The prevalence of heart failure (HF) based on data from the National Health and Nutrition Examination Survey (2013–2016) was 6.2 million Americans of age 20 years or older and it is projected to increase by 30% in the year 2030. The total costs for HF account for 1.5–4% of the health care costs and more than 50% of the cost is spent in hospitalization.1,2 The total costs for HF are projected to increase by 127% to $69.8 billion in 2030.3 The rising costs could be partly a result of increased prevalence of HF. Novel medical and surgical therapeutic strategies for management of HF with reduced ejection fraction (HFrEF) which have been demonstrated to improve survival and quality of life are labeled as cost-additive technological advances but very often lack cost-benefit analyses that will determine the incremental value to our patients and our health care systems after accounting for savings that might include decreasing the rehospitalization rate and the capacity for many of our patients to go back to work. One fundamental question for advanced cardiac disease teams caring for patients with advanced HFrEF is how to responsibly choose medical and surgical treatments in our tool box without adding burden to the health care system while primordially improving health status of patients with HF?
The American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) stages of HFrEF provide information regarding the progression and severity of HF (Figure 1). The functional capacity is gauged using the New York Heart Association (NYHA) functional classification. The ACCF/AHA staging and NYHA functional classification provide the clinician a guide to decision making regarding medical and surgical interventions.2 Patients with stage D or Advanced HF, refractory to medical therapy, are the target population for consideration of mechanical circulatory support (MCS) or heart transplantation (HT) or palliative inotropic therapy. The Interagency Registry for Mechanically Assisted Circulation (INTERMACS) classification stratifies patients with stage D HF into seven levels depending on disease severity and timing of MCS. Approximately 5% (300,000) have stage D HF and are in need for advanced therapies.4 With limited donor organ availability of approximately only 3,000 heart transplants per year, well over 90% of the stage D HF patients will need alternative durable options to improve survival and quality of life and this includes palliative therapeutic options to allow them comfort at the end of their lives.
The initial development and rapid technological advances in left ventricular assist devices (LVAD) with significantly improved survival compared with medical management (MM) over the past 40 years have resulted in increased LVAD implantation in stage D HF patients. More than 18,000 LVAD’s have been implanted from 2006 to 2017 based on the latest report from the Society of Thoracic Surgeon (STS)/INTERMACS.5 The implant volume in the report underestimates the real-world clinical volume because it did not include LVAD in clinical trials and implant centers that are not enrolled in INTERMACS. The 1 and 2 year survival for patients supported with LVADs is 83% and 73%, respectively.5 The 1 and 2 year survival of stage D HF patients on inotropic support is 47.6% and 38.4% in a contemporary cohort.6 Due to increased cost and complexities of care for short-term and long-term success, associated with the use of these devices, stringent criteria are used for patient selection to improve outcomes.
Cost-effectiveness is preferred over cost-benefit analysis in economic assessment of medical treatments because outcome measures like survival and quality of life rather than monetary value are used to assess benefits. The school of thought known as Extra-Welfarist seeks to define the output of health care interventions in terms of the contribution (individually or in sum) to health itself. Quality-adjusted life year (QALY) is a standardized composite measurement of survival and quality of life with medical interventions and assigns a unit for costs to be compared. Incremental cost-effectiveness ratio (ICER) provides the dollar amount per QALY to allow for comparison for interventions for disease management. The American College of Cardiology/AHA in their guideline statement of cost/value methodology recommends three categories for value assessment of medical interventions; high value: ICER <$50,000/QALY gained, intermediate value: $50,000–150,000/QALY gained and low value >$150,000/QALY gained. The thresholds are determined based on the gross domestic product of the nation.7
In this issue of the Journal, Silvestry et al.8 and Mahr et al.9 report the results of cost-effectiveness analyses of implantation of centrifugal pump in two separate studies using clinical trial data from ADVANCE Bridge-to-transplant (BTT) and associated Continued Access Protocol (CAP), ENDURANCE supplemental trial and HVAD LATERAL trial.10–12 The time horizon chosen to calculate cost-effectiveness was patient’s lifetime in both studies.
