One year follow-up of the multi-centre European PARTNER transcatheter heart valve study

BackgroundTranscatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option in high-risk patients with severe aortic stenosis.AimsPARTNER EU is the first study to evaluate prospectively the procedural and mid-term outcomes of transfemoral (TF) or transapical (TA) implantation of the Edwards SAPIEN® valve involving a multi-disciplinary approach.Methods and resultsPrimary safety endpoints were 30 days and 6 months mortality. Primary efficacy endpoints were haemodynamic and functional improvement at 12 months. One hundred and thirty patients (61 TF, 69 TA), aged 82.1 ± 5.5 years were included. TA patients had higher logistic EuroSCORE (33.8 vs. 25.7, P <0.0005) and more peripheral disease (49.3 vs. 16.4, P< 0.0001). Procedures were aborted in four TA (5.8) and six TF cases (9.8). Valve implantation was successful in the remaining patients in 95.4 and 96.4, respectively. Thirty days and 6 months survival were 81.2 and 58.0 (TA) and 91.8 and 90.2 (TF). In both groups, mean aortic gradient decreased from 46.9 ± 18.1 to 10.9 ± 5.4 mmHg 6 months post-TAVI. In total, 78.1 and 84.8 of patients experienced significant improvement in New York Heart Association (NYHA) class, whereas 73.9 and 72.7 had improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in TA and TF cohorts, respectively.ConclusionThis first team-based multi-centre European TAVI registry shows promising results in high-risk patients treated by TF or TA delivery. Survival rates differ significantly between TF and TA groups and probably reflect the higher risk profile of the TA cohort. Optimal patient screening, approach selection, and device refinement may improve outcomes

Prognostic significance of vascular and valvular calcifications in low- and high-gradient aortic stenosis

International audienceAims In low-gradient aortic stenosis (LGAS), the high valvulo-arterial impedance observed despite low valvular gradient suggests a high vascular load. Thoracic aortic calcifications (TACs) and valvular aortic calcifications (VACs) are, respectively, surrogates of aortic load and aortic valvular gradient. The aim of this study was to compare the respective contributions of TAC and VAC on 3-year cardiovascular (CV) mortality following TAVI in LGAS vs. high-gradient aortic stenosis (HGAS) patients. Methods and results A total of 1396 consecutive patients were included. TAC and VAC were measured on the pre-TAVI CT-scan. About 435 (31.2%) patients had LGAS and 961 (68.8%) HGAS. LGAS patients were more prone to have diabetes, coronary artery disease (CAD), atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P&lt;0.05 for all. During the 3 years after TAVI, 245(17.8%) patients experienced CV mortality, 92(21.6%) in LGAS and 153(16.2%) in HGAS patients, P=0.018. Multivariate analysis adjusted for age, gender, diabetes, AF, CAD, LVEF, renal function, vascular access, and aortic regurgitation showed that TAC but not VAC was associated with CV mortality in LGAS, hazard ratio (HR) 1.085 confidence interval (CI) (1.019–1.156), P=0.011, and HR 0.713 CI (0.439–1.8), P=0.235; the opposite was observed in HGAS patients with VAC but not TAC being associated with CV mortality, HR 1.342 CI (1.034–1.742), P=0.027, and HR 1.015 CI (0.955–1.079), P=0.626. Conclusion TAC plays a major prognostic role in LGAS while VAC remains the key in HGAS patients. This confirms that LGAS is a complex vascular and valvular disease

Sex-related disparities in aortic stenosis from disease awareness to treatment : a state-of-the-art review

This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Evaluation of current practices in transcatheter aortic valve implantation: The WRITTEN (WoRldwIde TAVI ExperieNce) survey

Background Transcatheter aortic valve implantation (TAVI) has been adopted worldwide as the standard treatment for severe aortic stenosis in symptomatic patients at prohibitive or high surgical risk, but there are still several areas where consensus and evidence are lacking. The purpose was to obtain a global view of current practice related to TAVI with the potential to identify the main areas of consensus and divergence between centers. Methods An online questionnaire was distributed in centers performing TAVI including a total of 58 questions concerning pre-procedural evaluation, procedural practices and post-procedural management. Results The survey was completed by 250 centers (with a cumulative experience of nearly 70,000 TAVI) from 38 different countries. Heart team meetings and surgical risk scores were routinely performed in most (&gt; 95%) centers, but frailty (44%) and quality of life (28%) assessments were less frequently performed. General anesthesia remained the most frequent type of anesthesia (60% of centers), and significant variability was detected in the examinations for residual aortic regurgitation assessment during the procedure and in post-procedural ECG monitoring and temporary pacemaker implementation (from none to ≥ 72 h post-TAVI). Dual antiplatelet therapy duration post-TAVI was highly variable (1, 3, and ≥ 6 months in 14%, 41% and 32% of centers, respectively) and lack of consensus in antithrombotic regimen was observed in patients with atrial fibrillation requiring anticoagulation therapy (anticoagulation alone, anticoagulation + aspirin, anticoagulation + clopidogrel, and triple therapy in 28%, 37%, 26% and 4% of centers, respectively). Conclusions The WRITTEN survey provided extensive data on current TAVI-related practice and identified important differences between centers in key aspects of pre-, intra-, and post-operative management. This highlights the urgent need for further studies and evidence-based data to guide multiple aspects of the TAVI field

Sex-Specific Considerations in Degenerative Aortic Stenosis for Female-Tailored Transfemoral Aortic Valve Implantation Management.

