Claudia Schmidtke

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.

Valve-sparing aortic root replacement (remodeling/reimplantation) in acute type A dissection

BACKGROUND High reoperation rates after supracommissural tube graft replacement for acute type A dissection due to sinus of Valsalva dilation have been reported. Valve-sparing operations focusing on the replacement of the sinus of Valsalva are an appealing alternative. The applicability of these techniques in acute type A dissection remains debatable and results are limited. METHODS From 1992 to 1998, 20 patients with acute type A dissection received a valve-sparing aortic root replacement. Two different types of aortic valve-sparing operations were performed: the remodeling technique in 11 patients and the reimplantation technique in 9 patients. Patients were followed for 26 +/- 18 months. Echocardiographic studies were performed every 6 months. RESULTS There were 2 early postoperative deaths and no late death, no reoperation, and no thromboembolic events. The latest echocardiographic studies of the 18 survivors showed a competent valve in 12 and a trivial aortic valve insufficiency in 6 patients. The mean aortic valve pressure gradient was 4.3 +/- 1.3 mm Hg. CONCLUSIONS These midterm results support the surgical strategy of valve-sparing aortic root replacement in patients with acute type A dissection.

Quality of life in aortic valve replacement: pulmonary autografts versus mechanical prostheses

OBJECTIVES We sought to determine whether the quality of life (QoL) is different in patients after aortic valve replacement with mechanical prostheses or pulmonary autografts. BACKGROUND Quality of life after mechanical valve replacement may be affected by the risk of thromboembolism and anticoagulation, and after autograft implantation, by the risk of degeneration and re-operation especially of the homograft. METHODS Two groups of 40 patients each--one after the autograft procedure (group I) and one after mechanical valve implantation (group II)--were matched for age, gender and length of follow-up. At latest follow-up, all patients underwent routine echocardiography, the short-form health survey (SF-36) QoL survey and an extensive psychological investigation. RESULTS Patients with an autograft showed better QoL scales, as compared with mechanical valve recipients. The difference was significant for both the physical (72.72+/-20.00 vs. 60.27+/-26.07, p = 0.021) and psychological health sum scores (74.71+/-21.03 vs. 64.71+/-23.49, p = 0.046) and for the subtests of physical functioning (73.72+/-22.44 vs. 62.77+/-25.42, p = 0.049), physical pain (88.39+/-19.13 vs. 73.36+/-27.08, p < or = 0.006), general health perception (64.37+/-17.88 vs. 51.86+/-22.86, p < or = 0.008) and health change (61.89+/-18.94 vs. 50.11+/-24.37, p = 0.02). The QoL variables did not correlate to pressure gradients, ejection fraction and New York Heart Association functional class. Psychometric tests revealed no meaningful differences between the groups. CONCLUSIONS This study provides some evidence that patients with pulmonary autografts have greater benefit in terms of QoL, as compared with recipients of mechanical valve substitutes.

SIZE AND DISTENSIBILITY OF THE AORTIC ROOT AND AORTIC VALVE FUNCTION AFTER DIFFERENT TECHNIQUES OF THE ROSS PROCEDURE

OBJECTIVES In the Ross procedure, 3 different techniques are used for aortic valve replacement with the pulmonary autograft: freestanding root, inclusion, and subcoronary implantation. The objective of this study was to evaluate echocardiographically the influence of the particular operative technique on dimension, distensibility, and valve function. METHODS Between February 1990 and August 1998, the Ross procedure was performed in 111 patients (mean age, 48.6 +/- 14.1 years; range, 15.2-70.6 years), with 1 early and 1 late death, 1 autograft replacement, and 1 patient lost to follow-up. The remaining patients underwent the freestanding root (n = 9 patients), inclusion (n = 14 patients), and subcoronary techniques (n = 84 patients). Echocardiography was performed at a mean follow-up of 26 +/- 21.3 months after operation and was compared with the echocardiographic findings of the control subjects (n = 10 subjects). Root sizes were measured at the level of the anulus, sinus, and supra-aortic ridge; the distensibility was calculated as pressure strain elastic modulus and percent change of radius. RESULTS Size and distensibility of the aortic root were normal, except for a larger diameter at the sinus level in the root technique in comparison to the subcoronary technique (P <.05; maximum diameter, 41.3 +/- 8.6 mm vs 32.6 +/- 4.0 mm). Aortic valve function was comparable among groups with low pressure gradients and most patients with no or trace aortic insufficiency. CONCLUSIONS The freestanding root, inclusion, and subcoronary techniques in the Ross procedure provide comparable excellent hemodynamics, normal root size, and distensibility, except for the enlarged sinus diameter in the freestanding root. These results may have some impact on the operative procedure and follow-up investigations.

