[Aortic Root Replacement with Homograft].

Infectious endocarditis is a severe infectious disease in cardiovascular surgery fields. Appropriate antibiotics administration is the principle of treatment, while surgical intervention is required when there is intensive tissue destruction, refractory infection, or high risk of embolism. Usually, surgical risks of infectious endocarditis are rather high as preoperative general condition is often poor. Homografts, which have excellent anti-infective properties, become one of the graft options for infectious endocarditis. Fortunately, we are able to use homografs without so much obstacles thanks to the presence of a tissue bank in our hospital. We will report our strategy and clinical courses of aortic root replacement using homograft for infective endocarditis.

[Aortic Root Pseudoaneurysm].

Aortic root pseudoaneurysm is often derived from suture sites after aortic root replacement on the basis of connective tissue disease, aortitis, or prosthetic valve endocarditis. Preoperative computed tomography (CT) and echocardiography are useful not only for diagnosing a pseudoaneurysm but also for planning to repair it. Redo aortic root replacement is necessary to repair it in most cases. When a giant pseudoaneurysm is close to a sternal posterior wall, resternotomy may be challenging. In such a case, precedent cardiopulmonary bypass with left ventricular apical vent under mild-moderate hypothermia is useful to control bleeding during resternotomy. Regarding graft selection, cryopreserved homograft is effective for repairing pseudoaneurysm in an active infectious phase, but modified Bentall procedure may be still considerable to expect long-term durability if infection is well controlled by preoperative sufficient antibiotic treatment and intraoperative debridement. In the author's institute, 45 patients with aortic root pseudoaneurysm underwent surgical repair since 2011. Thirty cases (67%) was infectious. Thirty-six patients( 80%) underwent aortic root replacement, including homograft in 14 patients and modified Bentall procedure in 22 patients. All the patients survived at discharge, and 1-year and 5-year survival were 96.8% and 74.9%, respectively. Preoperative infectious status and graft selection did not significantly affect remote-phase survival.

A 20-year experience with cryopreserved allografts as the valve replacement of choice in aortic root reconstruction for destructive endocarditis with abscess formation.

OBJECTIVES: The aim of this retrospective study was to assess the early- and long-term outcomes following the use of cryopreserved allografts in aortic valve endocarditis with peri-annular abscess formation. METHODS: From 2001 to 2021, 110 consecutive patients with active infective endocarditis and peri-annular abscess, underwent a cryopreserved allograft root replacement. In 100 patients (91%), the operation was performed <48 h after admission due to refractory heart failure and or septic shock. In 95 patients (86.4%), a redo operation was performed due to a prosthetic valve endocarditis. Preoperatively, 12 patients were dialysis-dependent and 30 patients suffered from a recent stroke. RESULTS: The 30-day mortality was 18% (20 patients). Freedom from reintervention was 98.3% (standard deviation: 1.7) at 1 year and 83.3% (standard deviation: 8.5) at 10 years. Four patients required a redo operation. Three patients did develop re-endocarditis. Freedom from re-endocarditis was 95% after 17 years of follow-up. Preoperative dialysis dependency (odds ratio: 22.75, 95% confidence interval: 4.79-108.14, P < 0.001), ejection fraction under 30% (odds ratio: 17.91, 95% confidence interval: 3.27-98.01, P < 0.001) and stroke within 14 days prior to operation (odds ratio: 5.21, 95% confidence interval: 1.28-21.2, P = 0.021) were incremental factors associated with the 30-day mortality. CONCLUSIONS: In aortic root endocarditis with abscesses formation, cryopreserved allografts exhibit excellent clinical performance with a low rate of reinfection and reintervention, which make its use as valve replacement a very desirable option. Dialysis dependency, ejection fraction under 30% and recent stroke have the highest impact on the 30-day mortality.

Cryopreserved aortic homografts for complex aortic valve or root endocarditis: a 28-year experience.

