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Competing Interests: Funding Support and Author Disclosures Dr Urena has received speaker fees from Edwards and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Competing Interests: Funding Support and Author Disclosures Dr Himbert is a proctor for Abbott Vascular and Edwards Lifesciences. Dr Brochet is a proctor for Abbott Vascular. Dr Ducrocq is a proctor for Abbott Vascular and Boston Scientific. Dr Urena has received speaker fees from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Growing evidence shows a major outcome impact and undertreatment of tricuspid regurgitation (TR), but large and comprehensive contemporary reports of management and outcome at the nationwide level are lacking., Methods: We gathered all consecutive patients admitted with a diagnosis of likely functional TR in 2014-2015 in France from the Programme de Médicalisation des Systèmes d'Information national database and collected rate of surgery, in-hospital mortality, 1-year mortality, or heart failure (HF) readmission rates., Results: In 2014-2015, 17,676 consecutive patients (75 ± 14 years of age, 51% female) were admitted with a TR diagnosis. Charlson index was ≥ 2 in 56% of the population and 46% presented with HF. TR was associated with prior cardiac surgery, ischemic/dilated cardiomyopathy, or mitral regurgitation in 73% of patients. Only 10% of TR patients overall and 67% of those undergoing mitral valve surgery received a tricuspid valve intervention. Among the 13,654 (77%) conservatively managed patients, in-hospital mortality, 1-year mortality, and 1-year mortality or HF readmission rates were 5.1%, 17.8%, and 41%, respectively, overall, and 5.3%,17.2%, and 37%, respectively, among those with no underlying medical conditions (8-fold higher than predicted for age and gender)., Conclusions: This nationwide cohort of patients admitted with TR included elderly patients with frequent comorbidities/underlying cardiac diseases. In patients conservatively managed, mortality and morbidity were considerably high over a short time span. Despite this poor prognosis, only 10% of patients underwent a tricuspid valve intervention. These nationwide data showing a considerable risk and potential underuse of treatment highlight the critical need to develop strategies to improve the management and outcomes of TR patients., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR)., Background: Quantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV., Methods: A total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality., Results: During median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023)., Conclusions: In patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration., Competing Interests: Funding Support and Author Disclosures Dr. Kamperidis received a European Society of Cardiology training grant, a European Association of Cardiovascular Imaging research grant, a Hellenic Cardiological Society training grant, and a Hellenic Foundation of Cardiology research grant. The Department of Cardiology of Leiden University Medical Centre received grants from Biotronik, Bioventrix, Bayer, Medtronic, Abbott Vascular, Boston Scientific Corporation, Edwards Lifesciences, and GE Healthcare. Drs. Ajmone Marsan and Bax received speaker fees from Abbott Vascular. Dr. Delgado received speaker fees from Abbott Vascular, Medtronic, Merck Sharp and Dohme, Edwards Lifesciences, and GE Healthcare. Dr. Stone has received speaker fees or other honoraria from Cook, Terumo, Qool Therapeutics, and Orchestra Biomed; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious Medical Technologies, Reva, and Matrizyme Pharma; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix Medical. Dr. Vahanian is a consultant for CardioValve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial., Background: It has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials., Methods: In a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months., Results: We observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm 2 , RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients., Conclusions: In the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698)., Competing Interests: Funding Support and Author Disclosures Funded by the French Ministry of Health and Research National Program and Abbott Vascular. Dr. Messika-Zeitoun has received consultant fees from Edwards Lifesciences. Dr. Iung, has received consultant fees from Edwards Lifesciences; and travel fees from Boehringer Ingelheim. Dr. Trochu has received speaker honoraria, travel, and grant support from Abbott and Novartis; honoraria for lectures or advisory boards from Amgen, Bayer, and Resmed; and grants from the EU programme Horizon 2020; and is an unpaid member of the Corvia Medical Scientific Advisory Group outside the submitted work. Dr. Donal has received research facilities from General Electric Healthcare; and consultant fees from Abbott. Dr. Brochet has served as proctor for Abbott. Dr. Piriou has received consultant fees from Abbott. Dr. Guerin has been a consultant for Abbott, Edwards Lifesciences, and Boston Scientific. Dr. Lefèvre has served as proctor for Abbott. Dr. Vahanian has been a consultant for Cardiovalve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the clinical outcome of baseline massive or torrential tricuspid regurgitation (TR) after transcatheter tricuspid valve intervention (TTVI)., Background: The use of TTVI to treat symptomatic severe TR has been increasing rapidly, but little is known regarding the impact of massive or torrential TR beyond severe TR., Methods: The study population comprised 333 patients with significant symptomatic TR from the TriValve Registry who underwent TTVI. Mid-term outcomes after TTVI were assessed according to the presence of massive or torrential TR, defined as vena contracta width ≥14 mm. Procedural success was defined as patient survival after successful device implantation and delivery system retrieval, with residual TR ≤2+. The primary endpoint comprised survival rate and freedom from rehospitalization for heart failure, survival rate, and rehospitalization at 1 year., Results: Baseline massive or torrential TR and severe TR were observed in 154 patients (46.2%) and 179 patients (53.8%), respectively. Patients with massive or torrential TR had a higher prevalence of ascites than those with severe TR (27.3% vs. 20.4%, respectively; p = 0.15) and demonstrated a similar procedural success rate (83.2% vs. 77.3%, respectively; p = 0.21). The incidence of peri-procedural adverse events was low, with no significant between-group differences. Freedom from the composite endpoint was significantly lower in patients with massive or torrential TR than in those with severe TR, which was significantly associated with an increased risk for 1-year death of any cause or rehospitalization for heart failure (adjusted hazard ratio: 1.91; 95% confidence interval: 1.10 to 3.34; p = 0.022). Freedom from the composite endpoint was significantly higher in patients with massive or torrential TR when procedural success was achieved (69.9% vs. 54.2%, p = 0.048)., Conclusions: Baseline massive or torrential TR is associated with an increased risk for all-cause mortality and rehospitalization for heart failure 1 year after TTVI. Procedural success is related to better outcomes, even in the presence of baseline massive or torrential TR. (International Multisite Transcatheter Tricuspid Valve Therapies Registry [TriValve]; NCT03416166)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to establish a computed tomography (CT)-based scoring system for grading mitral annular calcification (MAC) severity and potentially aid in predicting valve embolization during transcatheter mitral valve (MV) replacement using balloon-expandable aortic transcatheter heart valves., Background: Transcatheter MV replacement is emerging as an alternative treatment for patients with severe MAC who are not surgical candidates. Although cardiac CT is the imaging modality of choice in the evaluation of candidates for valve-in-MAC (ViMAC), a standardized grading system to quantify MAC severity has not been established., Methods: We performed a multicenter retrospective review of cardiac CT and clinical outcomes of patients undergoing ViMAC. A CT-based MAC score was created using the following features: average calcium thickness (mm), degrees of annulus circumference involved, calcification at one or both fibrous trigones, and calcification of one or both leaflets. Features were assigned points according to severity (total maximum score = 10) and severity grade was assigned based on total points (mild ≤3, moderate 4 to 6, and severe ≥7 points). The association between MAC score and device migration/embolization was evaluated., Results: Of 117 patients in the TMVR in MAC registry, 87 had baseline cardiac CT of adequate quality. Of these, 15 were treated with transatrial access and were not included. The total cohort included 72 (trans-septal = 37, transapical = 35). Mean patient age was 74 ± 12 years, 66.7% were female, and the mean Society of Thoracic Surgery risk score was 15.4 ± 10.5%. The mean MAC score was 7.7 ± 1.4. Embolization/migration rates were lower in higher scores: Patients with a MAC score of 7 had valve embolization/migration rate of 12.5%, MAC score ≥8 had a rate of 8.7%, and a MAC score of ≥9 had zero (p = 0.023). Patients with a MAC score of ≤6 had 60% embolization/migration rate versus 9.7% in patients with a MAC score ≥7 (p < 0.001). In multivariable analysis, a MAC score ≤6 was in independent predictor of valve embolization/migration (odds ratio [OR]: 5.86 [95% CI: 1.00 to 34.26]; p = 0.049)., Conclusions: This cardiac CT-based score provides a systematic method to grade MAC severity which may assist in predicting valve embolization/migration during trans-septal or transapical ViMAC procedures., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The interference of a transtricuspid cardiac implantable electronic device (CIED) lead with tricuspid valve function may contribute to the mechanism of tricuspid regurgitation (TR) and poses specific therapeutic challenges during transcatheter tricuspid valve intervention (TTVI). Feasibility and efficacy of TTVI in presence of a CIED is unclear., Background: Feasibility of TTVI in presence of a CIED lead has never been proven on a large basis., Methods: The study population consisted of 470 patients with severe symptomatic TR from the TriValve (Transcatheter Tricuspid Valve Therapies) registry who underwent TTVI at 21 centers between 2015 and 2018. The association of CIED and outcomes were assessed., Results: Pre-procedural CIED was present in 121 of 470 (25.7%) patients. The most frequent location of the CIED lead was the posteroseptal commissure (44.0%). As compared with patients without a transvalvular lead (no-CIED group), patients having a tricuspid lead (CIED group) were more symptomatic (New York Heart Association functional class III to IV in 95.9% vs. 92.3%; p = 0.02) and more frequently had previous episodes of right heart failure (87.8% vs. 69.0%; p = 0.002). No-CIED patients had more severe TR (effective regurgitant orifice area 0.7 ± 0.6 cm 2 vs. 0.6 ± 0.3 cm 2 ; p = 0.02), but