Silvestry et al.8 report the cost-effectiveness of implantation of centrifugal pump versus MM and subsequent HT for stage D HF patients using Markov modeling. Survival, adverse events, utilities like Euroqol-5D-3L (ADVANCE BTT+CAP), Euroqol-5D-5L (ENDURANCE Supplemental trial), Living on MM were used for model inputs. Costs were calculated using the Medicare sample data for calendar year (CY) 2015–2016. Costs included hospitalizations for adverse events. The authors excluded hospitalization involving biventricular assist devices and subjects with costs exceeding 1.96 times the standard deviation of the mean. The mean total cost of BTT patients with and without LVAD was $514,568 and $222,196, respectively. The total cost of destination therapy (DT) patients with and without LVAD are $404,691 and $93,754. The results of the cost-effectiveness analyses were $69,768/QALY for BTT and $102,587/QALY for DT. Analysis performed with 20% and 25% increase in cost for BTT patients showed an increase in ICER; $79,997/QALY and $82,554/QALY, respectively. For the DT trial, the results for 20% and 25% increase in cost were $114,752/QALY and $117,793/QALY, respectively. The ICER increased when lower transplant rates were used in the model. Using probability sensitivity analysis (PSA), the ICER was $70,018/QALY for BTT and $104,927/QALY for DT. The ICER thresholds for BTT patients remained below $100,000/QALY which is intermediate value based on ACC/AHA value assessments. The higher cost for the DT patients could be prolonged support on the LVAD compared to BTT patients.
Mahr et al.9 report the cost-effectiveness of thoracotomy approach for implantation of centrifugal pump when compared to MM and HT in the BTT population. The survival for the MM group was calculated using the Seattle Heart Failure Model (SHFM). The survival for BTT patients undergoing thoracotomy approach was calculated using LATERAL study data.12 The post-transplantation survival was obtained from the International Society for Heart and Lung Transplantation for the LVAD-supported patients and MM group. Costs were calculated using the Medicare cohort, extracted from Instant Health Data (IHD) for the CY2015–2016. The costs included hospitalizations for LVAD-related adverse events like stroke, pump thrombosis, gastrointestinal bleeding, right ventricular failure (RVF), or driveline infection. Quality of life measures using Euroqol-5D-3L were obtained from LATERAL, ADVANCE BTT+CAP, and ENDURANCE; Euroqol-5D-5L from ENDURANCE Supplemental trial. “Living with LVAD” and “Living on MM” utility were obtained from the LATERAL and ADVANCED BTT+CAP trials, respectively. The mean total cost for LVAD was $551,934 and MM was $334,117. Despite the increased cost, LVAD arm earned more life years (12.31 vs. 8.55) and QALY (9.77 vs. 6.40) compared with MM cohort who proceeded to heart transplant without LVAD. The ICER was $64,632/QALY. Incremental cost-effectiveness ratio analyses using three different scenarios were calculated. First, using hazard ratio (HR) of 0.15 and 0.1 (MM HR 0.23) ICER was $61,336/QALY and $59,527/QALY, respectively. The second scenario was modeled using lower transplant rates (10% and 20%) for patients on LVAD due to disadvantage as a result of the current United Network Organ Sharing (UNOS) allocation system and it generated ICER of $54,856/QALY and $58,545/QALY, respectively. Third, the thoracotomy approach was cost-effective compared to sternotomy approach: lower cost ($551,934 vs. $572,871) and higher QALY’s (9.77 vs. 9.42). The authors argue that thoracotomy approach decreases bleeding complications, RVF, and length of stay that translates into cost-effectiveness.
Remarkably, these two studies not only report significant gains in the cost-effectiveness of using an intrapericardial centrifugal pump as compared with studies using pulsatile and second-generation LVAD (Heartmate II, summarized in Table 1), but appear to arrive at very similar estimates of ICER using two independent study cohorts.13–16 If there was a singular message to take home from these well-performed analyses by Silvestry et al.8 and Mahr et al.9, it is that advancements in the technological application of continuous flow pumps and multidisciplinary team care starting with patient selection and continuing with intraoperative surgical and outpatient MM on LVAD support has resulted in lower cost with gains in survival and quality of life.
Table 1. -
Studies of Cost-Effectiveness of Left Ventricular Assist Devices in the United States
|Study (Device Type)
|Special report (2004) (Pulsatile Devices)
|Rogers et al.14 (HeartMate II)
|Long et al.15
||BTT-waitlist 12 months-$191,400/QALY
|Baras Shreibati et al.*16
|Mahr et al.9 (HeartWare HVAD)
|Silvestry et al.8 (HeartWare HVAD)
*Medicare beneficiaries 2009–2010.
