Autograft regurgitation and aortic root dimensions after the Ross procedure: the German Ross Registry experience.

BACKGROUND: Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation. METHODS AND RESULTS: Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2+/-15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n=521; root replacement, n=493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41+/-3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique. CONCLUSIONS: The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied.

Surgical interventions after emergency endovascular stent-grafting for acute type B aortic dissections.

In this retrospective study we reviewed our results of secondary surgery for complications after emergency placement of aortic stents for acute type B dissection. From October 2000 to June 2006, endovascular stent-grafting (ESG) was performed in 13 patients as an emergency procedure for acute type B dissection. Self-expanding nitinol stents (mean diameter 39.8+/-4.7 mm) were placed into the descending aorta distal to the left subclavian artery. In-hospital mortality was 15.4% (2/13) and related to persistent visceral malperfusion. Three patients (23%) required consecutive open surgery of the thoracic aorta after emergency endovascular stent-grafting for acute type B dissection. Indications for surgery included acute development of retrograde type A aortic dissection and acute stent dislocation by fractured wires and secondary leakage. Elective surgery was necessary in one patient 6 months after stent-grafting for late formation of an aneurysm of the descending aorta. There were no deaths or major morbidity after surgery of the thoracic aorta early or during follow-up. Mean follow-up was 38.0+/-13.9 months (range 1-70 months) and complete. We conclude from our study that stent-grafting of the descending aorta is a feasible, relatively safe and effective approach even in the emergency treatment of patients with complicated acute type B dissection. However, in a relevant number of patients emergency stent-grafting for acute type B aortic dissection results in complications that require secondary surgical treatment.

Remodeling or reimplantation for valve-sparing aortic root surgery?

BACKGROUND: Valve-sparing operations are gaining increasing acceptance; however, there is an ongoing discussion about the technique-specific indications. We present our experience with a follow-up of 123 months. METHODS: Between July 1993 and July 2005, 164 consecutive patients were operated on using the remodeling (group A, n = 96) or reimplantation technique (group B, n = 68). Fifty-seven patients presented with acute type A dissection. Aortic regurgitation was present in 84%. Follow-up was 54.7 +/- 28 in group A and 48.4 +/- 37.3 months in group B. RESULTS: After urgent operations, 4 patients died in each group, but none died after elective surgery. Late mortality was 8% in group A and 4% in group B. Seven patients of group A and 1 in group B required reoperation. Echocardiographic follow-up of reoperation-free survivors showed that 3 patients (all group A, 1.3%) had aortic regurgitation of more than grade II. Root diameter, valve pressure gradient, and valve orifice area were comparable. No gross thromboembolic or bleeding events occurred. CONCLUSIONS: Aortic valve-sparing operations can provide acceptable long-term results in both techniques. Particular care to the annulus in the remodeling technique and different prosthesis designs in the reimplantation technique may overcome the intrinsic problems of each procedure.

[Reconstructive surgery of the aortic valve: the Ross, David, and Yacoub procedures]. / Rekonstruktive Aortenklappenchirurgie: Ross-, David- und Yacoub-Verfahren.

