Jochen Reinöhl

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.

Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice

BACKGROUND Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).

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.

Conformational Pulsatile Changes of the Aortic Annulus: Impact on Prosthesis Sizing by Computed Tomography for Transcatheter Aortic Valve Replacement

OBJECTIVES This study sought to investigate pulsatile changes of the aortic annulus and their impact on prosthesis selection by computed tomography (CT). BACKGROUND Precise noninvasive prosthesis sizing is a prerequisite for transcatheter aortic valve replacement. METHODS A total of 110 patients with severe aortic stenosis (mean age: 82.9 ± 8 years, mean aortic valve area: 0.69 ± 0.18 cm(2)) underwent electrocardiogram-gated CT. Aortic annulus dimensions were planimetrically quantified as area-derived diameter (D(A) = 2 ×✓(CSA/π), where CSA is the cross-sectional area) and perimeter-derived diameter (D(P) = P/π, where P is the length of the perimeter) in 5% increments of the RR interval. Hypothetical prosthesis sizing was based on D(A) and D(P) (23-mm prosthesis for <22 mm; 26 mm: 22 to 25 mm; 29 mm: >25 mm) and compared between maximum and traditional cardiac CT reconstruction phases at 35% and 75% of RR. Agreement for prosthesis selection was calculated by κ statistics. RESULTS D(A) and D(P) were increased and eccentricity was reduced during systole, with D(A-MAX) and D(P-MAX) most often observed at 20% of RR. D(P) was consistently larger than D(A). Average net differences were 2.0 ± 0.6 mm and 1.7 ± 0.5 mm by D(A-MIN) versus D(A-MAX) and D(P-MIN) versus D(P-MAX). Agreement for prosthesis sizing was found in 93 of 110 patients (κ = 0.75) by D(A-75%) and in 80 of 110 patients (κ = 0.53) by D(A-MAX) compared with D(A-35%); and in 94 of 110 patients (κ = 0.73) by D(P-75%) and in 93 of 110 patients (κ = 0.73) by D(P-MAX) compared with D(P-35%). With sizing by D(A-75%) or D(P-75%), nominal prosthesis diameter was smaller than D(A-MAX) or D(P-MAX) in 15 and 6 patients respectively. CONCLUSIONS Aortic annulus morphology exhibits conformational pulsatile changes throughout the cardiac cycle due to deformation and stretch. These changes affect prosthesis selection. Prosthesis selection by diastolic perimeter- or area-derived dimensions harbors the risk of undersizing.

Combined Assessment of Aortic Root Anatomy and Aortoiliac Vasculature With Dual-Source CT as a Screening Tool in Patients Evaluated for Transcatheter Aortic Valve Implantation

OBJECTIVE The objective of our study was to investigate the feasibility, image quality, and clinical implications of a combined dual-source CT angiography (CTA) protocol to assess aortic root anatomy and aortoiliac vasculature in patients with severe aortic stenosis evaluated for transcatheter aortic valve implantation. SUBJECTS AND METHODS Eighty consecutive patients (47 women and 33 men; mean age, 82.3 ± 7.8 [SD] years) with severe aortic stenosis evaluated for transcatheter aortic valve implantation underwent a combined single-dose contrast-enhanced dual-source CTA protocol (body weight < 70 kg, 110 mL of contrast medium; ≥ 70 kg, 130 mL) consisting of ECG-gated dual-source CTA of the chest with integrated cardiac CT and ungated CTA of the abdomen and pelvis. Two independent observers measured the dimensions of the aortic root and the aortoiliac vasculature and rated image quality semiquantitatively. Vessel attenuation was assessed. Amenability to transfemoral access was evaluated on the basis of vessel diameter (> 7 mm), anatomy, and the presence of vascular disease. RESULTS Image quality of the aortic root was diagnostic in all 80 patients, and image quality of the aortoiliac vasculature was diagnostic in 79 patients. Vascular attenuation was greater than 200 HU at any vessel level. The mean diameter of the aortic annulus was 24.1 ± 2.9 (SD) mm. Inter- and intraobserver correlations for aortic root and aortoiliac measurements were high (r = 0.93-0.99). Aortic root dimensions were suitable for transcatheter aortic valve implantation in 65 patients (81%). Thirty-eight patients (48%) were deemed amenable to instant transfemoral access without another vasculature intervention. CONCLUSION The dimensions of the aortic root and the aortoiliac vasculature can be assessed with a combined single-dose contrast-enhanced dual-source CTA protocol, thereby allowing determination of patient eligibility for transcatheter aortic valve implantation, prosthesis sizing, and evaluation of the access route in one examination.

