Impact of COVID-19 on cardiac surgical training: Our experience in the United Kingdom.

The current evolving global pandemic caused by coronavirus disease-2019 (COVID-19) has dramatically impacted global health care systems, resulting in governments taking unprecedented measures to contain the spread of the infection, with adaptations by health care organizations. Research into understanding the pathophysiology behind this virus, to ascertain best medical management and treatment, has been accelerated to keep up with the rapidly evolving situation. There has been redeployment of medical and nursing staff to the frontlines and redistribution of health care resources. In addition, the cancellation of elective surgery and centralization of services to treat high-risk surgical cases will all, undeniably, have an impact on current surgical training with possible future implications. We aim to explore the impact COVID-19 is having on cardiac surgical training in the UK and what future implications this may have.

Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.

Chitosan is a biodegradable and biocompatible natural polymer that has been extensively explored in recent decades. The Food and Drug Administration has approved chitosan for wound treatment and nutritional use. Furthermore, chitosan has paved the way for advancements in different biomedical applications including as a nanocarrier and tissue-engineering scaffold. Its antibacterial, antioxidant, and haemostatic properties make it an excellent option for wound dressings. Because of its hydrophilic nature, chitosan is an ideal starting material for biocompatible and biodegradable hydrogels. To suit specific application demands, chitosan can be combined with fillers, such as hydroxyapatite, to modify the mechanical characteristics of pH-sensitive hydrogels. Furthermore, the cationic characteristics of chitosan have made it a popular choice for gene delivery and cancer therapy. Thus, the use of chitosan nanoparticles in developing novel drug delivery systems has received special attention. This review aims to provide an overview of chitosan-based nanoparticles, focusing on their versatile properties and different applications in biomedical sciences and engineering.

Comparison of cardiothoracic surgical training before and during the COVID-19 pandemic in the United Kingdom.

BACKGROUND: Cardiothoracic training during the Coronavirus disease 2019 (COVID-19) pandemic witnessed a dramatic change in the United Kingdom, resulting in changes in surgical provisions, centralization of services, and reduced surgical case volume. The aim of this study was to assess the impact COVID-19 on surgical training and seek opinions regarding the future role of surgical simulation in cardiothoracic training. METHODS: A cross-sectional survey was designed and distributed to 200 cardiothoracic national and non-national trainees in the United Kingdom. The survey consisted of 31 questions in 4 sections: Demographics, Service Provision, Training, and Simulation Training. RESULTS: Eighty-three of the 200 trainees (41.5%) completed the survey, including 44 of 129 national trainees (34.1%) and 39 of 71 non-national trainees (54.9%). Sixty-seven respondents (80.7%) agreed that cardiothoracic training had been negatively impacted as a result of COVID-19 (P < .001). In addition, 12% agreed that adequate resources were available for learning/practicing technical skills, 87% agreed that simulation had a role in cardiothoracic training, 81% recognized simulations is an important tool in improving their surgical skills, and 79.5% agreed that simulation should be used to meet the increasing need in training/education moving forward. CONCLUSIONS: COVID-19 has had a significant impact on surgical training, with concerns that these effects could have further implications downstream. Simulation training has been underused thus far, and trainees face an uphill challenge to enhance their skills and technical abilities in the operating room. Simulation is recommended by trainees and may represent a solution to the challenges of safe and effective cardiothoracic surgical training.

Effects of different concentration of organic and inorganic trace minerals (zinc, selenium, and chromium) supplementation on expression of chTLR4 gene and humoral immune response in broilers.

