Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Membranous Septum Length Predicts New Conduction Abnormalities in Surgical Aortic Valve Replacement: A Novel Predictor for Permanent Pacemaker Implantation After Surgical Aortic Valve Replacement.

INTRODUCTION: The membranous septum (MS) length measured by cardiac computed tomography (CT) is useful for the prediction of permanent pacemaker implantation (PPMI) and new left bundle branch block (LBBB) after transcatheter aortic valve replacement. However, its predictive value for patients undergoing surgical aortic valve replacement (SAVR) is unknown. METHODS: A total of 2531 consecutive patients were registered in the institutional Society of Thoracic Surgeons database between July 2017 and June 2020. Patients who underwent non-SAVR procedures, had prior pacemaker/implantable cardioverter defibrillator, prior SAVR, no preprocedural CT assessment, or suboptimal CT imaging were excluded. RESULTS: A total of 126 SAVR with preprocedural CT assessment were analyzed. Bicuspid aortic valve morphology was confirmed on CT in 59.5% of patients. There were three new PPMIs and five new LBBBs observed after SAVR at the time of discharge. In-hospital mortality was 0.8%. Low left ventricular (LV) ejection fraction (<50%), LV mass index >120 g/m2, large right coronary artery height, and MS length <1.5 mm predicted new PPMI/LBBB. Multivariate analysis showed LV mass index >120 g/m2 (odds ratio: 9.165; 95% confidence interval: 1.644-51.080; P = 0.011) and MS length <1.5 mm (odds ratio: 14.449; 95% confidence interval: 1.632-127.954; P = 0.016) were independent predictors for new PPMI/LBBB. CONCLUSIONS: Short MS length on preoperative cardiac CT is a powerful and novel predictor for the risk of new PPMI/LBBB after SAVR. Special care should be taken in patients with short MS length to avoid suture-mediated trauma.

Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

Evaluation of the safety and efficacy of a novel Anatomical classification and dUal anchoRing theory to Optimize the tavR strategy for pure severe Aortic regurgitation (AURORA): a prospective cohort study.

BACKGROUND: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet. METHODS: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria. DISCUSSION: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients. TRIAL REGISTRATION: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 .

Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

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.

Long-term outcomes after transcatheter aortic valve replacement with minimal contrast in chronic kidney disease.

BACKGROUND: Patients with renal insufficiency have poor short-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Retrospective chart review identified 575 consecutive patients not on hemodialysis who underwent TAVR between September 2014 and January 2017. Outcomes were defined by VARC-2 criteria. Primary outcome of all-cause mortality was evaluated at a median follow-up of 811 days (interquartile range 125-1,151). RESULTS: Preprocedural glomerular filtration rate (GFR) was ≥60 ml/min in 51.7%, 30-60 ml/min in 42.1%, and < 30 ml/min in 6.3%. Use of transfemoral access (98.8%) and achieved device success (91.0%) did not differ among groups, but less contrast was used with lower GFR (23 ml [15-33], 24 ml [14-33], 13 ml [8-20]; p < .001). Peri-procedural stroke (0.7%, 2.1%, 11.1%; p < .001) was higher with lower GFR. Core lab analysis of preprocedural computed tomography scans of patients who developed a peri-procedural stroke identified potential anatomic substrate for stroke in three out of four patients with GFR 30-60 ml/min and all three with GFR <30 ml/min (severe atheroma was the most common subtype of anatomical substrate present). Compared to GFR ≥60 ml/min, all-cause mortality was higher with GFR 30-60 ml/min (HR 1.61 [1.00-2.59]; aHR 1.61 [0.91-2.83]) and GFR <30 ml/min (HR 2.41 [1.06-5.48]; aHR 2.34 [0.90-6.09]) but not significant after multivariable adjustment. Follow-up echocardiographic data, available in 63%, demonstrated no difference in structural heart valve deterioration over time among groups. CONCLUSIONS: Patients with baseline renal insufficiency remain a challenging population with poor long-term outcomes despite procedural optimization with a transfemoral-first and an extremely low-contrast approach.

Transcatheter Aortic Valve Leaflet Thrombosis: Prevalence, Management, and Future Directions.

