Search

Summary Introduction: The Valve Academic Research Consor- tium (VARC) consensus document on outcome report- ing in transcatheter valves has recently been revised. We used these VARC-2 standardised endpoint defini- tions to report transcatheter aortic valve implantation (TAVI) outcome at our institution. Methods: The study included 350 consecutive patients undergoing TAVI at the University Hospital Zurich be- tween May 2008 and November 2012. The Edwards SAPIEN (n = 158; 45%), the Medtronic CoreValve (n = 189, 54%), and the Medtronic Engager (n = 3, 1%) pros- theses were implanted via either the transfemoral (83%) or the transapical (17%) access. Mean follow-up was 389 ± 405 days. Results: Device success within 72 hours was achieved in 88% of patients without significant differences be- tween access sites (p = 0.89) and prosthesis types (p = 0.24). Device failure was due to procedural mortality in 12 (3.4%) patients. In survivors, implantation of more than one prosthesis or malpositioning of the prosthesis was observed in six (1.7%) patients, an increased trans- valvular pressure gradient >20 mm Hg in four (1.1%) patients, and moderate aortic re- gurgitation in 19 (5.4%) patients, respectively. Severe aortic regurgi- tation was observed in one (0.3%) patient. All-cause mortality was 9.1% at 30 days (12.0% in the first half of the patients vs 6.3% in the second half; p = 0.07), and 21.2% at 1 year. The composite endpoint "early safety" was met in 67 (19.1%) patients at 30 days (23% in the first half of the patients vs 15% in the second half; p = 0.04). Stroke was o bserved in 2.9%, life-threatening bleeding in 4.6%, vascular compli- cations in 7.4% and acute renal failure in 5.7% of patients. Coro- nary obstruction was rarely observed (0.9%). Valve-re- lated dysfunction requiring repeat procedure occurred in two (0.6%) patients. With multivariate regression analysis, major and life-threatening bleeding within 30 days (hazard ratio (HR) 4.74, 95% confidence interval (CI) 2.03-11.07, p

Background— Endothelial dysfunction and injury are thought to play an important role in the progression of coronary artery disease (CAD). High-density lipoprotein from healthy subjects (HDL Healthy ) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein. The present study therefore aimed to compare effects of HDL CAD and HDL Healthy on the activation of endothelial anti- and proapoptotic pathways and to determine which changes of the lipoprotein are relevant for these processes. Methods and Results— HDL was isolated from patients with stable CAD (HDL sCAD ), an acute coronary syndrome (HDL ACS ), and healthy subjects. HDL Healthy induced expression of the endothelial antiapoptotic Bcl-2 protein Bcl-xL and reduced endothelial cell apoptosis in vitro and in apolipoprotein E–deficient mice in vivo. In contrast, HDL sCAD and HDL ACS did not inhibit endothelial apoptosis, failed to activate endothelial Bcl-xL, and stimulated endothelial proapoptotic pathways, in particular, p38-mitogen-activated protein kinase–mediated activation of the proapoptotic Bcl-2 protein tBid. Endothelial antiapoptotic effects of HDL Healthy were observed after inhibition of endothelial nitric oxide synthase and after delipidation, but not completely mimicked by apolipoprotein A-I or reconstituted HDL, suggesting an important role of the HDL proteome. HDL proteomics analyses and subsequent validations and functional characterizations suggested a reduced clusterin and increased apolipoprotein C-III content of HDL sCAD and HDL ACS as mechanisms leading to altered effects on endothelial apoptosis. Conclusions— The present study demonstrates for the first time that HDL CAD does not activate endothelial antiapoptotic pathways, but rather stimulates potential endothelial proapoptotic pathways. HDL-proteome remodeling plays an important role for these altered functional properties of HDL. These findings provide novel insights into mechanisms leading to altered vascular effects of HDL in coronary disease.

ObjectivesThis study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis.MethodsFifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up.ResultsMean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 ± 4 mm Hg) compared with the SAVR-ST (13 ± 5 mm Hg) and SAVR-SL (14 ± 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups.ConclusionsPAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR.

