Philipp Blanke

Time Dependence of Platelet Inhibition After a 600-mg Loading Dose of Clopidogrel in a Large, Unselected Cohort of Candidates for Percutaneous Coronary Intervention

Background—Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel. Methods and Results—Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 &mgr;mol/L ADP was 51±14% when catheterization was performed at <1 hour, 41±14% at 1 to <2 hours, 37±15% at 2 to <4 hours, 36±13% at 4 to <6 hours, and 35±14% at ≥6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (P>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (P=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point. Conclusions—After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.

Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis

AIMS Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION ClinicalTrials.gov #NCT01314313.

Dual-Energy CT Virtual Noncalcium Technique: Detecting Posttraumatic Bone Marrow Lesions—Feasibility Study

PURPOSE To evaluate traumatized bone marrow with a dual-energy (DE) computed tomographic (CT) virtual noncalcium technique. MATERIALS AND METHODS In this prospective institutional review board-approved study, 21 patients with an acute knee trauma underwent DE CT and magnetic resonance (MR) imaging. A software application was used to virtually subtract calcium from the images. Presence of fractures was noted, and presence of bone bruise was rated on a four-point scale for six femoral and tibial regions by two radiologists. CT numbers were obtained in the same regions. Consensus reading of independently read MR images served as the reference standard. Image ratings and CT numbers were subjected to receiver operating characteristic curve analysis. RESULTS After exclusion of 16 regions owing to artifacts, MR imaging revealed 59 bone bruises in the remaining 236 regions (19 of 114 femoral, 40 of 122 tibial). Fractures were present in eight patients. Visual rating revealed areas under the curve of 0.886 and 0.897 in the femur and 0.974 and 0.953 in the tibia for observers 1 and 2, respectively. For CT numbers, the respective areas under the curve were 0.922 and 0.974. If scores of 1 and 2 (strong or mild bone bruise) were counted as positive, sensitivities were 86.4% and 86.4% and specificities were 94.4% and 95.5% for observers 1 and 2, respectively. The kappa statistic demonstrated good to excellent agreement (femur, kappa = 0.78; tibia, kappa = 0.87). CONCLUSION This DE CT virtual noncalcium technique can subtract calcium from cancellous bone, allowing bone marrow assessment and potentially making posttraumatic bone bruises of the knee detectable with CT.

Early Aortic Transcatheter Heart Valve Thrombosis Diagnostic Value of Contrast-Enhanced Multidetector Computed Tomography

Background—Early stent valve thrombosis after transcatheter aortic valve implantation (TAVI) is a rare complication, which is diagnosed based on the appearance of clinical symptoms of heart failure and echocardiographic findings. After TAVI, transthoracic echocardiography is performed to assess transcatheter heart valve (THV) function. However, preliminary reports indicate the potential additive clinical value of multidetector computed tomography (MDCT) for the diagnosis of THV thrombosis. We sought to determine the value of MDCT for the diagnosis of THV thrombosis and the frequency of this complication after balloon-expandable TAVI. Methods and Results—MDCT was performed in 140 patients within 1 to 3 months after TAVI with the Edwards Sapien XT THV to assess the presence of THV thrombosis and THV stent geometry. Post-TAVI MDCT identified THV thrombosis in 5 patients (4%). Of note, 4 of these patients were asymptomatic and had a normal transthoracic echocardiographic examination without signs of thrombus formation or flow obstruction. In patients with THV thrombosis, a left ventricular ejection fraction of <35% was present in 3 (60%), whereas 2 (40%) did not receive standard post-TAVI dual-antiplatelet therapy. Neither THV underexpansion nor THV noncircularity was detected in patients with THV thrombosis. Conclusions—Post-TAVI MDCT is a valuable tool for the diagnosis of THV thrombosis, and this complication seems to be more common than previously anticipated. Larger studies are required to identify specific risk factors of THV thrombosis.

Prosthesis Oversizing in Balloon-Expandable Transcatheter Aortic Valve Implantation Is Associated With Contained Rupture of the Aortic Root