BACKGROUND AND AIM: Poultry production is the fastest-growing livestock sector in developing countries. In the poultry diet, trace minerals (zinc [Zn], selenium [Se], and chromium [Cr]) are normally administered in the inorganic form which has been traditionally considered as the most cost-effective and easily available but organic forms of these trace minerals have a higher bioavailability, lower dietary inclusion and cause less environmental pollution as compared to inorganic form. This study aimed to investigate the effect of different concentrations of organic and inorganic forms of trace minerals (Zn, Se, and Cr) supplementation (0-35 days) on expression of chTLR4gene and humoral immune response in broilers. MATERIALS AND METHODS: A total of 216 broilers were randomly divided into 12 groups and each group divided into three replicates consisting of six broilers each. T1 (R1, R2, and R3) group was kept as control. T2, T3, and T4 (R1, R2, and R3) groups were supplemented with inorganic form of Zn at 40 mg/kg of feed, organic form of Zn at 40 mg/kg of feed, and 50% organic form of Zn at 20 mg/kg of feed, respectively. T5, T6, and T7 (R1, R2, and R3) groups were supplemented with inorganic form of Se at 0.3 mg/kg of feed, organic form of Se at 0.3 mg/kg of feed, and 50% organic form of Se at 0.15 mg/kg of feed, respectively. T8, T9, and T10 (R1, R2, and R3) groups were supplemented with inorganic form of Cr at 2 mg/kg of feed, organic form of Cr at 2 mg/kg of feed, and 50% organic form of Cr at 1 mg/kg of feed, respectively. T11 and T12 (R1, R2, and R3) groups were supplemented with a combination of all three minerals from inorganic and organic forms, respectively. RESULTS: Reverse transcriptase-polymerase chain reaction gene expression analysis revealed that in bursa of Fabricius, maximum upregulation of chTLR4 (3.0214 fold) was observed in T6 group, and in spleen, maximum upregulation of chTLR4 (3.2140 fold) was observed in T3 group as compared to control group. On day 35, the maximum plasma immunoglobulin G concentration was observed in organic trace minerals (OTMs) supplemented, whereas the minimum concentration was recorded in control group. On day 28 and 35, the overall mean heterophil:lymphocyte ratio showed a significant difference (p<0.05) between control and OTM supplemented groups. A significantly higher immune organ weight (spleen and bursa of Fabricius) was recorded in OTM supplemented group as compared to control and other supplemented group. CONCLUSION: Supplementation of organic form of Zn, Se, and Cr either alone or in combination increase humoral immune response and upregulation of chTLR4 gene expression in bursa and spleen indicates a beneficial effect of OTM in augmentation of immune system in broilers.

Surgical management of valve disease in the early 21st century.

Surgery offers good results for patients with significant valvular heart disease. Valve replacement and repair are the main surgical options. Older patients and redo procedures are increasingly frequent.

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471).

Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial.

OBJECTIVES: Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. METHODS: One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes. RESULTS: RIPC reduced PMI magnitude by 26% (-9.303 difference (CI -15.618 to -2.987) 72 h hsTnT-AUC; p=0.003) compared with control. There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54% (11% RIPC vs 24% control; p=0.031) and decreased the incidence of acute kidney injury by 48% (10.0% RIPC vs 21.0% control; p=0.063), and intensive care unit stay by 1 day (2.0 days RIPC (CI 1.0 to 4.0) vs 3.0 days control (CI 2.0 to 4.5); p=0.043). In a post hoc analysis, we found that control patients administered intravenous glyceryl trinitrate (GTN) intraoperatively sustained 39% less PMI compared with those not receiving GTN, and RIPC did not appear to reduce PMI in patients given GTN. CONCLUSIONS: RIPC reduced the extent of PMI in patients undergoing CABG and/or valve surgery. RIPC may also have beneficial effects on short-term clinical outcomes, although this will need to be confirmed in future studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT00397163.

A retrospective analysis of myocardial preservation techniques during coronary artery bypass graft surgery: are we protecting the heart?

