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Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

J Heart Lung Transplant. 2022 Nov 17:S1053-2498(22)02213-6. doi: 10.1016/j.healun.2022.11.003. Online ahead of print.

ABSTRACT

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates.

METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management.

RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor.

CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

PMID:36564335 | DOI:10.1016/j.healun.2022.11.003

Categorías: Trasplante cardíaco

Sodium nitroprusside for advanced heart failure. A metanalysis of literature data

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Vascul Pharmacol. 2022 Dec 20:107140. doi: 10.1016/j.vph.2022.107140. Online ahead of print.

ABSTRACT

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

PMID:36563732 | DOI:10.1016/j.vph.2022.107140

Categorías: Trasplante cardíaco

Lung cancer screening

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Lancet. 2022 Dec 20:S0140-6736(22)01694-4. doi: 10.1016/S0140-6736(22)01694-4. Online ahead of print.

ABSTRACT

Randomised controlled trials, including the National Lung Screening Trial (NLST) and the NELSON trial, have shown reduced mortality with lung cancer screening with low-dose CT compared with chest radiography or no screening. Although research has provided clarity on key issues of lung cancer screening, uncertainty remains about aspects that might be critical to optimise clinical effectiveness and cost-effectiveness. This Review brings together current evidence on lung cancer screening, including an overview of clinical trials, considerations regarding the identification of individuals who benefit from lung cancer screening, management of screen-detected findings, smoking cessation interventions, cost-effectiveness, the role of artificial intelligence and biomarkers, and current challenges, solutions, and opportunities surrounding the implementation of lung cancer screening programmes from an international perspective. Further research into risk models for patient selection, personalised screening intervals, novel biomarkers, integrated cardiovascular disease and chronic obstructive pulmonary disease assessments, smoking cessation interventions, and artificial intelligence for lung nodule detection and risk stratification are key opportunities to increase the efficiency of lung cancer screening and ensure equity of access.

PMID:36563698 | DOI:10.1016/S0140-6736(22)01694-4

Categorías: Trasplante cardíaco

Circulating hemopexin modulates anthracycline cardiac toxicity in patients and in mice

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Sci Adv. 2022 Dec 23;8(51):eadc9245. doi: 10.1126/sciadv.adc9245. Epub 2022 Dec 23.

ABSTRACT

Anthracyclines such as doxorubicin (Dox) are effective chemotherapies, but their use is limited by cardiac toxicity. We hypothesized that plasma proteomics in women with breast cancer could identify new mechanisms of anthracycline cardiac toxicity. We measured changes in 1317 proteins in anthracycline-treated patients (n = 30) and replicated key findings in a second cohort (n = 31). An increase in the heme-binding protein hemopexin (Hpx) 3 months after anthracycline initiation was associated with cardiac toxicity by echocardiography. To assess the functional role of Hpx, we administered Hpx to wild-type (WT) mice treated with Dox and observed improved cardiac function. Conversely, Hpx-/- mice demonstrated increased Dox cardiac toxicity compared to WT mice. Initial mechanistic studies indicate that Hpx is likely transported to the heart by circulating monocytes/macrophages and that Hpx may mitigate Dox-induced ferroptosis to confer cardioprotection. Together, these observations suggest that Hpx induction represents a compensatory response during Dox treatment.

PMID:36563141 | DOI:10.1126/sciadv.adc9245

Categorías: Trasplante cardíaco

Sodium balance and peritoneal ultrafiltration in refractory heart failure

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

G Ital Nefrol. 2022 Oct 31;39(5):2022-vol5.

