Progression to malignancy in oral potentially malignant disorders: a retrospective study of 5,036 patients in Ontario, Canada.

OBJECTIVES: Determine the rate of malignant transformation (MT) of oral potentially malignant disorders (OPMDs) and risk factors for transformation. STUDY DESIGN: The OPMD database (2001-2015) from 2 biopsy services in Ontario, Canada, was linked to the Ontario Cancer Registry to determine the rate of progression to oral squamous cell carcinoma (OSCC). Clinical and histologic features of progressed and non-progressed cases were compared to determine risk factors for progression. RESULTS: The MT rate was 6.4% (322/5,036 cases). The mean time for cancer development was 51.2 months. 33.6% of cases (107/322) progressed after over 60 months. The risk of cancer increased with age and was higher in non-smokers. The MT rate was highest in the tongue (11.4%), followed by the floor of mouth (7.1%) and gingiva (6.5%). Histologic grade was associated with progression to cancer (P < .0001). Atypical verrucous-papillary lesions with no or mild dysplasia predominantly affected older patients' gingiva, and the progression rate was significantly higher than conventional mild dysplasia (9.2% vs 3.2%, P = .0002). CONCLUSIONS: Our population-based retrospective study showed that <10% of OPMDs progressed to cancer, which could take many years. Atypical papillary-verrucous proliferation without high-grade dysplasia is a subtype of OPMD requiring further study.

TNFα Signaling Is Increased in Progressing Oral Potentially Malignant Disorders and Regulates Malignant Transformation in an Oral Carcinogenesis Model.

Oral carcinogenesis represents a multi-stage process which encompasses several genetic and molecular changes that promote the progression of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinomas (OSCCs). A better understanding of critical pathways governing the progression of OMPDs to OSCCs is critical to improve oncologic outcomes in the future. Previous studies have identified an important role of tumor necrosis factor α (TNFα) and TNF receptor 1 (TNFR1) in the invasiveness of oral cancer cell lines. Here, we investigate the expression of TNFα and TNFR1 in human OPMDs that progress to OSCC compared to non-progressing OPMDs utilizing fluorescent immunohistochemistry (FIHC) to show increased TNFα/TNFR1 expression in progressing OPMDs. In order to interrogate the TNFα/TNFR1 signaling pathway, we utilized a 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis to demonstrate that TNFα/TNFR1 expression is upregulated in 4-NQO-induced OSCCs. TNFα neutralization decreased serum cytokines, inhibited the development of invasive lesions and reduced tumor-associated neutrophils in vivo. Combined, this data supports the role of TNFα in oral malignant transformation, suggesting that critical immunoregulatory events occur downstream of TNFR1 leading to malignant transformation. Our results advance the understanding of the mechanisms governing OSCC invasion and may serve as a basis for alternative diagnostic and therapeutic approaches to OPMDs and OSCC management.

Oral Squamous Cell Carcinoma Associated with Precursor Lesions.

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.

Characterization of Oral Squamous Cell Carcinoma Associated Inflammation: A Pilot Study.

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression. Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1. Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells. Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis.

CD301 mediates fusion in IL-4-driven multinucleated giant cell formation.

Multinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301+ MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold (P<0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.This article has an associated First Person interview with the first author of the paper.

Increase in detection of oral cancer and precursor lesions by dentists: Evidence from an oral and maxillofacial pathology service.

BACKGROUND: Dentists play an important role in the detection and diagnosis of oral diseases, including oral cancer and its precursor lesions. There are few comprehensive reviews in the recent literature that examine the scope and trends of oral disease diagnoses by dentists. METHODS: The authors analyzed all accessions to the Toronto Oral Pathology Service at the Faculty of Dentistry at the University of Toronto in Toronto, Ontario, Canada, from 2005 through 2015 using a custom-built database. They used these data to calculate the temporal trends in the diagnoses of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). RESULTS: A total of 63,483 biopsy specimens were submitted primarily by dentists from 2005 through 2015. From these, 2,679 cases of OED and 828 OSCC were diagnosed. The authors' results show a 3.8-fold increase in the number of epithelial dysplasias and a 1.8-fold increase in mucosal carcinomas over the study period. The rate of increase of OED and OSCC was significantly higher than the rate of increase of total oral carcinomas diagnosed in the region, the population changes, and the number of dentists in the region. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Within the limitations of a study of a single large oral pathology biopsy service, the analysis of diagnoses shows that dentists are increasingly involved in the detection of oral mucosal carcinoma and precursor lesions. The dental community plays an important and increasing role in the detection of oral cancer and potentially malignant disorders. Increased awareness among oral health care and nonoral health care professionals may increase early detection of OSCC.

Intraprocedural invasive hemodynamic parameters as predictors of short- and long-term outcomes in patients undergoing transcatheter aortic valve replacement.

