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Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current published reports on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS.

Surgical aortic valve replacement can be performed through a minimally invasive (MI) or full sternotomy (FS) approach. The present study compared outcomes of MI vs FS for isolated surgery among patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 3 low-risk trial.Patients with severe, symptomatic aortic stenosis at low surgical risk with anatomy suitable for transfemoral access were eligible for PARTNER 3 enrollment. The primary outcome was the composite end point of death, stroke, or rehospitalization (valve-, procedure-, or heart failure-related) at 1 year. Secondary outcomes included the individual components of the primary end point as well as patient-reported health status at 30 days and 1 year.In the PARTNER 3 study, 358 patients underwent isolated valve replacement at 68 centers through an MI (n = 107) or FS (n = 251) approach (8 patients were converted from MI to FS). Mean age and Society of Thoracic Surgeons score were similar between groups. The Kaplan-Meier estimate of the primary outcome was similar in the MI vs FS groups (16.9% vs 14.9%; hazard ratio, 1.15; 95% CI, 0.66-2.03; P = .618). There were no significant differences in the 1-year rates of all-cause death (2.8% vs 2.8%), all stroke (1.9% vs 3.6%), or rehospitalization (13.3% vs 10.6%, P.05 for all). Quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire score at 30 days or 1 year, was comparable in both groups.For patients at low risk for isolated surgery, MI and FS approaches were associated with similar in-hospital and 1-year outcomes.

Multidetector computed tomography (MDCT) can provide valuable information for preprocedural planning of transcatheter mitral valve interventions. However, no data exist on MDCT parameters predicting residual mitral regurgitation (MR) post-MitraClip (Abbott Laboratories, Abbott Park, IL, USA).We analyzed preprocedural MDCTs of 78 consecutive patients with secondary MR undergoing MitraClip implantation at our institution. Moderate-or-severe mitral leaflet calcification (MLC) was defined as calcification, with-or-without mitral annular calcification, extending beyond the mitral leaflet base. Residual MR was assessed by postprocedural transesophageal echocardiography, and clinical outcomes were assessed at 1-year.Fifteen patients (19 %) had residual MR ≥2+. Compared to patients with none-or-mild residual MR, MDCT-derived mitral valve orifice area (MVOA) to mitral annulus area (MAA) ratio was significantly lower (0.32 ± 0.06 vs. 0.39 ± 0.09; p = 0.003), and the prevalence of MLC was higher (40 % vs. 18 %; p = 0.057) in those with residual MR ≥2+. Furthermore, the MVOA/MAA ratio and MLC were independent predictors of residual MR ≥2+ post-MitraClip [adjusted odds ratio (ORIn patients with secondary MR undergoing the MitraClip procedure, preprocedural MDCT parameters, specifically MVOA/MAA ratio and MLC, are useful to predict postprocedural residual MR.

Physiologic right ventricle-pulmonary artery (RV-PA) coupling may be impaired in patients with aortic stenosis (AS).This study aimed to assess the incidence and prognostic significance of impaired RV-PA coupling in low-risk patients with symptomatic severe AS undergoing transcatheter aortic valve replacement or surgical aortic valve replacement.RV-PA coupling was measured by transthoracic echocardiography as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) in patients in the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial. The primary endpoint was the composite of all-cause mortality, stroke, and rehospitalization at the 2-year follow-up.Among 570 low-risk patients included in the analysis, RV-PA uncoupling was defined by a TAPSE/PASP ratio ≤ 0.55 mm/mm Hg. At baseline, 222 of 570 (38.9%) patients had RV-PA uncoupling. At 2 years, patients with baseline RV-PA uncoupling had an increased incidence of the primary endpoint (19.1% vs 9.9%, P = 0.002), all-cause mortality (5.9% vs 0.6%, P 0.001), cardiovascular mortality (4.1% vs 0.6%, P = 0.003), and rehospitalization (13.5% vs 7.3%, P = 0.018). On multivariable analysis, baseline RV-PA uncoupling remained an independent predictor of the primary endpoint at 2 years (HR: 1.92; 95% CI: 1.04-3.57; P = 0.038).In patients with symptomatic severe AS at low surgical risk undergoing transcatheter aortic valve replacement or surgical aortic valve replacement, baseline RV-PA uncoupling defined by TAPSE/PASP ≤ 0.55 mm Hg was associated with adverse clinical outcomes at 2 years, including all-cause mortality, cardiovascular mortality, and rehospitalization.

