Valve Type and Operative Risks in Surgical Explantation of Transcatheter Aortic Valves: A Systematic Review and Meta-Analysis.

Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients with longer life expectancy. We proposed to perform a systematic review and meta-analysis with metaregression to identify potential factors that can determine an increase in the high mortality and morbidity that characterize these surgical procedures. MEDLINE and Embase were searched for relevant studies. Twelve studies were eligible according to our inclusion criteria. TAVR explantation was confirmed as a procedure with high 30-day mortality (0.17; 95% CI, 0.14-0.21) and morbidity (stroke incidence 5%; 95% CI, 0.04-0.07; kidney injury incidence 16%; 95% CI, 0.11-0.24). The type of transcatheter valve implanted during the index procedure did not influence the outcomes after surgical explantation. The role of these high-risk operations is growing, and it will likely expand in the coming years. Specific tools for risk stratification are required.

Long-Term Outcomes of Bioprosthetic Valves in the Mitral Position: A Pooled Meta-Analysis of Reconstructed Time-to-Event Individual Patient Data.

Bioprosthetic mitral valve replacement (bMVR) use is increasing; however, data regarding long-term durability are lacking. We sought to perform a reconstructed individual patient data meta-analysis from published Kaplan-Meier curves to ascertain survival, freedom from valve degeneration, and reoperation in studies published since 2010. We explored the effects of age and valve type (bovine pericardial or porcine valve) on outcomes. We searched MEDLINE, OVID, Embase, and Cochrane CENTRAL for studies reporting at least 3 years of follow-up after bMVR and published since 2010. The Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool was used to assess methodologic quality. Kaplan-Meier curves were digitized to extract individual patient data and reconstructed estimates for overall survival, freedom from structural valve deterioration (SVD), and freedom from reoperation. A total of 20 studies (16,465 patients) were included. A total of 9 studies reported on porcine valves, 6 reported on bovine, and 7 did not specify the valve type. The overall survival after bMVR at 15 years was 40% (confidence interval 38% to 42%), freedom from reoperation at 15 years was 79% (confidence interval 76% to 82%), and freedom from SVD at 15 years was 64% (58% to 70%). Freedom from SVD was improved in the 70+ years age group (93% up to 25 years, hazard ratio 6.6 [2.5 to 17] for 18 to 59 vs >70 years, p <0.0001). There was no difference in valve durability or survival between bovine pericardial or porcine valves. In this meta-analysis of patients who underwent bMVR using newer generation valves, the inverse relation between age and SVD was reiterated in the 70+ years age group. The prosthesis type made no difference in the outcomes.

Frailty in acute coronary syndromes. A systematic review and narrative synthesis of frailty assessment tools and interventions from randomised controlled trials.

AIM: We aimed to review all randomised controlled trial (RCT) data to explore optimal identification and treatment strategies of frail patients with Acute Coronary Syndromes (ACS). METHODS: The protocol was preregistered (PROSPERO - CRD42021250235). We performed a systematic review including RCT's that 1; used at least one frailty assessment tool to assess frailty and its impact on outcomes in patients diagnosed with ACS and 2; used at least one intervention where change in frailty was measured in patients diagnosed with ACS. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched on the 1st April 2021 and updated on 4th July 2023. Owing to low search output results are presented as a narrative synthesis of available evidence. RESULTS: A single RCT used a frailty assessment tool. A single RCT specifically targeted frailty with their intervention. This precluded further quantitative analysis. There was indication of selection bias against frail participants, and a signal of value for physical activity measurement in frail ACS patients. There was a high level of uncertainty and low level of robustness of this evidence. CONCLUSIONS: Data from RCT's alone is inadequate in answering the reviews question. Future RCT's need to address ways to incorporate frail participants, whilst mitigating selection biases. Physical performance aspects of the frailty syndrome appear to be high yield modifiable targets that improve outcomes. Intervention trials should consider using change in frailty status as an outcome measure. Any trials that include frail participants should present data specifically attributable to this group.

Transcriptomic Analysis of Tight Junction Proteins Demonstrates the Aberrant Expression and Function of Zona Occludens 2 (ZO-2) Protein in Stanford Type A Aortic Dissection.

OBJECTIVE: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. METHODS: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. RESULTS: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. CONCLUSIONS: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.