Long-Term Results of 203 Young and Middle-Aged Patients With More Than 10 Years of Follow-Up After the Original Subcoronary Ross Operation

BACKGROUND The choice of prosthesis for aortic valve replacement in young and middle-aged patients remains challenging owing to the accelerated degeneration of bioprostheses in these age groups and the risks of thromboembolism and bleeding with mechanical valves. Theoretically, the living pulmonary autograft (Ross operation) would be advantageous. Long-term results of the various Ross techniques are needed for defining the value of this surgical concept. METHODS Of a total of 576 subcoronary Ross patients operated on between June 1994 and June 2011, we report on 203 consecutive subcoronary patients (mean age, 47.2±13.6 years, 155 male, 2,491 patient-years) with a follow-up of at least 10 years (mean, 12.3±2.9 years). RESULTS Early and late mortality were 0.98% (n=2) and 11.4% (n=23). Valve-related mortality was 2.5% (n=5). Survival did not differ from that of the general German population. Freedom from autograft or allograft reoperation was 92.2% at 10 years and 87.1% at 15 years. Five major bleeding (0.20%/patient-year) and 11 thromboembolic events (0.44%/patient-year) occurred in 5 and 10 patients, respectively. Neither a systematic increase in aortic regurgitation nor an increase in root dimensions with time could be observed. In the vast majority of patients, valvular hemodynamics at latest echocardiographic follow-up were excellent. CONCLUSIONS Long-term results of the original subcoronary Ross operation reveal normal survival, excellent hemodynamics, low risk of thromboembolism or bleeding, and small risk for reoperation. These results favor the pulmonary autograft concept in young and middle-aged patients in experienced centers and may serve to better define its role in surgical treatment of aortic valve disease in these patients.

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.

Toward individualized management of the ascending aorta in bicuspid aortic valve surgery: The role of valve phenotype in 1362 patients

OBJECTIVE Decision making regarding the management of the ascending aorta (AA) in patients with a bicuspid aortic valve (BAV) undergoing valve surgery has hardly been individualized and remains controversial. We analyzed our individualized, multifactorial approach, focusing on the BAV phenotype. METHODS In 1362 patients (1044 men) undergoing aortic valve surgery, the BAV phenotypes were intraoperatively classified and retrospectively analyzed. The mean follow-up was 5.4±3.6 years (range, 0-14; 7334 patient-years), and the data were 96.5% complete. The individualized AA management decision process mainly included the AA diameter, age, body surface area, macroscopic AA configuration, and the perceived tissue strength of the aortic wall resulting in 3 AA treatment groups: no intervention, aortoplasty (AoP), and AA replacement (AAR). RESULTS In 906 patients (66.5%), no intervention was performed and 172 (12.6%) and 284 (20.9%) underwent AoP and AAR, respectively. The hospital mortality was 1.1% for no intervention, 0.6% for AoP, and 0.4% for AAR (P=.4). The 10-year survival was similar for all 3 groups and comparable to that of the general population. Five reoperations on the AA occurred, 4 in the no intervention and 1 in the AoP group. BAV type 2/unicuspid patients were younger and more had undergone AAR in absolute numbers and after allowing for the AA diameter. Also, in patients with BAV type 1 LR and regurgitation, AAR was performed more often. CONCLUSIONS The individualized, multifactorial management of AA in patients with BAV during aortic valve surgery leads to excellent results. The threshold AA diameter for intervention (AoP or AAR) varied from 34 to 51 mm (mean, 43.9). BAV type 2/unicuspid and BAV type 1 LR with regurgitation emerged as determinants for more liberal AAR in our practice. Longer term follow-up is necessary to confirm our conclusions.