The aortic valve consists of three cusps attached to the wall of the aortic root. During the cardiac cycle, the aortic root undergoes complex movements that precede and aid opening and closing of the aortic valve. The aortic valve cusps themselves form thin-walled pocket-like structures, made from specialized tissue with fibrous, elastic, nervous, and muscular properties. The complex interactions of this tissue with the aortic root and within the cardiac cycle are only incompletely understood yet. In summary, the aortic valve is a complex structure which shows a perfect function in systole and diastole and under a wide range of hemodynamic conditions. No valve prosthesis (so far) can keep up with the function of the native aortic valve. Therefore, surgical techniques have been invented that aim at sparing the aortic valve or replacing it with very similar autologous tissue. Besides the resulting (near) normal valve function, one appealing advantage of these techniques is that oral anticoagulation can be abandoned completely. If the valve cusps themselves are normal, but the aortic root is aneurysmatic or dissected (with or without resulting secondary aortic insufficiency), the aortic valve can be spared by resecting the aortic root tissue and replacing it by a vascular graft. The aortic valve can then be implanted into the vascular graft in a way described by David, or can be remodeled into it (Yacoub technique) - in this case, the graft first needs to be incised at its base so that the three commissures of the valve can be sewn into the three incisions. This way pseudosinuses within the vascular graft are created. The sinuses within the aortic root are considered important for aortic valve function and coronary perfusion. On the other hand, incisions at the base of the vascular graft harbor the potential for redilatation of the aortic root because of a missing circular fixation. Such a fixation is achieved by the David technique. Therefore, there is a great debate in the surgical community which valve-sparing technique is the best and numerous modifications of the original techniques exist. A clear clinical advantage of one technique over the other could not be demonstrated so far, but many authorities advise that the David technique is to be used preferentially in patients with Marfan's syndrome (or other connective tissue disorders) and those with a very wide basal aortic root. If the aortic valve cusps themselves are diseased and cannot be reconstructed, the autologous pulmonary valve is the most physiological substitute. Replacing the aortic valve with the autologous pulmonary valve is named Ross procedure. The defect in the right ventricular outflow tract that is created while harvesting the autograft must be reconstructed during the same procedure; usually, a pulmonary valve allograft is used for this purpose. With all reconstructive surgical techniques and with all autologous replacements there is a risk of reoperation, mainly (besides technical issues) because it is feared that leaving autologous tissue in place leads to recurrence of the original illness. The published results, however, with aortic valve-sparing surgery and with the Ross procedure show that the risk of reoperation appears to be very acceptable. This statement is especially true for the Ross procedure for which more and longer experience exists worldwide. Echocardiographic studies show that the aortic valve function after valve-sparing techniques and - especially - after the Ross procedure is indeed excellent. Therefore, patients with aortic root pathologies or aortic valve diseases should be informed about valve-sparing aortic root reconstructive techniques or the Ross procedure. The choice of technique should be made in close contact between patient, cardiologist, and cardiac surgeon. However, the described techniques require extensive experience within the surgical team.

Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve.

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1-2% of the population. In a recent report, mutations in NOTCH1 a signaling and transcriptional regulator have been shown to cause BAV in two families. This study provides data on systematic sequencing in search for novel mutations in NOTCH1 gene in a large sample BAV. For the first time, we report results of a systematic mutation-analysis based on DNA-sequencing of all coding exons and adjacent splice consensus sequences of NOTCH1 gene. Our analyses revealed 57 NOTCH1 sequence variants. Twenty-one variants are located within exons and 36 within intronic or 5'-UTR sequences. Thirty-five variants were described previously as polymorphisms. The remaining 22, however, were neither listed in public SNP databases nor in the literature and were therefore considered novel. Seventeen variants were found only once (MAF = 1%), of these 15 were novel. Two sequence variants led to amino acid substitutions (p.T596M and p.P1797H) and are located in highly conserved regions of the NOTCH1 protein. In addition, these two mutations could not be detected in at least 327 healthy controls by using RFLP-analysis. The functional relevance of the other 13 novel and rare variants could not be proven without further functional examination. In this study, we provide a new evidence that the mutations in the NOTCH1 gene may trigger the underlying mechanism causing the valve calcification, especially in BAV. In conclusion, NOTCH1 gene mutations do not only play a role in familiar BAV, but can also be observed in approximately 4% of sporadic cases.

Mitochondrial DNA deletions and the aging heart.

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977 bp deletion of human mtDNA still many unanswered questions remain. Comparing mtDNA copy levels in different tissues revealed that cardiac muscle had the highest, while the cortex cerebelli showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy number showed no changes during aging. In heart tissue, the amount of 4977 bp mtDNA deletion increased in an age-dependent manner showing significant differences at the age of 40 years and older (p<0.005). In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis. Interestingly, OS induced apoptosis only in transformed human fibroblasts by activation of the intrinsic (mitochondrial-mediated) signalling pathway as indicated by morphological damage of mitochondria, DNA laddering and increase of the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

In vitro hydrodynamics, cusp-bending deformation, and root distensibility for different types of aortic valve-sparing operations: remodeling, sinus prosthesis, and reimplantation.

OBJECTIVE: Preserving aortic valve cusps during operations for aortic root pathology theoretically offers several advantages over alternative prosthetic valve-bearing conduits. Functional properties of different valve-sparing techniques under defined conditions are not well studied. METHODS: Fresh porcine aortic roots were investigated in a pulsatile flow simulator, either native root or after different types of valve-sparing procedures (remodeling, sinus prosthesis, and reimplantation). Functional parameters, such as transvalvular pressure gradient, closing volume, cusp-bending deformation, and distensibility at different levels of the root were analyzed. RESULTS: The mean pressure gradient was highest in reimplantation techniques (8.4 +/- 1.8 mm Hg) compared with sinus prostheses (7.2 +/- 0.9 mm Hg, P = .01) and remodeling techniques (6.8 +/- 1.0 mm Hg, P = .002), mirror imaging the closing volume (reimplantation, 1.5 +/- 0.4 mL; sinus prostheses, 2.3 +/- 0.7 mL [P < .001]; remodeling, 3.4 +/- 1.1 mL [P < .001]). Bending deformation indices increased significantly from remodeling (0.45 +/- 0.05) and sinus prostheses (0.58 +/- 0.06) to reimplantation techniques (0.73 +/- 0.09). Dynamic changes in area of all techniques were decreased at the sinotubular junction and the commissural and sinus levels when compared with those seen in native roots but increased at the annular level for techniques with unfixed annulus (remodeling and modified sinus prosthesis). CONCLUSIONS: In vitro the various aortic valve-sparing operations differed characteristically in their ability to spare valve function, none of them completely meeting native valve behavior. The remodeling techniques exhibited valve dynamics closest to those of the native aortic root. The more the aortic valve is fixed with noncompliant prosthetic material, the more the native root dynamics are impaired.

