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.

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.).

Available transcatheter aortic valve replacement technology.

Transcatheter aortic valve replacement (TAVR) is an alternative and now recommended therapy for patients who meet indications for surgical valve replacement and are high or prohibitive surgical risk. Available TAVR technologies are rapidly emerging to treat this complex patient population. This review discusses the specific valve designs of the transcatheter heart valves currently used, newer generation modifications to overcome limitations of earlier valve designs, and novel imaging modalities, such as computed tomographic angiography-fluoroscopy and echocardiography-fluoroscopy fusion imaging, available for pre-procedural planning and intra-procedural guidance.

Review of surgical prosthetic paravalvular leaks: diagnosis and catheter-based closure.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with surgical prosthetic valve implantation. Paravalvular leak can have significant clinical consequence such as congestive heart failure, haemolytic anaemia, and infective endocarditis. Recently, transcatheter therapy has been applied to the treatment of this disorder with reasonable procedural and clinical success. This review discusses the current state of PVLs, the utilization of multi-modality imaging in their diagnosis and treatment, and the available therapeutic options. Further aim of this review is to examine transcatheter therapy of PVLs including the principles, outcomes, and procedural-related complications.

Snare technique to facilitate 'tall-in-short' redo-TAVR.

An 82-year-old man with a prior history of transcatheter aortic valve replacement (TAVR) with a 23-mm balloon-expandable transcatheter heart valve (THV) presented with bioprosthetic stenosis.

Fusion Imaging Guidance for Coronary Reaccess After Valve-in-Valve Transcatheter Aortic Valve Replacement.

Coronary reaccess can be difficult after valve-in-valve transcatheter aortic valve replacement. We present a case whereby prior valve-in-valve transcatheter aortic valve replacement created difficulty with coronary reaccess. Computed tomography-fluoroscopy fusion imaging was used for guidance to successfully engage the coronary arteries and perform percutaneous coronary intervention.

Right Heart Morphology of Candidate Patients for Transcatheter Tricuspid Valve Interventions.

PURPOSE: This study quantitatively evaluated the phasic right heart morphology of candidate patients for a transcatheter tricuspid valve intervention (N=32) and of subjects with trace to no tricuspid regurgitation (N = 14). METHODS: Cardiac computed tomography angiography (CCTA) and transthoracic/transesophageal echocardiography (TTE/TEE) images were analyzed using dedicated research and clinical software. Using CCTA, the phasic right atrial and ventricular volumes, annulus dimensions, annulus-to-right coronary artery (RCA) distances, circumferential topography of the annular tissue shelf, vena cava dimensions (inferior and superior), vena cava positions, axis angles, and annular excursions were quantified. Using TTE/TEE, leaflet geometry, regurgitation, hemodynamics, and heart function were quantified. Measurements within and between groups were quantitatively compared with regression analyses to explore relationships between right heart features. RESULTS: The phasic position and orientation of the vena cava and the circumferential topography of the annular tissue shelf were quantitatively presented for the first time. The candidate patient group exhibited greater chamber dimensions, enlarged vena cava, distended vena cava positions, positional shallowing of the annular tissue shelf, geometric annular distortion, leaflet distention, moderate or greater regurgitation, and impaired ventricular function. Atrial volume correlated strongly with directional vena cava positions as well as with annular dimensions. Annulus-to-RCA distances and annular excursions were comparable between groups. CONCLUSIONS: This study provides new and further insight to the right heart morphology and functional characteristics of candidate patients for a transcatheter tricuspid valve intervention. These data provide a platform from which these patients can continue to be better understood for further improving transcatheter system design and use.

A method for standardized computed tomography angiography-based measurement of aortic valvar structures.