The fate of the bicuspid valve aortopathy after aortic valve replacement.

OBJECTIVES The fate of the aortic dimensions in patients with a bicuspid aortic valve (BAV) after aortic valve replacement (AVR) is unclear. We investigated the evolution of aortic root and ascending aorta dimensions in patients with a BAV after AVR. To neutralize the effect of pathological transvalvular haemodynamics on aortic dimensions, we evaluated our hypotheses in patients with normal transvalvular haemodynamics after a subcoronary autograft procedure, which preserves intact the native aortic wall. METHODS We excluded patients operated on for endocarditis; who developed autograft insufficiency > trivial and who required autograft reoperation during the follow-up. We included 448 patients (361 with BAV; 340 males; 44.6 ± 11.4 years; mean follow-up: 7.5 ± 3.9 years). Valve phenotype was determined during surgery. Annual echocardiographic examinations (n = 3336) were performed (follow-up completeness: 98%). To allow for somatometric, gender and age influences, z-values of measurements were calculated from the general population (GP) and analysed using longitudinal methods. RESULTS The increase in ascending aorta did not differ from that expected in the GP (0.04 z-values/year; P = 0.06). No difference could be observed in diameter increase rates between BAV and tricuspid aortic valve patients (TAV) (0.04 vs 0.06 z-values/year; P = 0.3), as well as between BAV phenotypes. The sinus increase did not differ from that expected in the GP (0.03 z-values/year; P = 0.1), and no significant differences could be observed between BAV phenotypes. In patients undergoing aortoplasty (n = 70), no significant difference in the rates of ascending aorta and sinus increase could be observed, compared with the GP. CONCLUSION For the time period of this study and in patients with normal aortic root haemodynamics after AVR, ascending aorta dimensions over time are similar to that of the matched GP. Patients with a BAV did not exhibit higher rates of ascending aorta dilatation after AVR than patients with TAV. At least for the first postoperative decade, transvalvular haemodynamics appear to exhibit a greater influence than the genetic component of BAV on the development of the BAV aortopathy.

Decellularized pulmonary homograft (SynerGraft) for reconstruction of the right ventricular outflow tract: first clinical experience

