Prevalence, mortality, cost, and disparities in transcatheter mitral valve repair and replacement in cancer patients: Artificial intelligence and propensity score national 5-year analysis of 7495 procedures.

INTRODUCTION: We conducted the first comprehensive evaluation of the therapeutic value and safety profile of transcatheter mitral edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR) in individuals concurrently afflicted with cancer. METHODS: Utilizing the National Inpatient Sample (NIS) dataset, we analyzed all adult hospitalizations between 2016 and 2020 (n = 148,755,036). The inclusion criteria for this retrospectively analyzed prospective cohort study were all adult hospitalizations (age 18 years and older). Regression and machine learning analyses in addition to model optimization were conducted using ML-PSr (Machine Learning-augmented Propensity Score adjusted multivariable regression) and BAyesian Machine learning-augmented Propensity Score (BAM-PS) multivariable regression. RESULTS: Of all adult hospitalizations, there were 5790 (0.004%) TMVRs and 1705 (0.001%) TEERs. Of the total TMVRs, 160 (2.76%) were done in active cancer. Of the total TEERs, 30 (1.76%) were done in active cancer. After the comparable rates of TEER/TMVR in active cancer in 2016, the prevalence of TEER/TMVR was significantly less in active cancer from 2017 to 2020 (2.61% versus 7.28% p < 0.001). From 2017 to 2020, active cancer significantly decreased the odds of receiving TEER or TMVR (OR 0.28, 95%CI 0.13-0.68, p = 0.008). In patients with active cancer who underwent TMVR/TEER, there were no significant differences in socio-economic disparities, mortality or total hospitalization costs. CONCLUSION: The presence of malignancy does not contribute to increased mortality, length of stay or procedural costs in TMVR or TEER. Whereas the prevalence of TMVR has increased in patients with active cancer, the utilization of TEER in the context of active cancer is declining despite a growing patient population.

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

AIMS: The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. METHODS AND RESULTS: A two-stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5 year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. CONCLUSIONS: MitraClip + guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Economic Analysis and Long-term Follow-up of Distant Referral for Degenerative Mitral Valve Repair.

BACKGROUND: Despite the superiority of mitral valve repair (MVr) over replacement for degenerative disease, repair rates vary widely across centers. Traveling to a mitral reference center (MRC) is 1 way to increase the odds of MVr. This study assessed the economic value (quality/cost) and long-term outcomes of distant referral to an MRC. METHODS: Among 746 mitral surgery patients between January 2011 and June 2013, low-risk patients with an ejection fraction greater than 40% undergoing isolated degenerative MVr were identified and included 26 out-of-state (DISTANT) and 104 in-state patients (LOCAL). Short- and long-term outcomes and institutional financial data (including travel expenses) were used to compare groups. National average and MRC-specific MVr rates, clinical outcomes, and marginal value of quality-adjusted life-years collected from The Society of Thoracic Surgeons database and Medicare estimates were used to perform a nationally representative cost-benefit analysis for distant referral. RESULTS: Age, ejection fraction, operative time, blood transfusions, and annuloplasty ring size did not differ between groups. Median charges were $76,022 for LOCAL and $74,171 for DISTANT (P = .35), whereas median payments (including travel expenses) were $57,795 for LOCAL and $58,477 for DISTANT (P = .70). Short- and long-term outcomes were similar between groups and median follow-up was 7.1 years. Estimated 5-year survival was 97% (96% for LOCAL and 100% for DISTANT; P = .24). Cost-benefit analysis showed a net benefit through distant referral to an MRC ranging from $436 to $6078 to the payer and $22,163 to $30,067 to the patient, combining for an estimated $22,599 to $32,528 societal benefit. CONCLUSIONS: These data suggest that distant referral to an MRC is achievable and reasonable.

Conflicting findings between the Mitra-Fr and the Coapt trials: Implications regarding the cost-effectiveness of percutaneous repair for heart failure patients with severe secondary mitral regurgitation.

