Impact of high-fat diet and vitamin D3 supplementation on aortic stenosis establishment in waved-2 epidermal growth factor receptor mutant mice.

OBJECTIVE: The use of animal models of aortic stenosis (AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed; data have indicated that while aortic regurgitation (AR) is effectively induced, development of AS is rare. We aimed to evaluate the effect of high-fat diet (HFD) and vitamin D3 supplementation in this model. METHODS: HFD and subcutaneous vitamin D3 injections were initiated at the age of 6 weeks until the age of 6 (n = 16, 6-month treatment group) and 9 (n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis (calcium, 1,25(OH)2D3 and cholesterol), histology and immunohistochemistry (CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment (6 or 9 months). RESULTS: Total cholesterol and 1,25(OH)2D3 were significantly increased relative to the control group. HFD and vitamin D3 supplementation did result in improvements to the model, since AS was only detected in 6 (15.3%) mice (2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group. CONCLUSION: These results suggest that HFD and vitamin D3 supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.

Local and general anaesthesia do not influence outcome of transfemoral aortic valve implantation.

BACKGROUND: There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1 year outcome. METHODS: Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%). RESULTS: A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6 months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1 year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505). CONCLUSIONS: Selection of anaesthesia appears to be more influenced by national practice and operator preference than patient characteristics. In the absence of an observed difference in outcomes for either approach, there is no compelling argument to suggest that operators and centres should change their anaesthetic practice.

Clinical outcomes and safety of transfemoral aortic valve implantation under general versus local anesthesia: subanalysis of the French Aortic National CoreValve and Edwards 2 registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) performed under local anesthesia (LA) is becoming increasingly common. We aimed to compare the clinical outcomes in patients who underwent transfemoral-TAVI under general anesthesia (GA) and LA. METHODS AND RESULTS: Data from 2326 patients in the French Aortic National CoreValve and Edwards 2 (FRANCE 2) registry who underwent transfemoral-TAVI were analyzed. During the study period, the percentage of LA procedures increased gradually from 14% in January 2010 to 59% in October 2011. The clinical outcomes for GA (n=1377) and LA (n=949) were compared. Numerous baseline characteristics differed between the 2 groups, and the use of transesophageal echocardiographic guidance was more common in GA than in LA (76.3% versus 16.9%; P<0.001). Device success and cumulative 30-day survival rates were similar in the 2 groups (97.6% versus 97.0%; P=0.41 and 91.6% versus 91.3%; P=0.69, respectively), whereas the incidence of postprocedural aortic regurgitation≥mild was significantly lower in GA than in LA (15.0% versus 19.1%; P=0.015). The groups were also analyzed using a propensity-matching model, including transesophageal echocardiographic usage (GA [n=401] versus LA [n=401]). This model indicated that there were no significant differences between the 2 groups in the rates of 30-day survival (GA [91.4%] versus LA [89.3%]; P=0.27] and postprocedural aortic regurgitation≥mild (GA [12.7%] versus LA [16.2%]; P=0.19). CONCLUSIONS: The less invasive transfemoral-TAVI under LA is preferred in clinical settings and seems to be acceptable; however, the higher incidence of postprocedural aortic regurgitation is emphasized. Therapeutic efforts should be made to reduce such complications during transfemoral-TAVI under LA.

Transfemoral aortic valve replacement with the Edwards SAPIEN and Edwards SAPIEN XT prosthesis using exclusively local anesthesia and fluoroscopic guidance: feasibility and 30-day outcomes.

OBJECTIVES: The authors report the feasibility and 30-day outcomes of transfemoral aortic valve replacement (TAVR), using the Edwards SAPIEN (Edwards Lifesciences, Irvine, California) and Edwards SAPIEN XT (Edwards Lifesciences) prosthesis, implanted using exclusively local anesthesia and fluoroscopic guidance. BACKGROUND: Transfemoral TAVR is often managed with general anesthesia. However, a simplified percutaneous approach using local anesthesia has become more popular because it offers multiple advantages in an elderly and fragile population. METHODS: Between May 2006 and January 2011, the authors prospectively evaluated 151 consecutive patients (logistic EuroSCORE: 22.8 ± 11.8%) who underwent TAVR (SAPIEN: n = 78, SAPIEN XT: n = 73) using only local anesthesia and fluoroscopic guidance. The primary endpoint was a combination of all-cause mortality, major stroke, life-threatening bleeding, stage 3 acute kidney injury (AKI), periprocedural myocardial infarction (MI), major vascular complication, and repeat procedure for valve-related dysfunction at 30 days. RESULTS: Transarterial femoral approach was surgical in all SAPIEN procedures and percutaneous in 97.3% of SAPIEN XT, using the ProStar vascular closure device, and was well tolerated in all cases. Conversion to general anesthesia was required in 3.3% (SAPIEN cases) and was related to complications. Vasopressors were required in 5.5%. Procedural success was 95.4%. The combined-safety endpoint was reached in 15.9%, including overall mortality (6.6%), major stroke (2.0%), life-threatening bleeding (7.9%), stage 3 AKI (0.7%), periprocedural MI (1.3%), major vascular complication (7.9%), and repeat procedure for valve-related dysfunction (2.0%) at 30 days. A permanent pacemaker was required in 5.3%. CONCLUSIONS: This single-center, prospective registry demonstrated the feasibility and safety of a simplified transfemoral TAVR performed using only local anesthesia and fluoroscopic guidance in high surgical risk patients with severe aortic stenosis.