoid suction. Thus, patients with a nondilated LV—as seen in restrictive or hypertrophic cardiomyopathies—have often been excluded from LVAD and routed to consideration of TAH, ECMO, or continuous inotropic support as BTT (or palliation/hospice for non-transplant-eligible patients). LVAD registries show that relatively few patients with hypertrophic and restrictive cardiomyopathy undergo LVAD implantation, and most who do display some features of a dilated cardiomyopathy. The overall survival and adverse event profiles of these patients were similar to traditional dilated cardiomyopathy (DCM) patients; however, in those with very small ventricles, survival was inferior.

Congenital heart disease may pose particular anatomic and physiologic problems for contemporary LVAD support. Additionally, chronic congestive hepatopathy can further complicate MCS in single-ventricle physiologies. A detailed discussion of the candidacy of various congenital heart diseases is provided in Chapter 18 . Needless to say, teamwork among advanced HF, adult congenital, and pediatric cardiac surgery is vital.

Prior cardiac surgery, most commonly from coronary artery bypass grafting or valve replacement, raises operative risk and should be factored into decisions about candidacy and surgical approach. Fortunately, in carefully selected patients treated by skilled cardiac surgical teams, prior surgery does not appear to significantly raise risk. All patients being considered for MCS, especially those who have a history of coronary artery bypass grafting, should have a chest computed tomography (CT) scan to define aortic calcification and provide the location and course of the bypass grafts to guide the surgical approach.

Valvular disease should also be factored into candidacy. See previous discussion for concerns about tricuspid regurgitation with RV dysfunction after LVAD. Mitral valve regurgitation does not appear to markedly affect LVAD outcomes, and repair at the time of LVAD placement also does not appear to offer a significant advantage. In contrast, aortic regurgitation has significant adverse effects on LVAD function and typically progresses after LVAD implantation. Therefore, even mild degrees of aortic regurgitation should be addressed at the time of LVAD implantation, usually through repair or oversewing of the aortic valve, although the latter may create subsequent issues. Transcatheter aortic valve replacement may be an option down the road after LVAD implantation, but there are concerns about anchoring of the device in noncalcified valves. Mechanical valves need to be addressed at the time of LVAD implantation, often through removal and replacement.