Mid-term results of different aortic valve-sparing procedures in Marfan syndrome.

BACKGROUND AND AIM OF THE STUDY: Marfan patients with aortic root aneurysm are typically treated with the Bentall procedure, though aortic valve-sparing procedures (AVSPs) are also possible. The study aim was to compare the authors' experience with two such techniques performed at their institution, namely a reimplantation according to David (David I) and remodeling according to Yacoub. METHODS: Between 1996 and 2009, a total of 37 Marfan patients underwent an AVSP at the authors' institution. Of these patients, 25 (mean age 32 +/- 14.9 years) underwent surgery according to David (group D), and 12 (mean age 35 +/- 10.9 years) according to Yacoub (group Y). The patients underwent both clinical and echocardiographic follow up examinations at a mean of 42.0 +/- 36.4 months after surgery. RESULTS: One patient from each group had moved abroad and was lost to follow up. The remaining 35 patients were alive at follow up, and none presented with any major neurological or bleeding complications. In addition, no significant differences were noted between the groups in terms of NYHA classification, left ventricular function, or left ventricular diameter. At follow up, aortic valve function was also comparable between groups, with a peak/mean gradient of 9.4 +/- 6.4/5.3 +/- 3.5 mmHg and 5.1 +/- 3.3/2.8 +/- 1.5 mmHg for groups D and Y, respectively (p = 0.081/0.058). The measured mean grades of aortic valve regurgitation were comparable in groups D and Y (0.6 +/- 0.7 and 1.1 +/- 0.6, respectively; p = 0.055). However, aortic root dimensions obtained via M-mode were smaller in group D patients (29.6 +/- 2.3 mm) than in group Y patients (36.1 +/- 6.6 mm) (p = 0.027). Only three patients from group Y required reoperation on the aortic valve due to valvular regurgitation (p = 0.028); two of these had presented with aortic dissection at the first operation. CONCLUSION: Both types of AVSP can be performed with comparably good interim clinical results, and also low mortality and morbidity, in patients with Marfan syndrome.

Elevation of matrix metalloproteinases in different areas of ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves.

Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal), concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV), whereas 10 had a tricuspid aortic valve (TAV). Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient.

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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708409.

Long-term Clinical and Echocardiographic Outcomes in Young and Middle-aged Adults Undergoing the Ross Procedure.

Importance: There is no ideal valve substitute for young adults requiring aortic valve replacement. Multicenter data supporting use of the Ross procedure with respect to long-term postoperative valve-related mortality and reintervention, as well as function of the autograft and pulmonary homograft, are needed. Objective: To determine the long-term clinical and echocardiographic outcomes in young and middle-aged patients undergoing the Ross procedure. Design, Setting, and Participants: A retrospective multicenter international cohort study with a median follow-up period of 9.2 years was conducted in 5 experienced centers regularly performing the Ross procedure. Consecutive patients aged 18 to 65 years were included by each center between 1991 and 2018. Main Outcomes and Measures: Survival and autograft-related and homograft-related reintervention. Serial echocardiographic measurements of valve function were analyzed using mixed-effects modeling. Results: During the study period, 1431 patients (74.3% men; n = 1063) were operated on at a median age of 48.5 years (mean [SD], 47.7 [9.5]; range, 18.1-65; interquartile range, 42.7-54.0). Implantation techniques were root inclusion in 355 (24.9%), root replacement in 485 (34.0%), and subcoronary implantation in 587 (41.1%). Right ventricular outflow tract reconstruction was performed with homografts in 98.6% (n = 1189) and bioprostheses in 1.4% (n = 17). Ten patients (0.7%) died before discharge. Median follow-up was 9.2 years (13 015 total patient-years). Survival after 10 and 15 years was 95.1% (95% CI, 93.8%-96.5%) and 88.5% (95% CI, 85.9%-91.1%), respectively. Freedom from autograft and homograft reintervention after 15 years was 92.0% and 97.2%, respectively. Late events were autograft endocarditis in 14 patients (0.11% per patient-year), homograft endocarditis in 11 patients (0.08% per patient-year), and stroke in 37 patients (0.3% per patient-year). Conclusions and Relevance: Given its excellent short-term and long-term outcome in young and middle-aged adults in this study, the Ross procedure should be considered in young and middle-aged adults who require aortic valve replacement. Patients should be referred to an experienced center with a program dedicated to the Ross procedure.

