Background Tetralogy of Fallot repair results in late occurrence of pulmonary regurgitation, which requires pulmonary valve replacement in a large proportion of patients. Both homografts and ...bioprostheses are used for pulmonary valve replacement as uncertainty remains on which prosthesis should be considered superior. We performed a long-term imaging and clinical comparison between these 2 strategies. Methods and Results We compared echocardiographic and clinical follow-up data of 209 patients with previous tetralogy of Fallot repair who underwent pulmonary valve replacement with homograft (n=75) or bioprosthesis (n=134) between 1995 and 2018 at a tertiary hospital. The primary end point was the composite of pulmonary valve replacement reintervention and structural valve deterioration, defined as a transpulmonary pressure decrease ≥50 mm Hg or pulmonary regurgitation degree of ≥2. Mixed linear model and Cox regression model were used for comparisons. Echocardiographic follow-up duration was longer in the homograft group (8 interquartile range, 4-12 versus 4 interquartile range, 3-6 years;
<0.001). At the latest echocardiographic follow-up, homografts showed a significantly lower transpulmonary systolic pressure decrease (16 interquartile range, 12-25 mm Hg) when compared with bioprostheses (28 interquartile range, 18-41 mm Hg; mixed model
<0.001) and a similar degree of pulmonary regurgitation (degree 0-4) (1 interquartile range, 0-2 versus 2 interquartile range, 0-2; mixed model
=0.19). At 9 years, freedom from structural valve deterioration and reintervention was 81.6% (95% CI, 71.5%-91.6%) versus 43.4% (95% CI, 23.6%-63.2%) in the homograft and bioprosthesis groups, respectively (adjusted hazard ratio, 0.27; 95% CI, 0.13-0.55;
<0.001). Conclusions When compared with bioprostheses, pulmonary homografts were associated lower transvalvular gradient during follow-up and were associated with a significantly lower risk of reintervention or structural valve degeneration.
Abstract Advanced chronic kidney disease (CKD) is associated with poor outcomes in patients undergoing surgical aortic valve replacement while its prognostic role in transcatheter aortic valve ...implantation (TAVI) remains unclear. This study aimed to investigate outcomes in patients with advanced CKD undergoing TAVI. 1904 consecutive patients undergoing balloon-expandable TAVI in 33 centers between 2007-2012 were enrolled in the I talian T ranscatheter Balloon- E xpandable Valve Implantation R egistry (ITER). Advanced CKD was defined according to estimated glomerular filtration rate (eGFR): 15-29 mL/min/1.73m2 stage 4 (S4), <15 mL/min/1.73m2 stage 5 (S5). Edwards Sapien or Sapien-XT prosthesis were used. Primary end-point was all-cause mortality during follow-up. Secondary end-points were 30-days and FU major-adverse-cardiac-events (MACE), defined with VARC-2 criteria. 421 patients were staged S5 (n=74) or S4 (n=347). S5 patients were younger, had more frequently porcelain aorta and lower incidence of previous stroke. Peri-procedural and 30-days outcomes were similar in S5 and S4 patients. During a 670 (±466) days of FU, S5 patients suffered higher mortality rates (69% vs. 39%, p<0.01) and cardiac death (19% vs. 9%, p=0.02) compared to S4. Male sex (HR 1.6, 95%CI 1.2-2.2), LVEF<30% (HR 2.3, 95% CI: 1.3-4), atrial fibrillation (HR 1.4, 95%CI:1.0-1.9) and S5 CKD (HR 1.5, 95%CI: 1.0-2.1) were independent predictors of death. In conclusion, TAVI in pre-dialytic or dialytic patients (i.e. S5) is independently associated with poor outcomes with more than double risk of death compared to patients with stage 4 renal function. Conversely, in severe CKD (i.e. S4) a rigorous risk stratification is required to avoid the risk of futility risk.
Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased ...significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes.
Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019-2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years.
The study was approved by the London-Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters.
ISRCTN17650644.
Coronary artery bypass grafting remains the standard treatment for patients with extensive coronary artery disease. Coronary surgery without use of cardiopulmonary bypass avoids the deleterious ...systemic inflammatory effects of the extracorporeal circuit. However there is an ongoing debate surrounding the clinical outcomes after on-pump versus off-pump coronary artery bypass (ONCAB versus OPCAB) surgery. The current review is based on evidence from randomized controlled trials (RCTs) and meta-analyses of randomized studies. It focuses on operative mortality, mid- and long-term survival, graft patency, completeness of revascularisation, neurologic and neurophysiologic outcomes, perioperative complications and outcomes in the high risk groups. Early and late survival rates for both OPCAB and ONCAB grafting are similar. Some studies suggest early poorer vein graft patency with off-pump when compared with on-pump, comparable midterm arterial conduit patency with no difference in long term venous and arterial graft patency. A recent, pooled analysis of randomised trials shows a reduction in stroke rates with use off-pump techniques. Furthermore, OPCAB grafting seems to reduce postoperative renal dysfunction, bleeding, transfusion requirement and respiratory complications while perioperative myocardial infarction rates are similar to ONCAB grafting. The high risk patient groups seem to benefit from off-pump coronary surgery.
Cardioplegic cardioprotection strategies used during paediatric open-heart surgery remain suboptimal. Sildenafil, a phosphodiesterase 5 (PDE-5) inhibitor, has been shown to be cardioprotective ...against ischemia/reperfusion injury in a variety of experimental models and this study therefore tested the efficacy of supplementation of cardioplegia with sildenafil in a piglet model of cardiopulmonary bypass and arrest, using both cold and warm cardioplegia protocols. Piglets were anaesthetized and placed on coronary pulmonary bypass (CPB), the aorta cross-clamped and the hearts arrested for 60 min with cardioplegia with or without sildenafil (10 nM). Twenty minutes after removal of cross clamp (reperfusion), attempts were made to wean the pigs from CPB. Termination was carried out after 60 min reperfusion. Throughout the protocol blood and left ventricular tissue samples were taken for analysis of selected metabolites (using HPLC) and troponin I. In both the cold and warm cardioplegia protocols there was evidence that sildenafil supplementation resulted in faster recovery of ATP levels, improved energy charge (a measure of metabolic flux) and altered release of hypoxanthine and inosine, two purine catabolites. There was no effect on troponin release within the studied short timeframe. In conclusion, sildenafil supplementation of cardioplegia resulted in improved cardiac energetics in a translational animal model of paediatric CPB surgery.
Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and ...lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy.
Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry.
Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded.
Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.
The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety ...and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA's blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft's growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.
Two patients with bicuspid aortic valve were selected for aortic valve repair using the Ozaki procedure. Patient-specific models of their aortic roots were generated based on computed tomography data ...and were 3-dimensional printed using a flexible resin. The models allowed sizing of the valve leaflets and practicing of leaflet suturing. (Level of Difficulty: Advanced.)
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Two patients with bicuspid aortic valve were selected for aortic valve repair using the Ozaki procedure. Patient-specific models of their aortic…
Cell therapy is a promising tool to prevent and treat heart failure in congenital heart disease. We report the first case of intramyocardial injection of allogeneic mesenchymal stromal cells as ...rescue therapy in a neonate with ischemic heart failure following arterial switch procedure for isolated transposition of the great arteries. (Level of Difficulty: Advanced.)
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