Transcatheter aortic valve replacement (TAVR) is generally performed without control over the alignment of the bioprosthesis to the native aortic valve (AV) commissures. Data on the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome after TAVR are scarce.The aim of this study was to investigate the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome in patients with severe tricuspid aortic stenosis undergoing TAVR using the balloon-expandable (BE) SAPIEN 3 valve (Edwards LifeSciences).Clinical data of consecutive patients who underwent BE TAVR at Cedars-Sinai Medical Center (Los Angeles, California, USA) enrolled in the RESOLVE (Assessment of TRanscathetER and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation) registry were retrospectively analyzed to evaluate CMA, which was defined as a neocommissure position30° compared with native commissures on computed tomography.A total of 324 patients (36.6% female, median Society of Thoracic Surgeons score of 3.9%) were included in the analysis. CMA was present in 171 individuals (52.8%). At 30 days, rates of aortic regurgitation greater than mild (5.6%) and a residual AV gradient ≥20 mm Hg (7.4%) were not different between CMA and non-CMA patients. Commissural orientation was independently associated with a relative AV mean gradient increase50% from discharge to 30 days (per increase of 10° misalignment; OR: 1.3; 95% CI: 1.0-1.4; P = 0.01). The long-term composite outcome of death or stroke was not different between groups (log-rank P = 0.29).In patients with severe tricuspid aortic stenosis who undergo SAPIEN 3 TAVR, the neocommissures align randomly. Our data demonstrate that commissural alignment may impact device performance and clinical outcomes in patients undergoing BE TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic VaLVve Dysfunction with Multimodality Imaging and Its TrEatment with Anticoagulation [RESOLVE]; NCT02318342).

The aim of this study was to report the outcomes of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) at 5 years.TAVR for degenerated surgical bioprostheses in patients at high risk for reoperative surgery is an important treatment option that may delay or obviate the need for surgical intervention; however, long-term outcomes of this procedure are unknown.The PARTNER (Placement of Aortic Transcatheter Valves) 2 ViV and continued access registries prospectively enrolled patients with failed surgical bioprostheses at high risk for reoperation. Five-year clinical and echocardiographic follow-up data were obtained in 95.9% of patients.In 365 (96 registry and 269 continued access) patients, the mean age was 78.9 ± 10.2 years, the mean Society of Thoracic Surgeons predicted risk of surgical mortality score was 9.1 ± 4.7%, and New York Heart Association functional class was III or IV in 90.4%. At 5 years, the Kaplan-Meier rates of all-cause mortality and any stroke were 50.6% and 10.5%, respectively. Using Valve Academic Research Consortium 3 definitions, the incidence of structural valve deterioration, related hemodynamic valve deterioration, or bioprosthetic valve failure at 5 years was 6.6%. Aortic valve re-replacement was performed in 6.3% (n = 14), the majority of which was due to stenosis (n = 6) and combined aortic insufficiency/paravalvular regurgitation (n = 3). The mean gradient, Doppler velocity index, paravalvular regurgitation, and quality of life measured by Kansas City Cardiomyopathy Questionnaire scores in survivors remained stable from 30 days postprocedure through 5 years.At the 5-year follow-up, TAVR for bioprosthetic aortic valve failure in high surgical risk patients was associated with sustained improvement in clinical and echocardiographic outcomes.

