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4.
Am J Cardiol ; 201: 8-15, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37348153

ABSTRACT

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.


Subject(s)
Mitral Valve Insufficiency , Humans , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/surgery , Echocardiography, Stress , Prognosis , Mitral Valve/diagnostic imaging , Dyspnea/diagnosis , Dyspnea/etiology , Ventricular Function, Left
5.
Eur Heart J Cardiovasc Imaging ; 24(9): 1252-1257, 2023 08 23.
Article in English | MEDLINE | ID: mdl-37140153

ABSTRACT

AIMS: Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery. METHODS AND RESULTS: Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment. CONCLUSION: Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.


Subject(s)
Mitral Valve Insufficiency , Mitral Valve Prolapse , Ventricular Dysfunction, Left , Humans , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Ventricular Function, Left , Prospective Studies , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging
6.
Aorta (Stamford) ; 11(1): 1-9, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36848907

ABSTRACT

OBJECTIVES: Surgical repair of Type A aortic dissection (TAAD) requires exclusion of the primary entry tear and reestablishment of flow into the distal true lumen. Provided that the majority of tears occur within the ascending aorta (AA), replacing only that segment seems a safe option; however, this strategy leaves the root susceptible to dilatation and need for reintervention. We aimed to review the outcomes of the two strategies: aortic root replacement (ARR) and isolated ascending aortic replacement. METHODS: Retrospective analysis of prospectively collected data for all consecutive patients who underwent repair of acute TAAD at our institution from 2015 to 2020 was conducted. Patients were divided into two groups: (1) ARR and (2) isolated AA replacement as index operation for TAAD repair. Primary outcomes were mortality and need for reintervention during the follow-up. RESULTS: A total of 194 patients were included in the study; 68 (35%) in the ARR group and 126 (65%) in the AA group. There were no significant differences in postoperative complications or in-hospital mortality (23%; p = 0.51) between groups. Seven patients (4.7%) died during follow-up and eight patients underwent aortic reinterventions, including proximal aortic segments (two patients) and distal procedures (six patients). CONCLUSION: Both aortic root and AA replacement are acceptable and safe techniques. The growth of an untouched root is slow, and reintervention in this aortic segment is infrequent compared with distal aortic segments, hence preserving the root could be an option for older patients provided that there is no primary tear within the root.

7.
J Clin Virol ; 155: 105248, 2022 10.
Article in English | MEDLINE | ID: mdl-35952426

ABSTRACT

Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers. Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial. Key eligibility criteria included absence of significant co-morbidity and no previous SARS-CoV-2 infection or vaccination. Participants were randomised to either the active agent nasal spray or placebo using computer generated random number tables. The nasal spray was administered 3 times daily over a 45 day course. The primary end point was the percentage of subjects who tested positive for IgGS (anti-spike, immunoglobulin G specific to the spike protein of SARS-CoV-2) at day 45. Results Between 16th April 2021 and 26th July 2021, 556 participants were analysed for the primary endpoint (275 Test; 281 Placebo). The test agent significantly reduced SARS-CoV-2 infection compared to placebo [36 cases (13.1%) Vs 97 cases (34.5%); OR 0.29 (95% CI; 0.18-0.45), p < 0.0001]. Fewer clinical symptoms were also seen in the test group [57 cases (17.6%) vs 112 cases (34.6%); OR 0.40, (95% CI; 0.27-0.59), p < 0.0001]. No harmful effects were associated with taking the test agent. Conclusion The test agent significantly reduced SARS-CoV-2 infection in healthcare workers, with 62% fewer infections when compared to placebo. It was found to be safe and well tolerated and offers a novel treatment option for prophylaxis against SARS-CoV-2 infection.


Subject(s)
COVID-19 , COVID-19/prevention & control , Humans , Nasal Sprays , Pandemics/prevention & control , Prospective Studies , SARS-CoV-2
8.
J Am Coll Cardiol ; 79(12): 1141-1151, 2022 03 29.
Article in English | MEDLINE | ID: mdl-35331408