Long-term outcomes of bioprosthetic valves in the mitral position a systematic review of studies published over the last 20 years.

OBJECTIVES: Although the use of bioprostheses for mitral valve replacement (bMVR) is on the rise, their long-term durability is not well described. Defining bMVR durability will be instrumental in setting the standard against which the performance of transcatheter mitral replacement is to be judged against. The authors of this systematic review aimed to identify, assess the quality and review the outcomes in studies reporting on long-term outcomes after bMVR published over the last 20 years. METHODS: Medline, Embase and Cochrane CENTRAL were searched for studies that have reported outcomes beyond a minimum of 5 years of follow-up after bMVR. Cohort characteristics, definitions of structural valve deterioration (SVD) and outcomes were summarized. The risk of bias in included studies was assessed using the Cochrane QUIPS tool. RESULTS: Twenty-one studies, including 15 833 patients, were identified. Sixty-four percent of all implants were porcine and the remaining bovine pericardial. Freedom from SVD at 10 years ranged from 58.9% to 100% and at 15 years from 58.3% to 93%. Freedom from reoperation ranged from 65% to 98.7% at 10 years and 78.5% to 91% at 15 years. Information on native valve pathology or dominant haemodynamic lesion was missing in 25% and 66% of studies, respectively. Reports of postoperative echocardiography were lacking, despite the heavy reliance on echocardiography for SVD diagnosis. CONCLUSIONS: There is considerable variability in reporting bMVR long-term outcomes. As such, it is difficult to generate an unbiased, generalizable understanding of long- term outcomes after bMVR across the spectrum of mitral disease phenotypes.

Sizing the Frozen Elephant Trunk Based on Aortic Pathology and the Importance of Pre-Operative Imaging.

The frozen elephant trunk is a formidable tool for the aortovascular surgeon. An appreciation of how to size the graft in different pathologies is key in achieving optimal results. Herein, we demonstrate worked examples of how imaging can be used to plan for a frozen elephant trunk and discuss the nuisances and uncertainties of sizing using three index cases: Type A aortic dissection, distal thoracic aortic aneurysm and chronic dissection.

Sarcopenia Adversely Affects Outcomes following Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Sarcopenia is a degenerative condition characterised by the loss of skeletal muscle mass and strength. Its impact on cardiac surgery outcomes remains poorly investigated. This meta-analysis aims to provide a comprehensive synthesis of the available evidence to determine the effect of sarcopenia on cardiac surgery outcomes. METHODS: A systematic review and meta-analysis followed PRISMA guidelines from inception to April 2023 in EMBASE, MEDLINE, Cochrane database, and Google Scholar. Twelve studies involving 2717 patients undergoing cardiac surgery were included. Primary outcomes were early and late mortality; secondary outcomes included surgical time, infection rates, and functional outcomes. Statistical analyses were performed using appropriate methods. RESULTS: Sarcopenic patients (906 patients) had a significantly higher risk of early mortality (OR: 2.40, 95% CI: 1.44 to 3.99, p = 0.0007) and late mortality (OR: 2.65, 95% CI: 1.57 to 4.48, p = 0.0003) compared to non-sarcopenic patients (1811 patients). There were no significant differences in overall surgical time or infection rates. However, sarcopenic patients had longer ICU stays, higher rates of renal dialysis, care home discharge, and longer intubation times. CONCLUSION: Sarcopenia significantly increases the risk of early and late mortality following cardiac surgery, and sarcopenic patients also experience poorer functional outcomes.

Role of Hypothermia in Adult Cardiac Surgery Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To review studies that assessed systemic hypothermia as an organ protection strategy in adults undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Randomized controlled trials, irrespective of blinding, language, publication status, and date of publication, were identified by searching the Cochrane Central register of Controlled Trials, MEDLINE, and Embase until November 2020. Risk of bias assessment was performed according to Cochrane methodology. Treatment effects were expressed as risk ratios and 95% confidence intervals. Heterogeneity was expressed as I2. INTERVENTIONS: Systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Forty-eight trials enrolling 6,690 patients were included in the analysis. Methodologic quality of the studies included was low, mostly due to insufficient allocation concealment or blinding. Random-effects meta-analysis did not resolve uncertainty as to the risks and benefits for hypothermia versus normothermia for key primary and secondary outcomes, including mortality (1.21, 0.94 to 1.56, I2 = 0%) and brain injury (0.87, 0.67 to 1.14, I2 = 0%). Sensitivity analyses restricted to trials at low risk of important bias demonstrated higher mortality with hypothermia (1.70, 1.05 to 2.75, I2 = 0%), with little or no treatment effect on brain injury (1.01, 0.69 to 1.49, I2 = 0%). There was no interaction between cardioplegia temperature and the effects of cardiopulmonary bypass temperature on outcomes. There was insufficient evidence to assess the effects of hypothermia in noncoronary artery bypass graft surgery. CONCLUSION: The existing evidence for an organ-protective effect of hypothermia in adult cardiac surgery is of low quality and inconsistent.