Background— To retrospectively investigate the potential cause of contained rupture of the aortic root in balloon-expandable transcatheter aortic valve implantation (TAVI) by means of pre- and postinterventional multislice computed tomography. Methods and Results— Seventy-two patients (mean age 82±7 years, mean aortic valve area 0.69±0.19 cm2) underwent balloon-expandable TAVI using the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm, n=3). Aortic annulus dimensions were quantified by multislice computed tomography–based cross-sectional area assessment and average diameter calculation (CAAD) before and after TAVI. Post-TAVI multislice computed tomography data sets were available in 65 patients; contained aortic root rupture was diagnosed in 3 patients. Pre-TAVI CAAD was 23.1±1.8 mm; post-TAVI CAAD was 22.9±1.3 mm. Median relative change in CAAD pre- and post-TAVI was −0.5% (interquartile range, 3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with contained rupture), relative increase >10% in 2 patients, both with contained rupture. Mean relative oversizing, calculated as the relative difference in diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis, was 9.8%±7.8%. Relative oversizing was significantly higher in patients with contained rupture compared with patients without contained rupture (24.6%±5.4% versus 9.1%±6.6%; P<0.001). Relative oversizing ≥20% occurred in 6 patients (3 with contained rupture). Conclusions— Contained rupture of the aortic root in balloon-expandable TAVI is associated with severe prosthesis oversizing. Multislice computed tomography–based assessment of aortic annulus dimension in conjunction with adapted sizing guidelines may reduce the incidence of severe oversizing.

Early hypo-attenuated leaflet thickening in balloon-expandable transcatheter aortic heart valves

AIMS We sought to evaluate the frequency of early hypo-attenuated leaflet thickening (HALT) of the SAPIEN 3 transcatheter aortic valve (S3). METHODS AND RESULTS Of 249 patients who had undergone S3 implantation, we studied 156 consecutive patients (85 women, median age 82.2 ± 5.5 years) by electrocardiogram (ECG)-triggered dual-source computed tomography angiography (CTA) after a median of 5 days post-transcatheter aortic valve implantation. The prosthesis was assessed for HALT. Apart from heparin, peri-interventional antithrombotic therapy consisted of single- (aspirin 29%) or dual- (aspirin plus clopidogrel 71%) antiplatelet therapy. Hypo-attenuated leaflet thickening was found in 16 patients [10.3% (95% confidence interval (CI) 5.5-15.0%)] of the patients. None of the baseline and procedural variables were significantly associated with HALT, nor did we find a significant association with the antithrombotic regimen, either peri-interventionally or at the time of CTA. Hypo-attenuated leaflet thickening was found in 6 of 45 patients with peri-interventional single-antiplatelet therapy and in 10 of 111 patients with dual-antiplatelet therapy at the time of intervention [13.3% (95% CI 3.4-23.3%) vs. 9% (95% CI 3.7-14.3%), P = 0.42]. Hypo-attenuated leaflet thickening was not associated with clinical symptoms, but a small, albeit significant difference in mean pressure gradient at the time of CTA (11.6 ± 3.4 vs. 14.9 ± 5.3 mmHg, P = 0.026). Full anticoagulation led to almost complete resolution of HALT in 13 patients with follow-up CTA. CONCLUSION Irrespective of the antiplatelet regimen, early HALT occurred in 10% of our patients undergoing transcatheter aortic S3 implantation. Early HALT is clinically inapparent and reversible by full anticoagulation.

Evaluation of 3D blood flow patterns and wall shear stress in the normal and dilated thoracic aorta using flow-sensitive 4D CMR

BackgroundThe purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers.MethodsThoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified.ResultsIncidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05).ConclusionsIncrease in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.

Assessment of aortic annulus dimensions for Edwards SAPIEN Transapical Heart Valve implantation by computed tomography: calculating average diameter using a virtual ring method

OBJECTIVE Accurate preoperative assessment of the aortic annulus dimensions is critical in patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS. Using multislice computed tomography (MSCT), we evaluated a novel approach to quantify aortic annulus dimensions using cross-sectional area (CSA) assessment and average diameter calculation compared with the commonly applied electronic caliper measurements in patients undergoing transapical implantation of the Edwards SAPIEN Transcatheter Heart Valve. METHODS Seventy-one patients underwent pre-TAVI MSCT with the following dimensions assessed at the level of the most basal attachment points of all three aortic cusps joined by a virtual ring: CSA, calculated average annulus diameter (CAAD), and minimal, maximum, sagittal and coronal diameters. Measurements were compared with post-TAVI MSCT data sets at the level of the ventricular stent ending in 24 patients. Pre-TAVI measurements were compared to those taken post-TAVI. Eligibility to balloon-expandable TAVI was evaluated based on the different measurements. RESULTS The Edwards SAPIEN valve (23 mm, n=8; 26 mm, n=16) was implanted 2.1±1.1 mm below the non-coronary sinus. Pre-TAVI CAAD was 23.0±1.6 mm; post-TAVI CAAD was 23.0±1.1 mm. Post-TAVI CSA was circular in 18 patients (75%) and ovoid in six (25%). Pre- and post-TAVI assessment showed strong correlation for CSA and CAAD (r=0.835, p<0.001; r=0.841, p<0.001, respectively). Minimal, maximum, coronal and sagittal dimension correlated weakly between pre- and post-TAVI measurements (r=0.435-0.632, p=0.001-0.034). CONCLUSION Pre-TAVI CSA assessment and average diameter calculation using a virtual ring method is able to predict the post-interventional configuration of the annulus after balloon-expandable TAVI. We regard this approach as the best-available method to select the appropriate prosthesis size for balloon-expandable TAVI. Specific MSCT-based sizing recommendations should be developed.

