Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery: Design and Rationale of the REPAIR MR Trial.

Background The current standard of care for the treatment of patients with primary mitral regurgitation (MR) is surgical mitral valve repair. Transcatheter edge-to-edge repair with the MitraClip device provides a less invasive treatment option for patients with both primary and secondary MR. Worldwide, >150 000 patients have been treated with the MitraClip device. However, in the United States, MitraClip is approved for use only in primary patients with MR who are at high or prohibitive risk for mitral valve surgery. The REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery) trial is designed to compare early and late outcomes associated with transcatheter edge-to-edge repair with the MitraClip and surgical repair of primary MR in older or moderate surgical risk patients. Methods and Results The REPAIR MR trial is a prospective, randomized, parallel-controlled, open-label multicenter, noninferiority trial for the treatment of severe primary MR (verified by an independent echocardiographic core laboratory). Patients with severe MR and indications for surgery because of symptoms (New York Heart Association class II-IV), or without symptoms with left ventricular ejection fraction ≤60%, pulmonary artery systolic pressure >50 mm Hg, or left ventricular end-systolic diameter ≥40 mm are eligible for the trial provided they meet the moderate surgical risk criteria as follows: (1) ≥75 years of age, or (2) if <75 years of age, then the subject has a Society of Thoracic Surgeons Predicted Risk Of Mortality score of ≥2% for mitral repair (or Society of Thoracic Surgeons replacement score of ≥4%), or the presence of a comorbidity that may introduce a surgery-specific risk. The local surgeon must determine that the mitral valve can be surgically repaired. Additionally, an independent eligibility committee will confirm that the MR can be reduced to mild or less with both the MitraClip and surgical mitral valve repair with a high degree of certainty. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive the MitraClip device or to undergo surgical mitral valve repair (control group). There are 2 co-primary end points for the trial, both of which will be evaluated at 2 years. Each subject will be followed for 10 years after enrollment. The study has received approval from both the Food and Drug Administration and the Centers for Medicare and Medicaid Services, and enrolled its first subject in July 2020. Conclusions The REPAIR MR trial will determine the safety and effectiveness of transcatheter edge-to-edge repair with the MitraClip in patients with primary MR who are at moderate surgical risk and are candidates for surgical MV repair. The trial will generate contemporary comparative clinical evidence for the MitraClip device and surgical MV repair. Registration https://clinicaltrials.gov/ct2/show/NCT04198870; NCT04198870.

Economics of Minimalist Transcatheter Aortic Valve Replacement: Results From the 3M-TAVR Economic Study.

BACKGROUND: The 3M-TAVR trial (3M-Transcatheter Aortic Valve Replacement) demonstrated the feasibility and safety of next-day hospital discharge after transfemoral TAVR with implementation of a minimalist pathway. However, the economic impact of this approach is unknown. Therefore, we evaluated costs for patients undergoing minimalist TAVR compared with conventional TAVR. METHODS: We used propensity matching to compare resource utilization and costs (from a US health care system perspective) for patients in the 3M-TAVR trial with those for transfemoral TAVR patients enrolled in the contemporaneous S3i trial (PARTNER SAPIEN-3 Intermediate Risk). Procedural costs were estimated using measured resource utilization for both groups. For the S3i group, all other costs through 30-day follow-up were assessed by linkage with Medicare claims; for 3M, these costs were assessed using regression models derived from S3i cost and resource utilization data. RESULTS: After 1:1 propensity matching, 351 pairs were included in our study (mean age 82, mean Society of Thoracic Surgery risk score 5.3%). There were no differences in death, stroke, or rehospitalization between the 3M-TAVR and S3i groups through 30-day follow-up. Index hospitalization costs were $10 843/patient lower in the 3M-TAVR cohort, driven by reductions in procedure duration, anesthesia costs, and length of stay. Between discharge and 30 days, costs were similar for the 2 groups such that cumulative 30-day costs were $11 305/patient lower in the 3M-TAVR cohort compared with the S3i cohort ($49 425 versus $60 729, 95% CI for difference $9378 to $13 138; P<0.001). CONCLUSIONS: Compared with conventional transfemoral TAVR, use of a minimalist pathway in intermediate-risk patients was associated with similar clinical outcomes and substantial in-hospital cost savings, which were sustained through 30 days. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02287662.

