Stefan Toggweiler

Outcomes and complications of transcatheter aortic valve replacement using a balloon expandable valve according to the Valve Academic Research Consortium (VARC) guidelines.

AIMS There is heterogeneity in the reporting of procedural outcomes and complications following transcatheter aortic valve replacement (TAVR). Recently, new definitions have been proposed by the Valve Academic Research Consortium (VARC) in an effort to standardise these outcomes and improve the quality of future clinical research. The aim of this study is to report the procedural outcomes and complication rates following TAVR in a large sequential patient cohort using a balloon expandable valve according to the new VARC definitions. METHODS AND RESULTS Three hundred and ten consecutive patients undergoing TAVR were assessed, including patients forming our early historical series at the infancy of TAVR. All complication rates were re-evaluated according to VARC definitions. Mean age was 82.2 ± 8.1 years and the Society of Thoracic Surgeons score was 9.4 ± 5.7%. Transfemoral 30-day mortality was 6.8% (3.8% in the second half of the cohort) and transapical 30-day mortality was 13.7% (9.4% in the second half of the cohort). Cardiovascular 30-day mortality was 7.4% and the composite safety endpoint at 30-days was 18.4%. Device success was 80% (post-procedural valve area ≤ 1.2 cm2 in 9.7%). Failure to deliver and deploy a valve occurred in only 3.5%, with 82% (nine cases) occurring in the first half of the experience. Of those who did not meet echocardiographic criteria for device success (valve area ≤ 1.2 cm2, transaortic gradient ≥ 20 mmHg or ≥ moderate aortic incompetence), 90% achieved a New York Heart Association class I/II. Life threatening bleeding complications occurred in 8.4%. In 7.7% of patients, red blood cell transfusions were given without evidence of overt bleeding. Major strokes occurred in 2.3% and acute kidney injury occurred in 6.5%. CONCLUSIONS The VARC consensus guidelines provide a standardised reporting framework for clinical endpoints and complications post TAVR. We report the first series to our knowledge of 30-day outcomes using these definitions utilising a balloon expandable valve system.

Clinical ResearchInterventional CardiologyTranscatheter Aortic Valve Replacement With the St. Jude Medical Portico Valve: First-in-Human Experience

OBJECTIVES The purpose of this study was to demonstrate the feasibility and procedural outcomes with a new self-expanding and repositionable transcatheter heart valve. BACKGROUND Transcatheter aortic valve replacement is a viable option for selected patients with severe symptomatic aortic stenosis. However, suboptimal prosthesis positioning may contribute to paravalvular regurgitation, atrioventricular conduction block, and mitral or coronary compromise. METHODS The repositionable Portico valve (St. Jude Medical, Minneapolis, Minnesota) was implanted in 10 patients with severe aortic stenosis utilizing percutaneous femoral arterial access. Patients underwent transthoracic and transesophageal echocardiography and multidetector computed tomography before and after valve implantation. Clinical and echocardiographic follow-up was obtained at 30 days. RESULTS Device implantation was successful in all patients. Prosthesis recapture and repositioning was performed in 4 patients. Intermittent prosthetic leaflet dysfunction in 1 patient required implantation of a second transcatheter valve. There was 1 minor stroke. At 30-day follow-up, echocardiographic mean transaortic gradient was reduced from 44.9 ± 16.7 mm Hg to 10.9 ± 3.8 mm Hg (p < 0.001), and valve area increased from 0.6 ± 0.1 cm(2) to 1.3 ± 0.2 cm(2) (p < 0.001). Paravalvular regurgitation was mild or less in 9 patients (90%) and moderate in 1 patient (10%). There were no major strokes, major vascular complications, major bleeds, or deaths. No patient required pacemaker implantation. All patients were in New York Heart Association functional class II or less. CONCLUSIONS Transcatheter aortic valve replacement with the repositionable Portico transcatheter heart valve is feasible, with good short-term clinical and hemodynamic outcomes.

Prediction of Optimal Deployment Projection for Transcatheter Aortic Valve Replacement Angiographic 3-Dimensional Reconstruction of the Aortic Root Versus Multidetector Computed Tomography