Einleitung: Kryokonservierte klappentragende Homografts werden zur Rekonstruktion des rechts- und linksventrikulären Ausflusstraktes eingesetzt. In Langzeitverlauf treten degenerative Veränderungen auf, wobei immunologisch vermittelte Phänomene ähnlich der chronischen Abstoßung als Mitursache angenommen werden. Durch die Entwicklung von dezellularisierten, nicht-glutaraldehydfixierten klappentragenden Konduits sollte eine nicht-immunogene bindegewebige Matrix geschaffen werden, die als Basis der autologen Rezellularisierung durch den Träger dient. Ziel der Untersuchung war die klinische und hämodynamische Charakterisierung nach erstem Einsatzes von dezellularisierten pulmonalen Homografts (SynerGraft) beim Menschen. Methode: Eine Rekonstruktion des rechtsventrikulären Ausflusstraktes wurde bei 17 Patienten durchgeführt: 15 Patienten mit Aortenklappenerkrankungen und Ross-Operation und zwei Patienten mit Reoperationen bei Fallotscher Tetralogie und schwerer Pulmonalinsuffizienz. Als Kontrollgruppe dienten Patienten mit Ross-Operation unter Verwendung konventioneller, kryokonservierter Homografts. Während der Verlaufsbeobachtung bis sechs Monaten wurden echokardiographisch morphologische und dynamische Parameter charakterisiert: maximaler und mittlerer Druckgradient über dem rechten und linken Ausflusstrakt, effektive Öffnungsfläche des rechten und linken Ausflusstraktes, Bestimmung einer Regurgitation über der Neopulmonal- und Neoaortenklappe. Ergebnisse: Ein Patient verstarb sechs Wochen postoperativ an einer nicht klappen-assoziierten therapierefraktären kardiopulmonalen Erkrankung, alle Patienten waren frei von klappen-bezogenen Komplikationen während der Verlaufsbeobachtung. Die Ross-Patienten der Kontrollgruppe wiesen einen stetigen, signifikanten Anstieg des maximalen und mittleren Druckgradienten über dem konventionellen Homograft auf (ΔP max 5,5±2,5 auf 11,4±6,4 mmHg, p=0,002; ΔP mean 3,0±1,3 auf 6,2±3,9 mmHg, p=0,003), in der SynerGraft-Gruppe war eine frühe, statistisch insignifikante Druckgradientzunahme messbar (ΔP max 7,1±3,7 auf 10,1±3,9mmHg, p=0,11; ΔP mean 3,6±1,6 auf 5,5±2,3mmHg, p=0,12). Die effektive Öffnungsfläche der Neopulmonalklappe nahm innerhalb der Periode der Verlaufsbeobachtung in der Kontrollgruppe von 1,74±0,33 auf 1,18±0,36 cm2/m2 ab (p=0,001), in der SynerGraft-Gruppe war die zeitabhängige Reduktion der effektiven Öffnungsfläche signifikant geringer (1,51±0,37 auf 1,25±0,26 cm2/m2; p=0,08). Schlussfolgerung: Bis zu einem halben Jahr nach Implantation erwiesen sich die dezellularisierten Homografts zur Rekonstruktion des rechtsventrikulären Ausflusstraktes als sicher, stabil und erfolgsversprechend in Hinblick auf die effektive Klappenöffnungsfläche und ihre Flussdynamik. Introduction: Cryopreserved homograft valve conduits have been used to reconstruct the right and left ventricular outflow tract. Long-term studies have shown homograft degeneration and calcification, and it has been postulated that immunological mediated phenomena in a manner similar to that seen in chronic rejection may contribute to the degeneration process. The development of a decellularized, non-glutaraldehyde-fixed valve conduit creates a non-immunogenic connective tissue matrix for autologous recellularization by host cells. The aim of the study was to characterize the clinical and hemodynamic pattern in human implants of the novel decellularized pulmonary homografts (SynerGraft). Methods: Reconstruction of the right ventricular outflow tract was performed in 17 patients: 15 patients with aortic valve disease and the Ross procedure, and two patients with redo procedures following Fallot tetralogy and severe pulmonary regurgitation. Patients with the Ross procedure with standard cryopreserved homografts as neopulmonic conduits served as controls. Within the follow-up over six months morphological and hemodynamic parameters were characterized by echocardiography: maximal and mean pressure gradient across the right and left ventricular outflow tract, their effective orifice areas, determination of neopulmonic and neoaortic regurgitation. Results: One patient died six weeks following surgical treatment due to non-valve related end-stage cardiopulmonary failure; all patients were free of valve-related complications during the follow-up period. The matched Ross patients showed a gradual but significant increase of both the maximal and mean pressure gradient across the right ventricular outflow tract (ΔP max 5.5±2.5 to 11.4±6.4 mmHg, p=0.002; ΔP mean 3.0±1.3 to 6.2±3.9 mmHg, p=0.003), whereas in the SynerGraft group increase of pressure gradients were measurable but did not reach statistical significance (ΔP max 7.1±3.7 to 10.1±3.9 mmHg, p=0.11; ΔP mean 3.6±1.6 to 5.5±2.3 mmHg, p=0.12). The pulmonary effective orifice areas decreased in the control group from 1.74±0.33 to 1.18±0.36cm2/m2 (p=0.001). Within the SynerGraft group time dependent reduction of the orifice area was significantly less (1.51±0.37 to 1.25±0.26 cm2/m2; p=0.08). Conclusion: Up to six months after implantation reconstruction of the right ventricular outflow tract with decellularized homografts was safe, stable, and the morphological and hemodynamic features are promising.

Pathway Analysis of Differentially Expressed Genes in Patients with Acute Aortic Dissection

Background Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk. Materials and Methods Aortic tissue was collected from 19 patients with AAD (mean age 61.7 ± 13.1 years), and from eight other patients (mean age 32.9 ± 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 ± 12.3 years) served as the control group. The PIQOR™ Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using PathwayAssist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed. Results Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 ± 0.4 vs. 6.1 ± 2.3 fold, p = 0.003) and of DCN (2.5 ± 1.0 vs. 8.5 ± 4.7 fold, p = 0.04) in AAD compared to MS and control samples. Conclusions Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.