Background We reported the first case of successful transapical transcatheter aortic valve implantation in a human subject in 2005 and have now completed a 12-month follow-up on our first 26 patients. This is, to date, the longest follow-up of patients undergoing transapical aortic valve implantation. Methods Between October 2005 and January 2007, 26 patients (13 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement because of unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-up was performed before discharge and at 1, 6, and 12 months. Data from the 17 patients who survived over 12 months were used for comparisons of the baseline and follow-up results. Results The mean age was 80 ± 9 years, and the predicted operative mortality was 37% ± 20% by using logistic EuroSCORE and 11% ± 6% by using the Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Six patients died within 30 days (30-day mortality, 23%), and 3 patients died from noncardiovascular causes after 30 days (late mortality, 12%). Among patients who survived at least 30 days, 12-month survival was 85%. There were no late valve-related complications. New York Heart Association functional class improved significantly. The aortic valve area and mean gradient remained stable at 12 months (1.6 ± 0.3 cm 2 and 9.6 ± 4.8 mm Hg, respectively). Conclusion Our 1-year clinical and echocardiographic outcomes suggest that transapical transcatheter aortic valve implantation is a viable alternative to conventional aortic valve replacement in selected high-risk patients.

Objectives: Early clinical outcomes in selected high-risk patients undergoing catheter-based aortic valve replacement (AVR) compare favorably with conventional surgical AVR. Improved understanding of the mechanisms of success and failure of transcatheter AVR will likely improve outcomes further. To this end, we examined our experience during the developmental phases of transcatheter AVR and describe the causes and management of prosthetic valve malposition. Methods: Transcatheter balloon-expandable AVR was performed in 170 patients at two centers. Malposition was defined as prosthetic valve implantation in a location other than within the native valve. Patients were prospectively identified and followed as part of an ongoing database. Results: Valve malposition occurred in 9 of 170 patients (5.3%). Final position was supravalvular in eight of nine cases. In all cases, embolization to the ascending aorta occurred within a few cardiac cycles following deployment. Importantly, late embolization was not observed. In most cases, the prosthesis was uneventfully repositioned in the more distal aorta. Positioning was subvalvular in one patient (0.6%), resulting in a severe regurgitation with residual native valve stenosis. Implantation of a second transcatheter valve was attempted in six patients and was successful in all. Conventional AVR was performed in two patients, with early mortality in one. At late follow-up (mean 412 days), seven of nine patients remain alive (78%) with a functioning prosthesis and relief of aortic stenosis. Conclusions: Malposition of current balloon-expandable aortic valves is a largely preventable complication. An improved understanding of the procedure will likely minimize this possibility and mitigate the consequences should malposition occur. © 2008 Wiley-Liss, Inc.

Objectives Transcatheter aortic valve replacement (AVR) is a promising approach to aortic valve disease. The implications of this new therapy are not entirely known. We describe the potential for the development of new atrioventricular (AV) block. Background Atrioventricular block is a known complication of conventional surgical AVR. Block is presumed to occur as a consequence of surgical trauma to the cardiac conduction tissue during excision of the diseased aortic valve and debridement of the calcified annulus. Whether AV block might occur as a consequence of nonsurgical implantation of an aortic stent valve is unknown. Methods We reviewed our experience with patients undergoing transcatheter AVR using both the percutaneous transarterial and the open-chest direct left ventricular apical ventriculotomy approaches. Patients were considered at high risk for conventional surgery because of comorbidities. Continuous arrhythmia monitoring was performed for at least 48 h after the valve implantation procedure. Patients who developed apparently new, clinically significant AV block were identified. Results Transcatheter AVR was successfully performed in 123 patients. Seventeen of these patients (13.8%) had pre-existing permanent pacemakers. Two patients (1.6%) required pacemaker implantation because of pre-existing intermittent bradycardia. Seven patients (5.7%) developed new and sustained complete AV block requiring pacemaker implantation. An additional 4 patients (3.3%) developed new and sustained left bundle branch block but did not require pacemaker implantation. Conclusions As with conventional AVR surgery, transcatheter AVR may result in impaired atrioventricular conduction. Physicians and patients should be aware of the potential for AV block and pacemaker dependence.