OBJECTIVES: The aim of this study was to evaluate early- and long-term outcomes of cryopreserved aortic homograft (CAH) implantation for aortic valve replacement (AVR) or aortic root replacement (ARR) in patients with or without complex infective endocarditis. METHODS: All adult patients undergoing AVR or ARR with CAH at our institution between January 1993 and July 2021 were included in the study. RESULTS: One hundred four patients, 75 males and 29 females, aged 59 ± 17 years, underwent AVR or ARR with CAH for infective endocarditis (n = 94, 90%) or aortic valve disease (n = 10, 10%). There were 33 (35%) native valve endocarditis and 61 (65%) prosthetic valve endocarditis, which were complicated by annular abscess in 77 (82%) patients, mitral valve endocarditis in 13 (14%) and tricuspid valve endocarditis in 13 (14%). The mean cardiopulmonary bypass time was 214 ± 80 min and the mean aortic cross-clamping time was 164 ± 56 min. There were 12 (12%) hospital deaths and 7 (7%) postoperative low cardiac output syndrome requiring extracorporeal membrane oxygenation in 4 patients and intra-aortic balloon pump in 3. Thirty-nine (42%) patients died during the follow-up (94% complete). The mean survival time was 13.9 ± 1.2 years. Twenty-five patients (26%) underwent late reoperation for aortic homograft degeneration (n = 17, 18%), homograft endocarditis (n = 6, 7%), homograft dehiscence (n = 1, 1%) and mitral valve regurgitation (n = 1, 1%). The mean survival free from reintervention was 15.7 ± 1.2 years. CONCLUSIONS: AVR or ARR with a CAH for complex endocarditis is associated with satisfactory hospital survival, considering the critical patient presentation at surgery, and excellent survival free from recurrent infection. Need for reoperation late after surgery is similar to other biological prostheses.

A Role for Peroxisome Proliferator-Activated Receptor Gamma Agonists in Counteracting the Degeneration of Cardiovascular Grafts.

ABSTRACT: Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

Aortic valve function post-replacement of severe aortic stenosis by transcatheter procedure versus surgery: a systematic review and metanalysis.

Transcatheter aortic valve replacement (TAVR) has shown to reduce mortality compared to surgical aortic valve replacement (sAVR). However, it is unknown which procedure is associated with better post-procedural valvular function. We conducted a meta-analysis of randomized clinical trials that compared TAVR to sAVR for at least 2 years. The primary outcome was post-procedural patient-prosthesis-mismatch (PPM). Secondary outcomes were post-procedural and 2-year: effective orifice area (EOA), paravalvular gradient (PVG) and moderate/severe paravalvular leak (PVL). We identified 6 trials with a total of 7022 participants with severe aortic stenosis. TAVR was associated with 37% (95% CI [0.51-0.78) mean RR reduction of post-procedural PPM, a decrease that was not affected by the surgical risk at inclusion, neither by the transcatheter heart valve system. Postprocedural changes in gradient and EOA were also in favor of TAVR as there was a pooled mean difference decrease of 0.56 (95% CI [0.73-0.38]) in gradient and an increase of 0.47 (95% CI [0.38-0.56]) in EOA. Additionally, self-expandable valves were associated with a higher decrease in gradient than balloon ones (beta = 0.38; 95% CI [0.12-0.64]). However, TAVR was associated with a higher risk of moderate/severe PVL (pooled RR: 9.54, 95% CI [5.53-16.46]). All results were sustainable at 2 years.

Long-term Outcomes of Aortic Valve Replacement With Aortic Homograft: 27 Years Experience.

BACKGROUND: Aortic homografts have been used in young patients requiring aortic valve replacement. Currently, these grafts are generally reserved for aortic valve endocarditis with or without root abscess; however, longitudinal data are lacking. Our aim was to assess the long-term safety and durability of homograft implantation. METHODS: All adult patients undergoing aortic homograft implantation at a single institution from 1992 to 2019 were included. Outcomes of interest included all-cause mortality and aortic valve reoperation, studied over a median follow-up duration of 19 years. RESULTS: In all, 252 patients with a mean age of 49 years were included. Infective endocarditis was the primary indication for surgery in 95 patients (38%). The endocarditis group, compared with the no-endocarditis group, had a higher prevalence of New York Heart Association class III-IV (56% vs 26%), chronic kidney disease (22% vs 1%), prior cardiac surgery (40% vs 10%), and emergency status (7% vs 0%; all P < .001). Operative mortality was higher among endocarditis patients (16% vs 0.6%, P < .001), which persisted after risk adjustment. Among patients who survived to discharge, however, there was no difference in long-term survival between the endocarditis group and no-endocarditis group. Overall survival and freedom from reoperation were 88.3% and 80% at 15 years and 87.2% and 78% at 25 years, respectively. Indications for reoperation included structural valve deterioration (83%), endocarditis (12%), and mitral valve disease (5%). Reoperative mortality occurred in 2 patients (4.9%). CONCLUSIONS: Aortic homografts are associated with good long-term survival and admissible freedom from reoperation. Operative mortality is high among patients with endocarditis; however, for those who survive to discharge, long-term survival and durability are the same as for patients without endocarditis.