PURPOSE OF REVIEW: We review the pathology, prevalence, diagnosis, hemodynamics, risk factors, prognosis, and treatment of leaflet thrombosis (LT), and suggest future directions in this field. RECENT FINDINGS: The latest meta-analysis showed the prevalence of overall LT is 5.4% (clinical LT of 1.2% and subclinical LT of 15.1%). Either subclinical or clinical LT is not associated with risk of mortality; however, clinical LT is associated with increased risk of stroke. Although LT can be reduced by oral anticoagulation therapy (OAT), routine use of OAT as primary prevention for high-risk patients is not recommended due to increased risk of mortality. Four-dimensional computed tomography plays an important role in the diagnosis of LT and the accumulation of qualitative or qualitative assessments of hypoattenuated leaflet thickening would provide more clues to clarify effective OAT strategies. In addition, further studies are warranted to evaluate the efficacy of other anticoagulants in low-intermediate risk patients.

Anticoagulation Therapy After Transcatheter Aortic Valve Replacement.

PURPOSE OF REVIEW: We review the prevalence; natural history; impact of subclinical clinical thrombosis on valve hemodynamics, clinical outcomes, and valve durability; and the role of anticoagulation after transcatheter aortic valve replacement (TAVR). RECENT FINDINGS: Subclinical leaflet thrombosis is a dynamic finding present in both transcatheter and surgical bioprosthetic aortic valves. This finding is less prevalent in patients on anticoagulation and resolves following initiation of anticoagulation. Routine anticoagulation after TAVR in high-surgical-risk patients was associated with increased mortality and thromboembolic complications. In the absence of a clinical indication for anticoagulation, there is no reason to initiate anticoagulation after TAVR for the prevention of subclinical leaflet thrombosis. In patients with an established indication for anticoagulation, for instance, atrial fibrillation, clinical or symptomatic valve thrombosis, or a clinical event related to valve thrombosis, anticoagulation should be initiated or continued after TAVR to treat the clinical indication.

A novel user-friendly transcatheter edge-to-edge mitral valve repair device in a porcine model.

OBJECTIVES: The present study was performed to evaluate the feasibility and safety of the ValveClamp system for transcatheter edge-to-edge mitral valve repair in a porcine model. BACKGROUND: The ValveClamp system is a novel, transapically delivered edge-to-edge mitral valve repair system designed for ease of operation. METHODS: Thirteen young adult swine were enrolled in the study. The procedure was performed via the transapical approach under epicardial echocardiography guidance. RESULTS: The acute procedure success rate was 92.3% (12/13). The catheter manipulation time was just 18.5 ± 8.2 min. Four pigs were explanted on the 14th day after the procedure. One pig died at the 20th day because of pneumonia. The other eight pigs lived to the study endpoint (140 days). No pig had severe mitral valve dysfunction. The gross observation showed that the clamp device was securely attached and created a double-orifice mitral valve in all pigs except the failed one. In the eight pigs living to the endpoint, the clamp device was noted to be completely endothelialized. None of the 13 pigs developed infective endocarditis, thrombosis, thromboembolism, or valve impairment. In two pigs for which mitral regurgitation (MR) was created, the degree of MR was reduced from severe to trace after the device implantation. CONCLUSIONS: It was feasible and safe to use ValveClamp to perform a catheter-mediated edge-to-edge mitral valve repair in a porcine model. This system is potentially applicable as a novel user-friendly system for the treatment of MR.

Preprocedural P2Y12 inhibition and decrease in platelet count following transcatheter aortic valve replacement.

BACKGROUND: Thrombocytopenia after transcatheter aortic valve replacement (TAVR) is associated with adverse clinical outcomes. Whether preprocedural P2Y12 inhibition prevents postprocedural thrombocytopenia is uncertain. METHODS: This retrospective analysis identified consecutive patients (n = 266) undergoing TAVR between November 2016 and July 2017. Preprocedure clopidogrel load ≥300 mg or maintenance P2Y12 inhibitor therapy defined preprocedural P2Y12 inhibition. Patients who did not consent for the registry (n = 8), with baseline severe thrombocytopenia (<90 × 103 platelets/µL; n = 14), or without baseline platelet count (n = 4) were excluded. The primary outcome was proportion of patients who developed >20% decrease in platelet count from baseline to day 1 post-TAVR. RESULTS: Patients with (n = 134) versus without (n = 106) preprocedural P2Y12 inhibition had no differences in platelet count at baseline. Patients with preprocedural P2Y12 inhibition had a significantly lower proportion of the primary outcome (34.3% vs. 57.5%, p = .001) and a lower absolute decrease in platelet count (32.8 × 103 vs. 45.8 × 103 platelet/µL, p = .01). Of patients without baseline thrombocytopenia (n = 198), a numerically lower rate of patients with versus without preprocedural P2Y12 inhibition developed thrombocytopenia on day 1 post-TAVR (25.5% vs. 36.4%, p = .1). CONCLUSION: Patients who received preprocedural P2Y12 inhibition prior to TAVR were less likely to demonstrate a decrease in platelet count after TAVR. Prospective studies to further understand the clinical implication of these findings are warranted.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus.

