Secondary Mitral Regurgitation: Cardiac Remodeling, Diagnosis, and Management.

Secondary mitral regurgitation (MR) refers to MR resulting from left ventricular or left atrial remodeling. In ischemic or nonischemic cardiomyopathy, left ventricular dilation (regional or global) leads to papillary muscle displacement, tethering, and leaflet malcoaptation. In atrial functional MR, MR occurs in patients with left atrial dilation and altered mitral annular geometry due to atrial fibrillation. In addition to cardiac remodeling, leaflet remodeling is increasingly recognized. Mitral leaflet tissue actively adapts through leaflet growth to ensure adequate coaptation. Leaflets, however, can also undergo maladaptive thickening and fibrosis, leading to increased stiffness. The balance of cardiac and leaflet remodeling is a key determinant in the development of secondary MR. Clinical management starts with detection, severity grading, and identification of the underlying mechanism, which relies heavily on echocardiography. Treatment of secondary MR consists of guideline-directed medical therapy, surgical repair or replacement, and transcatheter edge-to-edge repair. Based on a better understanding of pathophysiology, novel percutaneous mitral repair and replacement devices have been developed and clinical trials are underway.

Left atrial function and not volume predicts mid-to-late atrial fibrillation after mitral valve repair.

OBJECTIVES: Patients undergoing surgical mitral valve repair (MVr) for degenerative mitral regurgitation are at risk of even late postoperative atrial fibrillation (AF). Left atrial (LA) function has been shown superior to LA volume in evaluating the risk of AF in diverse cardiac conditions. We therefore investigated the prognostic value of LA function and volume in predicting mid-to-late postoperative AF after MVr (>30 days postoperatively). METHODS: We retrospectively identified all patients who underwent MVr for degenerative mitral regurgitation between 2012 and 2019 at our institution. Exclusion criteria were preoperative AF, concomitant procedures, re-operations, missing or insufficiently processable preoperative echocardiograms and missing follow-up. LA function and volume measurements were conducted using speckle-tracking strain echocardiographic analysis. Postoperative LA function was measured in a subgroup with sufficient postoperative echocardiograms. RESULTS: We included 251 patients, of whom 39 (15.5%) experienced AF in the mid-to-late postoperative period. Reduced LA strain parameters and more than mild preoperative tricuspid regurgitation were independently associated with mid-to-late postoperative AF. LA volume index had no association with mid-to-late postoperative AF in univariable analysis and did not improve the performance of multivariable models. Patients with mid-to-late AF exhibited diminished improvement in LA function after surgery. CONCLUSIONS: In MVr patients, LA function (but not volume) showed independent predictive value for mid-to-late postoperative AF. Including LA function into surgical decision-making and approach may identify patients who will benefit from earlier intervention with the aim to prevent irreversible LA damage with consequent risk of postoperative AF.

Long lasting effect on testes following methylene blue injection in laparoscopic lymphatic sparing varicocelectomy.