One-Year Costs Associated with Hospitalizations Due to Aortic Stenosis in Canada.

BACKGROUND: There is a lack of data on the burden of patients hospitalized with aortic stenosis (AS) in Canada. The primary study objective was to document the index and 1-year costs of hospitalized patients with AS in Canada. Secondary objectives were to explore results by treatment modality and Canadian provinces. METHODS: Hospitalized patients with a most responsible diagnosis (MRD) of AS during fiscal year 2014/2015 were identified using Canadian administrative databases. Costs were calculated for the index admission and for up to 1 year. For our secondary analyses, patients were classified according to the intervention received: surgical aortic valve replacement (SAVR), SAVR with coronary artery bypass graft, or transfemoral or transapical transcatheter aortic valve implantation. Hospitalized AS patients who did not undergo SAVR or transcatheter aortic valve implantation were classified as the untreated group. The data were also analyzed by Canadian provinces. RESULTS: During fiscal year 2014/15, a total of 7217 Canadians were hospitalized with an MRD of AS. The mean (standard deviation) age of our population was 74.2 (11.5) years, and 39% were female. The 1-year hospital costs associated with an MRD of AS in Canada were calculated at $393 million. Our secondary analyses suggest that patient demographics (mean age ranging from 69 to 82 years) and outcomes (median length of stay ranging from 6 to 12 days) differ among treatment modalities and Canadian provinces. CONCLUSIONS: AS hospitalizations result in a significant cost burden in Canada. Future research is needed to better understand variation among treatment modalities and Canadian provinces.

CONTEXTE: Les données sur le fardeau associé aux hospitalisations pour sténose aortique (SA) au Canada sont fragmentaires. L'étude avait pour principal objectif de déterminer le coût de référence et le coût d'une année d'hospitalisations pour SA au Canada. Les objectifs secondaires consistaient à étudier les résultats selon les modalités thérapeutiques ainsi que par province canadienne. MÉTHODOLOGIE: Les patients hospitalisés pour un diagnostic principal de SA pendant l'exercice financier 2014-2015 ont été répertoriés à partir de bases de données administratives canadiennes. Les coûts ont été calculés pour l'admission de référence et pour une période maximale d'un an. Pour nos analyses secondaires, les patients ont été classés selon l'intervention reçue : chirurgie de remplacement valvulaire aortique, chirurgie de remplacement valvulaire aortique avec pontage aortocoronarien, ou implantation valulaire aortique par chathéter par voie transfémorale ou transapicale. Les patients hospitalisés pour SA n'ayant subi aucune chirurgie de remplacement valvulaire aortique ni aucune implantation valvulaire aortique par cathéter ont été classés non traités. RÉSULTATS: Pendant l'exercice financier 2014-2015, un total de 7 217 Canadiens ont été hospitalisés pour un diagnostic principal de SA. L'âge moyen (écart-type) de notre population était de 74,2 (11,5) ans; 39 % étaient des femmes. Les coûts des hospitalisations pour SA comme diagnostic principal pour une année au Canada ont été calculés à 393 millions de dollars. Nos analyses secondaires laissent croire que les données démographiques des patients (âge moyen variant de 69 à 82 ans) et les issues (durée médiane des séjours variant de 6 à 12 jours) diffèrent selon les modalités thérapeutiques et les provinces canadiennes. CONCLUSIONS: Les hospitalisations pour SA constituent un important fardeau financier au Canada. D'autres recherches sont nécessaires pour mieux comprendre les variations en fonction des modalités thérapeutiques et des provinces canadiennes.

Inequity in Access to Transcatheter Aortic Valve Replacement: A Pan-Canadian Evaluation of Wait-Times.

BACKGROUND: There has been an exponential increase in the demand for transcatheter aortic valve replacement (TAVR). Our goal was to examine trends in TAVR capacity and wait-times across Canada. METHODS: All TAVR cases were identified from April 1, 2014, to March 31, 2017. Wait-time was defined as the duration in days from the initial referral to the TAVR procedure. TAVR capacity was defined as the number of TAVR procedures per million population/province/fiscal year. We performed multivariable multilevel Cox proportional hazards modelling of the time to TAVR as the dependant variable and the effect of provinces as random effects. We quantified the variation in wait-times among provinces using the median hazard ratio. RESULTS: We identified a total of 4906 TAVR procedures across 9 provinces. Despite a year over year increase in overall capacity, there was a greater than 3-fold difference in capacity between provinces. Crude median wait-times increased over time in all provinces, with marked variation from 71.5 days in Newfoundland to 190.5 and 203 days in Manitoba and Alberta, respectively. This suggests increasing demand outpaced the growth in capacity. We found a median hazard ratio of 1.62, indicating that in half of the possible pairwise comparisons, the time to TAVR for identical patients was at least 62% longer between different provinces. CONCLUSION: We found substantial geographic inequity in TAVR access. This calls for policy makers, clinicians, and administrators across Canada to address this inequity through revaluation of provincial funding mechanisms, as well as implementation of efficient care pathways.