PURPOSE: Two randomized controlled trials (RCTs), Mitra-Fr and Coapt, evaluating the benefit of percutaneous repair (PR) for heart failure (HF) patients with severe mitral regurgitation, have led to conflicting results. We aimed to evaluate the impact of these trial results on the cost-effectiveness of PR using effectiveness inputs from the two RCTs. METHODS: We developed a time varying Markov type model with three mutually exclusive health states: alive without HF hospitalisation, alive with HF hospitalisation, and dead. Clinically plausible extrapolations beyond observed data were obtained by developing parametric modelling for overall survival and HF hospitalisations using published data from each trial. We adopted the perspective of the French Health System and used a 30-year time horizon. Results were expressed as € / quality-adjusted life year (QALY) gained using utility inputs from literature. FINDINGS: Results are presented using treatment efficacy measures from Mitra-F and Coapt trials respectively. With the Mitra-Fr data, after annual discounting, the base case model generated an incremental 0.00387 QALY at a cost of €25,010, yielding an incremental cost effectiveness ratio (ICER) of €6,467,032 / QALY. The model was sensitive to changes made to model inputs. There was no potential of PR being cost-effective. With the Coapt data, the model generated 1.19 QALY gain at a cost of €26,130 yielding an ICER of €21,918 / QALY and at a threshold of >€50,000/QALY PR had a probability of 1 of being cost-effective. IMPLICATIONS: Cost effectiveness results were conflicting; reconciling differences between trials is a priority and could promote optimal cost effectiveness analyses and resource allocation.

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

Cost-effectiveness of coronary artery bypass grafting plus mitral valve repair versus coronary artery bypass grafting alone for moderate ischemic mitral regurgitation.

OBJECTIVE: The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. METHODS: We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. RESULTS: In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. CONCLUSIONS: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Pre- Versus Post-Procedure Health Care Resource Utilization in Patients Undergoing Commercial Transcatheter Mitral Valve Repair.

OBJECTIVES: The aim of this study was to assess the real-world impact of transcatheter mitral valve repair (TMVR) on hospitalizations and Medicare costs pre- versus post-TMVR. BACKGROUND: TMVR is effective in degenerative mitral regurgitation (MR) and appropriately selected patients with functional MR with high surgical risk. METHODS: Patients undergoing TMVR in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry from 2013 to 2018 were linked to Medicare claims data. Rates of hospitalizations, hospitalized days, and Medicare costs were compared 1-year pre-TMVR to 1-year post-TMVR. RESULTS: Across 246 sites, 4,970 patients with a median age of 83 years (interquartile range: 77 to 87 years) were analyzed. The TMVR indication was degenerative MR in 77.5% and functional MR in 16.7%. From pre- to post-TMVR, heart failure (HF) hospitalization rates (479 vs. 370 hospitalizations/1,000 person-years; rate ratio [RR]: 0.77) and cardiovascular hospitalizations (838 vs. 632; RR: 0.75) decreased significantly (p < 0.001 for all). Similarly, the rates of hospitalized days decreased for HF and cardiovascular causes (p < 0.05 for all). Following TMVR, the odds of having no Medicare costs for HF hospitalizations increased (69% vs. 79%; odds ratio: 1.67; p < 0.001). However, the average total Medicare costs per day alive among patients with any HF hospitalizations after TMVR increased significantly (p < 0.001). The HF hospitalization rates decreased for patients with functional MR (683 vs. 502; RR: 0.74) and those with degenerative MR (431 vs. 337; RR: 0.78) (p < 0.001). CONCLUSIONS: TMVR is associated with a decrease in cardiovascular and HF hospitalizations and a greater likelihood of having no HF Medicare costs in the year after TMVR, regardless of MR etiology. Further work is necessary to elucidate the reasons for increased costs among patients with HF hospitalizations post-TMVR.

Twelve-month healthcare utilization and expenditures in Medicare fee-for-service patients with clinically significant mitral regurgitation.

Aim: This study sought to quantify the healthcare burden of Medicare patients with clinically significant mitral regurgitation (sMR). Materials & methods: Proxy definitions were used for sMR, including MR surgery, atrial fibrillation, pulmonary hypertension or >2 echocardiograms. Results: In this study, 11,173 patients had significant degenerative MR (sDMR); 25,402 had significant functional MR (sFMR); and 12,232 had significant uncharacterized MR (sUMR). Patients with sFMR (18,880) were more likely to be hospitalized and present to the emergency department compared with patients with sDMR (9,795) or sUMR (10,587). Annual healthcare expenditures for sMR patients were: US$29,328 for sFMR; US$17,112 for sUMR; and US$12,870 for sDMR. Conclusion: Novel therapeutic interventions merit further evaluation to reduce the substantial healthcare burden of sMR in the Medicare population.

Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial.

BACKGROUND: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. METHODS: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. RESULTS: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained. CONCLUSIONS: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.

Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Robotic mitral valve operations by experienced surgeons are cost-neutral and durable at 1 year.

