Background— To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis. Methods and Results— TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81±6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27±14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7±5.9% at a follow-up interval of 110±77 days (range 1 to 255 days). Conclusions— TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.

To evaluate the feasibility of minimally invasive transapical beating heart aortic valve implantation (TAP-AVI) for high-risk patients with aortic stenosis. TAP-AVI was performed via a small anterolateral minithoracotomy in 50 patients from February 2006 to March 2007. A balloon expandable transcatheter xenograft (Edwards SAPIEN THV, Edwards Lifesciences, Irvine, CA, USA) was used. Mean age was 82.4+/-5 years and 39 (78%) were female. Implantation was performed in a hybrid operative theatre using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27.6+/-12%. Seven (14%) patients were re-operations with patent bypass grafts. TAP-AVI (13 patients 23 mm and 37 patients 26 mm) was successfully performed on the beating heart under temporary rapid ventricular pacing in 47 (94%) patients, and implantation was performed completely off-pump in 34 (68%) patients. Three patients required early conversion; two of them were successfully discharged. There was no prosthesis migration or embolization observed. Echocardiography revealed good hemodynamic function in all and minor incompetence in 23 patients, mostly paravalvular, without any signs of hemolysis. Mortality was due to the overall health condition and non-valve related in all patients. Actuarial survival at 1 month, 6 months and 1 year was 92+/-3.8%, 73.9+/-6.2% and 71.4+/-6.5%, respectively. Transapical minimally invasive aortic valve implantation is feasible using an off-pump technique. Good results have been achieved in the initial 50 patients, especially when considering the overall high-risk profile of these patients.

To evaluate the feasibility of minimally invasive transapical beating heart aortic valve implantation (TAP-AVI) for high-risk patients with aortic stenosis. TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Cribier-Edwards, Edwards Lifesciences, Irvine, CA, USA) was used. Thirty consecutive patients (82 +/- 5.1 years, 21 (70%) female) were operated from 02/06 until 09/06 at one center using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27 +/- 12%. Valve positioning was successful in 29 patients and one required early conversion to full sternotomy. Implantation (8 mm x 23 mm and 22 mm x 26 mm valves) was performed on the beating heart during brief periods of rapid ventricular pacing. ECC was applied in 13 patients. Neither coronary artery obstruction nor migration of the prosthesis was observed and all valves displayed good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 14 patients (trace in three, mild in nine and moderate in two). Three patients (10%) died, one on postoperative day (POD) three secondary to preoperative global myocardial failure and two on POD 18 and 86 due to abdominal complications. Minimally invasive beating heart TAP-AVI is feasible. Initial results are encouraging in view of the high-risk profile of the patients. Long-term studies as well as randomized protocols are required.

The aim of this study was to evaluate the impact of patient prosthesis mismatch (PPM) and additional risk factors on outcome after aortic valve replacement (AVR). Four thousand one hundred and thirty-one patients who were operated between May 1996 and April 2004 were evaluated. One thousand eight hundred and fifty-six patients received bileaflet mechanical AVR and 2275 stented xenograft AVR. PPM was defined as severe if manufacturers effective orifice area (EOA) divided by body surface area (BSA) was 70 years (n=1589, p=0.002, OR 1.85), emergency indication (n=374, p10 (n=494, p<0.001, OR 4.7) and additional cardiac procedures (n=2049, p<0.001, OR 2.0) as predictors for adverse outcome after AVR. Severe PPM is rare; moderate PPM is present in a quarter of patients. PPM has a significant impact on short- and long-term mortality after AVR.

Angiotensin (Ang)-(1–7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin–angiotensin system. Although it is well accepted that the G-protein–coupled receptor Mas is a receptor for the heptapeptide, the lack in knowing initial signaling molecules stimulated by Ang-(1–7) prevented definitive characterization of ligand/receptor pharmacology as well as identification of further hypothesized receptors for the heptapeptide. The study aimed to identify a second messenger stimulated by Ang-(1–7) allowing confirmation as well as discovery of the heptapeptide’s receptors. Ang-(1–7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, we provided pharmacological proof that Mas is a functional receptor for Ang-(1–7). Moreover, we identified the G-protein–coupled receptor MrgD as a second receptor for Ang-(1–7). Consequently, the heptapeptide failed to increase cAMP concentration in primary mesangial cells with genetic deficiency in both Mas and MrgD . Mice deficient in MrgD showed an impaired hemodynamic response after Ang-(1–7) administration. Furthermore, we excluded the Ang II type 2 receptor as a receptor for the heptapeptide but discovered that the Ang II type 2 blocker PD123319 can also block Mas and MrgD receptors. Our results lead to an expansion and partial revision of the renin–angiotensin system, by identifying a second receptor for Ang-(1–7), by excluding Ang II type 2 as a receptor for the heptapeptide, and by enforcing the revisit of such publications which concluded Ang II type 2 function by only using PD123319.