AIMS: Reliable assessment of the aortic valvar apparatus (AVAp) is essential as it may facilitate consistent outcomes with percutaneous aortic valvar therapies. The commonly referenced aortic annulus is problematic since this measurement does not correspond to any actual anatomic structure. We aim to describe a reliable method of measuring relevant structures of the AVAp based on widely available computed tomography analyses. METHODS AND RESULTS: Retrospective analysis of computed tomograms of 75 patients with severe aortic stenosis (45 females, age 81.2 +/- 7.8 years). Curved multiplaner reconstruction technique was used to measure average diameters of the 'Aortic Leaflets Basal Attachment Plane' (ALBAP), sinuses of Valsalva (SV), sinutubular junction (STJ), ascending aorta (AA), and distance from coronary arteries to the base of the cusps. Angulation between the AA and the left ventricle (LV) was measured in one plane that included the LV inflow long axis and the maximum visualization of the aortic root. Inter-rater reliability and absolute agreement among three raters were evaluated. Intra-class correlation coefficients for ALBAP, SV, STJ, and AA diameters were 0.90, 0.99, 0.95, and 0.94, respectively (P < 0.001) with 95% limits of agreement of the observed differences falling in the less than 1 mm range. Intra-class correlation coefficients were 0.82 for the angle and 0.61 and 0.78 for distances to the right and left coronary arteries (P < 0.001). CONCLUSION: This method showed a high degree of inter-rater reliability and absolute agreement for AVAp diameters. Agreement was lower for AA-LV angle and distance to coronary artery measurements, emphasizing the need for software improvements and standardized image acquisition protocols.

Successful New Generation LAA Closure Device Implantation After Prior Incomplete Surgical LAA Ligation.

We present a case of percutaneous closure of a prior incomplete surgical left atrial appendage (LAA) ligation after a failed closure attempt using the first-generation Watchman device. The new generation Watchman FLX device (Boston Scientific) was implanted in this technically and anatomically challenging LAA patient using multimodality fusion imaging. (Level of Difficulty: Advanced.).

Hinge point-based annular plane with abnormal aortic cusps in transcatheter aortic valve replacement.

A virtual aortic annular plane that is built using the three hinge points, known as the hinge point-based annular plane (HPAP), is routinely used during transcatheter aortic valve replacement (TAVR). Abnormal aortic cusps (AAC) with unequal length and size influence the relationship of the HPAP to the aortic root axis significantly and pose challenges to valve deployment, leading to paravalvular leak and valve embolisation. Obtaining a centreline-based aortic annular plane in addition may help to understand valve deployment behaviour in AAC better.

Usefulness of 64-detector computed tomographic angiography for diagnosing in-stent restenosis in native coronary arteries.

The purpose of this study was to evaluate the accuracy of detector computed tomographic angiographic qualitative and quantitative analyses for the detection of in-stent restenosis (ISR) Previous studies have used qualitative analyses exclusively and have excluded "unevaluable" stents. Multidetector computed tomographic angiography (MDCT) was performed before quantitative coronary angiography in 67 patients with 132 stents that were evaluated by 2 techniques: (1) qualitative, on the basis of degree of visual hypodensity, and (2) quantitative, comparing in-stent with prestent Hounsfield units. All stents were evaluated, irrespective of image quality. The incidence of ISR was 12.5%. The sensitivity (94%), specificity (74%), and positive predictive value (39%) of the qualitative evaluation were superior to the quantitative technique (82%, 54%, and 21%, respectively); negative predictive values were similar (99% vs 95%). Accuracies were equal in stents located in proximal and distal vessels. In conclusion, ISR can be evaluated qualitatively by 64-slice MDCT with excellent sensitivity and negative predictive accuracy without exclusion of unevaluable stents and with reasonable specificity but low positive predictive value. Quantitative analysis was less accurate.

Minimally Invasive Robotically Assisted Repair of Partial Anomalous Venous Connection.