ABSTRACT

About 5% of patients with heart failure (HF) reach the end-stage of disease, becoming refractory to therapy. The clinical course of end-stage HF is characterized by repeated hospitalizations, severe symptoms, and poor quality of life. Peritoneal ultrafiltration (PUF), removing water and sodium (Na+), can benefit patients with end-stage HF. However, effects on fluid and electrolyte removal have not been fully characterized. In this pilot study in patients with chronic HF and moderate chronic renal failure, we evaluated the effects of water and sodium removal through PUF on ventricular remodeling, re-hospitalization, and quality of life. Patients with end-stage HF (NYHA class IV, ≥3 HF hospitalization/year despite optimal therapy), not eligible for heart transplantation underwent peritoneal catheter positioning and began a single-day exchange with icodextrin at night (n=6), or 1-2 daily exchanges with hypertonic solution (3.86%) for 2 hours with 1.5-2 L fill volume (n=3). At baseline, average ultrafiltration was 500±200 ml with icodextrin, and 700±100 ml with hypertonic solution. Peritoneal excretion of Na+ was greater with icodextrin (68±4 mEq/exchange) compared to hypertonic solution (45±19 mEq/exchange). After a median 12-month follow-up, rehospitalizations decreased, while NYHA class and quality of life (by Minnesota Living with HF questionnaire), improved. In end-stage HF patients, PUF reduced re-hospitalization and improved quality of life. It can be an additional treatment to control volume and sodium balance.

PMID:36563073

Categorías: Trasplante cardíaco

A multicenter evaluation of external outflow graft obstruction with a fully magnetically levitated left ventricular assist device

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

J Thorac Cardiovasc Surg. 2022 Oct 3:S0022-5223(22)01042-X. doi: 10.1016/j.jtcvs.2022.09.051. Online ahead of print.

ABSTRACT

BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study.

METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases.

RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%).

CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.

PMID:36562497 | DOI:10.1016/j.jtcvs.2022.09.051

Categorías: Trasplante cardíaco

The potential for Treg-enhancing therapies in transplantation

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Clin Exp Immunol. 2022 Dec 23:uxac118. doi: 10.1093/cei/uxac118. Online ahead of print.

ABSTRACT

Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance against self-antigens, these cells have become a promising tool for the induction of donor-specific tolerance in transplantation medicine. The therapeutic potential of increasing in vivo Treg numbers for a favorable Treg to Teff cell ratio has already been demonstrated in several sophisticated pre-clinical models and clinical pilot trials. In addition to improving cell quantity, enhancing Treg function utilizing engineering techniques led to encouraging results in models of autoimmunity and transplantation. Here we aim to discuss the most promising approaches for Treg-enhancing therapies, starting with adoptive transfer approaches and ex vivo expansion cultures (polyclonal vs. antigen-specific), followed by selective in vivo stimulation methods. Furthermore, we address next generation concepts for Treg function enhancement (CARs, TRUCKs, BARs) as well as the advantages and caveats inherit to each approach. Finally, this review will discuss the clinical experience with Treg therapy in ongoing and already published clinical trials, however, data on long-term results and efficacy is still very limited and many questions that might complicate clinical translation remain open. Here, we discuss the hurdles for clinical translation and elaborate on current Treg based therapeutic options as well as their potencies for improving long-term graft survival in transplantation.

PMID:36562079 | DOI:10.1093/cei/uxac118

Categorías: Trasplante cardíaco

Data-independent acquisition proteomics reveals circulating biomarkers of coronary chronic total occlusion in humans

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Front Cardiovasc Med. 2022 Dec 5;9:960105. doi: 10.3389/fcvm.2022.960105. eCollection 2022.

ABSTRACT

INTRODUCTION: The pathophysiology of coronary chronic total occlusion (CTO) has not been fully elucidated.

METHODS: In the present study, we aimed to investigate the potential plasma biomarkers associated with the pathophysiologic progression of CTO and identify protein dynamics in the plasma of CTO vessels immediately after successful revascularization. We quantitatively analyzed the plasma proteome profiles of controls (CON, n = 10) and patients with CTO pre- and post- percutaneous coronary intervention (PCI) (CTO, n = 10) by data-independent acquisition proteomics. We performed enzyme-linked immunosorbent assay (ELISA) to further confirm the common DEPs in the two-group comparisons (CON vs. CTO and CTO vs. CTO-PCI).