Valvular surgery in donor hearts before orthotopic heart transplantation.

BACKGROUND: Donor heart shortage has extended the waiting time and increased the mortality of patients on the transplant waiting list. Widening old standard donor criteria has successfully increased the number of heart transplantations, but for many years, a valve disease in a donor heart has been considered a primary contraindication for organ donation. AIMS: To analyse the results of aortic and mitral valvular surgery in marginal donor hearts with valvulopathy before orthotopic heart transplantation. METHODS: Between January 2012 and November 2015, we performed 53 heart transplantations in our department. In four donors, echocardiography performed at the time of organ procurement showed a valvular disease: three had moderate-to-severe mitral regurgitation; and one had moderately severe aortic valve stenosis. RESULTS: The mean bench mitral repair and aortic replacement time, aortic cross-clamp time and total ischaemic time were: 18 (range 7-25) minutes, 78.7 (range 57-98) minutes and 184 (range 89-255) minutes, respectively. Intraoperative transoesophageal echocardiography showed good mitral repair or aortic prosthetic valve function, and good right and left ventricular function. One patient died of infectious pneumonia after 1 month. The mean duration of follow-up for the patients discharged home was 75±13 months, and all have returned to an active unrestricted lifestyle. CONCLUSIONS: Our limited series demonstrates that conventional valvular procedures performed on otherwise healthy donor hearts with mitral and aortic valve pathology can efficaciously expand the donor pool for orthotopic cardiac transplantation and decrease the mortality rate on the waiting list.

Implantation of a decellularized aortic homograft in a child.

The implantation of a decellularized aortic homograft in children and young adults has been shown to be a good alternative to existing surgical approaches. Lower risk of calcification and the potential of growth render a homograft a promising valve substitute. The child presented in this video tutorial is a 10-year-old boy diagnosed with congenital aortic stenosis which was treated by balloon valvuloplasty early in life. Current echocardiographic findings show severe aortic regurgitation and stenosis. The tutorial provides detailed insight into how to implant a decellularized aortic homograft as a total root replacement.

Estenosis aórtica y lesión severa de tronco coronario: tratamiento percutáneo exitoso / Severe aortic valve stenosis with co-existing critical obstruction of the main left coronary artery

Abstracts: Successful treatment following percutaneous angioplasty (PTCA) and percutaneous trans aortic valve aortic valve stenosis and critical obstruction of the main left coronary artery is presented. Due to a very high estimated surgical risk the patient underwent PTCA of the main left trunk followed, a week later, by trans catheter implantation of an aortic valve (TAVI). The procedure was uneventful, and the clinical condition of the patient was excellent at one year (Functional class I).

Mechanical and structural properties of human aortic and pulmonary allografts do not deteriorate in the first 10 years of cryopreservation and storage in nitrogen.

The aortic and pulmonary allograft heart valves (AHV) are used in the cardiac surgery for replacing the impaired semilunar valves. They are harvested from donor hearts and cryostored in tissue banks. The expiration period was set to 5 years arbitrarily. We hypothesized that their mechanical and structural properties do not deteriorate after this period. A total of 64 human AHV (31 aortic and 33 pulmonary) of different length of cryopreservation (fresh, 0-5, 5-10, over 10 years) were sampled to different tissue strips (artery, leaflet, ventriculo-arterial junction) and tested by tensile test with loading velocity 10 mm/min until tissue rupture. Neighbouring regions of tissue were processed histologically and evaluated for elastin and collagen area fraction. The results were evaluated statistically. In aortic AHV, the physical deformation response of wall samples to stress did not changed significantly neither during the process of cryopreservation nor during the first 10 years of storage. In pulmonary AHV, the ultimate strain dropped after 5 years of cryopreservation indicating that pulmonary artery was significantly less deformable at the time of rupture. On the other hand, the ultimate stress was equal during the first 10 years of cryostorage. The changes in collagen and elastin amount in the tissue samples were not associated with mechanical impairment. Neither elasticity, stiffness and solidity nor morphology of aortic and pulmonary AHV did not change reasonably with cryopreservation and in the first 10 years of cryostorage. This evidence suggests that the expiration period might be extended in the future.