BACKGROUND: Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon. METHODS: Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus). RESULTS: SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (R2=0.7, P<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. CONCLUSIONS: Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.

Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study.

BACKGROUND: Subclinical leaflet thrombosis of bioprosthetic aortic valves after transcatheter valve replacement (TAVR) and surgical aortic valve replacement (SAVR) has been found with CT imaging. The objective of this study was to report the prevalence of subclinical leaflet thrombosis in surgical and transcatheter aortic valves and the effect of novel oral anticoagulants (NOACs) on the subclinical leaflet thrombosis and subsequent valve haemodynamics and clinical outcomes on the basis of two registries of patients who had CT imaging done after TAVR or SAVR. METHODS: Patients enrolled between Dec 22, 2014, and Jan 18, 2017, in the RESOLVE registry, and between June 2, 2014, and Sept 28, 2016, in the SAVORY registry, had CT imaging done with a dedicated four-dimensional volume-rendered imaging protocol at varying intervals after TAVR and SAVR. We defined subclinical leaflet thrombosis as the presence of reduced leaflet motion, along with corresponding hypoattenuating lesions shown with CT. We collected data for baseline demographics, antithrombotic therapy, and clinical outcomes. We analysed all CT scans, echocardiograms, and neurological events in a masked fashion. FINDINGS: Of the 931 patients who had CT imaging done (657 [71%] in the RESOLVE registry and 274 [29%] in the SAVORY registry), 890 [96%] had interpretable CT scans (626 [70%] in the RESOLVE registry and 264 [30%] in the SAVORY registry). 106 (12%) of 890 patients had subclinical leaflet thrombosis, including five (4%) of 138 with thrombosis of surgical valves versus 101 (13%) of 752 with thrombosis of transcatheter valves (p=0·001). The median time from aortic valve replacement to CT for the entire cohort was 83 days (IQR 33-281). Subclinical leaflet thrombosis was less frequent among patients receiving anticoagulants (eight [4%] of 224) than among those receiving dual antiplatelet therapy (31 [15%] of 208; p<0·0001); NOACs were equally as effective as warfarin (three [3%] of 107 vs five [4%] of 117; p=0·72). Subclinical leaflet thrombosis resolved in 36 (100%) of 36 patients (warfarin 24 [67%]; NOACs 12 [33%]) receiving anticoagulants, whereas it persisted in 20 (91%) of 22 patients not receiving anticoagulants (p<0·0001). A greater proportion of patients with subclinical leaflet thrombosis had aortic valve gradients of more than 20 mm Hg and increases in aortic valve gradients of more than 10 mm Hg (12 [14%] of 88) than did those with normal leaflet motion (seven [1%] of 632; p<0·0001). Although stroke rates were not different between those with (4·12 strokes per 100 person-years) or without (1·92 strokes per 100 person-years) reduced leaflet motion (p=0·10), subclinical leaflet thrombosis was associated with increased rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001). INTERPRETATION: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. Anticoagulation (both NOACs and warfarin), but not dual antiplatelet therapy, was effective in prevention or treatment of subclinical leaflet thrombosis. Subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes or TIAs. Despite excellent outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes. FUNDING: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet).

Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.

BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation. METHODS: We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).

Complications after Transfemoral Transcatheter Aortic Valve Replacement with a Balloon-Expandable Prosthesis: The Importance of Preventative Measures and Contingency Planning.

Transcatheter aortic valve replacement (TAVR) with balloon-expandable Edwards-SAPIEN valve was superior to standard therapy in inoperable patients and noninferior to surgical aortic valve replacement in high surgical-risk, but operable patients, with severe symptomatic aortic stenosis in the randomized controlled PARTNER trial. Since the first case of TAVR with a balloon-expandable valve in 2002, several groups have reported their experience with balloon-expandable valves with high-procedural success. In the United States, the balloon-expandable Edwards-SAPIEN valve is the only transcatheter heart valve approved by the FDA for commercial use. Moreover, this is only in high-risk inoperable patients. Despite increasing experience with the TAVR procedure, it can be associated with complications, which can be technically challenging, even for an experienced operator. Complications associated with TAVR include vascular complications, valve malpositioning, regurgitation, embolization, coronary compromise, conduction abnormalities, stroke/transient ischemic attack, acute kidney injury, cardiac tamponade, and hemodynamic collapse. A thorough understanding of the procedure is essential for pre-emptive planning for procedural complications and early identification and management of complications are necessary for procedural success. We hereby review our experience of transfemoral TAVR with balloon-expandable valves, offer practical tips to maximize the likelihood of procedural success, describe pre-emptive strategies to prevent peri-procedural complications and bailout measures to manage them, should they occur. © 2018 Wiley Periodicals, Inc.