Background— Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. Methods and Results— Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 ( P =0.10), and 30-day mortality fell from 16% to 8% ( P =0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6±0.2 to 1.7±0.4 cm 2 . Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction ( P P =0.01), and functional class ( P Conclusion— Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

Mechanical forces and strain induced by tran-scatheter aortic valve implantation are usually named as origins for postoperative left ventricular arrhythmia associated with the technique. No quantitative data has been published so far to substantiate this common belief. As a first step towards quantitative analysis of the biomechanic situation at the aortic root after transapical aortic valve implantation, we present a spline-based method for reconstruction of the implanted stent from CT images and for locally measuring the deformation of the stent.

Background— Transcatheter aortic valve implantation is an alternative to open heart surgery in patients with aortic stenosis. However, long-term data on a programmatic approach to aortic valve implantation remain sparse. Methods and Results— Transcatheter aortic valve implantation was performed in 168 patients (median age, 84 years) in the setting of severe aortic stenosis and high surgical risk. Access was transarterial (n=113) or, in the presence of small iliofemoral artery diameter, transapical (n=55). The overall success rate was 94.1% in this early experience. Intraprocedural mortality was 1.2%. Operative (30-day) mortality was 11.3%, lower in the transarterial group than the transapical group (8.0% versus 18.2%; P =0.07). Overall mortality fell from 14.3% in the initial half to 8.3% in the second half of the experience, from 12.3% to 3.6% ( P =0.16) in transarterial patients and from 25% to 11.1% ( P =0.30) in transapical patients. Functional class improved over the 1-year postprocedure period ( P 3 years and a median of 221 days, structural valve failure was not observed. Conclusions— Transcatheter aortic valve implantation can result in early and sustained functional improvement in high-risk aortic stenosis patients. Late outcome is determined primarily by comorbidities unrelated to aortic valve disease.

The prognostic significance of pulmonary hypertension (PH) and the potential for reversibility in the setting of aortic stenosis (AS) have been debated. We examined the clinical correlates and prognostic significance of PH in high risk elderly patients with symptomatic severe AS undergoing transcatheter aortic valve implantation (AVI). AVI was performed in 143 patients. Adequate echocardiographic estimation of baseline pulmonary artery systolic pressure was available in 115 (80%). Patients were divided into 3 groups according to baseline pulmonary artery pressure estimated by transthoracic echocardiogram: I: 50 mmHg. Clinical and echocardiographic follow-up was obtained at 1, 6 and 12 months after AVI. Group I consisted of 17 patients (15%), group II 58 patients (50%) and group III 40 patients (35%). At baseline the three groups were similar in terms of age, functional status, presence of severe pulmonary disease, aortic valve area and mean gradient. Patients with severe PH (group III) were more likely to have left ventricular dysfunction (LVEF

Objectives: We describe the outcome of 168 patients with severe symptomatic aortic stenosis treated with transcatheter aortic valve implantation (TAVI). This cohort includes the first in man transarterial and off-pump transapical patients. Methods: The balloon-expandable aortic prosthesis was implanted via the femoral artery or left ventricular apex in 113 and 58 patients respectively. Data are described as 1–57, 58 –114 femoral and 1–58 apical procedures, respectively. Clinical and echocardiographic follow-up occurred at 1, 6, 12, and 24 months. Unsuccessful cases were censored at 30 days. Results: Mean age was 82.5 years (range 50 –97) with 57% males. Procedural success was 94.2% [88%, 96%, & 98%] with no unsuccessful procedures in the last 46 cases. One patient had a successful transfemoral procedure after a prior failure, and 3 patients had successful transapical procedures following failed transfemoral attempts. Logistic EuroSCORE and STS predicted 30-day surgical mortality was 31% [28.4%, 29.1% & 36%], and 10.4% [8.9%, 9.6% & 12.6%] respectively. Observed 30-day mortality was 10.5% [10.5%, 3.5%, & 17.2%], and 0% in the last 39 trans-femoral cases. Intra-procedural mortality was 1.1% [1.8%, 0% & 1.7%]. Peri-procedural stroke occurred in 4% [3.5%, 7%, & 1.7%]. Median hospital stay was 5 days [4, 5, & 7]. Survival at 1, 6, 12 and 24 months was 88%, 80%, 74% [73.9%, 84%, & 65.6%] and 61%. AVA, MG, LVEF and MR significantly improved post TAVI (Table 1 ), and MR, EF, and NYHA class significantly improved during follow-up. MG did not increase during follow-up, but AVA decreased slightly at 1 year (mean difference: 0.2±0.54cm 2 , p=0.04). Mild paravalvular AR was common but severe AR was not observed post-implant or at follow-up. Conclusion: TAVI provides sustained clinical benefit for up to 2 years in patients with symptomatic severe AS and high operative risk. Procedural outcome continues to improve with experience and device development. Table 1: Echocardiographic follow-up

