Hasan Jilaihawi

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).

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.

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.

Transcatheter Aortic Valve Replacement for Bicuspid Aortic Stenosis: Are We Ready for the Challenge?

Bicuspid aortic valve disease is the most common congenital heart disorder in adults, affecting 1% to 2% of the population worldwide. It is most frequently complicated by isolated valvular aortic stenosis (AS) [(1,2)][1], the result of accelerated leaflet degeneration and calcification secondary to

Relation Between Left Ventricular Outflow Tract Calcium and Mortality Following Transcatheter Aortic Valve Implantation

Left ventricular outflow tract (LVOT) calcium is known to be associated with adverse procedural outcomes after transcatheter aortic valve implantation (TAVI), yet its effect on midterm outcomes has not been previously investigated. The aim of this study was to determine the influence of LVOT calcium on 2-year mortality after TAVI. A total of 537 consecutive patients underwent TAVI and 2 groups were established, stratified based on the severity of the LVOT calcium. The primary outcome was 2-year overall survival rate. The ≥moderate LVOT calcium group included 107 patients (19.9%) and the remaining 430 patients (80.1%) were included in the ≤mild LVOT calcium group. After a median follow-up of 717 days (interquartile range 484 to 828), the Kaplan-Meier analysis revealed that the 2-year overall survival probability was significantly lower in the ≥moderate LVOT calcium group than in the ≤mild LVOT calcium group (log-rank p = 0.001). On a Cox hazard model, ≥moderate LVOT calcium was associated with increased all-cause mortality after TAVI (hazard ratio 1.74, p = 0.009). In the subgroup analysis, based on valve designs, SAPIEN 3-TAVI done in the setting of ≥moderate LVOT calcium had a relatively similar survival probability as those of ≤mild LVOT calcium (log-rank p = 0.18), which is in contrast with older generation valves (log-rank p = 0.001). In conclusion, patients with ≥moderate LVOT calcium were shown to have a lower survival probability in the midterm follow-up after TAVI, compared with those with ≤mild LVOT calcium. Patients with high-grade LVOT calcium should be monitored with longer-term follow-ups after TAVI.

Impact of Aortic Root Anatomy and Geometry on Paravalvular Leak in Transcatheter Aortic Valve Replacement With Extremely Large Annuli Using the Edwards SAPIEN 3 Valve

OBJECTIVES The aim of this study was to determine factors affecting paravalvular leak (PVL) in transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 (S3) valve in extremely large annuli. BACKGROUND The largest recommended annular area for the 29-mm S3 is 683 mm2. However, experience with S3 TAVR in annuli >683 mm2 has not been widely reported. METHODS From December 2013 to July 2017, 74 patients across 16 centers with mean area 721 ± 38 mm2 (range: 684 to 852 mm2) underwent S3 TAVR. The transfemoral approach was used in 95%, and 39% were under conscious sedation. Patient, anatomic, and procedural characteristics were retrospectively analyzed. Valve Academic Research Consortium-2 outcomes were reported. RESULTS Procedural success was 100%, with 2 deaths, 1 stroke, and 2 major vascular complications at 30 days. Post-dilatation occurred in 32%, with final balloon overfilling (1 to 5 ml extra) in 70% of patients. Implantation depth averaged 22.3 ± 12.4% at the noncoronary cusp and 20.7 ± 9.9% at the left coronary cusp. New left bundle branch block occurred in 17%, and 6.3% required new permanent pacemakers. Thirty-day echocardiography showed mild PVL in 22.3%, 6.9% moderate, and none severe. There was no annular rupture or coronary obstruction. Mild or greater PVL was associated with larger maximum annular and left ventricular outflow tract (LVOT) diameters, larger LVOT area and perimeter, LVOT area greater than annular area, and higher annular eccentricity. CONCLUSIONS TAVR with the 29-mm S3 valve beyond the recommended range by overexpansion is safe, with acceptable PVL and pacemaker rates. Larger LVOTs and more eccentric annuli were associated with more PVL. Longer term follow-up will be needed to determine durability of S3 TAVR in this population.

Effect of ascending aortic dimension on acute procedural success following self-expanding transcatheter aortic valve replacement: A multicenter retrospective analysis

AIMS Self-expanding (SE) valves are characterized with long stent frame design and the radial force of the device exists both in the inflow and outflow level. Therefore, we hypothesized that device success of SE-valves may be influenced by ascending aortic dimensions (AAD). The aim of this study was to determine the influence of AAD on acute device success rates following SE transcatheter aortic valve replacement (TAVR). METHODS & RESULTS In 4 centers in the United States and Asia, 214 consecutive patients underwent SE-TAVR. Outcomes were assessed in line with Valve Academic Research Consortium criteria. AAD was defined as the sum of the short and long axis aortic diameter divided by 2. Overall, device success rate was 85.0%. Multivariate analysis revealed that increased AAD (Odds ratio 1.27) and % oversizing (Odds ratio 0.88) were found to be independent predictors of unsuccessful device implantation. The c-statistic of the model for device success was area under the curve 0.79, sensitivity 81.3% and specificity 44.0%. Co-existence of several risk factors was associated with an exponential fall to 64.2% in device success rate. For a large AAD, however, optimally oversized SE-valves (threshold 16.2%) resulted with high device success rates compared to suboptimal oversizing (88.6% vs. 64.2%, p=0.005). CONCLUSIONS Larger AAD and smaller degrees of oversizing were confirmed to be the most relevant predictors of unsuccessful device implantation following SE-valve implantations. Optimal oversizing of great significance was noted, particularly that with a large AAD.

