Approximately 10% of patients with heart failure (HF) are in an advanced stage, characterized by persistent, limiting symptoms, frequent hospitalizations, poor quality of life, and high mortality despite receiving optimal guideline-directed therapy. In this context, advanced therapies such as heart transplantation (HT) and long-term left ventricular assist devices (LVADs) are considered. As we more accurately identify patients with advanced HF, the number of candidates for these therapies is expected to progressively increase.
HT continues to represent the treatment of choice for a selected group of advanced HF patients, yet despite expanded organ acceptance criteria and the incorporation of controlled donation after circulatory death (DCD), donor availability remains limited. On the other hand, technological advances have improved survival and reduced complications associated with new long-term LVADs, making them a viable alternative to HT.
Although both options improve survival and quality of life in patients with advanced HF, there are some differential characteristics. The latest data from the National Transplant Registry report a survival rate of 83% at one year and 74.9% at three years post-HT, with an average survival of approximately 14 years. Despite the risk of rejection and the side effects associated with immunosuppressive therapy, including infections and malignancies, most patients do not require hospitalization in the first year or later, maintaining a good quality of life. As for LVADs, the most recent data with HeartMate 3® devices show that, although one- and two-year survival rates are similar to HT, the five-year survival rate is 58%. While thrombotic complications and device dysfunction have significantly decreased, hemorrhagic complications and infections continue to be frequent, with 90% of patients being hospitalized in the first year post-implantation. LVADs provide only univentricular support and rely on an external battery, with all the associated implications, but they allow modification or reversal of transplant contraindications while the patient is being assisted and can improve HT candidacy if waiting times are prolonged.
Given all these considerations, how do we choose between HT and LVAD? The selection process for advanced HF patients is complex and requires an individualized, multidisciplinary approach that assesses eligibility for HT and/or LVAD without considering these options as mutually exclusive. Many of the variables considered in the evaluation process for HT and/or LVAD eligibility are common to both procedures, such as age, diabetes mellitus, renal or hepatic insufficiency, frailty, substance use, social support, and the presence of systemic diseases, as they will influence morbidity and mortality regardless of the chosen treatment. The assessment for HT involves identifying and evaluating, in particular, those conditions that increase the risk of mortality and could prevent the survival benefits of transplantation, impact the quality-of-life post-transplant, or worsen with immunosuppression. It is essential to rule out neoplasms, irreversible pulmonary hypertension, technical difficulties that may represent a formal contraindication to transplantation, or non-adherence that could contribute to poor outcomes. The LVAD assessment should focus particularly on evaluating the risk of right ventricular dysfunction (RV), identifying anatomical or physiological contraindications for LVAD, ruling out coagulopathies, and analyzing social support and the presence of caregivers who will help improve follow-up after implantation.
In a schematic way, after careful evaluation of the advanced HF patient, we may encounter four scenarios:
- The patient is eligible for HT but not for LVAD and therefore should be placed on the transplant waiting list.
- The patient is eligible only for LVAD, and the device should be implanted (usually due to age beyond the accepted criteria for HT or significant comorbidities contraindicating HT).
- The patient is eligible for LVAD but currently ineligible for HT due to a modifiable contraindication (irreversible severe pulmonary hypertension, substance use, or psychosocial issues, adherence problems, recent neoplasms with favorable prognosis, obesity, etc.). In this case, an LVAD should be implanted, and HT eligibility should be reevaluated during follow-up.
- The patient is eligible for both HT and LVAD, and HT should be preferred for better medium-to-long-term survival outcomes and lower morbidity. LVAD could be considered as a bridge to transplantation in clinically unstable patients or those with extended waiting times.
If the patient we are evaluating is in INTERMACS 2-3, how do we choose? Should we opt for urgent transplant or implant LVAD and reevaluate HT candidacy? The option of urgent HT in patients supported by short-term ventricular assist devices is a high-risk procedure, associated with higher mortality compared to elective transplant, requiring careful consideration of HT in order to optimize the distribution of limited organs. However, post-implantation mortality after LVAD in patients supported by ECMO is also high, so again, individualized and multidisciplinary decisions are required, considering the specificities of local donation and transplantation programs. Data from the ASIS-TC Registry, a multicenter Spanish registry on the use of short-term mechanical circulatory support devices as a bridge to urgent HT in Spain, show that from 2010 to 2020, 84.5% of urgent patients reached HT, with an average support duration of 6 days under urgency 0, achieving a one-year post-HT survival rate of 77.5%, influenced by the MCS device used.