RESULTS: A total of 1936 proteins with 69 differentially expressed proteins (DEPs) were detected in the plasma of patients with CTO through quantitative proteomics analysis. For all these DEPs, gene ontology (GO) analysis and protein-protein interaction (PPI) analysis were performed. The results showed that most of the proteins were related to the negative regulation of proteolysis, regulation of peptidase activity, negative regulation of hydrolase activity, humoral immune response, and lipid location. Furthermore, we identified 1927 proteins with 43 DEPs in the plasma of patients with CTO vessels after immediately successful revascularization compared to pre-PCI. GO analysis revealed that the above DEPs were enriched in the biological processes of extracellular structure organization, protein activation cascade, negative regulation of response to external stimulus, plasminogen activation, and fibrinolysis. More importantly, we generated a Venn diagram to identify the common DEPs in the two-group comparisons. Seven proteins, ADH4, CSF1, galectin, LPL, IGF2, IgH, and LGALS1, were found to be dynamically altered in plasma during the pathophysiological progression of CTO vessels and following successful revascularization, moreover, CSF1 and LGALS1 were validated via ELISA.

CONCLUSIONS: The results of this study reveal a dynamic pattern of the molecular response after CTO vessel immediate reperfusion, and identified seven proteins which would be the potential targets for novel therapeutic strategies to prevent coronary CTO.

PMID:36561774 | PMC:PMC9764215 | DOI:10.3389/fcvm.2022.960105

Categorías: Trasplante cardíaco

Condition of the Oral Cavity in Patients After Heart Transplantation: A Preliminary Report

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Ann Transplant. 2022 Dec 23;27:e937734. doi: 10.12659/AOT.937734.

ABSTRACT

BACKGROUND The constant impairment of the immune system caused by lifelong use of immunosuppressive drugs in patients after heart transplantation has a significant impact on oral cavity health. The aim of this study was to analyze the health of the oral cavity in patients after heart transplantation, with particular regard to occurring pathogens. MATERIAL AND METHODS The study included 25 patients after heart transplantation. The research scheme was divided into 2 parts. The first part consisted of a survey on general health and oral hygiene habits. The second part of the examination consisted of an analysis of the health of the oral cavity: the mucosa, periodontium, and hard dental tissues. Particular attention was paid to PET (test for the presence of pathogens causing periodontitis/periimplantitis) and CAT (diagnostic test for the presence of Candida in the oral cavity), which are real-time PCR tests used to detect pathogens causing periodontitis and microorganisms present in oral candidiasis. RESULTS The conducted research and in-depth analysis of the results showed that the oral health condition in patients after heart transplantation is not satisfactory, regardless of the time that has elapsed since the surgery, sex, age, hygiene habits, or the type of immunosuppression used. The oral cavity of patients after heart transplantation is colonized with Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Candida albicans. CONCLUSIONS The cooperation of the dentist with the attending physician at each stage of the treatment should play an unquestionable role.

PMID:36560867 | DOI:10.12659/AOT.937734

Categorías: Trasplante cardíaco

Novel combination of <em>FLNC</em> (c.5707G&gt;A; p. Glu1903Lys) and <em>BAG3</em> (c.610G&gt;A; p.Gly204Arg) genetic variant expressing restrictive cardiomyopathy phenotype in an adolescent girl

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

J Genet. 2022;101:54.

ABSTRACT

Pediatric restrictive cardiomyopathy (RCM) is the rarest in its group and accounts for only 2.5-5% of all the diagnosed cardiomyopathies in children. It is a relentless disease with poor prognosis, and heart transplantation is the only long-term treatment option. The aetiology of pediatric RCM varies and includes conditions such as endomyocardial fibrosis, storage disorder (Fabry's disease, MPS), drugs, radiation, post-cardiac transplantation and genetic. Genetic causes encompasses mutations in sarcomeric (troponin I and T, actin, myosin and titin) and nonsarcomeric protein-coding genes (Desmin, RSK2, lamin A/C and bcl-2-associated athanogene 3 (BAG3)). Inheritance of RCM could be autosomal dominant, autosomal recessive and X-linked. Here, we report a case of RCM in an adolescent girl, who was symptomatic with palpitations and breathlessness on exertion. The patient showed presence of rare variants in FLNC (c.5707G>A; p.Glu1903Lys) and BAG3 genes (c.610G>A; p.Gly204Arg). These two variants were detected individually in asymptomatic father and mother, respectively. FLNC gene codes for gamma filamin. These filamin proteins play important role in maintaining the structural integrity of the sarcomere. BAG3 is the main component of the chaperone-assisted selective autophagy (CASA) pathway. Mutant FLNC leads to the formation of protein aggregates which are cleared by an active protein quality control system including CASA pathway. For further verification, in silico protein-protein interaction was performed using online software and tools. The results showed evident interaction between FLNC and BAG3 with significant binding score (-826.6) between them.