OBJECTIVE: Evaluation of invasive hemodynamic parameters as prognostic markers of mortality in patients undergoing TAVR. BACKGROUND: The value of invasive intraprocedural hemodynamic evaluation of patients undergoing transcatheter aortic valve replacement is unclear. METHODS: Consecutive patients who underwent transfemoral TAVR and had complete prospectively collected intraprocedural invasive hemodynamic parameters were retrospectively analyzed. Patients with alternative access, planned general anesthesia, or baseline ≥moderate Tricuspid Regurgitation were excluded. Pre- and post-valve implant parameters included heart rate, systolic and diastolic blood pressures, cardiac output and index, pulmonary arterial systolic and diastolic pressures, transaortic pressure gradient and right atrial pressure. The primary end points were the association of the intraprocedural hemodynamic changes with all-cause mortality at 30days and 1year. Extensive Receiver Operating Characteristic analyses yielded dichotomized threshold of hemodynamic values in association with the binary outcome of mortality. RESULTS: A total of 312 patients (52% male, mean age 83years) were evaluated. A significant association with 30-day and 1-year mortality was found between intraprocedural post-valve implant cardiac index <1.9 vs. ≥1.9L/min/m2 (Log-ranked p=0.0286 and p=0.0432, respectively). Four subgroups with pre- and post-valve implant CI changes (L/min/m2) were compared: [1] pre<1.9, stable_post<1.9; [2] pre<1.9, improved_post≥1.9; [3] pre≥1.9, stable_post≥1.9; and [4] pre≥1.9, worsened_post<1.9. Group 1 (lower CI with no post-valve improvement) had the worst survival, and Group 3 (higher CI and stable post-valve) had the best survival at 1-year follow-up (Log-ranked p=0.0089). CONCLUSIONS: In patients with severe aortic stenosis undergoing TAVR, invasive monitoring can assess for hemodynamic prognostic markers of survival.

Does direct stenting with drug-eluting stents improve outcome? A meta-analysis of 10,900 patients.

OBJECTIVES: The aim of this study is to summarize the outcomes of patients undergoing direct stenting (DS) with drug-eluting stents (DES) compared to those who underwent balloon predilatation. BACKGROUND: DS has been associated with improved outcomes in the bare-metal stent era. Although DS with DES implantation has been increasingly adopted in clinical practice, its safety and effectiveness remain controversial. METHODS: The search criteria identified 546 studies in the Medline/PubMed, Cochrane, and EMBASE databases from 2001 to July 2014. From these, seven studies totaling 10,900 patients were selected. Summarized estimates [odds ratio (OR) and 95% confidence intervals] were obtained using a random-effects model. The primary outcomes were a composite of major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included a composite of death and MI and the rates of target lesion revascularization (TLR). RESULTS: Overall, 4101 (38%) and 6799 (62%) patients underwent DS with DES and balloon pre-dilatation, respectively. DS with DES reduced the likelihood of MACE (OR: 0.81 [0.71-0.93]). Additionally, DS with DES was associated with reduced rates of death/MI (OR: 0.76 [0.62-0.92]), and TLR (OR: 0.66 [0.44-0.98]). CONCLUSIONS: DS with DES is safe and may be associated with better outcomes in selected patients. © 2016 Wiley Periodicals, Inc.

Unusual presentation of squamous cell carcinoma of the maxilla in an 8-year-old child.

Oral squamous cell carcinoma (OSCC) is extremely rare in patients younger than 20 years of age. We present here a case of OSCC of the maxillary alveolar ridge in an otherwise healthy 8-year-old patient. The clinicohistologic presentation was not typical for mucosal SCC, and the possibility of an intrabony origin from the odontogenic epithelium was considered. The patient was treated with surgical resection, and treatment decisions were made with consideration of the need for eradication of tumor as well as tissue preservation to allow normal growth and development. A review of the literature indicated a preponderance of gingival-alveolar ridge as the site of OSCC in children with no known genetic predisposition to cancer. More studies of this rare subset of OSCC will help understand the underlying biology and guide treatment decisions.

The utilisation of the cardiovascular automated radiation reduction X-ray system (CARS) in the cardiac catheterisation laboratory aids in the reduction of the patient radiation dose.

