Are Ventricular Assist Devices Leading the Way in Patients With Advanced Heart Failure?

Abstract

It was 1966 and Dr. Debakey just placed a ventricular assist device (VAD) into a 37 year old who had her mitral and aortic valve replaced. This pneumatic pump successfully supported her for 10 days until recovery.(1) It was a major breakthrough even though there were issues of short battery life, infection, thrombosis, bleeding, and device deterioration.(2) The VAD could support a patient's failing heart until it recovered. This innovation revolutionized the care of the advanced heart failure patient. Even with the first heart transplant occurring the following year, development of the VAD continued.(3) Donor hearts were in such high demand. Many people waiting for a transplant would never get one. It is estimated that 25% of patients on the wait list might die before a donor heart is found.(4) These circumstances fostered the idea of using a VAD as a long-term support device if the heart did not recover or if a donor heart did not become available. The National Institute of Health investigated the feasibility of a VAD as a long-term option. Comparison of medical treatment to ineligible transplant candidates with a VAD resulted in better cardiac recovery, survival, and quality of life in patients with VAD implantation.(5) Shortly after the study results were published in 2001, the US Food and Drug Administration (FDA) approved the first VAD to be used for New York Heart Assocation Class IV patients who had “received optimal medical therapy for at least 60 of the last 90 days, who have a life expectancy of less than two years, and who are not eligible for cardiac transplantation”.(4) Today, durable VADs are implanted as a bridge to transplant (BTT), bridge to candidacy (BTC), and destination therapy (DT). Temporary VADs are placed as bridge to decision, BTC, and BTT. The Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) database was organized in 2005 by the National Heart, Lung Blood Institute, to track patient characteristics and outcomes of VAD patients, and later became the STS Intermacs.(6,7) Ninety-six percent of VAD implanting centers contribute to this comprehensive outcomes registry of patients receiving FDA-approved durable mechanical circulatory support (MCS) devices. Since the first annual report published in 2008, the analyzed data is used to improve the use of MCS and improve duration and quality of life. The 2022 Intermacs Annual Report revealed data from 2012-2021 regarding the yearly number of VADs placed, intention of the implant, patient characteristics, survival outcomes, adverse events, cause of death, and the impact of the recent revision of the adult heart transplant allocation system from the Organ Procurement and Transplantation Network / United Network for Organ Sharing (OPTN/UNOS). Three findings from the annual report include a decrease in the number of VAD implants, an improvement in the survival and adverse event statistics, and a change in the intention of VAD implantation.(8) The annual report divided the cohort into 2 groups: 2012-2016 and 2017-2021, which coincided with the 2017 FDA approval for the fully magnetically levitated centrifugal-flow left ventricular assist device.(9,10) The characteristics of patients in the recent era were more commonly female, Black, had severe diabetes, higher BMI, and need for dialysis pre-implant. The severity of illness was similar, however the use of temporary MCS was higher in the recent era. This was concurrent with the scientific statement on temporary MCS for cardiogenic shock from the American Heart Association, which indicated a change in the care and support of critical cardiogenic shock patients, and provided approaches for escalating and weaning MCS.(11) The increase in temporary MCS has affected the implant strategy of durable VADs. A greater proportion of patients are receiving VADs with the intention of destination (81.1% in 2021 vs. 51.2% in 2016) rather than bridge to candidacy (13.5% in 2021 vs. 24.1% in 2016) or transplant (5.3% in 2021 vs. 23.8% in 2016).(8) Progression of durable VAD support over the last decade has led to several device changes. The implanted devices were mainly the axial-flow device between 2012-2017, and mainly the centrifugal hybrid magnetic device and the centrifugal fully magnetic levitation device between 2018-2021. The axial-flow device, FDA-approved in 2008 for BTT and 2010 for DT, was phased out after the 2017 approval of the fully magnetically levitated device.(9,12,13) The hybrid magnetic device received FDA approval for BTT in 2012 and DT in 2017, and was implanted until 2021 when it was taken off the market due to adverse neurologic events.(14) The fully magnetically levitated device is currently the only FDA approved device available for durable VAD implantation. From the high of 3219 VAD implants in 2019, the number of patients that received a VAD has decreased annually, dropping 17% in 2020 and 23.5% in 2021 when compared to 2019.(8) The decrease in implants from the high in 2019 was attributed to both the COVID-19 pandemic and the revisions in the heart transplant allocation system. In 2021, 2464 primary VADs were implanted, meanwhile 3818 patients received a heart transplant, the highest number to that date.(8,15) Survival has improved over time, with 1-year survival at 83% and 5-year survival at 51.9% in the recent era, compared to 81.2% and 43% respectively, in the prior era. This is the highest 5-year survival rate, exceeding 50% for the first time. Lowest survival rates were observed with high disease severity, and better survival rates were observed with decreased disease severity. The 5-year survival rate of patients receiving a VAD for DT (47.6%) improved dramatically when compared to the earlier era (39.1%). Major adverse events included bleeding, infection, and renal dysfunction. Recent era complications were lower for GI bleeding, device malfunction / pump thrombosis, and incidence of stroke.(8) All implantations during the recent era had a higher probability of being alive, and also a lower probability of transplantation, compared to the earlier era.(8) The lower probability of transplantation is a consequence of the 2018 revision of the organ transplant allocation system. For patients who received a device for BTT prior to the allocation system change, the time at which the proportion that received a transplant surpassed the proportion that still had a device was 17 months. The time increased to 32 months after the heart allocation system change. That time then increased to 34 months for patients who received the fully magnetic device. Also, a low proportion of patients died with this device.