OBJECTIVE: Injection of methylene blue to testis has been shown to have adverse effect in animal studies but it is still being used frequently as lymphatic mapping agent during lymphatic sparing varicocelectomy in adolescent varicoceles. We aim to report postoperative ultrasound changes after subaortic injection of methylene blue in human testes. STUDY DESIGN: A retrospective observational study of consecutive patients under 18 years old undergoing laparoscopic varicocelectomy from August 2017 to August 2021 was performed. Demographics such as age, symptoms, pre-operative testicular volume was collected. Primary outcome was change on testicular ultrasound at 3, 6, 12 months after the operation. Secondary outcome was testicular volume difference between affected and unaffected testes, and growth rate of affected testis at 1 year after the operation. RESULTS: Fifty-eight patients were included, with median age of 15 years old (IQR 11-18 years). Thirty-one patients had non-lymphatic sparing varicocelectomy (Group A) and 27 patients had lymphatic sparing varicocelectomy (Group B). There was no statistical difference between the mean testicular volume difference between the two groups, but hydrocele rate was significantly higher in Group A (16% vs 0%, p = 0.03). In group B, 6 patients (22.2%, p = 0.005) developed testicular change detectable by ultrasound. No statistical difference could be demonstrated for median testicular size difference (between affected and unaffected testes) at 1 year between group with and without ultrasound change (-23% vs 0%, p = 0.36). Median follow up time was 20.4 months (IQR 5-32 months). DISCUSSION: Varicocele treatments improve testicular volume and increase total sperm concentration and lymphatic sparing surgery significantly decreased post-operative hydrocele rates [2]. Different agents have been used to delineate lymphatic vessels and one commonly used agent is methylene blue [10,15-16]. However it has been shown in other animal studies that intraparenchymal injection of methylene blue to rat testis result in degenerative changes [18]. Our study is the first to describe post-operative changes of human testes on imaging after lymphatic sparing varicocelectomy with subdartoic injection of methylene blue. Six patients (22.2%) demonstrated new onset testicular changes on post-operative ultrasound. Although no statistically significant testicular volume reduction was seen in the group with change on imaging, these observations may serve as a surrogate marker for testicular injury or reduced testicular function. It will be desirable for future studies if we can investigate it further with hormonal markers or semen analysis after puberty has been reached. CONCLUSION: Lymphatic sparing procedure reduced post-operative hydrocele in adolescent varicocele, however long-lasting effect on testis is evident with subdartoic injection of methylene blue. This agent must be used with caution and long term follow up of these patients are needed.

Prospective Randomized Controlled Trial Comparing Laparoscopic Palomo Surgery vs Scrotal Antegrade Sclerotherapy in Adolescent Varicocele.

PURPOSE: Varicocele is a common condition in adolescence and the most common correctable cause of infertility. This study aimed to analyze and compare the outcomes of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in a tertiary referral center. MATERIALS AND METHODS: Patients with left grade 3 varicocele indicated for surgery were prospectively enrolled and randomly allocated to the scrotal antegrade sclerotherapy and laparoscopic Palomo surgery groups, with their respective contralateral normal testes taken as controls. The primary outcome measures were clinical varicocele recurrence, testicular catch-up growth, and postoperative hydrocele. All patients were evaluated clinically and using Doppler ultrasound by radiologists. RESULTS: From 2015 to 2020, 113 patients completed the study and were statistically analyzed (scrotal antegrade sclerotherapy, n = 57; laparoscopic Palomo surgery, n = 56). All patients had significantly smaller testes preoperatively; the testicular volume differences with control testes were -23% in scrotal antegrade sclerotherapy and -19% in laparoscopic Palomo surgery. At 12-month follow-up, there were no statistically significant differences in clinical recurrences between the 2 groups (scrotal antegrade sclerotherapy = 5.3% vs laparoscopic Palomo surgery = 5.4%, P > .05, noninferiority test). Testicular catch-up growths were observed in both groups; the mean testicular volume difference between the treatment and control testes decreased from -23% to -8.1% in scrotal antegrade sclerotherapy (P < .001) and from -19% to -9.3% in laparoscopic Palomo surgery (P < .001) at 12-month follow-up. There was no postoperative hydrocele in the scrotal antegrade sclerotherapy group compared to 7 cases in the laparoscopic Palomo surgery group (0% vs 13%, P = .006). CONCLUSIONS: Both scrotal antegrade sclerotherapy and laparoscopic Palomo surgery are safe and effective procedures for treatment of adolescent varicocele with significant positive effect on testicular catch-up growth. Scrotal antegrade sclerotherapy is not inferior to laparoscopic Palomo surgery in terms of clinical recurrence rate and has significantly less postoperative hydrocele.

Racial and Ethnic Differences in the Clinical Diagnosis of Aortic Stenosis.