Surface biofunctionalization of the decellularized porcine aortic valve with VEGF-loaded nanoparticles for accelerating endothelialization.

The original intention for building a tissue-engineered heart valve (TEHV) was to simulate a normal heart valve and overcome the insufficiency of the commonly used heart valve replacement in the clinic. The endothelialization of the TEHV is very important as the endothelialized TEHV can decrease platelet adhesion and delay the valvular calcification decline process. In this work, we encapsulated vascular endothelial growth factor (VEGF) into polycaprolactone (PCL) nanoparticles. Then, through the Michael addition reaction, PCL nanoparticles were introduced onto the decellularized aortic valve to prepare a hybrid valve. The encapsulation efficiency of the PCL nanoparticles for VEGF was up to 82%, and the in vitro accumulated release rate was slow without an evident initial burst release. In addition, the hybrid valve had a decreased hemolysis ratio and possessed antiplatelet adhesion capacity, and it was able to promote the adhesion and proliferation of endothelial cells, covering the surface with a dense cell layer to accelerate endothelialization. An experiment involving the subcutaneous implant in SD rats showed that at week 8, lots of blood capillaries were formed in the hybrid valve. Mechanics performance testing indicated that the mechanical property of the hybrid valve was partly improved. Taken together, we applied a nano-drug controlled release system to fabricate TEHV, and provide an approach for the biofunctionalization of the TEHV scaffold for accelerating endothelialization.

Factors impacting long-term pulmonary autograft durability after the Ross procedure.

OBJECTIVE: Although the Ross procedure provides excellent long-term survival and a high quality of life, its use has been limited to relatively few centers. In this study, we evaluated long-term Ross procedure results in adults to assess the predictors of pulmonary autograft durability. METHODS: Between 1998 and 2015, 793 consecutive adult patients underwent the Ross procedure. The total root replacement technique was used in all patients. RESULTS: The early mortality rate was 2.9%. The mean follow-up duration was 6.5 ± 3.2 years, and the 10-year survival rate was 90.4%. Longitudinal mixed-effects ordinal regression identified a combination of bicuspid aortic valve and aortic insufficiency (odds ratio, 2.19; P < .001) as predictors for progression of autograft valve insufficiency at follow-up. The cumulative incidence of autograft reoperations at 10 years was 8.6%. Competing risk regression identified bicuspid aortic valve insufficiency as the independent predictor of autograft reoperation (subdistribution hazard ratio, 2.16; P = .030). Moreover, patients with bicuspid aortic valve and aortic insufficiency had greater increases in annulus (P < .001), sinus (P < .001), and ascending aorta (P < .001) diameters over time. CONCLUSIONS: For patients undergoing the Ross procedure, a combination of bicuspid aortic valves and aortic insufficiency is the main risk factor for late autograft dilatation and dysfunction.

Role of TGF-ß1 Signaling in Heart Valve Calcification Induced by Abnormal Mechanical Stimulation in a Tissue Engineering Model.

A tissue engineering model of heart valve calcification induced in a bioreactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms. Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs) were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and threeleaflet tissue engineered valves. The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A), low (1000 mL/min, group B), medium (2000 mL/min, group C), and high velocity (3000 mL/min, group D) for 14 days. Morphology and calcification were assessed by von Kossa staining, alkaline phosphatase (ALP) content, and Runx2 immunostaining. Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-ß1, bone morphogenetic protein 2 (BMP2), Smad1, and MSX2 were measured at different time points. ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions. The results showed that during 14 days of flow stimulation, huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A, B, and C. Under mechanical stimulation, huVICs showed a parallel growth pattern in the direction of the fluid flow, but huVICs exhibited disordered growth in the high-velocity flow environment. von Kossa staining, ALP measurement, and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D. Expression levels of TGF-ß1, BMP2, and MSX2 mRNA and protein were increased under fluid stimulation. ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced. In conclusion, abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model. The extent of calcification correlated positively with the flow velocity, as did the mRNA and protein levels of TGF-ß1, BMP2, and MSX2. These findings indicate that TGF-ß1/BMP2 signaling is involved in valve calcification induced by abnormal mechanical stimulation.