BTT, bridge-to-transplant; DT, destination therapy; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.
Several important limitations in the studies by Silvestry et al.8 and Mahr et al.9 merit mention. First, the MM cohort is not well characterized in both studies. In the Randomized Evaluation of Mechanical Assistance for the treatment of Congestive Heart Failure (REMATCH) study, stage D NYHA class IV Medicare beneficiaries incur significant costs during the last 2 years of life ($156,169) with 50% of the money spent in the final 6 months of life ($78,880.39). The increased cost in the past 6 months was due to increased frequency of hospitalizations for decompensation and intensive care unit costs.17 REMATCH study was performed before device-based therapies like cardiac resynchronization therapy (CRT), implantable cardioverter defibrillators (ICD) and percutaneous mitral valve procedures became widely used. Hence, the total lifetime cost incurred by a patient with HF as disease progresses on MM may be underestimated—if new device technologies were accounted for—or overestimated if the benefits in hospitalization are included. Second, an LVAD patient who proceeds to HT may incur higher costs during their lifetime compared with LVAD-supported DT patients or HT alone which is not addressed in the two studies. The billed charges for an HT encompassing a time period 30 days before transplant to 6 months after discharge including immunosuppressive therapy were $1,664,800 according to 2020 Milliman report on cost estimates for organ transplants. Third, out-of-pocket costs and indirect costs due to loss of work were not factored in for cost-effectiveness analysis in the two studies. This highlights the complexities of interpreting cost-effectiveness of medical and surgical treatments for end-stage systolic HF patients.
Heart failure is a progressive disease with patients incurring real lifetime costs with disease progression (Figure 1). For example “a systolic HF patient in ACCF/AHA stage B will have cost of MM and possible ICD ($34,000–70,200/QALY lifetime/cardiac resynchronization therapy-defibrillator implantation $43,000/QALY for 7 years).”18,19 As the disease progresses to stage C and worsening NYHA functional class, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker may be substituted for angiotensin receptor-neprilysin inhibitor (ICER 45,018/QALY over 30 years).20 Implantable hemodynamic monitoring devices using CardioMEMS may be considered to decrease HF hospitalizations($ICER 44,832/QALY for a 5 year period).21,22 The patient may be considered for percutaneous mitral valve repair due to persistent NYHA class II–IV symptoms on maximal guideline-directed medical therapy and moderate to severe mitral regurgitation (ICER $55,600/QALY-lifetime projection).23 Despite percutaneous mitral valve repair, patient may progress to stage D HF requiring LVAD or HT (7.6% of patients in the Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy study). With change in the UNOS allocation system, end-stage HF patients are bridged with temporary MCS devices before HT which can clearly drive costs from the device, potential adverse events, ICU length of stay, and total hospitalization including rehabilitation. As cost-effectiveness data are analyzed on the outcomes of HT after the new UNOS allocation system took effect in 2018, future studies will shed some light on how this evolving clinical strategy is impacting the incremental value of cardiac replacement therapy.
Despite these limitations, the studies by Silvestry et al.8 and Mahr et al.9, published jointly in this issue of the Journal, provide the most recent and highly relevant data in the field of continuous flow device therapy on the incremental value of long-term MCS in patients with end-stage HF applied either as BTT or DT. In the era of coronavirus disease 2019 (COVID-19) where health care resources are being challenged and stretched to a heretofore unparalleled degree, one could argue that the value to a health care system of avoiding a hospitalization should be weighted higher especially if survival continues to improve with LVAD therapy.
In conclusion, cost-effective analysis for patients with systolic HF is complex. Individual treatments may be cost-effective in terms of QALY’s earned but cumulatively a daunting “total cost” calls for a tailored approach to target implanted resynchronization and pulmonary artery monitoring devices for patients who will be most likely to be “responders.” As medical innovations add tools to the armamentarium for management of systolic HF, a personalized approach to HF management in careful selection of treatment modalities may be cost-effective and translate into reduced total health care costs. Although these are seemingly contradictory statements—new technological advances will drive the likelihood of increased costs yet innovation in the management of advanced HF may ultimately dampen the great individual and societal burden of this disease state, there is nevertheless some rationality here. As Bono appropriately stated, “right in the middle of a contradiction, that is where the action lies.”
1. Miller LW, Guglin M, Rogers J. Cost of ventricular assist devices: Can we afford the progress? Circulation 2013.127: 743–748.