ABSTRACT

BACKGROUND: Patients with previous coronary artery bypass graft (CABG) surgery typically have complex coronary disease and remain at high risk of adverse events. Quantitative myocardial perfusion indices predict outcomes in native vessel disease, but their prognostic performance in patients with prior CABG is unknown. OBJECTIVES: In this study, we sought to evaluate whether global stress myocardial blood flow (MBF) and perfusion reserve (MPR) derived from perfusion mapping cardiac magnetic resonance (CMR) independently predict adverse outcomes in patients with prior CABG. METHODS: This was a retrospective analysis of consecutive patients with prior CABG referred for adenosine stress perfusion CMR. Perfusion mapping was performed in-line with automated quantification of MBF. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular events defined as nonfatal myocardial infarction and unplanned revascularization. Associations were evaluated with the use of Cox proportional hazards models after adjusting for comorbidities and CMR parameters. RESULTS: A total of 341 patients (median age 67 years, 86% male) were included. Over a median follow-up of 638 days (IQR: 367-976 days), 81 patients (24%) reached the primary outcome. Both stress MBF and MPR independently predicted outcomes after adjusting for known prognostic factors (regional ischemia, infarction). The adjusted hazard ratio (HR) for 1 mL/g/min of decrease in stress MBF was 2.56 (95% CI: 1.45-4.35) and for 1 unit of decrease in MPR was 1.61 (95% CI: 1.08-2.38). CONCLUSIONS: Global stress MBF and MPR derived from perfusion CMR independently predict adverse outcomes in patients with previous CABG. This effect is independent from the presence of regional ischemia on visual assessment and the extent of previous infarction.


Subject(s)
Coronary Artery Disease , Myocardial Perfusion Imaging , Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Coronary Circulation/physiology , Female , Humans , Infarction , Ischemia , Male , Perfusion , Predictive Value of Tests , Retrospective Studies
9.
J Nucl Cardiol ; 29(5): 2119-2128, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34169473

ABSTRACT

BACKGROUND: International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. 18F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE. METHODS: Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded. RESULTS: 69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified. CONCLUSION: PET improves diagnostic certainty when combined with mDC in NVE and PVE.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Heart Valve Prosthesis , Prosthesis-Related Infections , Anti-Bacterial Agents , C-Reactive Protein , Endocarditis/diagnostic imaging , Endocarditis, Bacterial/diagnosis , Fluorodeoxyglucose F18 , Heart Valve Prosthesis/adverse effects , Humans , Positron Emission Tomography Computed Tomography , Prosthesis-Related Infections/diagnostic imaging , Retrospective Studies
10.
Lancet Reg Health Eur ; 7: 100131, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34557840

ABSTRACT

BACKGROUND: Little is known about variations in care and outcomes of patients undergoing surgical repair for type A aortic dissection(TAAD). We aim to investigate decade-long trends in TAAD surgical repair in England. METHODS: Retrospective review of the National Adult Cardiac Surgery Audit, which prospectively collects demographic and peri­operative information for all major adult cardiac surgery procedures performed in the UK. We identified patients undergoing surgery for TAAD from January 2009-December 2018, reviewed trends in operative frequency, patient demographics, and mortality. FINDINGS: Over the 10-year period,3,680 TAAD patients underwent surgical repair in England. A doubling in the overall number of operations conducted in England was observed (235 cases in 2009 to 510 in 2018). Number of procedures per hospital per year also doubled(9 in 2009 to 23 in 2018). Overall, in-hospital mortality was 17.4% with a trend toward lower mortality in recent years(23% in 2009 to 14.7% in 2018). There was a significant variation in operative mortality between hospitals and surgeons. We also found that most patients presented towards the middle of the week and during winter. INTERPRETATION: Surgery is the only treatment for acute TAAD but is associated with high mortality. Prompt diagnosis and referral to a specialist center is paramount. The number of operations conducted in England has doubled in 10 years and the associated survival has improved. Variations exist in service provision with a trend towards better survival in high volume centers. FUNDING: British Heart Foundation and NIHR Biomedical Research center(University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol).

11.
Eur Heart J ; 43(1): 44-52, 2021 12 28.
Article in English | MEDLINE | ID: mdl-34468733

ABSTRACT

AIMS: Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. METHODS AND RESULTS: We identified 4203 patients undergoing TAAAD surgery in the UK (2009-18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02-1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51-2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14-1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90-4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71-3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00-3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14-9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86-2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes. CONCLUSIONS: Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement.


Subject(s)
Aortic Dissection , Cardiac Surgical Procedures , Adult , Aortic Dissection/surgery , Hospital Mortality , Humans , Postoperative Complications , Retrospective Studies , Risk Factors , Stroke Volume , Treatment Outcome , United Kingdom/epidemiology , Ventricular Function, Left
12.
JCI Insight ; 6(16)2021 08 23.
Article in English | MEDLINE | ID: mdl-34283808

ABSTRACT

BACKGROUNDEpicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT's immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients.METHODSWe recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients' clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups.RESULTSFlow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls.CONCLUSIONAdaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile.FUNDINGBarts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.