Background— Identifying the optimal fluoroscopic projection of the aortic valve is important for successful transcatheter aortic valve replacement (TAVR). Various imaging modalities, including multidetector computed tomography (MDCT), have been proposed for prediction of the optimal deployment projection. We evaluated a method that provides 3-dimensional angiographic reconstructions (3DA) of the aortic root for prediction of the optimal deployment angle and compared it with MDCT. Methods and Results— Forty patients undergoing transfemoral TAVR at St Pauls Hospital, Vancouver, Canada, were evaluated. All underwent preimplant 3DA and 68% underwent preimplant MDCT. Three-dimensional angiographic reconstructions were generated from images of a C-arm rotational aortic root angiogram during breath-hold, rapid ventricular pacing, and injection of 32 mL contrast medium at 8 mL/s. Two independent operators prospectively predicted perpendicular valve projections. The implant angle was chosen at the discretion of the physician performing TAVR. The angles from 3DA, from MDCT, the implant angle, and the postdeployment perpendicular prosthesis view were compared. The shortest distance from the postdeployment perpendicular prosthesis projection to the regression line of predicted perpendicular projections was calculated. All but 1 patient had adequate image quality for reproducible angle predictions. There was a significant correlation between 3DA and MDCT for prediction of perpendicular valve projections (r=0.682, P<0.001). Deviation from the regression line of predicted angles to the postdeployment prosthesis view was 5.1±4.6° for 3DA and 7.9±4.9° for MDCT (P=0.01). Conclusions— Three-dimensional angiographic reconstructions and MDCT are safe, practical, and accurate imaging modalities for identifying the optimal perpendicular valve deployment projection during TAVR.

Management of Vascular Access in Transcatheter Aortic Valve Replacement: Part 1: Basic Anatomy, Imaging, Sheaths, Wires, and Access Routes

Transcatheter aortic valve implantation (TAVI) has emerged as a new therapy for patients with severe aortic stenosis who are inoperable or at very high risk of open heart surgery. Vascular complications are a potential limitation of TAVI and have been associated with bleeding, transfusions, and mortality. Transfemoral TAVI can be considered the least invasive approach and is therefore the most widely used access for TAVI. With the current 18-F to 24-F sheaths, the majority of patients can be treated via the transfemoral route. Initially, open surgical access was routinely used to introduce the large sheaths and catheters. Subsequently, percutaneous techniques have emerged as the new standard, resulting in a less invasive, fully percutaneous procedure. Stiff wires allow insertion of the sheath and delivery of the device without causing trauma to the artery. Given the high burden of vascular disease in TAVI candidates, increasing the effectiveness of pre-procedural screening is key. This often begins with conventional angiography, but computed tomography allows visualization of the artery in 3 dimensions, thereby overcoming some of the limitations of conventional angiography. Approximately one third of patients do not have adequate anatomy to allow safe transfemoral access. In such patients, alternative access routes such as the transapical, transaxillary, or direct aortic access are preferred. These alternative routes all have specific advantages and disadvantages.

Impact of low-profile sheaths on vascular complications during transfemoral transcatheter aortic valve replacement.

AIMS We sought to assess the impact of low-profile sheaths on vascular complications during transfemoral transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS This retrospective single-study population comprised a total of 375 consecutive patients with severe aortic stenosis who underwent transfemoral TAVR from January 2008 to November 2012. Of these, 204 (54.4%) underwent TAVR using 14-18 Fr sheaths (low-profile sheath [LPS] group), and 171 (45.6%) using 19-24 Fr sheaths (high-profile sheath [HPS] group). Vascular complications and bleeding were defined according to the VARC-2 definitions. Lower-profile sheaths were associated with a lower incidence of major vascular complications (0.5% vs. 10.5%, p<0.001), as well as a lower rate of life-threatening or major bleeding (3.4% vs. 8.3%, p=0.038). Finally, at multivariable analysis, sheath size ≥19 Fr (adjusted odds ratio [OR]: 3.06, 95% confidence interval [CI]: 1.20-7.83; p=0.019) and a sheath external diameter/minimal femoral artery diameter ratio ≥1.05 (adjusted OR: 5.79, 95% CI: 1.29-15.92, p=0.022) were found to be the only independent predictors of major and minor vascular complications. CONCLUSIONS The introduction of lower-profile sheaths has dramatically reduced the incidence of vascular complications after transfemoral TAVR, thus enhancing the safety of the procedure.