significantly better right ventricular function (tricuspid annular plane systolic excursion = 16.7 ± 5.0 mm vs. 15.9 ± 4.0 mm; p = 0.04). Overall, 373 patients (79%) were treated with the MitraClip (Abbott Vascular, Santa Clara, California) (106 [87.0%] in the CIED group). Among them, 154 (33%) patients had concomitant transcatheter mitral repair (55 [46.0%] in the CIED group, all MitraClip). Procedural success was achieved in 80.0% of no-CIED patients and in 78.6% of CIED patients (p = 0.74), with an in-hospital mortality of 2.9% and 3.7%, respectively (p = 0.70). At 30 days, residual TR ≤2+ was observed in 70.8% of no-CIED and in 73.7% of CIED patients (p = 0.6). Symptomatic improvement was observed in both groups (NYHA functional class I to II at 30 days: 66.0% vs. 65.0%; p = 0.30). Survival at 12 months was 80.7 ± 3.0% in the no-CIED patients and 73.6 ± 5.0% in the CIED patients (p = 0.30)., Conclusions: TTVI is feasible in selected patients with CIED leads and acute procedural success and short-term clinical outcomes are comparable to those observed in patients without a transtricuspid lead., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Objectives: A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices., Background: TTVI for native tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR)., Methods: The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up., Results: A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm 2 ). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved., Conclusions: TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mitral annulus (MA) enlargement can be observed in various cardiac conditions but respective influence of left atrial (LA) and left ventricle (LV) size remained unclear., Methods: In 120 patients who underwent a clinically indicated 3D-transesophageal-echocardiography, 30 atrial fibrillation (AF), 30 secondary mitral regurgitation (SMR), 30 primary myxomatous mitral regurgitation (PMR) and 30 mitral stenosis (MS), we evaluated the association between MA area (MA-area) and LA volume (LAvol) measured using the biplane area-length method, end-diastolic (LVEDV) and end-systolic (LVESV) volumes measured using the biplane Simpson method. MA-area was measured based on 3D datasets using QLab10., Results: MA-area was correlated to LVEDV (r = 0.42, p < 0.0001), LVESV (r = 0.29, p = 0.001) but more markedly to LAvol (r = 0.62, p < 0.0001). Correlation between MA-area and LAvol was sustained in all subsets whereas MA-area was not correlated to LVEDV and LVESV in patients with SMR and with PMR (all p > 0.10). In multivariate analysis main predictors of MA-area were LAvol (p < 0.0001) and myxomatous etiology of MR (p = 0.0003) followed by LVEDV (p = 0.006) and LVESV (p = 0.02)., Conclusion: In a population of patients with a wide range of LA/LV size related to various conditions, LA volume and myxomatous MR etiology appeared as main predictors of MA size whereas LV size had a more modest influence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Aortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated., Methods: In our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements., Results: We enrolled 296 patients (74 ± 10 years,73% men); mean follow-up duration was 3.0 ± 1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ± 0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17)., Conclusions: In a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: This study sought to evaluate the prognostic value of mean pressure gradient (MPG) increase and peak systolic pulmonary artery pressure (SPAP) measured during exercise stress echocardiography in asymptomatic patients with aortic stenosis (AS)., Background: Exercise testing is recommended in asymptomatic AS patients, but the additional value of exercise-stress echocardiography, especially the prognostic value of MPG increase and peak SPAP, is still debated., Methods: We enrolled all consecutive patients with pure, isolated, asymptomatic AS and preserved ejection fraction ≥50% and normal SPAP (<50 mm Hg) who underwent symptom-limited exercise echocardiography at our institution. Occurrence of AS-related events (symptoms or congestive heart failure) or occurrence of aortic valve replacement was recorded., Results: We enrolled 148 patients (66 ± 15 years of age; 74% males; MPG: 47 ± 13 mm Hg; SPAP: 34 ± 6 mm Hg). No complications were observed. Thirty-six patients (24%) had an abnormal exercise test result (occurrence of symptoms, fall in blood pressure, and/or ST-segment depression) and were referred for surgery. Among the 112 patients with a normal exercise test result, 38 patients (34%) had abnormal exercise echocardiography scores (MPG increase >20 mm Hg and/or SPAP at peak exercise >60 mm Hg). These 112 patients were managed conservatively. During a mean follow-up of 14 ± 8 months, an AS-related event occurred in 30 patients, and 25 patients underwent surgery. Neither MPG increase >20 mm Hg nor peak SPAP >60 mm Hg was predictive of occurrence of AS-related events or aortic valve replacement (all p > 0.20). In contrast, baseline AS severity was an important prognostic factor (all p < 0.01)., Conclusions: In this observational study including 148 patients with asymptomatic AS, we confirmed and extended the importance of exercise testing for unveiling functional limitation. More importantly, neither the increase in MPG nor in SPAP at peak exercise was predictive of outcome. Our results do not support the use of these parameters in risk-stratification and clinical management of asymptomatic AS patients., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)