Incidence and Severity of Paravalvular Aortic Regurgitation With Multidetector Computed Tomography Nominal Area Oversizing or Undersizing After Transcatheter Heart Valve Replacement With the Sapien 3 : A Comparison With the Sapien XT

OBJECTIVES This study sought to compare the influence of the extent of multidetector computed tomography (MDCT) area oversizing on the incidence of paravalvular aortic regurgitation (PAR) between the Sapien 3 and the Sapien XT transcatheter heart valve (THV) to define a new MDCT sizing guideline suitable for the Sapien 3 platform. BACKGROUND The inverse relationship of PAR occurrence and oversizing has been demonstrated for the Sapien XT but the incidence of PAR with comparable oversizing with the Sapien 3 is not known. METHODS Sixty-one prospectively enrolled patients who underwent transcatheter aortic valve replacement with the Sapien 3 THV were compared with 92 patients who underwent transcatheter aortic valve replacement with the Sapien XT THV. Patients were categorized depending on the degree of MDCT area oversizing percentage: undersizing (below 0%), 0% to 5%, 5% to 10%, and above 10%. The primary endpoint was mild or greater PAR on transthoracic echocardiography. RESULTS Mild or greater PAR was present in 19.7% of patients (12 of 61) in the Sapien 3 group and in 54.3% of patients (50 of 92) in the Sapien XT group (p < 0.01). The Sapien 3 group, compared with the Sapien XT group, consistently demonstrated significantly lower rates of mild or greater PAR except for oversizing >10% (p for interaction = 0.54). Moderate or severe PAR rates were also lower in the Sapien 3 group than in the Sapien XT group (3.3% vs. 13.0%, p = 0.04). In the Sapien 3 group, a MDCT area oversizing percentage value of ≤4.17% was identified as the optimal cutoff value to discriminate patients with or without mild or greater PAR. CONCLUSIONS Our retrospective analysis suggests that the Sapien 3 THV displays significantly lower rates of PAR than does the Sapien XT THV. A lesser degree of MDCT area oversizing may be employed for this new balloon-expandable THV.

First-in-man Experience of a Novel Transcatheter Repair System for Treating Severe Tricuspid Regurgitation

BACKGROUND Isolated tricuspid valve surgery is associated with high morbidity and mortality, especially in patients with prior cardiac surgery. The transcatheter Forma Repair System (Edwards Lifesciences, Irvine, California) is designed to provide a surface for native leaflet coaptation to reduce tricuspid regurgitation (TR) by occupying the regurgitant orifice area. OBJECTIVES This study sought to evaluate the feasibility and exploratory efficacy with this transcatheter repair system for the treatment of severe TR. METHODS Seven high-risk patients with severe TR and clinical signs of heart failure were declined for surgery and offered transcatheter treatment with this device. All procedures were performed within a cardiac catheterization laboratory or hybrid operating room under general anesthesia with transesophageal echocardiographic guidance. Vascular access was via the left axillary vein. Baseline characteristics, procedural and in-hospital outcomes, as well as 30-day follow-up were prospectively collected. RESULTS All patients had severe TR and New York Heart Association (NYHA) functional class II to IV (mean age 76 ± 13 years; mean logistic EuroSCORE 25.7 ± 17.4%), and underwent device implantation to improve tricuspid leaflet coaptation, thereby reducing TR. Device implantation was successful without procedural complications in all patients, with significant reductions in TR severity (moderate in 3 patients and mild in 4 patients). Median hospital length of stay was 4 days. At 30-day follow-up, all patients but 1 demonstrated improvements in NYHA functional status (to class II) with pronounced reductions in the presence and severity of peripheral edema. TR severity was assessed as being moderate at 30-day transthoracic echocardiography follow-up in all patients. No complications related to the device or vascular access were observed during follow-up. CONCLUSIONS A transcatheter-based treatment option for severe TR appears safe and feasible with this repair system. Improvements in TR severity were documented in all patients, which were accompanied by improvements in peripheral edema and functional status.