Comparison of different approaches for optimization of atrioventricular and interventricular delay in biventricular pacing

AIMS It has been shown that optimizing atrioventricular (AV) and interventricular (VV) delay improves cardiac performance in patients with biventricular pacemakers. However, there is no standard method for optimization available yet. The aim of this study was to compare echocardiographic parameters-displacement imaging, A wave duration, and aortic velocity time integral (VTI)-and acoustic cardiography derived electromechanical activation time (EMAT) using different approaches of AV and VV delay optimization. We tested whether the initial optimization of the AV interval followed by VV optimization at that optimal AV interval or initial optimization of the VV interval followed by AV optimization at the determined optimal VV interval was accurate and consistent, and how this compared to testing every conceivable combination of AV and VV intervals available. METHODS AND RESULTS A group of 20 patients with biventricular pacemakers was included. Displacement imaging, A wave duration, and aortic VTI were determined at different combinations of AV (100, 150, 200, 250 ms) and VV (RV40, 0, LV40 ms) intervals. If AV duration was determined first, displacement imaging identified the best setting in 8/20, aortic VTI in 10/20, A duration in 13/20, and EMAT in 18/20 patients. With VV duration determined first, the best setting was more difficult to identify regardless of the method used. There was a poor agreement in optimal AV and VV delays of the different methods, and there was no single patient in whom all four methods yielded the same delay combination. CONCLUSION It is advisable to measure a full grid of AV and VV delays to identify optimal settings rather than optimizing one of the two delays first. Different techniques for delay optimization resulted in different optimal delay combinations.

Procedural Results and Clinical Outcomes of Transcatheter Aortic Valve Implantation in Switzerland: An Observational Cohort Study of Sapien 3 Versus Sapien XT Transcatheter Heart Valves

Background—New generation transcatheter heart valves (THV) may improve clinical outcomes of transcatheter aortic valve implantation. Methods and Results—In a nationwide, prospective, multicenter cohort study (Swiss Transcatheter Aortic Valve Implantation Registry, NCT01368250), outcomes of consecutive transfemoral transcatheter aortic valve implantation patients treated with the Sapien 3 THV (S3) versus the Sapien XT THV (XT) were investigated. An overall of 153 consecutive S3 patients were compared with 445 consecutive XT patients. Postprocedural mean transprosthetic gradient (6.5±3.0 versus 7.8±6.3 mm Hg, P=0.17) did not differ between S3 and XT patients, respectively. The rate of more than mild paravalvular regurgitation (1.3% versus 5.3%, P=0.04) and of vascular (5.3% versus 16.9%, P<0.01) complications were significantly lower in S3 patients. A higher rate of new permanent pacemaker implantations was observed in patients receiving the S3 valve (17.0% versus 11.0%, P=0.01). There were no significant differences for disabling stroke (S3 1.3% versus XT 3.1%, P=0.29) and all-cause mortality (S3 3.3% versus XT 4.5%, P=0.27). Conclusions—The use of the new generation S3 balloon-expandable THV reduced the risk of more than mild paravalvular regurgitation and vascular complications but was associated with an increased permanent pacemaker rate compared with the XT. Transcatheter aortic valve implantation using the newest generation balloon-expandable THV is associated with a low risk of stroke and favorable clinical outcomes. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01368250.

Frequency and Predictors of Hyperkalemia in Patients ≥60 Years of Age With Heart Failure Undergoing Intense Medical Therapy

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.

T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis

AIMS The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. METHODS AND RESULTS Immunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n = 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n = 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n = 162). In both patient groups there was a significant (P = 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions. CONCLUSION Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.

Short-term clinical outcomes among patients undergoing transcatheter aortic valve implantation in Switzerland: the Swiss TAVI registry

AIMS To evaluate short-term clinical outcomes following transcatheter aortic valve implantation (TAVI) using CE-mark approved devices in Switzerland. METHODS AND RESULTS The Swiss TAVI registry is a national, prospective, multicentre, monitored cohort study evaluating clinical outcomes in consecutive patients undergoing TAVI at cardiovascular centres in Switzerland. From February 2011 to March 2013, a total of 697 patients underwent TAVI for native aortic valve stenosis (98.1%), degenerative aortic bioprosthesis (1.6%) or severe aortic regurgitation (0.3%). Patients were elderly (82.4±6 years), 52% were females, and the majority highly symptomatic (73.1% NYHA III/IV). Patients with severe aortic stenosis (mean gradient 44.8±17 mmHg, aortic valve area 0.7±0.3 cm²) were either deemed inoperable or at high risk for conventional surgery (STS 8.2%±7). The transfemoral access was the most frequently used (79.1%), followed by transapical (18.1%), direct aortic (1.7%) and subclavian access (1.1%). At 30 days, rates of all-cause mortality, cerebrovascular events and myocardial infarction were 4.8%, 3.3% and 0.4%, respectively. The most frequently observed adverse events were access-related complications (11.8%), permanent pacemaker implantation (20.5%) and bleeding complications (16.6%). The Swiss TAVI registry is registered at ClinicalTrials.gov (NCT01368250). CONCLUSIONS The Swiss TAVI registry is a national cohort study evaluating consecutive TAVI procedures in Switzerland. This first outcome report provides favourable short-term clinical outcomes in unselected TAVI patients.