CLINICAL SUMMARY An 88-year-old man with symptomatic severe aortic stenosis underwent percutaneous TAVI with a 26-mm SAPIEN valve (Edwards Lifesciences LLC, Irvine, Calif). Comorbid conditions included coronary artery bypass with patent retrosternal grafts, transient ischemic attacks, bilateral carotid endarterectomies, atrial fibrillation, repaired abdominal aneurysm, prostate cancer, and renal failure. Estimated 30day mortality for AVR was 35% by means of logistic EuroSCORE and 11.1% by means of the Society of Thoracic Surgeons National Database Risk Calculator. The procedure was performed without difficulty, but the final valve position was suboptimal, being slightly low (ventricularly), with the ventricular aspect of the stent abutting the anterior leaflet of the mitral valve (MV). Moderate paravalvular aortic regurgitation (AR) was treated with repeated balloon redilation without altering the valve position. Six-month transthoracic echocardiographic analysis showed trivial AR and mitral regurgitation. The patient presented 11 months after implantation with fever and Streptococcus angiosus in blood cultures. Also noted were a dental visit 6 weeks before and lack of compliance with endocarditis prophylaxis. Transesophageal echocardiographic analysis demonstrated mild-to-moderate paravalvular AR, a 13 3 8–mm ruptured anterior mitral leaflet aneurysm contiguous with the aortic prosthesis, and severe mitral regurgitation (Figure 1). Redo sternotomy was performed during cardiopulmonary bypass after cannulating the right axillary artery and right internal jugular vein. The bioprosthesis was well-seated below the coronary arteries with incomplete endothelialization of the uppermost struts and covered with nodular excrescences (Figure 2). It withstood extraction while fully expanded but was removable when grasped with forceps, which were

Objective: To evaluate and compare the expression of Toll-like receptors 2 and 4 (TLR-2 and -4) in thrombi obtained at the site of coronary occlusion of patients with acute coronary syndrome (ACS) with their expression in peripheral blood (PBL) of the same patients and healthy controls. Methods: Thrombi were mechanically disrupted, treated with actilyse for 12 hours in RPMI + 10% FCS. The amount of erythrocytes was reduced by isotonic lysis. Peripheral blood from the same patients (n = 14) and from age- and sex-matched healthy controls (n = 10) were treated in the same manner. Adherent cells were detached by Accutase and mixed with the non-adhering cells. CD14+ and CD66b+ (FITC) cells were stained for TLR-2 and TLR-4 (PE) and analysed by flow cytometry. Results: TLR-4 was detected in the thrombi by immunohistochemistry. The proportion of TLR-4+ cells was markedly increased in the monocyte gate of cells isolated from the thrombus, in comparison to peripheral blood cells from the same patient or healthy controls. Most importantly, the expression of TLR-4, measured as the mean fluorescence intensity, was significantly elevated on CD14+ monocytes of the thrombus, compared to peripheral blood CD14+ cells from the same patient or healthy controls (Figure 1 ). No such differences could be found for expression of TLR 2, TLR 3 or TLR 9. Conclusion: Thrombi of patients with ACS contain an increased proportion of TLR-4+ monocytes. Thus, our results suggest that activation of innate immunity through TLR-4 is involved in ACS. This may be a part of a link between induction of heat shock proteins and thrombosis.