The purpose of this study was to characterize the anatomic relationship between the inferior vena cava (IVC) and tricuspid annulus (TA) and its potential impact on the performance of transcatheter TV interventions.Transcatheter tricuspid valve (TV) interventions are emerging as a therapeutic alternative for the treatment of severe, symptomatic tricuspid regurgitation (TR). Progression of TR is associated with right heart dilatation. These anatomic changes may distort the IVC-TA relationship and impact successful implantation of transcatheter devices.Fifty patients who presented with symptomatic TR for consideration of transcatheter TV therapy with an available CT were included in the study. Comprehensive transesophageal echocardiogram and CT analyses were performed to assess the right-sided cardiac chambers, TA and IVC-TA relationship.The mean age of the study cohort was 78.4 ± 8.9 years. Torrential TR was present in 54% (n = 27). There was considerable variation in the short axis mid-IVC to mid-TA offset (SAXThe IVC-to-TA relationship exhibits significant variability in patients with symptomatic TR. CT analysis of the tricuspid anatomy, including the relationship to the surrounding structures and the IVC, is essential for planning transcatheter TV interventions. Further studies are needed to define whether the IVC-to-TA relationship is a predictor of technical success in the context of specific transcatheter delivery systems.

Objectives The aim of this study was to evaluate the clinical impact of computed tomography (CT)–derived pulmonary artery dilatation (PAD) in patients undergoing transcatheter aortic valve replacement (TAVR). Background Several studies have reported an association between pulmonary hypertension and cardiovascular events, but the prognostic value of PAD in patients undergoing TAVR remains unclear. Methods The preprocedural computed tomographic studies of patients who underwent TAVR at Cedars-Sinai Medical Center between November 2013 and December 2017 were analyzed. Patients were divided into 2 groups according to the presence of PAD assessed on CT (pulmonary artery [PA] diameter ≥29 mm). The primary endpoint was all-cause mortality at 2 years. Results A total of 895 patients were included (mean age 81.3 ± 8.5 years), with a mean Society of Thoracic Surgeons score of 4.8%. The median PA diameter was 28.0 mm, and PAD was observed in 369 patients (41.2%). Compared with the no-PAD group, the PAD group had higher Society of Thoracic Surgeons scores and higher rates of atrial fibrillation, chronic kidney disease, and chronic obstructive pulmonary disease. The PAD group had higher 2-year all-cause mortality than the no-PAD group (28.9% vs 12.8%; P 36 mm Hg). Conclusions CT-derived PAD is a significant prognostic factor in patients undergoing TAVR.

Bicuspid aortic insufficiency (BAI) patients with root aneurysm often require aortic valve and root replacement in a composite procedure. The valve-sparing root replacement (VSARR) procedure is aimed at preserving the native valve when possible. This case highlights a successful transcatheter aortic valve replacement procedure in a BAI patient previously treated with VSARR. (Level of Difficulty: Intermediate.), Central Illustration

Aims Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. Methods and results We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15 684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82–1.01, P = 0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P Conclusion SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure.

Objectives This study sought to investigate the impact of computed tomography (CT)–based area and perimeter oversizing on the incidence of paravalvular regurgitation (PVR) and valve hemody...

The aim of this study was to compare 5-year cardiovascular, renal, and bioprosthetic valve durability outcomes in patients with severe aortic stenosis (AS) and chronic kidney disease (CKD) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).Patients with severe AS and CKD undergoing TAVR or SAVR are a challenging, understudied clinical subset.Intermediate-risk patients with moderate to severe CKD (estimated glomerular filtration rate 60 mL/min/mThe study population included 1,045 TAVR patients (512 SAPIEN XT, 533 SAPIEN 3) and 479 SAVR patients. At 5 years, SAVR was better than SAPIEN XT TAVR (52.8% vs 68.0%; P = 0.04) but similar to SAPIEN 3 TAVR (52.8% vs 58.7%; P = 0.89). Perioperative AKI was more common after SAVR than TAVR (26.3% vs 10.3%; P 0.001) and was independently associated with long-term outcomes. Compared with SAVR, bioprosthetic valve failure and stage 2 or 3 structural valve deterioration were significantly greater for SAPIEN XT TAVR (P 0.05) but not for SAPIEN 3 TAVR.In intermediate-risk patients with AS and CKD, SAPIEN 3 TAVR and SAVR were associated with a similar risk for the primary endpoint at 5 years. AKI was more common after SAVR than TAVR, and SAPIEN 3 valve durability was comparable with that of surgical bioprostheses.