BACKGROUND: Retrograde perfusion into coronary sinus during coronary artery bypass graft (CABG) surgery reduces the need for cardioplegic interruptions and ensures the distribution of cardioplegia to stenosed vessel territories, therefore enhancing the delivery of cardioplegia to the subendocardium. Peri-operative myocardial injury (PMI), as measured by the rise of serum level of cardiac biomarkers, has been associated with short and long-term clinical outcomes. We conducted a retrospective analysis to investigate whether the combination of antegrade and retrograde techniques of cardioplegia delivery is associated with a reduced PMI than that observed with the traditional methods of myocardial preservation. METHODS: Fifty-four consecutive patients underwent CABG surgery using either antegrade cold blood cardioplegia (group 1, n = 28) or cross-clamp fibrillation (group 2, n = 16) or antegrade retrograde warm blood cardioplegia (group 3, n = 10). The study primary end-point was PMI, evaluated with total area under the curve (AUC) of high-sensitivity Troponin-T (hsTnT), measured pre-operatively and at 6, 12, 24, 48 and 72 hours post-surgery. Secondary endpoints were acute kidney injury (AKI) and inotrope scores, length of intensive care unit (ICU) and hospital stay, new onset atrial fibrillation (AF) and clinical outcomes at 6 weeks (death, non-fatal myocardial infarction, coronary artery revascularization, stroke). RESULTS: There was evidence that mean total AUC of hsTnT was different among the three groups (P = 0.050). In particular mean total AUC of hsTnT was significantly lower in group 3 compared to both group 1 (-16.55; 95% CI: -30.08, -3.01; P = 0.018) with slightly weaker evidence of a lower mean hsTnT in group 3 when compared to group 2 (-15.13; 95% CI -29.87, -0.39; P = 0.044). There was no evidence of a difference when comparing group 2 to group 1 (-1.42,; 95% CI: -12.95, 10.12, P = 0.806). CONCLUSIONS: Our retrospective analysis suggests that, compared to traditional methods of myocardial preservation, antegrade retrograde cardioplegia may reduce PMI in patients undergoing first time CABG surgery.

T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique.

OBJECTIVES: The aim of this study was to determine the accuracy of the contrast "bolus only" T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV). BACKGROUND: Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. METHODS: One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. RESULTS: The ECV by both techniques correlated with histological CVF (n = 18, r² = 0.69, p < 0.01 vs. r² = 0.71, p < 0.01, p = 0.42 for comparison). Across health and disease, there was strong correlation between the techniques (r² = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV <0.4 = -0.004 ± 0.037 vs. ECV >0.4 = 0.040 ± 0.075, p < 0.001). CONCLUSIONS: Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.

Predictors of low cardiac output syndrome after isolated mitral valve surgery.

BACKGROUND: Low cardiac output syndrome is defined as the need for a postoperative intra-aortic balloon pump or inotropic support for longer than 30 minutes in the intensive care unit. Mitral valve surgery is increasingly being performed in high-risk patients who might require mechanical circulatory support for low cardiac output syndrome. Therefore the aim of this study was to identify the preoperative predictors of low cardiac output syndrome after mitral valve surgery. METHODS: We conducted a retrospective review of data prospectively entered into an institutional database. Between 1990 and February 2008, 3039 patients underwent isolated mitral valve surgery with or without coronary bypass surgery. The independent predictors of low cardiac output syndrome and operative mortality were determined by means of stepwise logistic regression analysis. RESULTS: The overall prevalence of low cardiac output syndrome was 7%. The independent predictors of low cardiac output syndrome were urgency of the operation (odds ratio, 2.9), earlier year of operation (odds ratio, 2.4), left ventricular ejection fraction of less than 40% (odds ratio, 2.1), New York Heart Association class IV (odds ratio, 2), body surface area of 1.7 m(2) or less (odds ratio, 1.6), ischemic mitral valve pathology (odds ratio, 1.6), and cardiopulmonary bypass time (odds ratio, 1.02). The operative mortality was higher in patients with low cardiac output syndrome (30% vs 1.3%, P < .001). Overall operative mortality was 3.4%. The independent predictors of mortality were urgency of the operation (odds ratio, 7.1), renal failure (odds ratio, 4.3), nonuse of polytetrafluoroethylene sutures (Gore-Tex; W. L. Gore & Associates, Inc, Austin, Tex; odds ratio, 2.1), any reoperative surgical intervention (odds ratio, 1.8), increasing age (odds ratio, 1.03), and cardiopulmonary bypass time (odds ratio, 1.02). CONCLUSIONS: Low cardiac output syndrome is associated with significantly increased morbidity and mortality. Novel strategies to preserve renal function, optimization of pre-existing heart failure symptoms, and use of artificial polytetrafluoroethylene sutures might reduce the incidence of low cardiac output syndrome and lead to improved results after mitral valve surgery.