Ageing is an independent risk factor for the development of cardiovascular disease. The ageing process is known to be associated with increased oxidative stress and an increased risk for cardiovascular and other diseases, such as cancer. To delay this process, therapeutic strategies involving the use of naturally occurring antioxidants, such as vitamin A, have gained considerable interest. Therefore, we wanted to investigate in a model of mammalian ageing whether changes in tissue and plasma levels of vitamin A occur with increasing age. This would constitute a prime rationale for its dietary supplementation. Experiments were performed in three different age groups (4-6 months old, 19 months old, 32-35 months old) of F1 (F344 x BN) healthy male rats that were fed a normal diet without any additional supplementation. Vitamin A and carotenoids in plasma and major organs were measured by reverse-phase high-performance liquid chromatography. In 3-year-old rats, vitamin A levels were found to be decreased in plasma (P < 0.0001) as compared with young and middle-aged animals. However, they were markedly increased in the main storage organ (ie, the liver) (P < 0.01-0.0001), and also in the aortic vessel wall. They were undetectable in the heart, irrespective of age. Increased tissue levels of vitamin A, especially in the vasculature, may be part of an age-associated self-regulatory process of adaptation, possibly as a counter-regulation against oxidative tissue damage. Based upon the assumption that in elderly humans, as in our animal model, a similar demand-regulated mechanism may work independently of additional dietary vitamin A supplementation, one may question the strategy of large clinical interventional trials using vitamin A or its derivatives beyond normal dietary intake.

After cloning and sequencing chicken connective tissue growth factor (cCTGF) we showed that in serum-deprived chicken embryo fibroblasts (CEF) the initial decline of cCTGF mRNA was followed by an increase. Human CTGF that was produced as a soluble protein in Escherichia coli by thioredoxin co-expression inhibited serum-deprivation induced apoptosis of CEF at I(50) of approximately 8pM, demonstrating a function of CTGF at concentrations observed in supernatants of fibroblasts. CTGF was neither mitogenic for CEF nor for other cell types. In conclusion CTGF supports very efficiently survival of certain cells without stimulating their cell growth.

Background — Aging is an independent risk factor for the development of cardiovascular disease. Therefore, therapies to delay vascular aging may have enormous medical consequences. In this context, vitamin E is of particular interest, mainly because of its antioxidative properties. Methods and Results — In 3-year-old rats, which are not susceptible to atherosclerosis, vitamin E levels, as measured by reversed-phase high-performance liquid chromatography, were markedly increased both in plasma and in major organs ( P P Conclusions — This unexpected accumulation of vitamin E appears to be a compensatory mechanism that attempts to counterbalance age-associated oxidative stress and that may represent a self-regulatory protective adaptation.

Nebivolol is a newer beta1-selective adrenergic receptor antagonist, which unlike classic beta-blockers, lowers systemic vascular resistance by direct vasodilator effects possibly involving NO. This study was designed to determine the effects of nebivolol on small arteries, which contribute to the most part of systemic vascular resistance. Mesenteric arteries, isolated from 9-week-old Wistar-Kyoto (WKY) rats, were studied under perfused and pressurized conditions using a video dimension analyzer. Aortic rings from the same animals were suspended in organ chambers, and isometric tension was measured. Experiments were performed during contraction to prostaglandin F2alpha. In small arteries, nebivolol (10(-9) to 3 x 10(-5) M) induced concentration-dependent relaxations (maximum, 55 +/- 8%). The relaxations were less pronounced as compared with those to acetylcholine (maximum, 99 +/- 2%; p0.05), but were significantly greater than those to atenolol (maximum, 2 +/- 0%; p0.05). Nebivolol-induced responses were markedly reduced by the NO-synthase inhibitor N(omega)-nitro-L-arginine methylester (L-NAME; 10(-4) M; maximum, 11 +/- 2%; p0.05). This inhibition could be entirely reversed by pretreatment with L-arginine (10(-3) M; maximum, 46 +/- 7%), a precursor of NO. In contrast to mesenteric arteries, nebivolol did not affect vascular tension of precontracted aortas. These findings indicate that nebivolol induces NO-mediated relaxations in small arteries but not large elastic vessels and therefore, independent of its antihypertensive action, might be effective in protecting the microcirculation in various cardiovascular disease states.