BACKGROUND: Robotic mitral valve surgery has potential advantages in patient satisfaction and 30-day outcome. Cost concerns and repair durability limit wider adoption of robotic technology. This study examined detailed cost differences between robotic and sternotomy techniques in relation to outcomes and durability following robotic mitral program initiation. METHODS: Between April 2013 and October 2015, 30-day and 1-year outcomes of 328 consecutive patients undergoing robotic or sternotomy mitral valve repair or replacement by experienced surgeons were examined. Multivariable logistic regression informed propensity matching to derive a cohort of 182 patients. Echocardiographic follow-up was completed at 1 year in all robotic patients. Detailed activity-based cost accounting was applied to include direct, semidirect, and indirect costs with special respect to robotic depreciation, maintenance, and supplies. A quantitative analysis of all hospital costs was applied directly to each patient encounter for comparative financial analyses. RESULTS: Mean predicted risk of mortality was similar in both the robotic (n = 91) and sternotomy (n = 91) groups (0.9% vs 0.8%; P > .431). The total costs of robotic mitral operations were similar to those of sternotomy ($27,662 vs $28,241; P = .273). Early direct costs were higher in the robotic group. There was a marked increase in late indirect cost with the sternotomy cohort related to increased length of stay, transfusion requirements, and readmission rates. Robotic repair technique was associated with no echocardiographic recurrence greater than trace to only mild regurgitation at 1 year. CONCLUSIONS: Experienced mitral surgeons can initiate a robotic program in a cost-neutral manner that maintains clinical outcome integrity as well as repair durability.

Cost-Effectiveness of Mitral Valve Repair Versus Replacement for Severe Ischemic Mitral Regurgitation: A Randomized Clinical Trial From the Cardiothoracic Surgical Trials Network

BACKGROUND: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed. METHODS AND RESULTS: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −7784­21 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 253­17 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve. CONCLUSIONS: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040.

Cardiovascular events and hospital resource utilization pre- and post-transcatheter mitral valve repair in high-surgical risk patients.

MitraClip is an approved therapy for mitral regurgitation (MR); however, health care resource utilization pre- and post-MitraClip remains understudied. METHODS: Patients with functional and degenerative MR at high surgical risk in the EVEREST II High-Risk Registry and REALISM Continued-Access Study were linked to Medicare data. Pre- and post-MitraClip all-cause death, stroke, myocardial infarction, heart failure (HF), and bleeding hospitalizations were identified. Inpatient costs, adjusted to 2010 US dollars, were calculated, and event rate ratios and cost ratios were estimated with multivariable modeling. RESULTS: Among 403 linked patients, the mean age was 80 years, 60% were male, mean baseline left ventricular ejection fraction was 49.6%, 83.3% were New York Heart Association class III/IV, 78.2% were MR grade 3+/4+, and 63.3% had functional MR. All-cause hospitalization decreased from 1,854 to 1,435/1,000 person-years (P<.001). HF hospitalization decreased following MitraClip (749 vs 332/1000 person-years, P<.001), but bleeding increased (199 vs 298/1000 person-years, P<.001). Changes in stroke and myocardial infarction were not statistically significant. Overall mean Medicare costs per patient were similar pre- and post-MitraClip, although there was a significant decrease in mean costs among those that survived a full year after MitraClip ($18,131 [SD $25,130] vs $11,679 [SD $22,486], P=.02). CONCLUSIONS: MitraClip was associated with a reduced rate of all-cause and HF hospitalizations and an increased rate of bleeding hospitalizations. One-year Medicare costs were reduced in those who survived a full year after the MitraClip procedure. Payors and providers seeking to reduce HF hospitalizations and associated Medicare costs may consider MitraClip among appropriate patients likely to survive 1 year.

What type of clinical evidence is needed to assess medical devices?

The objective of this mini-review is to discuss the role of real-world studies as a source of clinical evidence when experimental studies, such as randomised controlled trials (RCTs), are not available. Waiting for RCT evidence when the technology is diffusing could be anti-economical, inefficient from the policy perspective and methodologically questionable.We explain how real-world studies could provide relevant evidence to decision makers. Matching techniques are discussed as a viable solution for bias reduction.We describe a case study concerning a cost-effectiveness analysis based on real-world data of a technology already in use: Mitraclip combined with medical therapy versus medical therapy alone in patients with moderate-to-severe mitral regurgitation. The CEA has encountered the scepticism of most reviewers, due not to the statistical methodology but to the fact that the study was observational and not experimental. Editors and reviewers converged in considering real-world economic evaluations premature in the absence of a RCT, even if in the meantime the technology had been implanted >30 000 times. We believe there is a need to acknowledge the importance of real-world studies, and engage the scientific community in the promotion and use of clinical evidence produced through observational studies.