Background Racial and ethnic minority groups are underrepresented among patients undergoing aortic valve replacement in the United States. We evaluated the impact of race and ethnicity on the diagnosis of aortic stenosis (AS). Methods and Results In patients with transthoracic echocardiography (TTE)-confirmed AS, we assessed rates of AS diagnosis as defined by assignment of an International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) code for AS within a large multicenter electronic health record. Multivariable Cox proportional hazard and competing risk regression models were used to evaluate the 1-year rate of AS diagnosis by race and ethnicity. Among 14 800 patients with AS, the 1-year diagnosis rate for AS following TTE was 37.4%. Increasing AS severity was associated with an increased likelihood of receiving an AS diagnosis (moderate: hazard ratio [HR], 3.05 [95% CI, 2.86-3.25]; P<0.0001; severe: HR, 4.82 [95% CI, 4.41-5.28]; P<0.0001). Compared with non-Hispanic White, non-Hispanic Black (HR, 0.65 [95% CI, 0.54-0.77]; P<0.0001) and non-Hispanic Asian individuals (HR, 0.72 [95% CI, 0.57-0.90], P=0.004) were less likely to receive a diagnosis of AS. Additional factors associated with a decreased likelihood of receiving an AS diagnosis included a noncardiology TTE ordering provider (HR, 0.92 [95% CI, 0.86-0.97]; P=0.005) and TTE performed in the inpatient setting (HR, 0.72 [95% CI, 0.66-0.78]; P<0.0001). Conclusions Rates of receiving an ICD diagnostic code for AS following a diagnostic TTE are low and vary significantly by race and ethnicity and disease severity. Further studies are needed to determine if efforts to maximize the clinical recognition of TTE-confirmed AS may help to mitigate disparities in treatment.

Indexing Left Atrial Volumes: Alternative Indexing Methods Better Predict Outcomes in Overweight and Obese Populations.

BACKGROUND: Left atrial volume (LAV) is often adjusted for body surface area (BSA). In overweight individuals this may result in underestimation of left atrial (LA) dilation. The authors investigated whether alternative indexing techniques better predict mortality and cardiovascular (CV) events. OBJECTIVES: The purpose of this study was to evaluate the efficacy of different methods of indexing LAV in predicting mortality and CV events across a range of body sizes. METHODS: LAV was adjusted for BSA, idealized BSA (iBSA), height, and height-squared (H2) in patients aged over 50 years who underwent outpatient echocardiography and longitudinal follow-up at our institution. LA dilation was categorized using published criteria. Mortality and CV events were assessed via medical records. RESULTS: LAVs were calculated in 17,454 individuals. In this study, 71.2% were overweight or obese. Indexing using iBSA, height, and H2 resulted in reclassification of LA size in up to 28.4% (P < 0.001) compared with indexing using BSA. In severely obese individuals (body mass index [BMI] ≥40 kg/m2), LA dilation indexed for BSA no longer predicted mortality (P = 0.70). Other indexing methods remained predictive of mortality. Height, H2, and iBSA all had greater performance, compared with BSA, for prediction of mortality and CV events in all overweight patients with H2 showing the best overall performance (P < 0.001). Net reclassification index for mortality was significant for all alternative indexing techniques (P < 0.001) and patients whose LA was reclassified from normal to dilated had increased risk of mortality (P < 0.001) and CV events (P < 0.001) across all BMI categories. CONCLUSIONS: LA dilation based on standard indexing using BSA is nondiscriminatory for prediction of mortality in the severely obese. Indexing using height, H2, or iBSA to diagnose LA dilation better predicts mortality in this population and has better overall predictive performance across all overweight and obese populations. Using BSA indexing may lead to underappreciation of LA dilation and underestimation of patients at increased risk.

Sex Differences and Similarities in Valvular Heart Disease.

As populations age worldwide, the burden of valvular heart disease has grown exponentially, and so has the proportion of affected women. Although rheumatic valve disease is declining in high-income countries, degenerative age-related causes are rising. Calcific aortic stenosis and degenerative mitral regurgitation affect a significant proportion of elderly women, particularly those with comorbidities. Women with valvular heart disease have been underrepresented in many of the landmark studies which form the basis for guideline recommendations. As a consequence, surgical referrals in women have often been delayed, with worse postoperative outcomes compared with men. As described in this review, a more recent effort to include women in research studies and clinical trials has increased our knowledge about sex-based differences in epidemiology, pathophysiology, diagnostic criteria, treatment options, outcomes, and prognosis.

Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients.

Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans. Methods: MVs were obtained by the Cardiothoracic Surgical Trials Network from 17 patients with ischemic mitral regurgitation (IMR). Echo-doppler imaging assessed MV function at time of resection. Cryosections of MVs were analyzed using a multi-faceted histology and immunofluorescence examination of cell populations. MVs were further analyzed using unbiased label-free proteomics. Echo-Doppler imaging, histo-cytometry measures and proteomic analysis were then integrated. Results: MVs from patients with greater MR exhibited proteomic changes associated with proteolysis-, inflammatory- and oxidative stress-related processes compared to MVs with less MR. Cryosections of MVs from patients with IMR displayed activated valvular interstitial cells (aVICs) and double positive CD31+ αSMA+ cells, a hallmark of EndMT. Univariable and multivariable association with echocardiography measures revealed a positive correlation of MR severity with both cellular and geometric changes (e.g., aVICs, EndMT, leaflet thickness, leaflet tenting). Finally, proteomic changes associated with EndMT showed gene-ontology enrichment in vesicle-, inflammatory- and oxidative stress-related processes. This discovery approach indicated new candidate proteins associated with EndMT regulation in IMR. Conclusion: We describe an atypical cellular composition and distinctive proteome of human MVs from patients with IMR, which highlighted new candidate proteins implicated in EndMT-related processes, associated with maladaptive MV fibrotic remodeling.

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap.

OBJECTIVE: To examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR). PATIENTS AND METHODS: We retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed. RESULTS: At baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m2 was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11). CONCLUSION: In contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m2 or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.

2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: A Report of the American College of Cardiology Solution Set Oversight Committee.

Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges. This expert consensus decision pathway emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as consideration of the indications for treatment. The document is a focused update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation, with some sections updated and others added in light of the publication of new trial data related to secondary MR, among other developments. A structured approach to evaluation based on clinical findings, accurate echocardiographic imaging, and, when necessary, adjunctive testing can help clarify decision making. Treatment goals include timely intervention by an experienced multidisciplinary heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death.

Effect of Residual Interatrial Shunt on Migraine Burden After Transcatheter Closure of Patent Foramen Ovale.

OBJECTIVES: This study sought to evaluate the long-term effect of transcatheter patent foramen ovale (PFO) closure on migraineurs with and without aura and examine the effect of residual right-to-left shunt. BACKGROUND: Many studies reported improvement in migraine symptoms after PFO closure, yet randomized trials failed to reach its clinical endpoints. METHODS: The study retrospectively analyzed data from 474 patients who underwent transcatheter PFO closure at Massachusetts General Hospital. Patients completed a migraine burden questionnaire at baseline and at follow-up. Migraine severity is reported as migraine frequency (days/month), average duration (min), and migraine burden (days × min/month). Improvement following closure was defined as complete abolishment of symptoms or >50% reduction in migraine burden. RESULTS: A total of 110 migraineurs who underwent PFO closure were included; 77.0% had aura and 23.0% were without aura, and 91.0% had a cryptogenic stroke. During long-term median follow-up of 3.2 (interquartile range: 2.1 to 4.9) years, there was a significant improvement in migraine symptoms in migraineurs with or without aura. Migraine burden was reduced by >50% in 87.0% of patients, and symptoms were completely abolished in 48%. Presence of aura was associated with abolishment of migraine (odds ratio: 4.30; 95% confidence interval: 1.50 to 12.30; p = 0.006). At 6 months after PFO closure, residual right-to-left shunt was present in 26% of patients. Absence of right-to-left shunt was associated with improvement in migraine burden by >50% (odds ratio: 4.60; 95% confidence interval: 1.30 to 16.10; p = 0.017). CONCLUSIONS: Long-term follow-up after transcatheter PFO closure was associated with significant improvement in migraine burden. Aura was a predictor of abolishing symptoms. Absence of residual right-to-left shunt was a predictor of significant reduction in migraine burden.

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.

Comparison of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in treatment of adolescent varicocele: A 15-year review.