We describe a novel robotically assisted minimally invasive surgical technique for repair of partial anomalous pulmonary vein connection (PAPVC). Partial anomalous pulmonary vein connection is a rare congenital anomaly that consists in drainage of one or more pulmonary veins into the systemic venous system. Traditionally, large thoracotomy incision and sometimes establishment of cardiopulmonary bypass are needed to redirect the abnormal pulmonary vein to the left-sided reservoir. We describe a robotically assisted, minimally invasive, off-pump technique for the treatment of the left PAPVC in a 57-year-old patient with signs of progressive right ventricular dilatation. The Da Vinci robot was used for mediastinal dissection and isolation of the distal aspect of the left superior anomalous pulmonary vein from the brachiocephalic vein. Through a left minithoracotomy, under direct vision, the pulmonary vein was reanastomosed to the left atrial appendage, thus reconstituting a normal venous return pattern. The use of the da Vinci robot is a valid adjunct for correction of the left PAPVC. It helps mediastinal dissection and allows reconnection of the pulmonary vein to the left venous system via a small thoracotomic incision and without the use of cardiopulmonary bypass.

Systematic CT Methodology for the Evaluation of Subclinical Leaflet Thrombosis.

Subclinical leaflet thrombosis was recently described in a randomized trial of transcatheter aortic valve replacement. It was subsequently demonstrated in a series of registries that this was a commonly observed imaging finding seen in all transcatheter and surgical bioprostheses. The phenomenon has aroused considerable interest due to the as-yet-undefined risk for later clinical events and the possibility of pharmacological intervention with anticoagulation. Subclinical leaflet thrombosis is easily detected noninvasively by technically suitable computed tomography (CT) with a high degree of concordance to transesophageal echocardiography findings. The CT hallmarks were noted to be hypoattenuated leaflet thickening (HALT) associated with reduced leaflet motion (RELM). The combination of HALT and RELM signified hypoattenuation affecting motion, the standardized imaging endpoint used. This paper describes the systematic CT evaluation methodology that was devised during the Portico trial investigation and U.S. Food and Drug Administration submission; it also highlights the need for an ongoing discussion among experts to enable, with the help of the Valve Academic Research Consortium, standardization of reporting of this imaging finding to cater to the present and future needs of clinical trials.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis: An Expert Statement.

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.

Use of Computed Tomography to Guide Mitral Interventions.

With increasing utilization of cardiac computed tomographic angiography (CTA) and widespread adoption of fusion imaging technology allowing the merger of pre-procedural CTA with fluoroscopy, the ability of CTA to guide structural heart interventions has evolved significantly. It has opened new possibilities in mitral valve (MV) interventions with improved pre-procedural planning and intra-procedural guidance. Given the lack of fluoroscopic landmarks of the mitral apparatus and continued growth of native MV device technologies, the value of CTA will continue to develop. The goal of this chapter is to detail the role of CTA in MV imaging and support for transcatheter therapies.

Right Atrial Vacuum-Assisted Thrombectomy: Single-Center Experience.

BACKGROUND: Right heart thrombus in the absence of structural heart disease, atrial fibrillation, or intracardiac catheter is rare. It typically represents a thrombus migrating from the venous system to the lung, known as thrombi-in-transit, and can lead to a life-threatening pulmonary embolism. The optimal therapy for thrombi-in-transit remains controversial. We report our experience using percutaneous removal of right heart thrombus using vacuum aspiration. METHODS: Patients with right atrial mass who were hemodynamically stable and underwent vacuum thombectomy using the AngioVac system (AngioDynamics) at our institution were included in this analysis. Between December 2012 and August 2014, a total of 7 patients (2 men, 5 women) with a mean age of 51.5 years (range, 20-83 years) underwent right atrial thrombectomy. Data during the procedure and follow-up period were collected and analyzed. RESULTS: All patients were hemodynamically stable before the procedure. The procedure was considered successful in 6 patients. All patients survived through hospitalization. No periprocedural bleeding, stroke, or myocardial infarction occurred. One patient developed cardiogenic shock after the procedure that required extracorporeal membrane oxygenation support for <24 hours. There was no recurrent venous thromboembolism at a mean follow-up of 9 months. CONCLUSION: Vacuum-assisted thrombectomy can be a potential treatment option for hemodynamically stable patients with large right-sided intracardiac thrombus who are not surgical candidates.