Real-world cost effectiveness of MitraClip combined with Medical Therapy Versus Medical therapy alone in patients with moderate or severe mitral regurgitation.

BACKGROUND: We evaluated the real-world cost-effectiveness of the MitraClip system (Abbott Vascular Inc., Menlo Park, CA) plus medical therapy for patients with moderate/severe mitral regurgitation, as compared with medical therapy (MT) alone. METHODS: Clinical records of patients with moderate to severe functional mitral regurgitation treated with MitraClip (N=232) or with MT (N=151) were collected and outcome analyzed with propensity score adjustment to reduce selection bias. Twelve-month outcomes were modeled over a lifetime horizon to conduct a cost-effectiveness analysis, in the payer's perspective. Costs and benefits were discounted at an annual rate of 3.5%. RESULTS: After propensity score adjustment, the average treatment effect was -9.5% probability of dying at 12months and, following lifetime modeling, 3.35±0.75 incremental life years and 3.01±0.57 incremental quality-adjusted life years. MitraClip contributed to a higher decrease in re-hospitalizations at 12months (difference=-0.54±0.08) and generated a more likely improvement in the New York Heart Association (NYHA) class at 12months versus NYHA at enrollment. Incremental costs, adapted to five possible scenarios, ranged from 14,493 to 29,795 € contributing to an incremental cost-effectiveness ratio ranging from 4796 to 7908 €. CONCLUSIONS: Compared to MT alone and given conventional threshold values, MitraClip can be considered a cost-effective procedure. The cost-effectiveness of MitraClip is in line or superior to the one of other non-pharmaceutical strategies for heart failure.

MitraClip therapy in mitral regurgitation: a Markov model for the cost-effectiveness of a new therapeutic option.

Introduction Mitral regurgitation is a heart condition resulting from blood flowing from the left ventricle towards the left atrium, increasing the risk of heart failure and mortality. While surgery can greatly reduce these risks, some patients are not eligible, resulting in medication being their only therapeutic alternative. The MitraClip (Abbot Vascular) is a medical device that is percutaneously implanted and designed to eliminate leaking of the mitral valve. Methods The efficacy of the MitraClip strategy vs medical management was assessed using a 4-state Markov model based on the mitral regurgitation grade (mitral regurgitation grade 0, I/II, and III/IV, and death). At each 1-month cycle, patients were or were not hospitalized. The model analyzed a fictional population of 1000 patients over a 5-year period from a national Health Insurance perspective. The primary end-point was the number of deaths avoided. Data from the EVEREST II High Risk Study patients were used along with a literature review. Results At 5 years, among the 1000 patients, 276 deaths were found to be avoidable with the MitraClip strategy. The incremental cost-effectiveness ratio (ICER) was €93,363 per death avoided. The annual ICER was calculated to take into consideration excess costs resulting from the MitraClip over the first year (€29,984 vs €8557 for the reference strategy) and the reduction of costs in following years (€3122 for MitraClip vs €8557 for reference strategy). Thus, the mean ICER was calculated to be €20,720 per death avoided. Conclusion The MitraClip is a novel alternative therapy for mitral insufficiency in patients ineligible for surgery that may offer a medico-economic advantage.

Mitral Valve Clip for Treatment of Mitral Regurgitation: An Evidence-Based Analysis.

BACKGROUND: Many of the 500,000 North American patients with chronic mitral regurgitation may be poor candidates for mitral valve surgery. OBJECTIVE: The objective of this study was to investigate the comparative effectiveness, harms, and cost-effectiveness of percutaneous mitral valve repair using mitral valve clips in candidates at prohibitive risk for surgery. DATA SOURCES: We searched articles in MEDLINE, Embase, and the Cochrane Library published from 1994 to February 2014 for evidence of effectiveness and harms; for economic literature we also searched NHS EED and Tufts CEA registry. Grey literature was also searched. REVIEW METHODS: Primary studies were sought from existing systematic reviews that had employed reliable search and screening methods. Newer studies were sought by searching the period subsequent to the last search date of the review. Two reviewers screened records and assessed study validity. We used the Cochrane risk of bias tool for randomized, generic assessment for non-randomized studies, and the Phillips checklist for economic studies. RESULTS: Ten studies including 1 randomized trial were included. The majority of the direct comparative evidence compared the mitral valve clip repair with surgery in patients not particularly at prohibitive surgical risk. Irrespective of degenerative or functional chronic mitral regurgitation etiology, evidence of effectiveness and harms is inconclusive and of very low quality. Very-low-quality evidence indicates that percutaneous mitral valve clip repair may provide a survival advantage, at least during the first 1 to 2 years, particularly in medically managed chronic functional mitral regurgitation. Because of limitations in the design of studies, the cost-effectiveness of mitral valve clips in patients at prohibitive risk for surgery also could not be established. LIMITATIONS: Because of serious concerns of risk of bias, indirectness, and imprecision, evidence is of very low quality. CONCLUSIONS: No meaningful conclusions can be drawn about the comparative effectiveness, harms, and cost-effectiveness of mitral valve clips in the population with chronic mitral regurgitation who are at prohibitive risk for surgery.