INTRODUCTION/OBJECTIVE: Varicocele is a common condition seen in adolescence and associated with adult subfertility. Numerous types of intervention have been described with differences in success and complication rates. This study aims to review and compare the surgical outcomes of laparoscopic Palomo surgery and scrotal antegrade sclerotherapy at our center. STUDY DESIGN: A retrospective analysis was done of all patients younger than 18 years old with idiopathic varicocele treated operatively between February 2001 and December 2016. Demographics such as age at operation, side, varicocele grade, operative date, and types of operation were collected. Primary outcomes were clinical recurrence, defined as any grading noted on follow-up within 1 year post-op and post-operative hydrocele. Secondary outcomes were operative time, length of stay, and other surgical complications. Mann-Whitney U test, independent t test and chi-square tests were used for analysis. All p-values were two-sided and considered statistically significant at p ≤ 0.05. RESULTS: A total of 119 patients fit the criteria, of whom 117 patients were included in data analysis (Table). Sixty-two patients had laparoscopic Palomo surgery (LPS) and 55 had scrotal antegrade sclerotherapy (SAS). Clinical recurrence (grade 2-3) within 1 year was similar between the two groups, with four out of 48 patients in the SAS group and six out of 62 patients in the LPS group (8.4% in SAS vs. 9.7% in LPS, p = 1.00). Of the 11 patients who had recurrence in the SAS group, seven had grade 1 recurrence (14.5%), two (4.2%) had grade 2 recurrence, and two (4.2%) had grade 3 recurrence. For the LPS group, 17 out of 62 patients had clinical recurrence within 1 year, of whom 11 (17.7%) had grade 1 recurrence, one (1.6%) had grade 2, and five (8.1%) had grade 3 recurrence. Post-operative hydrocele was significantly higher in the LPS group; there was none in the SAS group but 11 patients in the LPS group (0% in SAS vs. 17.7%, p = 0.002). Three patients had clinically significant hydrocele requiring Jaboulays' procedure. Complications other than hydrocele were noted in three patients in the SAS group and one patient in the LPS group (5.5% in SAS vs. 1.6% in LPS, p = 0.158). None required operative intervention. No conversion to open procedure was seen in the LPS group and there were no perioperative complications. Mean operative time was 62.9 min in the SAS group and 60.7 min in the LPS group (p = 0.624). Mean length of stay was 17.5 h in the SAS group and 31.7 h in the LPS group (p < 0.001). CONCLUSION: Both SAS and LPS are safe procedures for treatment of adolescent varicocele with similar clinical recurrence rate within 1 year. SAS has a significantly lower rate of post-operative hydrocele.

Clinical features and prognosis of patients with isolated severe aortic stenosis and valve area less than 1.0 cm2.

OBJECTIVE: Current guidelines define severe aortic stenosis (AS) as an aortic valve area (AVA)≤1.0 cm2, but some authors have suggested that the AVA cut-off be decreased to 0.8 cm2. The aim of this study was, therefore, to better describe the clinical features and prognosis of patients with an AVA of 0.8-0.99 cm2. METHODS: Patients with isolated, severe AS and ejection fraction ≥55% with an AVA of 0.8-0.99 cm2 (n=105) were compared with those with an AVA<0.8 cm2 (n=155) and 1.0-1.3 cm2 (n=81). The endpoint of this study was a combination of death from any cause or aortic valve replacement at or before 3 years. RESULTS: Patients with an AVA of 0.8-0.99 cm2 group comprised predominantly normal-flow, low-gradient (NFLG) AS, while high gradients and low flow were more often observed with an AVA<0.8 cm2. The frequency of symptoms was not significantly different between an AVA of 0.8-0.99 cm2 and 1.0-1.3 cm2. The combined endpoint was achieved in 71%, 52% and 21% of patients with an AVA of 0.8 cm2, 0.8-0.99 cm2and 1.0-1.3 cm2, respectively (p<0.001). Among patients with an AVA of 0.8-0.99 cm2, NFLG AS was associated with a lower hazard (HR=0.40, 95% CI 0.23 to 0.68, p=0.001) of achieving the combined endpoint with outcomes similar to moderate AS in the first 1.5 years of follow-up. Patients with high-gradient or low-flow AS with an AVA of 0.8-0.99 cm2 had outcomes similar to those with an AVA<0.8 cm2. The sensitivity for the combined endpoint was 61% for an AVA cut-off of 0.8 cm2 and 91% for a cut-off of 1.0 cm2. CONCLUSIONS: The outcomes of patients with AS with an AVA of 0.8-0.99 cm2 are variable and are more precisely defined by flow-gradient status. Our findings support the current AVA cut-off of 1.0 cm2.

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.