A Bicuspid Aortic Valve Imaging Classification for the TAVR Era.

OBJECTIVES: This study sought to evaluate transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) aortic stenosis (AS), with a particular emphasis on TAVR-directed bicuspid aortic valve imaging (BAVi) of morphological classification. BACKGROUND: TAVR has been used to treat BAV-AS but with heterogeneous outcomes and uncertainty regarding the relevance of morphology. METHODS: In 14 centers in the United States, Canada, Europe, and Asia, 130 BAV-AS patients underwent TAVR. Baseline cardiac computed tomography (CT) was analyzed by a dedicated Corelab. Outcomes were assessed in line with Valve Academic Research Consortium criteria. RESULTS: Bicommissural BAV (vs. tricommissural) accounted for 68.9% of those treated in North America, 88.9% in Europe, and 95.5% in Asia (p = 0.003). For bicommissural bicuspids, non-raphe type (vs. raphe type) BAV accounted for 11.9% of those treated in North America, 9.4% in Europe, and 61.9% in Asia (p < 0.001). Overall rates of 30-day mortality (3.8%) and cerebrovascular events (3.2%) were favorable and similar among anatomical subsets. The rate of new permanent pacemaker insertion was high (26.2%) and similar between balloon-expandable (BE) and self-expanding (SE) designs (BE: 25.5% vs. SE: 26.9%; p = 0.83); there was a trend to greater permanent pacemaker insertion in BE TAVR in the presence of coronary cusp fusion BAV morphology. Paravalvular aortic regurgitation (PAR) ≥ moderate was 18.1% overall but lower at 11.5% in those with pre-procedural CT. In the absence of pre-procedural CT, there was an excess of PAR in BE TAVR that was not the case in those with a pre-procedural CT; SE TAVR required more post-dilation. Predictors of PAR included intercommissural distance for bicommissural bicuspids (odd ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02 to 1.84; p = 0.036) and lack of a baseline CT for annular measurement (OR: 3.03; 95% CI: 1.20 to 7.69; p = 0.018). CONCLUSIONS: In this multicenter study, TAVR achieved favorable outcomes in patients with pre-procedural CT, with the exception of high permanent pacemaker rates for all devices and shapes.

Percutaneous complete repair of failed mitral valve prosthesis: simultaneous closure of mitral paravalvular leaks and transcatheter mitral valve implantation - single-centre experience.

AIMS: Structural deterioration and paravalvular leak (PVL) are complications associated with surgically implanted prosthetic valves, historically requiring reoperation. We present our experience of complete transcatheter repair of a degenerated mitral bioprosthesis. METHODS AND RESULTS: From March 2012 to October 2012, we reviewed consecutive, high-risk surgical patients (n=5) who underwent transcatheter repair of a failed mitral bioprosthesis with severe paravalvular regurgitation (PVR). Manufacturer valve sizes ranged from 27 to 33 mm, regurgitation (n=1), stenosis (n=1), or both (n=3). Percutaneous transapical and transseptal access were achieved with PVL closure performed transapically. An arteriovenous rail was created for transseptal delivery of a Melody valve. All patients had successful PVL closure with no residual PVR. Valve-in-valve (ViV) implantation was successful in four patients. Overall, mean transvalvular mitral gradient was 11.2 mmHg pre-procedure which improved to 5 mmHg post-procedure. Improvement of NYHA Class ≥2 was achieved in all patients (19±3 months). One patient had controlled Melody valve embolisation which required emergent surgical replacement. Inner valve diameter was 26 mm, too large for Melody valve implantation. CONCLUSIONS: Complete transcatheter repair of a degenerated mitral bioprosthesis with PVR can be performed in the high-risk patient. Accurate measurement is necessary prior to intervention, with concern for embolisation among the larger valve sizes (>31 mm).