These results support urgent HT as a reasonable and acceptable option for patients supported by short-term MCS devices, especially in environments with shorter waiting times. The higher mortality in urgent HT cases requires distribution criteria that ensure equitable access to HT, prioritizing clinically severe patients while avoiding futility. In 2023, new HT allocation criteria were established in Spain, defining strict criteria for multiorgan failure for urgency status, eliminating the temporary duration of short-term circulatory support as long as there are no complications, and facilitating HT access for non-LVAD candidates. In this way, more clinically severe patients are prioritized while improving post-HT survival. These criteria were previously analyzed in a prior blog commentary. It will be necessary to evaluate the clinical outcomes of these new criteria after implementation. In other environments, such as central European countries where waiting times are longer even in urgent situations, the option of urgent HT is less feasible. In 2020, the results of an observational study conducted in 11 European centers in Germany, Italy, Austria, and the Netherlands were published, including 531 patients who underwent LVAD implantation from ECMO support between 2010 and 2018. The average duration of ECMO support before LVAD implantation was 5 days, the 30-day survival rate was 77%, and the one-year survival rate was 53%. The predictors of mortality identified were age, female sex, lactate levels, BMI >30 kg/m2, MELD score, presence of atrial fibrillation, and previous cardiac surgery. 42% developed RV dysfunction requiring mechanical support. 21% of the patients received a heart transplant during follow-up. A recent study compared the outcomes of patients supported by ECMO prior to HT or LVAD implantation, analyzing data from the UNOS and INTERMACS registries. Although both strategies are rare, of 20,939 LVAD implants, only 2.8% were ECMO-to-LVAD (ECMO-LVAD), and of 30,093 heart transplants, only 1.1% were ECMO-to-HT (ECMO-HT). In fact, the change in transplant distribution criteria in the USA in 2018, where ECMO now has the highest priority, has led to a significant increase in ECMO-assisted transplanted patients. In general, ECMO-HT patients were younger, more often female, and had non-ischemic etiologies compared to ECMO-LVAD patients. ECMO-HT patients with RV dysfunction had better outcomes, and ischemia time was a significant predictor of mortality in the ECMO-HT strategy. Mortality rates for ECMO-HT and ECMO-LVAD strategies were similar (29.3% at 1 year, 33.4% at 2 years, and 38.2% at 5 years for ECMO-HT vs. 30.8% at 1 year, 37.4% at 2 years, and 43.5% at 5 years for ECMO-LVAD), with authors concluding that ECMO-LVAD is a non-inferior strategy in terms of mortality compared to ECMO-HT, and further studies are needed to identify which patients are better candidates for one strategy or the other.
In recent years, due to improved LVAD device outcomes, new potential scenarios for their indication have emerged. The possibility of myocardial recovery in assisted hearts may lead to using devices to delay or avoid the need for a transplant, especially in treatment-naïve patients. Predictors of myocardial recovery before LVAD implantation include certain etiologies (myocarditis, anthracycline-induced cardiomyopathy, peripartum cardiomyopathy), shorter time from symptom onset to LVAD implantation, age at implantation, preserved renal function, lower natriuretic peptide levels, and smaller left ventricular dilation (LVEDD <6.5 cm). The latest Mechanical Circulatory Support Guidelines from the International Society for Heart and Lung Transplantation (ISHLT) recommend consideration of ventricular support as a bridge to recovery in selected, optimally treated patients, including cardiac rehabilitation, with close follow-up and meticulous evaluation as a Class IIa recommendation and level B evidence.
Choosing the advanced therapy for a patient with HF is a complex process. The first step is to correctly identify patients with advanced HF and refer them to specialized units for early evaluation. It requires an individualized, multidisciplinary approach and simultaneous evaluation of both options. Contraindications must be ruled out, the patient’s clinical situation carefully assessed, and management strategies established according to their evolution, while also informing and discussing the different therapeutic options with the patient. Technological advances in devices and their impact on morbidity and mortality, along with the evolution of donation and transplantation activities, may influence and modify our decisions in the future.
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