Major adverse cardiac events after the Ross operation in 1606 patients: current status of the German-Dutch Ross registry with up to 19 years follow-up

Background: The Ross operation has reached the 5th decade with good long term results from the pioneer series. There is gaining concern however about autograft and allograft durability over time. Furthermore, reports about major adverse cardiac events (MACE) as required by the latest guidelines update, in a large Ross patient cohort are scarce in the literature. It was the aim of this study to report the MACE in patients being treated with the Ross procedure. Methods: 1606 patients (mean age 39.3±16.1, range 0.0 –70.5y), male=1202, female=404) underwent a Ross procedure with a mean follow-up of 5.4±3.9y (7817 pt years, range 0.1–18.7y). Data from the prospective German-Dutch Ross Registry with 12 participating centers were evaluated in accordance to the 2008 guidelines of reporting mortality and morbidity after cardiac valve interventions. Results: Follow-up was complete in 94.6%. All cause mortality was n=69 (4.3%, cardiac=40, 2.5%, unknown=1). Overall survival was 97.7% at 5y and 95.2% at 10y. Structural and non-structural autograft failure with the need of reoperation occurred in n=70 (4.4%), autograft endocarditis with reoperation was present in n=12 (0.8%) resulting in a freedom from autograft reoperation of 97,1% at 5y and 93.0 % at 10y (mean time to reoperation 6.1±4.72y, median 5.7y). Allograft failure with the need of reoperation occurred in n=56 (3.5%) with a freedom from allograft reoperation of 96.9% at 5y and 93.7% at 10y (mean time to reoperation 4,3±3.8y, median 2,6y). 10 valvuloplasties were included in these numbers. Freedom from autograft and allograft reoperation was 94.5% at 5y and 88.1% at 10y. Infective endocarditis (conservative or medically treated) occurred in n=45 (linearized occurrence rate 0.57%/patient-year), thrombotic and thromboembolic events (including transient ischemic attacks) were observed in n=38 (linearized occurrence rate 0.48%/patient-year). Conclusion: A low rate of MACE in the long term after the Ross operation was observed in the registry. The large cohort enables to define subsets of patients who could be at risk for autograft reoperation. Caution ought to be attended to allograft and autograft endocarditis, since almost one fifth of all reoperations were associated with infective endocarditis

Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo

In an effort to find new therapeutic interventions addressing the unmet medical need of patients with idiopathic pulmonary fibrosis, we initiated a program to identify new autotaxin (ATX) inhibitors. Starting from a recently published compound (PF-8380), we identified several highly potent ATX inhibitors with improved pharmacokinetic and safety profiles. Further optimization efforts resulted in the identification of a single-digit nanomolar lead compound (BI-2545) that shows substantial lowering of LPA in vivo and is therefore considered a valuable tool for further studies

Reoperations on the pulmonary autograft and pulmonary homograft after the Ross procedure: An update on the German Dutch Ross Registry

Objectives: Reinterventions after the Ross procedure are a concern for patients and treating physicians. The scope of the present report was to provide an update on the reinterventions observed in the large patient population of the German-Dutch Ross Registry. Patients and Methods: From 1988 to 2011, 2023 patients (age, 39.05 +/- 16.5 years; male patients, 1502; adults, 1642) underwent a Ross procedure in 13 centers. The mean follow-up was 7.1 +/- 4.6 years (range, 0-22 years; 13,168 patient-years). Results: In the adult population, 120 autograft reinterventions in 113 patients (1.03%/patient-year) and 76 homograft reinterventions in 67 patients (0.65%/patient-year) and, in the pediatric population, 14 autograft reinterventions in 13 patients (0.91%/patient-year) and 42 homograft reinterventions in 31 patients (2.72%/patient-year) were observed. Of the autograft and homograft reinterventions, 17.9% and 21.2% were performed because of endocarditis, respectively. The subcoronary technique in Conclusions: The autograft principle remains a valid option for young patients requiring aortic valve replacement. The risk of reoperation depends largely on the surgical technique used and the preoperative hemodynamics. Center experience and expertise also influence the long-term results. Adequate endocarditis prophylaxis might further reduce the need for reoperation. (J Thorac Cardiovasc Surg 2012; 144: 813-23

Autograft Reinforcement to Preserve Autograft Function After the Ross Procedure A Report From the German-Dutch Ross Registry

Background-Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. Methods and Results-1335 adult patients (mean age: 43.5 +/- 12.0 years) underwent a Ross procedure (subcoronary, SC, n=637; root replacement, Root, n=698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean: 6.09 +/- 3.97, range: 0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (Root-R) group was associated with a 6x increased reoperation rate compared to Root with R (Root+R), SC with R (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%. versus 2.6%, respectively; P<0.001). SC and Root groups had similar rate of aortic regurgitation (AR) development over time. Root+R patients had no progression of AR, whereas Root-R had 6 times higher AR development compared to Root+R. In SC, R had no remarkable effect on the annual AR progression. The SC technique was associated with lower rates of autograft dilatation at all levels of the aortic root compared to the Root techniques. R did not influence autograft dilatation rates in the Root group. Conclusions-For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure. (Circulation. 2009; 120[suppl 1]: S146-S154.

Major Adverse Cardiac and Cerebrovascular Events After the Ross Procedure A Report From the German-Dutch Ross Registry

Background-The purpose of the study is to report major cardiac and cerebrovascular events after the Ross procedure in the large adult and pediatric population of the German-Dutch Ross registry. These data could provide an additional basis for discussions among physicians and a source of information for patients. Methods and Results-One thousand six hundred twenty patients (1420 adults; 1211 male; mean age, 39.2+/-16.2 years) underwent a Ross procedure between 1988 and 2008. Follow-up was performed on an annual basis (median, 6.2 years; 10 747 patient-years). Early and late mortality were 1.2% (n=19) and 3.6% (n=58; 0.54%/patient-year), respectively. Ninety-three patients underwent 99 reinterventions on the autograft (0.92%/patient-year); 78 reinterventions in 63 patients on the pulmonary conduit were performed (0.73%/patient-year). Freedom from autograft or pulmonary conduit reoperation was 98.2%, 95.1%, and 89% at 1, 5, and 10 years, respectively. Preoperative aortic regurgitation and the root replacement technique without surgical autograft reinforcement were associated with a greater hazard for autograft reoperation. Major internal or external bleeding occurred in 17 (0.15%/patient-year), and a total of 38 patients had composite end point of thrombosis, embolism, or bleeding (0.35%/patient-year). Late endocarditis with medical (n=16) or surgical treatment (n=29) was observed in 38 patients (0.38%/patient-year). Freedom from any valve-related event was 94.9% at 1 year, 90.7% at 5 years, and 82.5% at 10 years. Conclusions-Although longer follow-up of patients who undergo Ross operation is needed, the present series confirms that the autograft procedure is a valid option to treat aortic valve disease in selected patients. The nonreinforced full root technique and preoperative aortic regurgitation are predictors for autograft failure and warrant further consideration