Concomitant mitral annular calcification and severe aortic stenosis: prevalence, characteristics and outcome following transcatheter aortic valve replacement.

AIMS: Calcified aortic stenosis (AS) and mitral annular calcification (MAC) have certain similar etiology and pathophysiological mechanisms. MAC is frequently encountered in pre-procedural computed tomography (CT) imaging of patients that undergo transcatheter aortic valve replacement (TAVR), but its prognostic implications for these patients have not been thoroughly investigated. This study sought to evaluate the prevalence of MAC among patients with severe AS and to assess the clinical implications of MAC on these patients during and following TAVR. METHODS AND RESULTS: Consecutive patients that underwent TAVR were compared according to the existence of MAC and its severity in pre-TAVR CT scans. From the entire cohort of 761 patients, 49.3% had MAC, and 50.7% did not have MAC. Mild MAC was present in 231 patients (30.4%), moderate MAC in 72 patients (9.5%), and severe MAC in 72 patients (9.5%). Thirty-day mortality and major complications were similar between patients with and without MAC. In a multivariable survival analysis, severe MAC was found to be an independent strong predictor of overall mortality following TAVR (all-cause mortality: hazards ratio [HR] 1.95, 95% confidence interval [CI] 1.24-3.07, P = 0.004; cardiovascular mortality: HR 2.35, 95% CI 1.19-4.66; P = 0.01). Severe MAC was also found to be an independent strong predictor of new permanent pacemaker implantation (PPI) after TAVR (OR 2.83, 95% CI 1.08-7.47; P = 0.03). CONCLUSION: Half of the patients with severe AS evaluated for TAVR were found to have MAC. Severe MAC is associated with increased all-cause and cardiovascular mortality and with conduction abnormalities following TAVR and should be included in future risk stratification models for TAVR.

Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves.

AIMS: Four-dimensional volume-rendered computed tomography (4DCT) has demonstrated instances of hypo-attenuating leaflet thickening (HALT) with or without hypo-attenuation affecting motion (HAM) after transcatheter and surgical aortic valve implantation (TAVI, SAVR). The temporal pattern of evolution of these phenomena is uncertain. METHODS AND RESULTS: The SAVORY registry enrolled patients treated by TAVI (n = 75) or SAVR (n = 30) with two 4DCT scans fully interpretable for HALT and HAM as well as unchanged anti-thrombotic medication between the scans. Logistic regression analysis was performed to examine the evolution of HALT and HAM while accounting for demographic and baseline variables, timing of both CT scans, valve type and antithrombotic therapy. The analysis population consisted of 84 patients, in whom first and second CT scans were performed at 140 ± 152 days and 298 ± 141 days after valve implantation, respectively. Hypo-attenuating leaflet thickening was noted in 32 patients (38.1%), with HAM in 17 (20.2%). Both findings were dynamic, showing progression in 13 (15.5%) and regression and 9 (10.7%) patients. Compared with antiplatelet therapy, progression was less likely among patients on oral anticoagulation with vitamin-K antagonists or non-VKA oral anticoagulants (odds ratio: 0.014, P = 0.036). Maintenance on chronic oral anticoagulation was not a significant predictor of regression. These findings were similar for both transcatheter and surgical bioprosthetic aortic valves. No patients developed symptoms of valve dysfunction and leaflet thickening was not clearly associated with any clinical events. CONCLUSIONS: Subclinical leaflet thrombosis is a common finding after TAVI and SAVR, and may progress from normal leaflet over HALT to the more severe HAM. The phenomenon can develop and regress at variable intervals after valve implantation. Anticoagulants may have a protective effect against the development of HALT, but HALT can also regress without anticoagulation therapy. REGISTERED AT CLINICALTRIALS.GOV: NCT02426307.

Outcome of paravalvular leak repair after transcatheter aortic valve replacement with a balloon-expandable prosthesis.