Aortic valve-sparing operations: dealing with the coronary artery that is too close to the aortic annulus.

During aortic root surgery, one of the coronary ostia is sometimes found to lie too close to one of the commissures to allow its safe detachment as a button while still preserving the native aortic valve. In the past, this has prevented aortic valve-sparing root replacement in cases of aortic root aneurysm. We describe a technique pertaining to the reimplantation method of aortic valve-sparing root replacement to deal with such a displaced coronary artery.

Outcomes of surgical intervention for isolated active mitral valve endocarditis.

OBJECTIVE: Although several studies have examined the outcomes of mitral valve repair for infective endocarditis, no studies have documented the long-term outcomes of surgical intervention for active endocarditis confined to the mitral valve. METHODS: One hundred four patients underwent surgical intervention for active infective endocarditis confined to the mitral valve over a 27-year period (mean age, 50 +/- 18 years; 52% female). The infected valve was native in 81 patients, previously repaired 6 patients, and prosthetic in 17 patients. Staphylococcus aureus was the most commonly isolated (32%) source of infection. Twenty-eight (27%) patients had annular abscesses. Surgical intervention consisted of valve repair or replacement for limited infection and radical resection, annular patch reconstruction, and valve replacement for annular abscess. Mean follow-up was 5.6 +/- 4.4 years (range, 0-20 years) and was complete. RESULTS: There were 9 (8.7%) in-hospital deaths and 28 (27%) late deaths. Overall survival at 5, 7, and 10 years was 73% +/- 5%, 68% +/- 5%, and 58% +/- 6%, respectively. At 7 years, freedom from recurrent endocarditis was 89% +/- 4% and freedom from reoperation was 94% +/- 3%. Event-free survival at 7 and 10 years was 60% +/- 6% and 46% +/- 7%, respectively, and was significantly higher in patients with native endocarditis versus those with nonnative endocarditis (ie, prosthetic or previously repaired; 7 years: 63% +/- 7% vs 50% +/- 12%, P < .005). Preoperative shock, S aureus infection, and bioprosthesis insertion were independent predictors of death from all causes. The patients in the bioprosthesis group were older (57 +/- 20 years vs 44 +/- 15 years in the mechanical group and 46 +/- 12 years in the repair group, P = .003). CONCLUSIONS: Surgical intervention for isolated active mitral valve endocarditis remains difficult, with high morbidity and mortality in the long term. Event-free survival is worse in those who have nonnative mitral valve endocarditis.

Outcomes of double valve surgery for active infective endocarditis.

OBJECTIVE: In active infective endocarditis the need for operating simultaneously on the aortic and mitral valves is frequent. There are no studies in the literature documenting long-term outcomes of double valve surgery for active endocarditis. METHODS: Ninety patients underwent double valve surgery for active endocarditis over a 26-year period (mean age, 53 +/- 16 years; 71% male patients). Prosthetic endocarditis was seen in 32 patients. Staphylococcus species was isolated in 29%. Forty-six (51%) patients had abscesses. Surgical intervention consisted of valve repair or replacement with limited infection or radical resection, patch reconstruction, and valve replacement for abscesses. Mean follow-up was 5.9 +/- 4.7 years (range, 0-18 years) and was complete. RESULTS: There were 14 (15.6%) in-hospital deaths and 29 (32.2%) late deaths. Overall survival at 5, 7, and 10 years was 68% +/- 5%, 59% +/- 6%, and 49% +/- 6%, respectively, and was reduced in those undergoing operations for prosthetic compared with native endocarditis (7-year survival, 39% +/- 9% vs 71% +/- 7%; P < .001). Freedom from recurrent endocarditis was 84% +/- 5% at 10 years. Freedom from reoperation was 91% +/- 4% at 10 years. Event-free survival at 7 and 10 years was 60% +/- 6% and 47% +/- 7%, respectively. No difference was observed between the native and prosthetic groups for recurrent endocarditis, late reoperation, or event-free survival. Prosthetic endocarditis, increasing age, preoperative shock, and diabetes mellitus were independent predictors of death from all causes. CONCLUSIONS: Double valve surgery for active endocarditis remains technically challenging and associated with significant morbidity and mortality perioperatively and in the longer term. Outcomes are worse in those who have prosthetic valve endocarditis.

Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model.

OBJECTIVE: Right ventricular hypertrophy and subsequent dysfunction is common in patients with congenital heart defects, but the molecular mechanisms underlying change from adaptive hypertrophy to dysfunction remain elusive. We used the novel technique of proteomics to characterize protein changes in right ventricular myocardium in a neonatal model of right ventricular hypertrophy and early dysfunction. METHODS: Twelve neonatal piglets were equally randomized to pulmonary artery banding (PAB group), or sham operation (thoracotomy without banding). After 4 weeks, right ventricular morphology and function were assessed in vivo using magnetic resonance imaging. Animals were humanely killed. Proteomics of right ventricular myocardium was performed. Purified right ventricular proteins were separated by 2-dimensional difference gel electrophoresis using fluorescent cyanine dyes. After gel imaging, software analysis revealed protein spots differentially expressed between the 2 groups; these spots were excised and identified by mass spectrometry. RESULTS: On magnetic resonance imaging, animals with pulmonary artery banding demonstrated significant right ventricular hypertrophy, cavity dilatation, and mild systolic impairment (right ventricular ejection fraction 39.8% +/- 15% vs 56.7% +/- 10% controls; P < .05). Right ventricular free wall mass on harvest confirmed right ventricular hypertrophy. Proteomic analysis revealed 18 proteins that were significantly differentially expressed: 5 structural proteins, 6 metabolic enzymes, 2 stress proteins, and 5 miscellaneous proteins. Expression of calsarcin-1 and vinculin was increased, as were certain metabolic enzymes, although F(1)-ATPase beta-chain and heat shock protein 70 decreased. CONCLUSIONS: This is the first study characterizing right ventricular protein changes in a large animal model specifically capturing the change from compensated to maladaptive hypertrophy. These findings can guide future work at elucidating the mechanisms in the pathophysiology of neonatal right ventricular hypertrophy and dysfunction.

Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest.

OBJECTIVE: Concern over neurologic injury limits safe duration of deep hypothermic circulatory arrest (DHCA) in surgery for congenital cardiac disease. Proteomics is a novel and powerful technique to study global protein changes in a given protein system. Using a neonatal model of cardiopulmonary bypass with DHCA, we sought to characterize the protein changes associated with DHCA brain injury. METHODS: Ten neonatal piglets were randomized to cardiopulmonary bypass with DHCA or sham operation. DHCA animals underwent induction of bypass (100 mL x kg(-1) x min(-1)), cooling to 18 degrees C, then DHCA for 60 minutes. Animals were rewarmed to normothermia, weaned from bypass, and harvested after 30 minutes off bypass. Sham animals underwent sternotomy without further instrumentation. Plasma samples were taken before bypass and before harvest. Proteins differentially expressed in the cerebral neocortex between the 2 groups were determined by 2-dimensional differential gel electrophoresis using fluorescent cyanine dyes and mass spectrometry. A second group of 4 piglets were similarly randomized and, after the experiment, tissues underwent perfusion-fixation for histologic examination. RESULTS: Cardiopulmonary bypass with DHCA caused extensive histologic and ultrastructural cerebral injury. Proteomic analysis of cerebral cortex found 10 protein spots to be differentially expressed; 9 were identified by mass spectrometry to represent 6 proteins, including apolipoprotein A-1, neurofilament-M protein, and enolase. Decreased expression of plasma apolipoprotein A-1 was found in DHCA. CONCLUSIONS: The acute protein changes associated with cerebral injury in a neonatal model of cardiopulmonary bypass with DHCA have been characterized. These may direct further research aimed at attenuating injury seen from cardiopulmonary bypass with DHCA.