Multidetector computed tomography (MDCT) can provide valuable information for preprocedural planning of transcatheter mitral valve interventions. However, no data exists on pre-MDCT parameters predicting high transmitral pressure gradient (TMPG) post-MitraClip procedure. We analyzed the preprocedural MDCTs of 156 consecutive patients with mitral regurgitation undergoing MitraClip implantation at our institution. The mean TMPG was assessed by periprocedural transesophageal and pre-discharge transthoracic echocardiography. MDCT-derived mitral annulus area (MAA), anterior-posterior (AP) and medial-lateral (ML) mitral annulus diameters, and mitral valve orifice area (MVOA) were smaller in patients with mean TMPG ≥5 mmHg than those with mean TMPG5 mmHg after 1-or 2-clip implantation. Small MAA, AP and ML diameters, and MVOA were moderately correlated with high TMPG post-MitraClip, in which MAA and MVOA had the highest degree of correlation after 1-clip (r = -0.46 both), whereas MAA and ML had the strongest degree of correlation after 2-clip (r = -0.39 both) and at discharge (r = -0.38 both). From the receiver-operating-characteristic curve analyses, no significant differences in the area under the curve were observed among these MDCT parameters for low TMPG after MitraClip implantation, except for those between MAA and AP diameter at discharge (p=0.026). For optimal cutoff values, MAA ≥1100 and ≥1300 mm

OBJECTIVES The aim of this study was to characterize the feasibility of coronary angiography (CA) and percutaneous coronary intervention (PCI) in acute settings among patients who have undergone transcatheter aortic valve replacement (TAVR). BACKGROUND Impaired coronary access after TAVR may be challenging and particularly in acute settings could have deleterious consequences. METHODS In this international registry, data from patients with prior TAVR requiring urgent or emergent CA were retrospectively collected. A total of 449 patients from 25 sites with acute coronary syndromes (89.1%) and other acute cardiovascular situations (10.9%) were included. RESULTS Success rates were high for CA of the right coronary artery (98.3%) and left coronary artery (99.3%) and were higher among patients with short stent-frame prostheses (SFPs) than in those with long SFPs for CA of the right coronary artery (99.6% vs 95.9%; P��=��0.005) but not for CA of the left coronary artery (99.7% vs 98.7%; P��=��0.24). PCI of native coronary arteries was successful in 91.4% of cases and independent of valve type (short SFP 90.4% vs long SFP 93.4%; P��=��0.44). Guide engagement failed in 6 patients, of whom 3 underwent emergent coronary artery bypass grafting and another 3 died in the hospital. Among patients requiring revascularization of native vessels, independent predictors of 30-day all-cause mortality were prior diabetes, cardiogenic shock, and failed PCI but not valve type or success of coronary engagement. CONCLUSIONS CA or PCI after TAVR in acute settings is usually successful, but selective coronary engagement may be more challenging in the presence of long SFPs. Among patients requiring PCI, prior diabetes, cardiogenic shock, and failed PCI were predictors of early mortality.

The aim of this study was to assess the association between Doppler velocity index (DVI) and 2-year outcomes for balloon-expandable SAPIEN 3 transcatheter aortic valve replacement (TAVR) and for surgical aortic valve replacement (SAVR).DVI0.35 is normal for a prosthetic valve, but recent studies suggest that DVI 0.50 is associated with poor outcomes following TAVR.Patients with severe aortic stenosis enrolled in the PARTNER (Placement of Aortic Transcatheter Valve) 2 (intermediate surgical risk) or PARTNER 3 (low surgical risk) trial undergoing TAVR (n = 1,450) or SAVR (n = 1,303) were included. Patients were divided into 3 DVI groups on the basis of core laboratory-assessed discharge or 30-day echocardiograms: DVIFollowing TAVR, there were no differences among the 3 DVI groups in composite outcomes of death, stroke, or rehospitalization or in any individual components of 2-year outcomes (P0.70 for all). Following SAVR, there was no difference among DVI groups in the composite outcome (P = 0.27), but there was a significant association with rehospitalization (P = 0.02). Restricted cubic-spline analysis for combined outcomes showed an increased risk with post-SAVR DVI ≤0.35 but no relationship post-TAVR. DVI ≤0.35 was associated with increased 2-year composite outcome for SAVR (HR: 1.81; 95% CI: 1.29-2.54; P 0.001), with no adverse outcomes for TAVR (P = 0.86).In intermediate- and low-risk cohorts of the PARTNER trials, DVI ≤0.35 predicted worse 2-year outcomes following SAVR, driven primarily by rehospitalization, with no adverse outcomes associated with DVI following TAVR with the balloon-expandable SAPIEN 3 valve.