(8) This change indicates a shift in the probability of receiving a heart transplant after durable VAD implantation. Of the patients who received a durable VAD between 2018-2021, 17.2% subsequently received a heart transplant, compared to 31.9% who had received a durable VAD between 2016-2018.(8) The heart transplant allocation system started in 1988. Initially it was a 2 tiered system, then changed to 3 tier system in 1998, and 6 tiers in 2018.(16) The changes in the allocation system sought to increase the efficacy of the transplant registry and waitlist, and to differentiate wait listed patients based on clinical condition and urgency of transplant. This was done in an attempt to decrease wait list mortality and broaden geographical sharing of donor organs.(16, 17) Over the next decade after the first revision, the number of patients listed on the transplant list increased along with the wait list mortality as patients were waiting longer for organs. Implementation of the latest revisions of the organ allocation policy began in 2018. After the most recent change, a study of over 15,000 patients showed higher risk patients are undergoing transplant. More patients receiving transplants are being bridged with temporary MCS. Wait list outcomes have improved as well as reductions in wait list mortality.(17) Highest priority on the waitlist now include patients with extracorporeal membrane oxygenation or other “non-dischargeable” MCS while lower priority include stable patients with durable VAD.(17,18) Lower priority was given to durable VAD patients as a result of improved survival and reduction in adverse events.(17) The priority change in this new allocation system impacts patients using this modality as bridge to transplant.(18) Under the new system, patients bridged to transplantation with intra-aortic balloon pumps (IABP) have higher priority than patients supported with inotropes or durable VAD.(19) The title of a 2010 review by Boyle raised an interesting question: “Are Ventricular Assist Devices Underutilized?” The author stated that to expand the pool of potential MCS patients, device reliability needed to be improved, as well as functional capacity and quality of life.(20) Advanced heart failure patients have frequent hospital admissions, poor quality of life, and high mortality.(21) It is estimated that 49-73% of healthcare costs for heart failure patients is related to hospitalizations, and each hospitalization averages $17,000.(22,23) VADs have been shown to improve quality of life and survival when compared to medical therapies.(5) It is estimated that nearly 250,000 people have advanced heart failure, yet a very low percentage receive a durable VAD.(21) Transplant is not an option for many of them simply because there are not enough donor organs. We should consider durable VAD as an option for more heart failure patients. Although VADs are not usually considered for non-inotropic dependent patients, there is good reason to consider it now since the centrifugal fully magnetic levitation VAD has demonstrated the best survival outcomes thus far.(24,25) Improved outcomes have increased patient stability. Therefore, VAD patients have a lower listing priority on the transplant registry wait list, and wait times for transplant-eligible VAD patients has increased since the 2018 revision of the organ allocation system. Patients are now being placed on temporary MCS to increase their priority on the transplant waiting list.(10) Patients with temporary MCS require hospitalization, increasing length of stay and costs. Alternatives to decrease costs and resource utilization should be encouraged, as healthcare costs continue to rise. Placement of durable, rather than temporary VAD, may improve resource utilization by sending patients home while waiting for an organ. Temporary MCS may prevent other patients from receiving in-patient hospital care. The COVID pandemic that utilized so many hospital beds is not in the distant past, and prudent resource utilization is a significant issue.(26) During the hospitalization for ECMO patients, 82% of costs were related to personnel use, 7% for blood products, 2.5% for lab and radiology, 3% for disposable items, and 1.5% for medication.(27) A 2021 study calculated the average cost per hospital day for an ECMO patient to be almost $12,000 and the average cost totaled greater than $330,000, compared to the average cost of LVAD implantation of $175,000.(24,28) The cost comparison of ECMO and VAD utilization could make it prohibitive for extensive ECMO use when waiting for an organ transplant for an unknown duration. Perhaps an analysis of the Intermacs database can lead to further revision of the organ allocation policy to increase equitability and decrease costs. Possible underutilization of durable VAD not only exists in transplant eligible patients, but also in women and elderly. There is a higher incidence of cardiogenic shock in women. Women also present with more co-morbidities and higher STS mortality scores.(29) The proportion of women with LVAD (19%) was also lower than the proportion of women with advanced heart failure (33.3%).(30) VAD implantation could also be considered in elderly patients, since these patients have the least access to heart transplantation. VAD patients older than 75 years of age have been shown to have good survival outcomes and a decrease in late event complications (>90 days after LVAD implant) making this an optimal option for these patients. VAD DT has been underutilized in the elderly and should be increased.(31) It has also been found that VADs increased survival in high-risk patients by 2.84 life-years when compared to medical management.(24) The 2022 Intermacs Annual report revealed some positive findings regarding improved survival and adverse event rates. VAD implantation has been shown to be a viable additional therapy to heart transplantation for heart failure patients. Durable VAD utilization should be increased in patients who do not have the opportunity of receiving a heart transplant. Perhaps it is time that we re-think our strategy for VAD implantation and consider VAD as an option for more heart failure patients.