PMID:36560844

Categorías: Trasplante cardíaco

Fecal Microbiota Transplantation and Other Gut Microbiota Manipulation Strategies

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Microorganisms. 2022 Dec 7;10(12):2424. doi: 10.3390/microorganisms10122424.

ABSTRACT

The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.

PMID:36557677 | PMC:PMC9781458 | DOI:10.3390/microorganisms10122424

Categorías: Trasplante cardíaco

Assessment of Anti-Human Leukocyte Antigen (HLA)-Antibody-Dependent Humoral Response in Patients before and after Lung Transplantation

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Medicina (Kaunas). 2022 Nov 30;58(12):1771. doi: 10.3390/medicina58121771.

ABSTRACT

Background and Objectives: Testing for anti-human leukocyte antigen (HLA) antibodies both before and after transplantation is of fundamental significance for the success of lung transplantation. The aim of this study was the evaluation of anti-HLA immunization of patients before and after lung transplant who were subjected to qualification and transplantation. Materials and Methods: Prior to the transplantation, patients were examined for the presence of IgG class anti-HLA antibodies (anti-human leukocyte antigen), the so-called panel-reactive antibodies (PRA), using the flow cytometry method. After the transplantation, the class and specificity of anti-HLA antibodies (also IgG) were determined using Luminex. Results: In the group examined, the PRA results ranged from 0.1% to 66.4%. Low (30%) and average (30-80%) immunization was found in only 9.7% of the group examined. Presence of class I anti-HLA antibodies with MFI (mean fluorescence intensity) greater than 1000 was found in 42.7% of the patients examined, while class II anti-HLA antibodies were found in 38.4%. Immunization levels before and after the transplantation were compared. In 10.87% of patients, DSA antibodies (donor-specific antibodies) with MFI of over 1000 were found. Conclusions: It seems that it is possible to confirm the correlation between pre- and post-transplantation immunization with the use of the two presented methods of determining IgG class anti-HLA antibodies by increasing the size of the group studied and conducting a long-term observation thereof.

PMID:36556973 | PMC:PMC9781897 | DOI:10.3390/medicina58121771

Categorías: Trasplante cardíaco

An Up-to-Date Literature Review on Ventricular Assist Devices Experience in Pediatric Hearts

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Life (Basel). 2022 Nov 30;12(12):2001. doi: 10.3390/life12122001.

ABSTRACT

Ventricular assist devices (VAD) have gained popularity in the pediatric population during recent years, as more and more children require a heart transplant due to improved palliation methods, allowing congenital heart defect patients and children with cardiomyopathies to live longer. Eventually, these children may require heart transplantation, and ventricular assist devices provide a bridge to transplantation in these cases. The FDA has so far approved two types of device: pulsatile and continuous flow (non-pulsatile), which can be axial and centrifugal. Potential eligible studies were searched in three databases: Medline, Embase, and ScienceDirect. Our endeavor retrieved 16 eligible studies focusing on five ventricular assist devices in children. We critically reviewed ventricular assist devices approved for pediatric use in terms of implant indication, main adverse effects, and outcomes. The main adverse effects associated with these devices have been noted to be thromboembolism, infection, bleeding, and hemolysis. However, utilizing left VAD early on, before end-organ dysfunction and deterioration of heart function, may give the patient enough time to recuperate before considering a more long-term solution for ventricular support.

PMID:36556366 | PMC:PMC9788166 | DOI:10.3390/life12122001

Categorías: Trasplante cardíaco

Impact of Left Ventricular Assist Devices on Days Alive and Out of Hospital in Hemodynamically Stable Patients with End-Stage Heart Failure: A Propensity Score Matched Study

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

Life (Basel). 2022 Nov 24;12(12):1966. doi: 10.3390/life12121966.