2. Yancy CW, Jessup M, Bozkurt B, et al.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines: 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013.62: e147–e239.
3. Virani SS, Alonso A, Benjamin EJ, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics-2020 update: A report from the American Heart Association. Circulation 2020.141: e139–e596.
4. Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: Patient selection and outcomes. Eur J Heart Fail 2017.19: 595–602.
5. Kormos RL, Cowger J, Pagani FD, et al. The society of thoracic surgeons intermacs database annual report: Evolving indications, outcomes, and scientific partnerships. Ann Thorac Surg 2019.107: 341–353.
6. Hashim T, Sanam K, Revilla-Martinez M, et al. Clinical characteristics and outcomes of intravenous inotropic therapy in Advanced Heart Failure. Circ Heart Fail 2015.8: 880–886.
7. Anderson JL, Heidenreich PA, Barnett PG, et al.; ACC/AHA Task Force on Performance Measures; ACC/AHA Task Force on Practice Guidelines: ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: A report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. Circulation 2014. 129: 2329–2345.
8. Silvestry SC, Mahr C, Slaughter MS. Cost-effectiveness of a small intrapericardial centrifugal LVAD versus medical management and heart transplantation. ASAIO J 2020. e66: 862–870.
9. Mahr C, McGee E Jr, Cheung A, et al. Cost-effectiveness of thoracotomy approach for the implantation of a centrifugal LVAD. ASAIO J 2020.66: 855–861.
10. Milano CA, Rogers JG, Tatooles AJ, et al.; ENDURANCE Investigators: HVAD: The ENDURANCE supplemental trial. JACC Heart Fail 2018.6: 792–802.
11. Slaughter MS, Pagani FD, McGee EC, et al.; HeartWare Bridge to Transplant ADVANCE Trial Investigators: HeartWare ventricular assist system for bridge to transplant: Combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2013.32: 675–683.
12. McGee E Jr, Danter M, Strueber M, et al. Evaluation of a lateral thoracotomy implant approach for a centrifugal-flow left ventricular assist device: The LATERAL clinical trial. J Heart Lung Transplant 2019.38: 344–351.
13. Special report: cost-effectiveness of left-ventricular assist devices as destination therapy for end-stage heart failure. Technol Eval Cent Assess Program Exec Summ 2004.19: 1.
14. Rogers JG, Bostic RR, Tong KB, Adamson R, Russo M, Slaughter MS. Cost-effectiveness analysis of continuous-flow left ventricular assist devices as destination therapy. Circ Heart Fail 2012.5: 10–16.
15. Long EF, Swain GW, Mangi AA. Comparative survival and cost-effectiveness of advanced therapies for end-stage heart failure. Circ Heart Fail 2014.7: 470–478.
16. Baras Shreibati J, Goldhaber-Fiebert JD, Banerjee D, Owens DK, Hlatky MA. Cost-effectiveness of left ventricular assist devices in ambulatory patients with advanced heart failure. JACC Heart Fail 2017.5: 110–119.
17. Russo MJ, Gelijns AC, Stevenson LW, et al.; REMATCH Investigators: The cost of medical management in advanced heart failure during the final two years of life. J Card Fail 2008.14: 651–658.
18. Sanders GD, Bayoumi AM, Sundaram V, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med 2005.352: 570–585.
19. Feldman AM, de Lissovoy G, Bristow MR, et al. Cost effectiveness of cardiac resynchronization therapy in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial. J Am Coll Cardiol 2005.46: 2311–2321.
20. Gaziano TA, Fonarow GC, Claggett B, et al. Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction. JAMA Cardiol 2016.1: 666–672.
21. Givertz MM, Stevenson LW, Costanzo MR, et al.; CHAMPION Trial Investigators: Pulmonary artery pressure-guided management of patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 2017.70: 1875–1886.
22. Schmier JK, Ong KL, Fonarow GC. Cost-effectiveness of remote cardiac monitoring with the cardioMEMS heart failure system. Clin Cardiol 2017.40: 430–436.
23. Baron SJ, Wang K, Arnold SV, et al.; COAPT Investigators: Cost-effectiveness of transcatheter mitral valve repair versus medical therapy in patients with heart failure and secondary mitral regurgitation: Results from the COAPT trial. Circulation 2019.140: 1881–1891.