P2Y6 Deficiency Limits Vascular Inflammation and Atherosclerosis in Mice

Objective— Nucleotides such as ATP, ADP, UTP, and UDP serve as proinflammatory danger signals via purinergic receptors on their release to the extracellular space by activated or dying cells. UDP binds to the purinergic receptor Y6 (P2Y6) and propagates vascular inflammation by inducing the expression of chemokines such as monocyte chemoattractant protein 1, interleukin-8, or its mouse homologsCCL1 (chemokine [C-C motif] ligand 1)/keratinocyte chemokine, CXCL2 (chemokine [C-X-C motif] ligand 2)/macrophage inflammatory protein 2, and CXCL5 (chemokine [C-X-C motif] ligand 5)/LIX, and adhesion molecules such as vascular cell adhesion molecule 1 and intercellular cell adhesion molecule 1. Thus, P2Y6 contributes to leukocyte recruitment and inflammation in conditions such as allergic asthma or sepsis. Because atherosclerosis is a chronic inflammatory disease driven by leukocyte recruitment to the vessel wall, we hypothesized a role of P2Y6 in atherogenesis. Approach and Results— Intraperitoneal stimulation of wild-type mice with UDP induced rolling and adhesion of leukocytes to the vessel wall as assessed by intravital microscopy. This effect was not present in P2Y6-deficient mice. Atherosclerotic aortas of low-density lipoprotein receptor–deficient mice consuming high-cholesterol diet for 16 weeks expressed significantly more transcripts and protein of P2Y6 than respective controls. Finally, P2Y6 −/−/low-density lipoprotein receptor–deficient mice consuming high-cholesterol diet for 16 weeks developed significantly smaller atherosclerotic lesions compared with P2Y6 +/+/low-density lipoprotein receptor–deficient mice. Bone marrow transplantation identified a crucial role of P2Y6 on vascular resident cells, most likely endothelial cells, on leukocyte recruitment and atherogenesis. Atherosclerotic lesions of P2Y6-deficient mice contained fewer macrophages and fewer lipids as determined by immunohistochemistry. Mechanistically, RNA expression of vascular cell adhesion molecule 1 and interleukin-6 was decreased in these lesions and P2Y6-deficient macrophages took up less modified low-density lipoprotein cholesterol. Conclusions— We show for the first time that P2Y6 deficiency limits atherosclerosis and plaque inflammation in mice.

Purinergic Receptor Y6 Deficiency Limits Vascular Inflammation and Atherosclerosis in Mice