AIMS: The radiation exposure resulting from cardiovascular procedures may increase the risk of cancer, and/or cause skin injury. Whether the novel cardiovascular automated radiation reduction X-ray system (CARS) can help reduce the patient radiation dose in daily clinical practice remains unknown. The aim of this study was to evaluate the reduction in patient radiation dose with the use of CARS in the cardiac catheterisation laboratory (CCL). METHODS AND RESULTS: This study retrospectively analysed 1,403 consecutives patients who underwent a cardiac catheterisation with coronary angiography (CA) and/or a percutaneous coronary intervention (PCI) in the Brest University Hospital over the course of one year. Patient radiation doses (dose area product and air kerma) were collected and compared between the CCL with (new CCL) and without (control CCL) CARS. Additionally, the patient radiation doses according to femoral versus radial access, procedural complexity and body mass index were compared. The radiation lesion position on the skin was assessed by automatically optimising the X-ray source to image distance (SID) and subsequently generating a radiation Dose-Map for those procedures exceeding 3 Gray of exposure. Overall, 447 patients underwent procedures in the control CCL and 956 in the new CCL. Baseline patient and procedural characteristics were similar between the two groups, with the exception of male gender and primary PCI, which were more prevalent in the new CCL group. Compared to the control CCL, the utilisation of the CARS in the new CCL resulted in a reduction of dose area product by 46% for CA, 56% for PCI alone and 54% for CA and PCI during the same procedure. Of note, radial access generated a higher radiation dose than femoral access (p<0.001). In this study, seven patients had an air kerma exceeding 3 Gray; however, only one patient had a skin dose greater than 3 Gray. CONCLUSIONS: The utilisation of the CARS resulted in a significant reduction in patient radiation doses compared to the control equipment. A real-time Dose-Map may help the operator change the projection during complex procedures to reduce the patient skin dose.

Impact of baseline mitral regurgitation on short- and long-term outcomes following transcatheter aortic valve replacement.

BACKGROUND: The prevalence of concomitant significant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) ranges from 2% to 33%. The impact of significant MR on post-TAVR outcomes remains controversial. METHODS: The data from a cohort of patients with symptomatic severe AS undergoing TAVR at out institution were retrospectively analyzed. The last transthoracic echocardiogram (TTE) before the index TAVR procedure was selected as the baseline assessment of the degree of MR. The total study cohort (N = 589) was divided into 2 groups: significant ≥moderate MR (n = 68) versus nonsignificant

Comparison of clinical outcomes with the utilization of monitored anesthesia care vs. general anesthesia in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: There is no clear consensus in regard to the optimal anesthesia utilization during transcatheter aortic valve replacement (TAVR). The aim was to compare outcomes of transfemoral (TF) TAVR under monitored anesthesia care (MAC) vs. general anesthesia (GA) and evaluate the rates and causes of intra-procedural MAC failure. METHODS: All consecutive patients who underwent TF TAVR from April 2007 through March 2015 were retrospectively analyzed and dichotomized into two groups: TAVR under MAC vs. GA. The main endpoints of the study included 30-day and 1-year mortality, the rates and reasons for failure of MAC, in-hospital clinical safety outcomes, and post-procedural hospital and intensive care unit length-of-stays. RESULTS: A total of 533 patients (51% male, mean-age 83years) underwent TF TAVR under MAC (n=467) or GA (n=66). Fifty-six patients (12%) in the MAC group required conversion to GA. The MAC group had significantly shorter post-procedural hospital (6.0 vs. 7.9, p=0.023) and numerically shorter ICU (2.4 vs. 2.8, p=0.355) mean length-of-stays in days. The clinical safety outcomes were similar in both groups. Kaplan-Meier unadjusted cumulative in-hospital and 30-day mortality rates were higher in the GA group but similar in both groups at 1-year. CONCLUSIONS: TF TAVR under MAC is feasible and safe, results in shorter hospital stays, can be performed in the majority of cases, and should be utilized as the default strategy. Trans-esophageal echocardiography utilization during TAVR with MAC is safe and feasible. The most common cause for conversion of MAC to GA is cardiac instability and hypotension. The complete heart team should be available at all times in case the need arises for a rapid conversion to GA.

The adjunctive use of Angio-Seal in femoral vascular closure following percutaneous transcatheter aortic valve replacement.

AIMS: The objective of this study was to describe and evaluate the adjunctive technique of Angio-Seal (AS) use to augment the dual Perclose ProGlide (PP) in achieving haemostasis in patients undergoing transfemoral percutaneous transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: All patients who underwent TAVR from May 2007 to January 2015 via a planned transfemoral percutaneous approach with a dual PP pre-close strategy were retrospectively analysed. This cohort was divided into two groups: dual PP versus dual PP with adjunctive AS (PP+AS) use based on the specific status of intraprocedural haemostasis. The baseline and procedural characteristics and in-hospital outcomes were prospectively collected and retrospectively compared. Overall, a total of 387 consecutive patients (55% male, mean age 83 years) with dual PP (n=179) vs. dual PP+AS (n=208) were evaluated. There were no statistically significant differences between the dual PP vs. dual PP+AS groups with regard to the in-hospital Valve Academic Research Consortium-2 (VARC-2) primary endpoints of major vascular complications (8.0% vs. 6.6%, p=0.592), minor vascular complications (18.4% vs. 13.7%, p=0.218), life-threatening or disabling bleeding (5.1% vs. 3.0%, p=0.291), major bleeding (1.7% vs. 1.5%, p=1.000), and minor bleeding (14.4% vs. 10.6%, p=0.271). CONCLUSIONS: The adjunctive Angio-Seal technique to augment the dual PP pre-close strategy for patients undergoing percutaneous femoral closure following TAVR is feasible and safe and may be considered as a bail-out or an alternative strategy when the dual PP closure technique fails to obtain complete haemostasis.