Twenty-four-hour holter monitor follow-up does not provide accurate heart rhythm status after surgical atrial fibrillation ablation therapy: up to 12 months experience with a novel permanently implantable heart rhythm monitor device.

BACKGROUND: Twenty-four-hour Holter monitoring (24HM) is commonly used to assess cardiac rhythm after surgical therapy of atrial fibrillation (AF). However, this "snapshot" documentation leaves a considerable diagnostic window and only stores short-time cardiac rhythm episodes. To improve accuracy of rhythm surveillance after surgical ablation therapy and to compare continuous heart rhythm surveillance versus 24HM follow-up intraindividually, we evaluated a novel implantable continuous cardiac rhythm monitoring (IMD) device (Reveal XT 9525). METHODS AND RESULTS: Forty-five cardiac surgical patients (male 37, mean age 69.7+/-9.2 years) with a mean preoperative AF duration of 38+/-45 m were treated with either left atrial epicardial high-intensity focus ultrasound ablation (n=33) or endocardial cryothermy (n=12) in case of concomitant mitral valve surgery. Rhythm control readings were derived simultaneously from 24HM and IMD at 3-month intervals with a total recording of 2021 hours for 24HM and 220 766 hours for IMD. Mean follow-up was 8.30+/-3.97 m (range 0 to 12 m). Mean postoperative AF burden (time period spent in AF) as indicated by IMD was 37+/-43%. Sinus rhythm was documented in 53 readings of 24HM, but in only 34 of these instances by the IMD in the time period before 24HM readings (64%, P<0.0001), reflecting a 24HM sensitivity of 0.60 and a negative predictive value of 0.64 for detecting AF recurrence. CONCLUSIONS: For "real-life" cardiac rhythm documentation, continuous heart rhythm surveillance instead of any conventional 24HM follow-up strategy is necessary. This is particularly important for further judgment of ablation techniques, devices as well as anticoagulation and antiarrhythmic therapy.

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.

Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves.

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV), the most common form of congenital heart disease, is a leading cause of aortic stenosis (AS) and aortic insufficiency (AI). AS is typically caused by calcific valve disease. Recently, microRNAs (miRNAs) have been shown to modulate gene expression. The study aim was to examine the miRNAs that were altered in the aortic valve leaflets of patients with AS compared to those in patients with AI. In-vitro experiments were also carried out to determine if these miRNAs could modulate calcification-related genes. METHODS: Aortic valve samples (fused and unfused leaflets) were collected from nine male patients (mean age 44.9 +/- 13.8 years) undergoing aortic valve replacement (AVR). PIQOR miRXplore Microarrays containing 1,421 miRNAs were used and hybridized to fused leaflet samples labeled with Cy5; unfused samples were used as controls and labeled with Cy3. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the miRNA array results. Cultured human aortic valve interstitial cells (AVICs) were treated with miRNA mimics, and qRT-PCR was carried out to determine any changes in mRNAs. RESULTS: By microarray analysis, seven miRNAs were shown to be statistically different between the AS and AI patients. In the stenotic samples, the MiR-26a and miR-195 levels were shown (by qRT-PCR) to be reduced by 65% and 59%, respectively (p < 0.05), and MiR-30b to be reduced by 62% (p < 0.06). Human AVICs treated with miR-26a or miR-30b mimics showed decreased mRNA levels of calcification-related genes. MiR-26a repressed BMP2 by 36%, alkaline phosphatase (ALPL) by 38%, and SMAD1 by 26%, while MiR-30b reduced the expression of SMAD1 by 18% and of SMAD3 by 12%. In contrast, miR-195-treated AVICs had increased mRNA levels of calcification-related genes, such as BMP2 by 68% and RUNX2 by 11%. CONCLUSION: MiR-26a, miR-30b, and miR-195 were each decreased in the aortic valves of patients requiring AVR due to AS, compared to those requiring replacement due to AI. These miRNAs appear to modulate calcification-related genes in vitro.

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.

In-vitro hemodynamics of stented bioprosthetic heart valves in the tilted implantation position.