Objective— Nucleotides such as ATP, ADP, UTP, and UDP serve as proinflammatory danger signals via purinergic receptors on their release to the extracellular space by activated or dying cells. UDP binds to the purinergic receptor Y6 (P2Y6) and propagates vascular inflammation by inducing the expression of chemokines such as monocyte chemoattractant protein 1, interleukin-8, or its mouse homologsCCL1 (chemokine [C-C motif] ligand 1)/keratinocyte chemokine, CXCL2 (chemokine [C-X-C motif] ligand 2)/macrophage inflammatory protein 2, and CXCL5 (chemokine [C-X-C motif] ligand 5)/LIX, and adhesion molecules such as vascular cell adhesion molecule 1 and intercellular cell adhesion molecule 1. Thus, P2Y6 contributes to leukocyte recruitment and inflammation in conditions such as allergic asthma or sepsis. Because atherosclerosis is a chronic inflammatory disease driven by leukocyte recruitment to the vessel wall, we hypothesized a role of P2Y6 in atherogenesis. Approach and Results— Intraperitoneal stimulation of wild-type mice with UDP induced rolling and adhesion of leukocytes to the vessel wall as assessed by intravital microscopy. This effect was not present in P2Y6-deficient mice. Atherosclerotic aortas of low-density lipoprotein receptor–deficient mice consuming high-cholesterol diet for 16 weeks expressed significantly more transcripts and protein of P2Y6 than respective controls. Finally, P2Y6 −/−/low-density lipoprotein receptor–deficient mice consuming high-cholesterol diet for 16 weeks developed significantly smaller atherosclerotic lesions compared with P2Y6 +/+/low-density lipoprotein receptor–deficient mice. Bone marrow transplantation identified a crucial role of P2Y6 on vascular resident cells, most likely endothelial cells, on leukocyte recruitment and atherogenesis. Atherosclerotic lesions of P2Y6-deficient mice contained fewer macrophages and fewer lipids as determined by immunohistochemistry. Mechanistically, RNA expression of vascular cell adhesion molecule 1 and interleukin-6 was decreased in these lesions and P2Y6-deficient macrophages took up less modified low-density lipoprotein cholesterol. Conclusions— We show for the first time that P2Y6 deficiency limits atherosclerosis and plaque inflammation in mice.

Current periprocedural anticoagulation in transcatheter aortic valve replacement: could bivalirudin be an option? Rationale and design of the BRAVO 2/3 studies

Transcatheter aortic valve replacement (TAVR) is considered an important option in the management of patients with critical aortic valve stenosis that are either inoperable or have a high surgical risk. Despite continued advances in the procedural aspects of TAVR and decreasing complications rates, the risks of major vascular complications and stroke remain significant, which may in turn confer worse clinical outcomes and impact morbidity and mortality. In this review, we outline certain limitations of the currently recommended periprocedural anticoagulation in TAVR, namely unfractionated heparin that is guided by activated clotting times and protamine use if the bleeding risk is high. We will explore the potential for bivalirudin in this setting, which has become a frontrunner in acute coronary syndrome management because of favorable pharmacokinetics and lower bleeding complications. Finally, we will describe an ongoing large multicenter multinational trial that compares intravenous bivalirudin to unfractionated heparin during TAVR procedures using standardized clinical endpoints.

Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor Y2 in Mice

Objective—A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y2 in vascular inflammation and atherosclerosis. Approach and Results—Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor−/− mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y2-deficient or P2Y2-competent mice. In P2Y2-deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y2-expressing macrophages. To investigate the functional role of P2Y2 in atherogenesis, P2Y2-deficient low-density lipoprotein receptor−/− mice consumed high cholesterol diet. After 16 weeks, P2Y2-deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y2-competent mice (n=11; aortic arch: control group, 0.25 mm2; P2Y2-deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y2-deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. Conclusions—We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y2.

Two-year survival of patients screened for transcatheter aortic valve replacement with potentially malignant incidental findings in initial body computed tomography

Aims Recently, transcatheter aortic valve replacement (TAVR) has evolved as the standard treatment in patients with inoperable aortic valve stenosis. According to TAVR guidelines, body computed tomography (CT) is recommended for pre-procedural planning. Due to the advanced age of these patients, multiple radiological potentially malignant incidental findings (pmIFs) appear in this cohort. It is unknown how pmIFs influence the decision by the heart team to intervene and the mortality. Methods and results We evaluated in a retrospective single-centre observational study 414 participants screened for TAVR with dual-source CT between October 2010 and December 2012. pmIFs are common and appeared in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart team and the role of pmIF in decision-making and time to treatment with TAVR or SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835] or time to treatment (91 ± 152 vs. 61 ± 109 days, respectively). Several findings, which are highly suspicious for malignancy, were less likely associated with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for at least 2 years until January 2014. Two-year survival of patients after TAVR or SAVR, treated according to the heart team decision, was ∼75% and independent from the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF. Conclusion The study indicates that frequently occurring radiologic pmIF did not influence 2-year survival after a decision to intervene was made by an interdisciplinary heart team.