Severe symptomatic degenerative mitral regurgitation (DMR) has a poor prognosis in the absence of treatment, and new transcatheter options are emerging.The CLASP IID randomized trial (NCT03706833) is the first to evaluate the safety and effectiveness of the PASCAL system compared to the MitraClip system in patients with significant symptomatic DMR. In this report, we present the primary safety and effectiveness endpoints for the trial.Patients with 3+ or 4+ DMR at prohibitive surgical risk were assessed by a central screening committee and randomized 2:1 (PASCAL:MitraClip). Study oversight also included an echocardiographic core laboratory and a clinical events committee. The primary safety endpoint was a composite major adverse event (MAE) rate at 30 days. The primary effectiveness endpoint was the proportion of patients with MR ≤2+ at 6 months.A pre-specified interim analysis in 180 patients demonstrated non-inferiority of the PASCAL system vs. MitraClip system for the primary safety and effectiveness endpoints, MAE: 3.4% vs. 4.8%, MR ≤2+: 96.5% vs. 96.8%, respectively. Functional and quality-of-life outcomes significantly improved in both groups (p0.05). The proportion of patients with MR ≤1+ was durable in the PASCAL group from discharge to 6 months [PASCAL: 87.2% and 83.7% (p=0.317 vs. discharge); MitraClip: 88.5% and 71.2% (p=0.003 vs. discharge), respectively].The CLASP IID trial demonstrated safety and effectiveness of the PASCAL system and met non-inferiority endpoints, expanding transcatheter treatment options for prohibitive surgical risk patients with significant symptomatic DMR.

BACKGROUND The aim of this study was to clarify the clinical outcomes of patients with atrial functional mitral regurgitation (FMR) who underwent the MitraClip procedure compared with those with conventional FMR and sinus rhythm (SR).Methods and Results:Of 303 patients with FMR who underwent the MitraClip procedure, 40 with "atrial-FMR" defined as FMR with permanent atrial fibrillation and normal left ventricular (LV) function/size and 115 with "sinus-FMR" defined as FMR with SR and LV dysfunction were reviewed. Transthoracic and 3D transesophageal echocardiography, and the cardiac complication rate (composite of all-cause death, heart failure admission, mitral valve (MV) surgery, and redo MitraClip procedure) during the 12-month follow-up were compared between the groups. After the MitraClip procedure, reductions in the mitral annular area and its anteroposterior dimension and in the leaflet closure area were observed in both groups. MV orifice area was smaller with greater transmitral pressure gradient (P