ABSTRACT

The two main surgical options to treat end-stage heart failure are heart transplantation (HTx) or left ventricular assist device (LVAD) implantation. In hemodynamically stable patients, the decision for HTx listing with or without LVADs is challenging. We analyzed the impact of both options on days alive and out of hospital (DAOH) and survival. This retrospective study screened all patients with HTx or LVAD implantation between 2010 and 2020. The main inclusion criterion was hemodynamic stability defined as independence of intravenous inotropic/vasoactive support at decision. Propensity score matching (PSM) was performed. The primary endpoint was DAOH within one year after the decision. Secondary endpoints included survival, duration until HTx, and hospitalizations. In total, 187 patients received HTx and 227 patients underwent LVAD implantation. There were 21 bridge-to-transplant (BTT)-LVAD patients (implantation less than a month after HTx listing or listing after implantation) and 44 HTx-waiting patients included. PSM identified 17 matched pairs. Median DAOH at one year was not significantly different between the groups (BTT-LVAD: median 281, IQR 89; HTx waiting: median 329, IQR 74; p = 0.448). Secondary endpoints did not differ significantly. Our data suggest that BTT-LVAD implantation may not be favorable in terms of DAOH within one year for hemodynamically stable patients compared to waiting for HTx. Further investigations on quality of life and long-term outcomes are warranted.

PMID:36556331 | PMC:PMC9782187 | DOI:10.3390/life12121966

Categorías: Trasplante cardíaco

Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis

Trasplante cardíaco - Vie, 12/23/2022 - 11:00

J Clin Med. 2022 Dec 14;11(24):7406. doi: 10.3390/jcm11247406.

ABSTRACT

BACKGROUND: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

METHODS: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle.

RESULTS: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08-1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04-1.76, I2 21%).

CONCLUSIONS: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.

PMID:36556021 | PMC:PMC9785985 | DOI:10.3390/jcm11247406

Categorías: Trasplante cardíaco

Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease

Congenital cardiac surgery - Vie, 12/23/2022 - 11:00

Cell. 2022 Dec 22;185(26):4937-4953.e23. doi: 10.1016/j.cell.2022.11.028.

ABSTRACT

To define the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development, we generated single-cell chromatin accessibility maps of human fetal heart tissues. We identified eight major differentiation trajectories involving primary cardiac cell types, each associated with dynamic transcription factor (TF) activity signatures. We contrasted regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts, which enabled optimization of in vitro differentiation of epicardial cells. Further, we interpreted sequence based deep learning models of cell-type-resolved chromatin accessibility profiles to decipher underlying TF motif lexicons. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in congenital heart disease (CHD) cases vs. controls. In vitro studies in iPSCs validated the functional impact of identified variation on the predicted developmental cell types. This work thus defines the cell-type-resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements in CHD.

PMID:36563664 | DOI:10.1016/j.cell.2022.11.028

Categorías: Cirugía congénitos

Development of the Residual Lesion Score for congenital heart surgery: the RAND Delphi methodology

Congenital cardiac surgery - Vie, 12/23/2022 - 11:00

Cardiol Young. 2022 Dec 23:1-14. doi: 10.1017/S1047951122003791. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology.

METHODS: A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the "final" Residual Lesion Score.

RESULTS: The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the "final" Residual Lesion Score.

CONCLUSION: Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network's Residual Lesion Score study.

PMID:36562256 | DOI:10.1017/S1047951122003791

Categorías: Cirugía congénitos

Routine Detachment of the Anterior and Septal Tricuspid Leaflets Simplifies VSD Closure and Improves the Outcomes

Congenital cardiac surgery - Vie, 12/23/2022 - 11:00

Medicina (Kaunas). 2022 Dec 15;58(12):1849. doi: 10.3390/medicina58121849.