Precautions and Procedures for Coronary and Structural Cardiac Interventions During the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology.

The globe is currently in the midst of a COVID-19 pandemic, resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology- Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the cardiac catheterization laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients and staff and maintaining the overall health care resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. Although some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.

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.

Sex-Specific Determinants of Outcomes After Transcatheter Aortic Valve Replacement.

Background Women account for a large proportion of patients treated with transcatheter aortic valve replacement, yet there remain conflicting reports about the effect of sex on outcomes. Moreover, the sex-specific prevalence and prognostic impact of frailty has not been systematically studied in the context of transcatheter aortic valve replacement. Methods and Results A preplanned analysis of the FRAILTY-AVR study (Frailty Aortic Valve Replacement) was performed to analyze the determinants of outcomes in older women and men undergoing transcatheter aortic valve replacement. FRAILTY-AVR was a multinational, prospective, observational cohort assembled at 14 institutions in North America and Europe from 2012 to 2017. Multivariable logistic regression models were stratified by sex and adjusted for covariates. Interaction between sex and each of these covariates was assessed. The primary outcome was 12-month mortality, and the secondary outcome was 1-month composite mortality or major morbidity. The cohort consisted of 340 women and 419 men. Women were older and had higher predicted risk of mortality. Women were more likely to have physical frailty traits, but not cognitive or psychosocial frailty traits, and global indices of frailty were similarly associated with adverse events regardless of sex. Women were more likely to require discharge to a rehabilitation facility, particularly those with physical frailty at baseline, although their functional status was similar to men at 12 months. The risk of 1-month mortality or major morbidity was greater in women, particularly those treated with larger prostheses. The risk of 12-month mortality was not greater in women, with the exception of those with pulmonary hypertension, in whom, there was a significant interaction for increased mortality. Conclusions The present study highlights sex-specific differences in older adults undergoing transcatheter aortic valve replacement and draws attention to the impact of physical frailty in women and their potential risk associated with oversized prostheses and pulmonary hypertension.

Profiling Hospital Performance Based on Mortality After Transcatheter Aortic Valve Replacement in Ontario, Canada.

BACKGROUND: Public reporting of hospital-level outcomes is increasingly common as a means to target quality improvement strategies to ensure the delivery of optimal care. Despite the rapid dissemination of transcatheter aortic valve replacement (TAVR), there is a paucity of reliable case-mix adjustment models for hospital profiling in TAVR. Our objective was to develop and evaluate different models for calculating risk-standardized all-cause mortality rates (RSMRs) post-TAVR. METHODS AND RESULTS: In this population-based study in Ontario, Canada, we identified all patients who underwent a TAVR procedure between April 1, 2012, and March 31, 2016. For each hospital, we calculated 30-day and 1-year RSMR, using 2-level hierarchical logistic regression models that accounted for patient-specific demographic and clinical characteristics, as well as the clustering of patients within the same hospital using a hospital-specific random effects. We classified each hospital into one of 3 groups: performing worse than expected, better than expected, or performing as expected, based on whether the 95% CI of the RSMR was above, below, or included the provincial average mortality rate, respectively. Our cohort consisted of 2129 TAVR procedures performed at 10 hospitals. The observed mortality was 7.0% at 30 days and 16.4% at 1 year, with a range of 4% to 10% and 8% to 22%, respectively, across hospitals. We developed case-mix adjustment models using 28 clinically relevant variables. Using 30-day and 1-year RSMR to profile each hospital, we found that all hospitals performed as expected, with 95% CI that included the provincial average. CONCLUSIONS: We found no significant interhospital variation in RSMR among hospitals, suggesting that quality improvement efforts should be directed at aspects other than the variation in observed mortality.