Objectives The authors report 1-year outcomes of high-risk patients with failed surgical annuloplasty rings undergoing transseptal mitral valve–in–ring (MViR) with the SAPIEN 3 aortic transcatheter heart valve (THV). Background The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study evaluating transseptal MViR with the SAPIEN 3 aortic THV in high-risk patients with failed surgical annuloplasty rings. Methods Prospective enrollment of high-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis and failed annuloplasty rings at 13 U.S. sites. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). Results Thirty patients were enrolled between January 2016 and October 2017 (median age 71.5 years [interquartile range: 67.0 to 76.8 years], 36.7% women, median Society of Thoracic Surgeons score 7.6% [interquartile range: 5.1% to 11.8%], 76.7% in New York Heart Association functional class III or IV). Technical success was 66.7% (driven primarily by need for a second valve in 6 patients). There was no intraprocedural mortality or conversion to surgery. The primary performance endpoint was achieved in 85.7% of survivors at 30 days (24 of 28) and 89.5% of patients alive at 1 year with echocardiographic data available (17 of 19). All-cause mortality at 30 days was 6.7% and at 1 year was 23.3%. Among survivors at 1-year follow-up, 84.2% were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.0 mm Hg (interquartile range: 4.7 to 7.3 mm Hg), and all had ≤1+ MR. Conclusions Transseptal MViR was associated with a 30-day mortality rate lower than predicted by the Society of Thoracic Surgeons score. At 1 year, transseptal MViR was associated with symptom improvement and stable THV performance.

Background In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year. Objectives This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial. Methods This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis. Results Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years. Conclusions At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114 )

Limited data exist on optimal medical therapy post-transcatheter aortic valve implantation (TAVI) for late cardiovascular events prevention. We aimed to evaluate the benefits of beta-blocker (BB), renin-angiotensin system inhibitor (RASi), and their combination on outcomes following successful TAVI. In a consecutive cohort of 1,684 patients with severe aortic stenosis undergoing TAVI, the status of BB and RASi treatment at discharge was collected, and patients were classified into 4 groups: no-treatment, BB alone, RASi alone, and combination groups. The primary outcome was a composite of all-cause mortality and rehospitalization for heart failure (HHF) at 2-year. There were 415 (25%), 462 (27%), 349 (21%), and 458 (27%) patients in no-treatment, BB alone, RASi alone, and combination groups, respectively. The primary outcome was lower in RASi alone (21%; adjusted hazard ratio [HR]adj: 0.58; 95% confidence interval [CI]: 0.42 to 0.81) and combination (22%; HRadj: 0.53; 95% CI: 0.39 to 0.72) groups than in no-treatment group (34%) but no significant difference between RASi alone and combination groups (HRadj: 1.14; 95% CI: 0.80 to 1.62). The primary outcome results were maintained in a sensitivity analysis of patients with reduced left ventricular systolic function. Furthermore, RASi treatment was an independent predictor of 2-year all-cause mortality (HRadj: 0.68; 95% CI: 0.51 to 0.90), while that was not observed in BB therapy (HRadj: 0.94; 95% CI: 0.71 to 1.25). In conclusion, post-TAVI treatment with RASi, but not with BB, was associated with lower all-cause mortality and HHF at 2-year. The combination of RASi and BB did not add an incremental reduction in the primary outcome over RASi alone.

Off-label transcatheter tricuspid valve edge-to-edge repair (tricuspid clip) with the United States Food and Drug Administration (FDA) approved commercially available MitraClip system (Abbott, Sant...

The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p 0.01).In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.

The aim of this study was to evaluate the risk of coronary obstruction due to sinus sequestration in redo transcatheter aortic valve replacement (TAVR) using post-TAVR computed tomography (CT).Little information is available regarding the risk of coronary obstruction due to sinus sequestration in redo TAVR inside a previously implanted TAV.Post-TAVR CT of 66 patients who received an Evolut R or Evolut PRO and 345 patients who received a SAPIEN 3 were analyzed. Redo TAVR was considered at risk of coronary obstruction due to sinus sequestration if: 1) the prior TAV commissure level was above sinotubular junction (STJ); and 2) the distance between TAV and STJ was 2.0 mm in each coronary sinus.In total, 45.5% in the Evolut R/Evolut PRO group and 2.0% in the SAPIEN 3 group had CT-identified risk of sinus sequestration at 1 or both coronary arteries (p 0.001). CT-identified risk of sinus sequestration was observed in 39.4% for the left coronary artery and 24.2% for the right coronary artery in the Evolut R/Evolut PRO group, while those percentages were 2.0% for the left coronary artery and 0.6% for the right coronary artery in the SAPIEN 3 group. In a coronary-level analysis, overlaps between the first TAV commissural posts and coronary ostium were observed in 45.2% in the Evolut R/Evolut PRO group and 11.1% in in the SAPIEN 3 group among coronary arteries at CT-identified risk of sinus sequestration.The risk of sinus sequestration in redo TAVR should be carefully screened by CT, especially in patients with low STJ height. TAV with low commissure height that was designed to achieve commissure-to-commissure alignment with the native aortic valves may be preferable to avoid the risk of coronary obstruction due to sinus sequestration and allow for a preventive leaflet laceration procedure in future redo TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation [RESOLVE]; NCT02318342).