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.

CT-Fluoroscopic Real Time Fusion—Ready for Primetime?

Transcatheter interventions have disrupted the treatment of valvular and structural disease over the last 15 years. With the advent of transarterial transcatheter aortic valve replacement (TAVR) in 2004 through to modern mitral and tricuspid interventions, we have witnessed a veritable explosion of technologies all with varied imaging needs to support patient selection, device sizing, and deployment. The rapidity of development of these interventions seemed to have initially caught the imaging field off guard. Early TAVR was supported by limited 2-dimensional echocardiography with a significant time lag before 3-dimensional multiple detector computed tomography (MDCT) and echocardiography was integrated into practice. The opportunities to improve clinical outcomes with advanced imaging has driven a great deal of interest in the field and has resulted in extensive research andmaturation of the field. CT is now considered a requirement for TAVR device selection and both MDCT and advanced transesophageal echocardiography (TEE) applications are playing important and complementary roles in transcatheter mitral valve and tricuspid valve interventions. Beyond the heart, advanced CT imaging has been shown to be helpful not only with patient selection and device sizing but also with intraprocedural guidance and device deployment. Fusion of CT with procedural fluoroscopy has been shown to be useful in endovascular aortic aneurysm repair allowing for a reduction in fluoroscopic time, radiation dose, and contrast usage. Integration of CT fusion techniques in cardiac structural interventions has proven much more difficult owing to issues of cardiac motion and the impact of loading conditions and volume status. Over the last few years, the technology has matured with improvements in co-registration enabling improved image fusion. In this issue of Structural Heart, Neill and colleagues share some of their early experiences with a new CT fusion technology used to assist with complex left-sided interventions. In total the authors provide insight into five clinical cases in total in four patients (n = 3 mitral paravalvular leak, n = 2 mitraclip) highlighting the capability of fluoroscopic overlay of landmarks from pre-procedural CT to aid with trans-septal puncture and procedural guidance. Importantly, the technique was feasible in all five procedures. While the authors could not determine the impact on procedural or fluoroscopic time they did report that the technique did not impact workflow. The opportunities to obtain better 3D orientation of the trans-septal using CT-fluoroscopy image fusion appear to be meaningful. This case series adds to the growing number of case series evaluating the role of fusion techniques to aid in structural heart disease interventions. For years, the excitement around CT fusion was overwhelmingly greater than its practical application. Issues with real time co-registration, patient positioning and changing volume status made this technology largely impractical. In addition, procedures such as TAVR and left atrial appendage occlusion matured at a time when CT fusion was not possible resulting in a lack of clinical need for the technology and in fact the perception that it would simply complicate an increasingly well understood and routine procedure. Given the nascency of Transcatheter Mitral Valve Replacement and other minimally invasive rightand leftsided interventions there is an opportunity to integrate more mature CT fusion techniques into procedural guidance. While these opportunities are real, there remains major data gaps and outstanding technical challenges. Before requiring additional imaging and potentially complicating a procedure, the value of the technique should be validated in a more meaningful way. Assessing the value of imaging for procedural guidance has not typically been done through randomization in a blinded fashion but there really is no reason why it cannot be. End points such as procedural success, fluoroscopic time, and even proceduralist confidence could be considered for such an assessment. This need not be on a large scale but even single center or small multicenter data sets would be helpful to determine the incremental value of CT fusion. This is in fact what was needed to define the role of pre-procedural CT in TAVR for device sizing when TEE was already well established. These data were essential to shift practice and in turn improve clinical outcomes. By highlighting the potential of fusion imaging, Neill and colleagues have really reminded the field of what needs to be done. The question is who will take up the challenge and help drive the field forward to advance our collective understanding? There is little doubt that it is not a matter of if but rather when. Ours is a field of innovation and vision, driven constantly with an almost obsessive desire for progress on behalf of our collective patients.

Characteristics of aorto-iliofemoral arterial tree according to aortic valve morphology in chinese patients considered for TAVR

To characterize the anatomy of aorto-iliofemoral arterial tree according to aortic valve phenotype by CT in patients referred for transcatheter aortic valve replacement (TAVR). We retrospectively enrolled 215 patients screened for TAVR who underwent CT. Dimensions, calcification, vascular tortuosity index score and other putative risk features of 13 different regions were evaluated for bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) morphology. The study consisted of 44% BAVs with younger age than TAVs. The dimensions of the annulus, sinus of Valsalva, ascending aorta and aortic arch were consistently larger in BAVs. The prevalence of calcification of aortic arch was significantly higher in TAVs even after adjustment for atherosclerotic risk factors. BAVs was associated with two-fold higher odds of having over I degree AA calcification (odds ratio 2.02; 95% CI 1.60–5.31; p < 0.001). The prevalence of severe iliac tortuosity was higher among BAVs (11.7 vs. 2.5%, p = 0.015). BAVs had a trend to more atheroma than TAVs in the abdominal aortic artery and iliofemoral artery. BAV anatomy is common in Chinese AS patients screened for TAVR. Aorto-iliofemoral pathology varies according to aortic valve phenotype, which may contribute to technical challenges in BAV vs. TAV anatomy and support the need for the integrated risk assessment for each valve phenotype.