http://repub.eur.nl/res/aut/30332/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37353/ 2012-10-01T00:00:00Z 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 the adult population resulted in significantly superior autograft durability (freedom from autograft reintervention: 97% at 10 years and 91% at 12 years; P < .001). The root replacement technique without root reinforcement (hazard ratio, 2.4; 95% confidence interval, 1.4-4.1) and the presence of pure aortic insufficiency preoperatively (hazard ratio, 2.3; 95% confidence interval, 1.5-3.5) were statistically significant predictors for a shorter time to reoperation. The center volume had a significant influence on the long-term results. The freedom from homograft reoperation for the adults and pediatric population was 97% and 87% at 5 years and 93% and 79% at 12 years, respectively (P < .001), with younger recipient and donor age being significant predictors of a shorter time to homograft reoperation. 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. http://repub.eur.nl/res/pub/27366/ 2010-09-14T00:00:00Z 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. http://repub.eur.nl/res/pub/28308/ 2010-05-01T00:00:00Z Background: For children who require aortic valve replacement, the pulmonary autograft may be the ideal substitute. However, re-operations for conduit exchange in the pulmonary position are inevitable. In addition, re-operations on the autograft may be necessary due to dilatation and neo-aortic insufficiency. We sought to assess predictors for re-intervention in an international Ross-operated paediatric population. Methods: Data of 152 children below 16 years of age at the time of the Ross operation were analysed using Cox proportional hazard modelling. Mean follow-up time was 6.1 ± 4.2 years. Results: The median age at the time of the Ross operation was 10.1 years (range 54 days to 15 years). Early mortality was 2.6%. Survival at 5 and 10 years was 93.9 ± 2.0% and 90.4 ± 3.1%, respectively. Seven patients required autograft re-intervention (explantation n = 6 and reconstruction n = 1). Freedom from autograft re-intervention at 5 and 10 years was 99.3 ± 0.7% and 95.5 ± 2.7%, respectively. Prior endocarditis (p = 0.061), prior aortic regurgitation (p = 0.061) and longer follow-up time (p = 0.036) emerged as risk factors for autograft re-intervention. Seventeen patients required 36 conduit re-interventions (replacement n = 16, percutaneous valvuloplasty n = 10). Freedom from conduit re-intervention at 5 and 10 years was 89.3 ± 2.9% and 79.6 ± 6.1%, respectively. Implantation of an aortic homograft (p = 0.013), and smaller conduit size (p = 0.074) emerged as risk factors for conduit re-intervention. Conclusions: There is a consistent need for conduit re-intervention following the Ross operation in children. Re-interventions on the autograft are rare within the first decade after surgery. However, the number of autograft re-interventions may increase after the first decade, since longer follow-up time is a risk factor for autograft failure. http://repub.eur.nl/res/pub/25287/ 2009-09-15T00:00:00Z 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. http://repub.eur.nl/res/pub/24280/ 2009-08-01T00:00:00Z Background: For children who require aortic valve replacement, the Ross operation provides a unique advantage of growth potential of the pulmonary autograft in the aortic position. This study assessed the progression of autograft root diameters and its effect on aortic regurgitation (AR). Methods: Neoaortic echo dimensions from 48 children (<16 years) undergoing Ross operation who had follow-up echocardiograms before age 20 were analyzed (mean follow-up, 5.1 ± 3.3 years). Results: The mean age at the time of the Ross operation was 10.0 ± 4.3 years. Mean z values of the neoaortic annulus (1.5 ± 0.4), sinus (2.5 ± 0.4), and sinotubular junction (2.6 ± 0.9) when the autograft was implanted were significantly larger compared with normal values (p < 0.001, all). The mean z values significantly increased with follow-up at the level of the sinus (0.5 ± 0.1/year, p < 0.001) and the sinotubular junction (0.7 ± 0.2, p < 0.001), but not at the level of the annulus (0.1 ± 0.1, p = 0.59). AR increased with follow-up time (0.07 ± 0.02 grade/year, p < 0.001). AR increased with sinotubular junction diameter (p = 0.028), but there was not significant evidence of an association with annulus diameter (p = 0.25) or sinus diameter (p = 0.40). Conclusions: Children undergoing Ross operation have larger neoaortic root dimensions than healthy children. Growth of the annulus matches somatic growth. The diameters of the sinus and the sinotubular junction increase significantly relative to somatic growth. The latter may explain the development of AR. http://repub.eur.nl/res/pub/24281/ 2009-08-01T00:00:00Z Background: The Ross operation may be the ideal aortic valve replacement in pediatric patients. However, reoperations for replacement of the homograft in the pulmonary position are inevitable. This study determined influencing factors for the development of homograft stenosis and regurgitation in pediatric Ross patients. Methods: Follow-up echocardiograms of 116 children (86 boys) undergoing Ross operations at a mean age, 9.3 ± 4.9 years were analyzed using hierarchic multilevel modeling. Mean duration of the echocardiographic follow-up was 5.3 ± 4.2 years (609 patient-years, 398 examinations). Results: Median homograft diameter z value was 0.3 (range -2.2 to +7.3). Mean homograft pressure gradient at implantation was 5.0 mm Hg with a significant increase of 4.2 mm Hg/y (p < 0.001) within the first 2 years and a steady state thereafter. Older donor age was significantly associated with lower mean pressure gradient at implantation (p = 0.037). Larger z value had no significant influence on the annual increase of pressure gradient (p = 0.87). Mean grade of regurgitation at implantation was 0.9, without significant annual increase (0.02 grade/y, (p = = 0.32). Older recipient (p = 0.005) and donor age (p < 0.0001) were significantly associated with lower mean regurgitation at implantation. Larger z value was associated with a higher annual increase of regurgitation (p = 0.014). Conclusions: Relevant midterm homograft regurgitation is rare in children after the Ross operation. However, a significant annual increase occurs in the pressure gradient that cannot be influenced by larger graft size. Homograft oversizing may lead to a higher annual increase of regurgitation. http://repub.eur.nl/res/pub/29345/ 2008-09-01T00:00:00Z Despite the success of antivirals in preventing clinically overt CMV disease in cardiac allograft recipients, sub-clinical active CMV infection remains a major concern because of its association with allograft rejection and vasculopathy. The measurement of CMV specific T-cell responses is a promising approach to assessing this situation. For simplicity, class-I MHC/peptide-multimers staining CD8 T-cells directly are often used but this ignores a much wider range of responses including the whole CD4 T-cell compartment. CD4 T-cells, however, were recently shown to be critical to reducing CMV load early after transplantation. To determine how extensive T-cell responses to CMV are, the responses to two dominant CMV proteins, IE-1 and pp65, were dissected in detail accounting for T-cell lineage, frequencies, epitope recognition and changes over time in more than 25 heart transplant recipients. Cross-sectional results from over 30 healthy CMV-carriers were analyzed for comparison. Responses were unexpectedly complex, with considerable inter-individual variation in terms of dominance, breadth, and recognized epitopes. Whereas the use of MHC/peptide-multimers for clinical CD8 T-cell response monitoring alone can be justified in some situations, short term T-cell activation combined with intracellular cytokine staining was clearly found to be of more general usefulness. The performance of IFN-gamma, TNF-alpha, or IL-2 as single read-outs in identifying activated T-cells was examined and confirmed that the frequently used IFN-gamma was best suited. These results should be used to inform the design of clinically applicable and diagnostically useful approaches to monitoring CMV specific responses in heart transplant recipients.