The aim of this study was to characterize the safety profile of an intra-annular self-expanding valve with a next-generation low-profile delivery system (DS).Key design modifications to the FlexNav DS include the addition of a hydrophilic-coated, integrated sheath and stability layer to facilitate gradual, controlled deployment in vessels with diameter ≥5 mm.Patients were pooled from 2 concurrent prospective, multicenter, single-arm studies (FlexNav DS arm of PORTICO IDE [Portico Re-Sheathable Transcatheter Aortic Valve System U.S. IDE Trial] [n = 134] and the FlexNav EU CE Mark Study [n = 46]) for the analysis. The primary endpoint was Valve Academic Research Consortium-2-defined major vascular complications at 30 days. Clinical outcomes and valve performance were assessed through 30 days by an independent clinical events committee and an echocardiography core laboratory, respectively.One hundred forty high-risk and 40 extreme-risk subjects enrolled between October 15, 2018, and December 10, 2019, from 28 sites in the United States, Australia, and Europe who underwent attempted transfemoral Portico valve implantation were included. The mean age was 85.1 ± 5.6 years, 60% were women, the mean Society of Thoracic Surgeons score was 5.3%, and 96.1% presented with ≥1 frailty factor. Technical device success was 96.7%. At 30 days, the rate of major vascular complications was 5.0%, with 4.4% of complications adjudicated as access site-related (3.3% transcatheter aortic valve replacement DS access site-related). Death (0.6%) and disabling stroke (1.1%) were rare. The rate of new permanent pacemaker implantation was 15.4%. Echocardiography revealed a mean gradient of 7.1 ± 3.2 mm Hg, mean valve area of 1.77 ± 0.41 cmPortico valve implantation with the FlexNav DS was associated with an excellent safety profile at 30 days.

The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR).The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported.Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year.One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p 0.001 for all).The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study [CLASP]; NCT03170349).

Background It is unknown whether transcatheter valves will have similar durability as surgical bioprosthetic valves. Definitions of structural valve deterioration (SVD), based on valve rel...

Although aortic valve replacement with implantation of a bioprosthesis has been widely performed for more than 50 years, appreciation of the development of bioprosthetic leaflet thrombosis has incr...

Summary Background Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. Methods In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. Findings Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI −0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI −3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. Interpretation The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. Funding Abbott.

Aims Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and results We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. Trial registration Clinicaltrials.gov identifier: NCT01458405.

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality in adults, and symptoms typically develops in adulthood. In the majority of cases, BAV disease progresses with age and surgical aortic valve replacement (AVR) is performed with excellent operative outcomes. Based on a series of randomized trials, transcatheter AVR (TAVR) has evolved from a novel technology to an established therapy for patients with symptomatic severe aortic stenosis (AS) regardless of risk profile. Despite exclusion of bicuspid anatomy from the randomized trials, an increasing number of patients with BAV-AS have been treated with TAVR. Recent observational studies showed the comparable outcomes of TAVR between bicuspid and tricuspid AS. However, worse outcomes in patients with unfavorable bicuspid anatomy such as calcified raphe plus excessive leaflet calcification have raised concerns for TAVR in younger and lower risk population. For the further expansion of TAVR toward BAV-AS population, we need randomized trials of TAVR in this population. Until then, previous registry data combined with computed tomographic-based anatomical assessment may guide the optimal therapy in patients with bicuspid anatomy.

Background Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction. Objectives The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes. Methods The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low–surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory. Results The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04). Conclusions Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.