BACKGROUND AND AIM OF THE STUDY: Although, in small aortic annulus or aortic annulus calcification, it is recommended that valves are implanted in a tilted position, mechanical valves show impaired hemodynamic performance when positioned in this way. To date, no investigations have been conducted with biological valves implanted in a tilted position. METHODS: Measurements were performed in a pulsatile flow simulator. The aortic roots were mounted in a fluid reservoir and tested with bioprosthetic valves implanted in the regular position (21 mm; n = 7) or at a 200 tilt (23 mm; n = 7). Additional 21 mm valves were implanted in both positions with a systemic pressure of 120/80 mmHg. Subsequently, the valves were implanted into a glass model and flow visualization monitored by adding air bubbles illuminated with a laser diode. RESULTS: The 21 mm valves showed a slightly higher transvalvular gradient in the tilted than in the regular position, while 23 mm valves in a tilted position showed a lower gradient than 21 mm valves in the regular position. Flow in the regular position was seen to be straight and central, but in the tilted position was diverted and impacted on the aortic wall. Vortex formation in the tilted position was more pronounced than in the regular position, with certain low-flow areas being observed. CONCLUSION: The implantation of a one size-larger bioprosthetic valve at a 20 degree tilt in a small aortic root resulted in a slight reduction in transvalvular gradient compared to a smaller valve implanted in the regular position. Whilst mechanical valve performance is markedly compromised in the tilted position, the bioprosthetic valve showed only minor impairment of transvalvular pressure gradient due to tilting, and this was overcompensated by the larger valve size. However, the advantage of a greater orifice area must be traded against the consequences of the observed flow disturbances.

A critical reappraisal of the Ross operation: renaissance of the subcoronary implantation technique?

BACKGROUND: The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle. METHODS AND RESULTS: Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44+/-13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9+/-2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure-related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4+/-6.2/3.7+/-2.1 mm Hg across the autograft and 15.3+/-9.4/7.6+/-5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%). CONCLUSIONS: Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.

Quadricuspid aortic valve in a patient with Turner syndrome.

A quadricuspid aortic valve is an uncommon congenital anomaly that is often associated with other cardiac disorders. Most reported cases of quadricuspid aortic valves are detected incidentally during necropsy or aortic valve replacement and, therefore, the potential clinical course still remains unclear. A case of a 47-year-old woman with grade III to IV aortic insufficiency and mild left ventricular dilation with an end-diastolic diameter of 59 mm is presented. During surgery for aortic valve replacement (Ross procedure), a quadricuspid aortic valve was identified. Two years after the successful Ross procedure, a molecular genetic study of this rare anomaly was performed using karyotyping, fluorescence in situ hybridisation and polymerase chain reaction. Cytogenetic analysis detected chromosomal aberration 45,X0/46,XX, indicating a low-level X chromosome mosaicism; repeat karyotypes were normal. This is the first reported case of a quadricuspid aortic valve in a woman with Turner syndrome.

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.

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.

Is the outcome in acute aortic dissection type A influenced by of femoral versus central cannulation?

BACKGROUND: The purpose of this study was to evaluate the single-center experience in initial femoral versus central cannulation of the extracorporeal circulation for acute aortic dissection type A (AADA). METHODS: Between January 2003 and December 2015, 235 patients underwent repair of AADA. All patients were evaluated for the type of arterial cannulation (femoral vs. central) for initial bypass. Demographic data and outcome parameters were accessed. RESULTS: One hundred and twenty seven (54.0%) were initially cannulated in the central aortic vessels (ascending aorta or subclavian/axillary artery) and 108 (46.0%) in the femoral artery. Patients were comparable between age (62.4±14.4 vs. 62.9±14.4 years, P=0.805), gender (male, 62.2 vs. 69.4%, P=0.152) and previous sternotomy (15.7 vs. 16.7%, P=0.861) between both cannulation groups; while EuroSCORE I (11.5±4.0 vs. 12.7±4.2, P=0.031) and ASA Score (3.5±0.81 vs. 3.8±0.57, P=0.011) were significantly higher in the femoral artery cannulation group. Bypass (249±102 vs. 240±81 min, P=0.474), X-clamp (166±85 vs. 157±67 min, P=0.418) and circulatory arrest time (51.6±28.7 vs. 48.3±21.7 min, P=0.365) were similar between the groups as were lowest temperature (18.1±2.0 vs. 18.1±2.2, P=0.775). Postoperative neurologic deficit and 30-day mortality were comparable between both cannulation groups (11.7 vs. 7.2%, P=0.449 and 20.2 vs. 16.9%, P=0.699, central vs. peripheral cannulation). Multivariate analysis revealed only EuroScore I above 13 as single preoperative predictor for mortality. CONCLUSIONS: AADA can be operated with both femoral and central cannulation with similar results. Risk for early mortality was driven by the preoperative clinical and hemodynamic status before operation rather than the cannulation technique.