Cost consequence analysis of use of a balloon expandable vascular access system and standard vascular sheath for transcatheter aortic valve implantation.

BACKGROUND: Vascular complications are an important complication of transcatheter aortic valve implantation and are associated with increased morbidity and mortality as well as cost. The Solopath device is an expandable vascular access system that has previously been shown to be associated with lower rates of vascular complications. This study sought to evaluate the impact of the use of this system on vascular complications and costs in a decision model analysis. METHODS: A cost-consequence analysis was undertaken utilizing event rate data from the PARTNER trials and a published retrospective analysis of the Solopath device. The decision model estimated costs and benefits in a hypothetical cohort of patients with aortic stenosis undergoing TAVI using either a standard sheath or Solopath. The modeled analysis compared the occurrence of vascular complications and mortality at 30 days and 1 year using TreeAge Pro. RESULTS: The decision model demonstrated that use of the Solopath sheath resulted in 36 fewer major vascular complications, three fewer deaths at 30 days, and five fewer deaths at 1 year, resulting in a discounted cost savings of $846 CDN. Results were sensitive to decreasing rates of vascular complications with newer generation devices, however maintained modest cost-savings. CONCLUSIONS: Reduction in vascular complications is an important part of improving care for TAVI patients. The Solopath vascular access device offers an alternative to standard sheaths with a potential reduction in complications and cost-savings.

Clinical outcomes and economic impact of transcatheter mitral leaflet repair in heart failure patients.

BACKGROUND: Mitral regurgitation (MR) is a common valvular heart disorder requiring intervention once it becomes severe. Transcatheter mitral repair with the MitraClip device is a safe and effective therapy for selected patients denied surgery. The authors sought to evaluate the clinical outcomes and economic impact of this therapy compared to medical management in heart-failure patients with symptomatic mitral regurgitation. METHODS AND RESULTS: The study was comprised of two phases; an observational study of patients with heart failure and mitral regurgitation treated with either medical therapy or the MitraClip, and an economic model. Results of the observational study were used to estimate parameters for the decision model, which estimated costs, and benefits in a hypothetical cohort of patients with heart failure and moderate-to-severe mitral regurgitation treated with either standard medical therapy or MitraClip. The cohort of patients treated with the MitraClip was propensity matched to a population of heart failure patients, and their outcomes compared. At a mean follow-up of 22 months, all-cause mortality was 21% in the MitraClip cohort and 42% in the medical management cohort (p = .007). The decision model demonstrated that MitraClip increased life expectancy from 1.87-3.60 years and quality-adjusted life years (QALY) from 1.13-2.76 years. The incremental cost was $52,500 Canadian dollars, corresponding to an incremental cost-effectiveness ratio (ICER) of $32,300.00 per QALY gained. Results were sensitive to the survival benefit. CONCLUSION: In heart failure patients with symptomatic moderate-severe mitral regurgitation, therapy with the MitraClip is associated with superior survival and is cost-effective compared to medical therapy.

Structural heart diseases interventional training in Canada.

Structural heart disease interventions have evolved into an important component of interventional cardiology fellowship programs worldwide. Given the complexity of such interventions, the breadth of knowledge needed for optimal patient selection and postprocedural management, and the skills to perform them efficiently, advanced training has become mandatory. Postgraduate medical training in Canada has always been on the cutting edge of new technology, and excellent care is provided to the increasing population of adult patients with congenital heart disease. The current survey sought to collect relevant information and assess the opinion of interventional cardiology program directors in Canada regarding training in structural interventions. Our study reports the approximate number of structural procedures performed by interventional cardiology fellows in Canadian interventional cardiology fellowship programs, the form of the structural training, and the suggestions of program directors who are actively trying to integrate structural training into interventional cardiology fellowship programs.

Unusual coronary occlusion post transcatheter aortic implantation: the importance of clinical assessment.

Despite the increasing experience with transcatheter aortic valve implantation, the incidence of severe complications is still relevant. One of the most feared complications is coronary obstruction. This life-threatening complication, occurring in up to 1% of patients, might be catastrophic, presenting with hemodynamic instability but allowing for rapid detection and treatment. To date, all published cases have reported ostial occlusions of either the left main or the right coronary artery. We describe an uncommon presentation of distal right coronary artery obstruction post transcatheter aortic valve implantation that was diagnosed after the patient developed chest pain in the recovery room.