ABSTRACT

Background and Objectives: The closure of perimembranous ventricular septal defects (VSDs) is one of the most common surgeries performed in infancy. The technique of detachment of the anterior and septal leaflets of the tricuspid valve (TV) with subsequent leaflet augmentation is frequently used for isolated as well as non-isolated VSD closure. In this study, we compared the incidence of tricuspid regurgitation (TR) in patients who underwent a VSD repair with and without detachment of the TV in the short- and long-term follow-up. Materials and Methods: A retrospective study that included 140 patients who underwent perimembranous VSD closure at our center from 2011-2016, where 102 of these patients underwent the procedure with detachment of the TV, was performed. The follow-up data were obtained from postoperative echocardiography performed in the follow-up visits. A total of 62 patients underwent follow-up at our center, where the follow-up time ranged from 1 to 9 years, with a mean of 71 ± 2.47 months. Results: Regarding patients who underwent a VSD repair with a detachment of the TV, 98.1% of the patients had none to mild TR, compared to 94.7% in patients without intraoperative TV detachment at the time of discharge. There were no reported cases of moderate to severe TR, atrioventricular blocks, aortic insufficiency, or deaths. A total of 98.1% of patients who underwent follow-up at our center with a TV detachment had none to mild TR compared to 94.7% in the group without TV detachment. Conclusion: TV detachment with leaflet augmentation for VSD closure is safe and effective and does not increase the incidence of TR in the short- and long-term follow-up.

PMID:36557051 | PMC:PMC9787562 | DOI:10.3390/medicina58121849

Categorías: Cirugía congénitos

Outcomes after Transcatheter Mitral Valve Implantation: A Literature Review

Congenital cardiac surgery - Vie, 12/23/2022 - 11:00

J Pers Med. 2022 Dec 16;12(12):2074. doi: 10.3390/jpm12122074.

ABSTRACT

Mitral valve disease is the most common heart valve disease worldwide. Surgical mitral valve replacement or repair has been an established therapy in patients with severe mitral valve disease for many years. On the other hand, many patients with advanced mitral valve disease and severe comorbidities are treated conservatively and are excluded from the surgical procedure. Furthermore, in patients with severe comorbidities, transcatheter mitral valve repair by edge-to-edge technique with MitraClip or transcatheter mitral valve repair with a non-absorbable ring have been added as therapeutic options over the last few years. Alternative procedures for the treatment of patients with advanced prosthetic or native mitral valve diseases include transcatheter access for replacement or implantation of a new prosthetic valve in the diseased mitral valve. Promising results were published about short-term outcomes of patients who underwent the transcatheter mitral valve replacement. The current view and results of the transcatheter mitral valve implantation in patients with advanced native or prosthetic mitral valve disease are briefly discussed.

PMID:36556294 | PMC:PMC9783604 | DOI:10.3390/jpm12122074

Categorías: Cirugía congénitos

Clinical Risk Factors for Aortic Root Dilation in Patients with 22q11.2 Deletion Syndrome: A Longitudinal Single-Center Study

Congenital cardiac surgery - Vie, 12/23/2022 - 11:00

Genes (Basel). 2022 Dec 10;13(12):2334. doi: 10.3390/genes13122334.

ABSTRACT

BACKGROUND: Aortic root dilation (ARD) has been described in 22q11.2DS, even without congenital heart disease (CHD). However, the clinical implications and longitudinal course are unclear. In this study, we evaluated aortic root (AR) dimensions in 22q112.DS adolescents/adults without major intracardiac CHDs, analyzed the progression over time and investigated correlations with extracardiac comorbidities.

METHODS: AR dimensions were evaluated in 74 patients, measuring the sinus of Valsalva (VS) and proximal ascending aorta (AA), using Z-score to define mild, moderate and severe degrees. Changes in AR dimensions during longitudinal echocardiographic follow-up were investigated. Phenotypic characteristics have been collected.

RESULTS: Twenty-four patients (32.4%) showed ARD in terms of VS Z-score (2.43; IQR 2.08-3.01), eight (33.3%) of a moderate/severe degree. Thirteen (54.2%) had concomitant AAD (Z-score 2.34; IQR 1.60-2.85). The risk of ARD was significantly directly related to skeletal/connective tissue disorders (OR 12.82, 95% CI 1.43-115.31; p = 0.023) and inversely related to BMI (OR 0.86, 95% CI 0.77-0.97; p = 0.011). A significant increase in AR diameter's absolute value (p = 0.001) over time has been detected.

CONCLUSION: Isolated ARD is common in 22q11.2DS. Although some clinical risk factors have been identified, pathogenetic mechanisms and risk of complications are undefined. Regular cardiac evaluations should be part of the 22q11.2DS follow-up, and also in non-CHDs patients, to improve long-term outcome.

PMID:36553601 | PMC:PMC9778342 | DOI:10.3390/genes13122334

Categorías: Cirugía congénitos
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