Ross procedure and left ventricular mass regression.

BACKGROUND: Return of left ventricular mass to normal is considered to be a favorable result of aortic valve replacement. The Ross procedure provides near normal hemodynamics and thus allows studies of left ventricular (LV) reverse remodeling. LV mass regression may be influenced by surgical technique (subcoronary [SC] versus root replacement [RR]). METHODS AND RESULTS: Data from the German Ross Registry were analyzed. A total of 646 patients (mean age: 43.6+/-12.7 years, range: 16 to 71 years; SC technique n=295, RR technique n=351) underwent a Ross procedure in 7 participating centers from 1990 to 2004. The patients underwent preoperative and postoperative echocardiographic evaluations. Mean follow-up time was 3.5+/-2.5 years (range 0.12 to 13.7 years). Follow-up completeness was 97%. The LV mass index (LVMI) decreased significantly during follow-up in both groups (SC: 209+/-53 preoperatively to 154+/-48 at 1-year follow-up, [P<0.01 versus preoperative values] to 149+/-51 g/m2 at 2-year follow-up, [P=NS 1-year versus 2-year follow-up] versus RR: from 195+/-56 preoperatively to 144+/-51 at 1-year follow-up [P<0.01 versus preoperative values] to 140+/-49 g/m2 [P=NS 1-year versus 2-year follow-up]). LVMI regression remained stagnant 1 year after the Ross procedure in most patients in both groups. On the basis of multivariate analysis, predictors for incomplete LVMI regression after the autograft procedure were high preoperative LVMI, smoking, and uncontrolled diastolic hypertension. CONCLUSIONS: At mid-term echocardiographic follow-up, patients of both groups had favorable autograft hemodynamics. Risk factors for incomplete postoperative LVMI regression in our study were smoking and persistent diastolic hypertension. This emphasizes the importance of cessation of smoking and treatment of arterial hypertension, even in younger patients, after corrected aortic valve disease.

Mid-term findings on echocardiography and computed tomography after RVOT-reconstruction: comparison of decellularized (SynerGraft) and conventional allografts.

OBJECTIVE: The immune response against human-leucocyte-antigens on donor-cells may be an important factor contributing to the degeneration of allograft-valves. We have previously reported that the use of the decellularized allograft SynerGraft (CryoLife) reduces the immunologic response of the allograft-recipient. In this study we compare the echocardiographic and computed tomography angiographic (CTA) findings of SynerGrafts with conventional cryopreserved allografts. METHODS: 22 patients who received a pulmonary SynerGraft (SG-group) (21 during a Ross-procedure) underwent CTA and resting echocardiography (median: 10 months postoperatively). 47 randomly chosen patients who underwent a Ross-procedure served as controls (C-group) (median: 32 months postoperatively). RESULTS: Neither the pressure gradients (mean: SG=9+/-4 vs C=10+/-4mmHg; P=0.64) across the allograft, nor the effective orifice area (EOAI) (SG=0.93+/-0.80 vs C=0.93+/-0.42cm(2)/m(2); P=0.96) differed between the groups. The EOAI showed a significant correlation with the smallest allograft-conduit-area measured on CTA (r=0.81; P<0.001) which was most frequently (n=34) found in the proximal postvalvular tubular part of the conduit. Calcifications (n=11) or a fibroproliferative reaction (n=15) were rarely observed. Overall, there were no radiologic differences between the groups. On CTA, the smallest diameter of the allograft-conduits was significantly smaller than the diameter given on the cryopreservation protocol (SG=16+/-3 and C=17+/-3mm vs 25mm in both groups; P<0.001 each) whereas the diameter of the distal part of the allograft was not (SG=24+/-2, P=0.066, and C=25+/-3mm, P=0.82). CONCLUSIONS: Despite a significant shorter follow-up in the SynerGraft-group, no functional or radiologic differences were observed as compared to control-patients. The smallest diameter is located almost exclusively at the proximal level of allograft-conduits.