Vascular access in critical limb ischemia.

Currently, percutaneous endovascular intervention is considered a first line of therapy for treating patients with critical limb ischemia. As the result of remarkable development of techniques and technologies, percutaneous endovascular intervention has led to rates of limb salvage comparable to those achieved with bypass surgery, with fewer complications, even in the presence of lower rates of long-term patency. Currently, interventionalists have a multiplicity of access routes including smaller arteries, with both antegrade and retrograde approaches. Therefore, the choice of the optimal access site has become an integral part of the success of the percutaneous intervention. By understanding the technical aspects, as well as the advantages and limitations of each approach, the interventionalists can improve clinical outcomes in patients with severe peripheral arterial disease. This article reviews the access routes in critical limb ischemia, their advantages and disadvantages, and the clinical outcomes of each.

Aortic Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement With the Self-Expanding CoreValve Versus the Balloon-Expandable SAPIEN XT Valve.

The incidence of aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) in a self-expanding and a balloon-expandable system is controversial. This study aimed to examine the incidence and severity of post-TAVR AR with the CoreValve (CV) versus the Edwards XT Valve (XT). Baseline, procedural, and postprocedural inhospital outcomes were compared. The primary end point was the incidence of post-TAVR AR of any severity, assessed with a transthoracic echocardiogram, in the CV versus XT groups. A multivariate logistic regression analysis was completed to evaluate for correlates of the primary end point. The secondary end points included the change in severity of AR at 30-day and 1-year follow-up. A total of 223 consecutive patients (53% men, mean age 82 years) who had transfemoral TAVR with either a CV (n = 119) or XT (n = 104) were evaluated. The rates of post-TAVR AR in the groups were similar, and there was no evidence of more-than-moderate AR in either group. There were significant differences in the rates of intraprocedural balloon postdilation with the CV (17.1%) versus XT valve (5.8%; p = 0.009) and in the rates of intraprocedural implantation of a second valve-in-valve prosthesis with the CV (9.9%) versus XT valve (2.2%; p = 0.036). There were no significant differences in inhospital safety outcomes between the 2 groups. In conclusion, the incidence of post-TAVR AR is similar between the CV and the XT valve when performed by experienced operators using optimal intraprocedural strategies, as deemed appropriate, to mitigate the severity of AR.

Clinical profiles and correlates of mortality in nonagenarians with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported. METHODS: A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed. RESULTS: Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups. CONCLUSION: Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age.

Impact of Functional Versus Organic Baseline Mitral Regurgitation on Short- and Long-Term Outcomes After Transcatheter Aortic Valve Replacement.

The impact of the specific etiology of mitral regurgitation (MR) on outcomes in the transcatheter aortic valve replacement (TAVR) population is unknown. This study aimed to evaluate the longitudinal changes in functional versus organic MR after TAVR in addition to their impact on survival. Consecutive patients who underwent TAVR from May 2007 to May 2015 who had baseline significant (moderate or greater) MR were included. Transthoracic echocardiography was used to evaluate the cohort at baseline, post-procedure, 30-day, 6-month, and 1-year follow-up. The primary outcomes included mortality at 30 days and 1 year. Longitudinal, mixed-model regression analyses were performed to assess the differences in the magnitude of longitudinal changes of MR, left ventricular (LV) ejection fraction, and New York Heart Association functional class. Seventy patients (44% men, mean 83 years) with moderate or greater MR at baseline (30 functional vs 40 organic) were included, with the functional group having a statistically significant mean younger age and higher rates of previous coronary artery bypass grafting. Kaplan-Meier cumulative mortality rates were similar: 30 days (10% vs 17.5%, unadjusted log-ranked p = 0.413) and 1 year (29.4% vs 23.2%, unadjusted log-ranked p = 0.746) in the functional versus organic MR groups, respectively. There were greater degrees of short- and long-term improvement in MR severity (slope difference p = 0.0008), LV ejection fraction (slope difference p = 0.0009), and New York Heart Association class (slope difference p = 0.0054) in the functional versus organic group. In conclusion, patients with significant functional versus organic MR who underwent TAVR have similar short- and long-term survival; nevertheless, those with a functional origin are more likely to have significant improvements in MR severity, LV-positive remodeling, and functional class. These findings may help strategize therapies for MR in patients with combined aortic and mitral valve disease who are undergoing TAVR.