Unligated vertical vein presenting as a large atrio-portal shunt in adulthood: a case report.

A 28-year-old male with infra-cardiac totally anomalous pulmonary venous connection (TAPVC) repaired as new-born presented in adulthood with right heart strain and very large left atrium to portal vein vessel. Residual connections from pulmonary veins to systemic circulation are believed to represent persistent 'vertical veins' (VV) not ligated at the time of the initial surgery. In our patient, since endovascular occlusion was not judged suitable, the anomalous vessel was surgically ligated and resected. A review of the literature failed to find such a procedure reported in an adult patient and analyzed the intra-operative ligation of VV during repair of TAPVC.

Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure.

Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix® (PM; 3-D Matrix, Ltd), has been reported for clinical hemostasis and in research models. This study demonstrates the feasibility and efficacy of an advanced approach for MSC-therapy, that is coating of the epicardium with the instantly-produced PM hydrogel incorporating MSCs (epicardial PM-MSC therapy). We optimized the conditions/procedure to produce "instant" 2PM-MSC complexes. After spreading on the epicardium by easy pipetting, the PM-MSC complex promptly and stably adhere to the beating heart. Of note, this treatment achieved more extensive improvement of cardiac function, with greater initial retention and survival of donor MSCs, compared to intramyocardial MSC injection in rat heart failure models. This enhanced efficacy was underpinned by amplified myocardial upregulation of a group of tissue repair-related genes, which led to enhanced repair of the damaged myocardium, i.e. augmented microvascular formation and reduced interstitial fibrosis. These data suggest a potential for epicardial PM-MSC therapy to be a widely-adopted treatment of heart failure. This approach may also be useful for treating diseases in other organs than the heart.

Evaluation of splenic switch off in a tertiary imaging centre: validation and assessment of utility.

AIMS: Adenosine can induce splenic vasoconstriction (splenic switch-off, SSO). In this study, we aim to evaluate the utility of identifying a lack of SSO for detecting false-negative adenosine stress perfusion cardiac magnetic resonance (CMR) scans. METHODS AND RESULTS: We visually analysed 492 adenosine stress perfusion CMR scans reported as negative in a cohort of patients with no previous history of coronary artery disease. A lack of SSO was identified in 11%. We quantified the phenomenon by drawing regions of interest on the spleen and comparing intensity between stress and rest scans, the spleen intensity ratio (SIR). Inter-rater agreement for qualitative determination of SSO was κ = 0.81 and inter-class correlation for quantitative determination of SSO was 0.94. The optimal threshold for SIR as an indicator of SSO was 0.40 (sensitivity = 82.5%, specificity = 92.3%, AUC = 0.91). 23 065 CMR scans and 9926 invasive coronary angiogram reports were retrospectively examined to identify patients with negative CMR scans who required coronary intervention in the subsequent 12 months (false negatives). We compared these scans with true positives who had positive adenosine stress perfusion CMR scans followed by coronary intervention. The rate of lack of SSO was 20.7% in the false-negative group versus 13.1% in true positives (P = 0.37). CONCLUSION: The lack of SSO is prevalent, easily measureable, and has potential to improve on haemodynamic criteria as a marker of adenosine understress in CMR perfusion scans.

Dermatology - a compulsory part of the UK medical school curriculum?

Dermatological conditions form a significant number of consultations seen by general practitioners on a daily basis. There is a lack of training and formal assessment of dermatology during medical school and we propose that there should be a mandatory component in OSCEs for dermatology during medical school to enhance one's diagnostic and clinical reasoning skills which will ultimately lead to better care for the patient and efficacious use of NHS resources.