The impact of sex on pathophysiological processes, clinical presentation, treatment options, as well as outcomes of degenerative aortic stenosis remain poorly understood. Female patients are well represented in transfemoral aortic valve implantation (TAVI) trials and appear to derive favorable outcomes with TAVI. However, higher incidences of major bleeding, vascular complications, and stroke have been reported in women following TAVI. The anatomical characteristics and pathophysiological features of aortic stenosis in women might guide a tailored planning of the percutaneous approach. We highlight whether a sex-based TAVI management strategy might impact on clinical outcomes. This review aimed to evaluate the impact of sex from diagnosis to treatment of degenerative aortic stenosis, discussing the latest evidence on epidemiology, pathophysiology, clinical presentation, therapeutic options, and outcomes. Furthermore, we focused on technical sex-oriented considerations in TAVI including the preprocedural screening, device selection, implantation strategy, and postprocedural management

The risk-to-benefit ratio of transcatheter aortic valve implantation in specific patient cohorts: a single-centre experience

Transcatheter aortic valve implantation (TAVI) has recently developed into an acceptable alternative to conventional surgery in high-risk patients. However, information on the identification of patients gaining most benefit from this procedure is still limited. The aim of this study was to evaluate safety and efficacy of TAVI in different patient cohorts. Between August 2008 and December 2010, 180 high-risk patients underwent TAVI at our institution (97 transapical and 83 transfemoral approaches). Periprocedural complications as well as mortality and incidence of MACCE during follow-up were recorded. Mean age was 82 +/- A 5 years, and mean logistic EuroScore 27 +/- A 14%. In the total cohort, 30-day mortality was 8.9% and 12-month survival (according to Kaplan-Meier-analysis) 72%, with no significant differences between the two approaches. However, a significant difference in survival was obvious after stratification of patients according to logistic EuroScore mortality estimates. Survival proportions at 1 year were 62% in patients with logistic EuroScore > 40%, 71% in patients with EuroScore 20-40% and 80% in octogenarians with EuroScore < 20% (P = 0.009). Furthermore, the observed median event-free survival as an indicator for morbidity ranged between 315 days in the first, 442 days in the second and 710 days in the third group (P = 0.1). TAVI proved to be feasible with reproducible results. However, mortality and rehospitalization rates were considerably high in specific patient cohorts, suggesting that the risk-to-benefit ratio of TAVI should be validated individually. In the present study, octogenarians with logistic EuroScore < 20% could be identified as candidates apparently gaining high benefit from the procedure

Long-Term Durability of Transcatheter Aortic Valves in Patients With Bicuspid Aortic Stenosis

Background: Data concerning the long-term durability of transcatheter aortic valves (TAVs) in patients with bicuspid aortic stenosis (AS) are lacking. Aims: The study aims to report data on long-term valve durability following transcatheter aortic valve replacement (TAVR) in bicuspid AS. Methods: This multicentre registry included patients who underwent TAVR for bicuspid AS with at least 2-year echocardiographic follow-up. The incidence of structural valve deterioration (SVD), bioprosthetic valve dysfunction (BVD), and bioprosthetic valve failure (BVF) was determined according to Valve Academic Research Consortium (VARC)-3 criteria. Results: Among 894 patients (mean age: 75.6 years; 39% female), the median echocardiographic follow-up was 48.7 months with a 5-year cumulative incidence of moderate-to-severe SVD, severe SVD, severe BVD, and BVF of 8.1%, 3.2%, 11.4%, and 6.1%, respectively. Younger age (≤ 75 years) was associated with a higher likelihood of reintervention (HR 2.40, log-rank p = 0.04). TAV downsizing was associated with higher rates of moderate-to-severe SVD (HR 3.05, log-rank p &lt; 0.001), severe BVD (HR 2.07, log-rank p = 0.003), and BVF (HR 3.25, log-rank p = 0.002). In the sub-group with small annuli (area ≤ 430 mm2), implantation of balloon-expandable TAVs was associated with a higher rate of BVD in comparison with self-expanding TAVs (HR: 3.27, log-rank p = 0.008). Conclusions: TAVs demonstrated favorable 5-year durability in patients with bicuspid AS, although younger patients were more likely to require valve reintervention. Nominal TAV sizing was associated with better durability outcomes as compared to TAV downsizing. Self-expanding valves were associated with superior hemodynamics in patients with small annuli.</p

Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents - Three-year results of the RAVEL trial

Background— The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term. Methods and Results— This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months. Conclusions— Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation

ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION): A Randomized Clinical Trial.

OBJECTIVES: This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). BACKGROUND: PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. METHODS: Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. RESULTS: At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). CONCLUSIONS: Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930)