BACKGROUND: Significant paravalvular leak (PVL) occurs in up to 13% of patients after transcatheter aortic valve replacement (TAVR) with a balloon-expandable bioprosthesis. Transcatheter PVL repair has emerged as a less invasive alternative for this problem. OBJECTIVES: The aim of this study was to evaluate the safety, feasibility, and clinical outcomes of transcatheter PVL repair after TAVR with balloon-expandable valve. METHODS: We retrospectively identified 15 patients who underwent 16 PVL repair procedures after the TAVR at our center. Procedural characteristics, results, and clinical outcomes were analyzed. The association of PVL repairs with subsequent hospitalizations and mortality was assessed and compared to 57 patients who did not undergo repair for at least moderate PVL after TAVR. RESULTS: The PVL repair was successful in 13 (87%) patients, without significant procedure or device related complications. In patients with successful PVL repair, there was an improvement in symptom status, subsequent hospitalizations, and B-type natriuretic peptide levels. There was 1 (out of 13, 8%) death in the group of patients who successfully underwent PVL repair whereas 24 (out of 57, 42%) patients died during follow up in the group that did not undergo repair of their PVL. Similarly, there was significant reduction in the subsequent heart failure related hospitalization after the PVL repair, compared with the patients who did not undergo PVL repair (P = 0.03). CONCLUSION: Transcatheter repair of PVL after TAVR can be safely and effectively accomplished in carefully selected patients, and may lead to reduction in hospitalizations, improvement in symptoms, and long-term survival. © 2016 Wiley Periodicals, Inc.

Impact of Mitral Annular Displacement on Left Ventricular Diastolic Function Improvement After Transcatheter Aortic Valve Implantation.

BACKGROUND: The clinical significance of left ventricular (LV) diastolic function (DF) improvement after transcatheter aortic valve implantation (TAVI) is not fully elucidated. We sought to investigate the long-term clinical and hemodynamic effects of post-TAVI DF improvement and to identify its determinants.Methods and Results:Clinical and serial echocardiographic data before and after TAVI were retrospectively reviewed together with measurement of mitral annular displacement (MAD) representing longitudinal myocardial function in 98 patients with severe aortic stenosis and ejection fraction >55%. DF grade was determined as 0-III according to the current guideline. Patients with ≥1-grade improvement in DF at 1 year (n=59, 60%) showed a better recovery of New York Heart Association functional class, plasma B-type natriuretic peptide level, stroke volume index, and averaged e', and a greater decrease in systolic pulmonary artery pressure than those without DF improvement (all P<0.05). Coronary artery disease (odds ratio (OR), 0.30; 95% confidence interval (CI), 0.11-0.84; P=0.022) and averaged MAD (per 2.5 mm increase; OR, 4.11; 95% CI, 2.18-7.72; P<0.001) were predictors of post-TAVI DF improvement. An averaged MAD cutoff value of 10.7 mm discriminated cases of improvement with a sensitivity of 88% and specificity of 64%. CONCLUSIONS: Post-TAVI DF improvement may be associated with preserved LV longitudinal function and when present may be accompanied by more favorable clinical and hemodynamic changes.

Transcatheter Aortic Valve Replacement With Different Valve Types in Elliptic Aortic Annuli.

BACKGROUND: The aim of this study was to determine the influence of an elliptic annulus on acute device success rates following self-expanding (SE) transcatheter aortic valve replacement (TAVR) vs. balloon-expandable (BE) TAVR.Methods and Results:Outcomes were assessed using Valve Academic Research Consortium-2 definitions. Aortic annulus ratio (AAR) was measured as short axis diameter/long axis diameter. Mean AAR was 0.81±0.06. Patients were therefore divided into 2 groups: AAR <0.82 and AAR ≥0.82. For circular annuli (AAR ≥0.82; 363 patients), high device success rates were achieved in both valve groups (SE valve, 90.5% vs. BE valve, 95.0%, P=0.14). Conversely, for AAR <0.82 (374 patients), SE valves had lower device success rates than BE valves (82.5% vs. 95.3%, P=0.002). For elliptic annuli, SE-TAVR was an independent predictor of unsuccessful device implantation (OR, 6.34, P<0.001). Nonetheless, increased oversizing of SE valves for elliptic annuli was associated with an exponential rise in device success (threshold ≥17.5%; area under the curve, 0.83) but not for BE-TAVR. Furthermore, optimally oversized SE valves and BE valves had a similarly high device success for elliptic annuli (SE valve, 96.2% vs. BE valve, 95.3%). CONCLUSIONS: For circular annuli, similarly high device success was achieved for the 2 valve types. Conversely, for elliptic annuli, SE valves had a lower device success than BE valves. Device success following optimal oversizing of SE valves, however, was similar to that for BE valves.