The Extracellular Matrix Signature in Vein Graft Disease.

BACKGROUND: Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen cross-links are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease. METHODS: Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1. CONCLUSIONS: Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease.

Collagen analysis of the ascending aortic dilatation associated with bicuspid aortic valve disease compared with tricuspid aortic valve.

Dilatation of the ascending aorta is a common occurrence in patients with bicuspid aortic valve (BAV). The aim of the current study was to characterize collagen content in advanced glycation end products (AGEs) of dilated aortic tissue from two distinct areas, concave and convex aortic sites in patients with BAV and TAV. Collagen contents extracted from 100 mg tissue was isolated by enzymatic digestion using pepsin and the nondigested material was further digested using cyanogen bromide, insoluble collagen fraction (ICF) was extracted by hydrochloric acid hydrolysis. BAV tissue showed diminished fluorescence of the pepsin extracted fraction (PEF) compared with TAV tissue (12.4 ± 1.0% vs 32.9 ± 7.6%, p = 0.05). Patients with BAV had PEF of collagens significantly diminished in the dilated ascending aorta, especially in its convex portion, in course of aging and increment of dilated diameters. It is suggestible that BAV patients present more highly AGE-modified collagens in their ascending aorta.

Midterm results of the Ross procedure preserving the patient's aortic root.

BACKGROUND: Since the early 1990s, the pulmonary autograft is predominantly implanted as a freestanding root for less aortic valve regurgitation is reported. However, there is a certain risk of dilatation of the root over time potentially impairing valve function. We favor since 8 years the original subcoronary or inclusion technique to preserve the root of the patient as a restrain to dilatation. METHODS AND RESULTS: Between June 1994 and May 2002 the subcoronary (n=228) and inclusion technique (n=17) were performed in 245 patients (191 male, 54 female), mean age 45.7+/-13.4 (15-70) years. The underlying aortic valve disease was an aortic insufficiency in n=83, stenosis in n=48, a combined aortic valve disease in n=111 and an acute endocarditis in n=19 patients. Previous aortic valve surgery was performed in n=23. Last follow-up investigations (within last year) including echocardiography was performed at a mean follow-up of 29.4+/-24.7 months (553.7 patient years). Hospital mortality was n=2, late mortality n=4 (all noncardiac). Two patients were lost to follow-up (99% complete clinical follow-up). Reoperations were necessary in n=7 valves (autograft: endocarditis n=1, malpositioning n=1, leaflet prolapse n=1; homograft: stenosis n=2, insufficiency n=2). Autograft insufficiency (AI) was AI 0 in n=154, AI I n=66, AI II n=8. The maximum/mean pressure gradient across the autograft was 6.6+/-3.4 (2.1 to 25.9)/3.6+/-1.8 (1.2 to 13.2) mm Hg, respectively. Homograft insufficiency was 0 in n=167, I in n=54, II in n=9, and III in n=1. Maximum and mean transhomograft pressure gradients were 11.7+/-6.8 (2.2 to 42.6)/6.2+/-3.8 (1.2 to 24.5) mm Hg. Most patients were NYHA class I (n=214), class II (n=19), class III (n=2). Significant aortic root dilatation was not observed. CONCLUSIONS: Aortic valve replacement with a pulmonary autograft in the subcoronary or inclusion technique provides excellent hemodynamics with no root dilatation at least in a mid term postoperative period. Transhomograft pressure gradients are slightly increased. Longer term results with special emphasis on the pulmonary homograft are necessary.

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.