Economic burden of functional and organic mitral valve regurgitation.

BACKGROUND: Very little is known about the costs of mitral regurgitation (MR) in Europe. AIM: To evaluate the cost of MR from a French National Payer perspective, based on annual costs of surgical and non-surgical patients. METHODS: A 12-month retrospective population-based analysis of patient demographics, outcomes and acute hospital and post-discharge resource utilizations, extracted from the 2009 French Medical Information System. RESULTS: A total of 19,868 patients with MR were identified. Surgical group (n=4099): index hospitalization length of stay (LOS), 17±14.7 days; patients discharged to rehabilitation, 72% (LOS 23±16 days); 12-month rehospitalization rate, 25%; total cost per surgical patient, €24,871±13,940 (ranging from €21,970±11,787 for mitral valve repair [n=2567, 62.6%] to €29,732±15,796 for mitral valve replacement). Non-surgical group (n=15,769): number of hospitalizations over 12 months, 3.1±1.5 (LOS 23.5±20.4 days); admitted to rehabilitation, 24% (LOS 38.8±37.6 days); total cost per patient, €12,177±10,913 (varying between €9957±9080 and €13,538±11,692 for those without and with heart failure [HF], respectively). The total observed cost for 19,868 MR patients over 12 months was €292.8 million: surgical group, €100.8 million; medical group €192.0 million. Patients with MR and HF who were managed medically consumed 45% (€132.3 million) of the overall annual cost of MR. CONCLUSION: The costs of care associated with MR are highly heterogeneous. There are significant differences in costs and resources used between the surgical and medical MR subgroups, with further differences depending on type of surgery and presence of HF.

Hospital-based health technology assessment on the use of mitral clips in the treatment of mitral regurgitation.

BACKGROUND: This study, carried out at the Florence Teaching Hospital Careggi (AOUC), reports the technological evaluation, through the use of Health Technology Assessment (HTA), on the application of mitral clips in the treatment of mitral insufficiency. OBJECTIVE: The assessment, carried out by analyzing the clinical, technological, social, procedural, safety and economic elements, sought to answer the following research questions: Evaluation of the general technological status of the mitral clips in the treatment process of mitral regurgitation, with particular reference to traditional methods; and contextualisation of the analyses within the hospital structure, by identifying criticality issues and improvements. METHODS: The methodology was based on the following steps: technological description; areas of evaluation and the selection of Key Performance Indicators; research of scientific facts and the collection of expert opinions; evaluation and reporting of findings. RESULTS: The results are based on an analysis which included a total of 50 indicators, effectively evaluating 86.5% of them, from the least from the clinical sector (80%) to the most in the areas of procedure, safety and social (100%). Traditional surgery (repair or valve replacement) still represents the gold standard for the treatment of mitral regurgitation due to its maturity both on a technological and clinical level. The minimally invasive procedures which use the mitral clips present interesting opportunities both on a social level (minimum stay in hospital and no post-operative rehabilitation) and clinical level, especially as an alternative to medication, even if they are still at an emergent level (the long-term results are unknown) and complex to use. From the clinical point of view they show some interesting findings related to immediate and post-operative mortality (none during the operation and a minor and equal amount 30 days and 12 months later in comparison to traditional methods) whilst economically, despite the fact that the cost of the device is greater than those used in traditional interventions, the cost-refund relationship does not show significant differences compared to the traditional types of treatment. CONCLUSION: The HTA evaluation of minimally invasive technologies that use clips for the treatment of mitral regurgitation shows, in the hospital setting, very interesting results, particularly for inoperable patients, where the clinical and social improvements are significant compared to pharmacological treatments, whilst for 'operable' patients, the traditional techniques are still the most appropriate.