Warning hint of a hidden early left main stem bifurcation during antegrade cardioplegia.

The short left main trunk with early bifurcation is a common variation of the left coronary anatomy and is easily overlooked during antegrade selective cardioplegia resulting in the risk of single branch perfusion. We describe an obvious characteristic sign to detect this pitfall during blood cardioplegia.

Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a chronic hypercholesterolemic porcine model.

OBJECTIVE: The value of prophylactic brachytherapy on vein graft disease is unknown. METHODS AND RESULTS: Vein bypass grafts in 23 hypercholesterolemic pigs after ex vivo gamma irradiation of the vein grafts (10, 20, and 40Gy) and 16 control veins were analyzed regarding: (1) expression of platelet-derived growth factor (PDGF-AA and -BB, ELISA); (2) smooth muscle cell (SMC) proliferation/cell death (double-immunohistochemistry Mib-1/TUNEL/SMC alpha-actin); and (3) vessel wall dimensions. Planimetric data on vessel wall dimensions revealed no positive effect of gamma radiation on neointima formation and inner lumen diameter. On the contrary, vein grafts subjected to 40Gy were significantly more likely to be occluded and to have reduced inner lumen and increased neointima formation. Radiation therapy had no effect on PDGF expression and SMC proliferation/cell death. The mean inner lumen diameter decreased as PDGF-AA expression increased. CONCLUSIONS: Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a hypercholesterolemic porcine model. High-dose radiation (40Gy) resulted in more frequent graft occlusion and vein sclerosis.

Up to 7 years' experience with valve-sparing aortic root remodeling/reimplantation for acute type A dissection.

BACKGROUND: Aortic valve-sparing operations for acute type A dissection are appealing and innovative but less well defined surgical techniques requiring further evaluation. METHODS: We reviewed all consecutive patients with acute type A dissection who underwent either the remodeling (group 1, n = 21) or the reimplantation valve-sparing technique (group 2, n = 15) since October 1994. Patients were followed up clinically and echocardiographically for as long as 41.3 months (group 1) and 87 months (group 2). RESULTS: Hospital mortality was 19% (n = 4) for group 1 and 20% (n = 3) for group 2. Permanent new neurologic symptomatology occurred in 1 patient (3.6%). Three patients in group 1 required reoperation owing to redissection. No patient had an aortic insufficiency of more than grade 1. No late neurologic or thrombembolic events occurred. There was no statistically significant difference between both groups with respect to clinical and hemodynamic data. CONCLUSIONS: Remodeling and reimplantation aortic valve-preserving operations in acute type A dissection can be performed with adequate perioperative risk and excellent midterm aortic valve function. We found no evidence of one technique being superior to the other, however durability of the remodeling technique needs critical consideration especially in Marfan syndrome and when glue is used.

Histopathological grading of ascending aortic aneurysm: comparison of patients with bicuspid versus tricuspid aortic valve.

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is a common inherited condition that is often accompanied by ascending aortic aneurysm. A high level of histological wall abnormalities was reported to be present in non-dilated aortas of patients with BAV. In patients with tricuspid aortic valve, there appears to exist a direct relationship between the diameter of the ascending aorta and degree of histopathological aortic wall abnormalities. Whether this situation exists in patients with BAV has not yet been investigated. METHODS: Surgical and medical records of all patients undergoing surgery of the ascending aorta were reviewed. A total of 65 patients was identified in whom an aortic wall specimen was obtained intraoperatively. These specimens were systematically re-evaluated, and graded according to the severity of seven histopathological conditions: fibrosis, atherosclerosis, medionecrosis, cystic medial necrosis, smooth muscle cell orientation, elastic fiber fragmentation, and inflammation. RESULTS: BAVs were present in 26 patients (40%). Patients with BAV had significantly less aortic wall alterations than patients with tricuspid aortic valves (p < 0.001) in all variables examined. The severity of aortic wall abnormalities was significantly dependent on aortic diameter in patients with BAV as well as tricuspid aortic valve (p = 0.036 and 0.019), but dependent on age (p = 0.009) only in patients with tricuspid aortic valve. CONCLUSION: The study results provide evidence that ascending aortic aneurysm in patients with BAV differs clinically and histologically from that in patients with tricuspid aortic valve. Further studies are needed to elucidate the impact of inherited and acquired aortic wall abnormalities on the development of aneurysms.