Subject(s)
Adipose Tissue/immunology , Diabetes Mellitus/epidemiology , Obesity/epidemiology , Pericarditis/epidemiology , Pericardium/pathology , Adaptive Immunity , Adipose Tissue/cytology , Adipose Tissue/pathology , Aged , Cardiometabolic Risk Factors , Comorbidity , Coronary Artery Bypass , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Coronary Artery Disease/metabolism , Coronary Artery Disease/surgery , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Female , Humans , Immunophenotyping , Male , Middle Aged , Obesity/blood , Obesity/immunology , Obesity/metabolism , Pericarditis/immunology , Pericarditis/pathology , Pericardium/surgery , RNA-Seq
13.
Eur J Cardiothorac Surg ; 60(6): 1437-1444, 2021 12 01.
Article in English | MEDLINE | ID: mdl-33963362

ABSTRACT

OBJECTIVES: The risk of brain injury following surgery for type A aortic dissection (TAAD) remains substantial and no consensus has still been reached on which neuroprotective technique should be preferred. We aimed to investigate the association between neuroprotective strategies and clinical outcomes following TAAD repair. METHODS: Using the UK National Adult Cardiac Surgical Audit, we identified 1929 patients undergoing surgery for TAAD (2011-2018). Deep hypothermic circulatory arrest (DHCA) only, unilateral (uACP), bilateral antegrade cerebral perfusion (bACP) and retrograde cerebral perfusion were used in 830, 117, 760 and 222 patients, respectively. The primary end point was a composite of death and/or cerebrovascular accident (CVA). Generalized linear mixed model was used to adjust the effect of neuroprotective strategies for other confounders. RESULTS: The use of bACP was associated with longer circulatory arrest (CA) compared to other strategies. There was a trend towards lower incidence of death and/or CVA using uACP only for shorter CA. In particular, primary end point rate was 27.7% overall and 26.5%, 12.5%, 28.0% and 22.9% for CA <30 min and 28.6%, 30.4%, 33.3% and 33.0% for CA ≥30 min with DHCA only, uACP, bACP and retrograde cerebral perfusion, respectively. The use of DHCA only was associated with five-fold [odds ratio (OR) 5.35, 95% confidence interval (CI) 1.36-21.02] and two-fold (OR 1.77, 95% CI 1.01-3.09) increased risk of death and/or CVA compared to uACP and bACP, respectively, but the effect of uACP was significantly associated with CA duration (hazard ratio 0.97, 95% CI 0.94-0.99; P = 0.04). CONCLUSIONS: In TAAD repair, the use of uACP and bACP was associated with a lower adjusted risk of death and/or CVA when compared to DHCA. uACP can offer some advantage but only for a shorter CA duration.


Subject(s)
Aortic Dissection , Circulatory Arrest, Deep Hypothermia Induced , Adult , Aortic Dissection/epidemiology , Aortic Dissection/etiology , Aortic Dissection/surgery , Aorta, Thoracic/surgery , Cerebrovascular Circulation , Circulatory Arrest, Deep Hypothermia Induced/methods , Hospital Mortality , Humans , Perfusion/methods , Retrospective Studies , Treatment Outcome , United Kingdom/epidemiology
14.
J Card Surg ; 36(8): 2865-2875, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33982282

ABSTRACT

It is now 50 years since the development of the first pericardial valve in 1971. In this time significant progress has been made in refining valve design aimed at improving the longevity of the prostheses. This article reviews the current literature regarding the longevity of pericardial heart valves in the aortic position. Side by side comparisons of freedom from structural valve degeneration are made for the valves most commonly used in clinical practice today, including stented, stentless, and sutureless valves. Strategies to reduce structural valve degeneration are also discussed including methods of tissue fixation and anti-calcification, ways to minimise mechanical stress on the valve, and the role of patient prosthesis mismatch.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Aortic Valve/surgery , Humans , Prosthesis Design , Stents
15.
Echocardiography ; 38(4): 590-595, 2021 04.
Article in English | MEDLINE | ID: mdl-33711172

ABSTRACT

BACKGROUND: Patients with acute severe aortic regurgitation (AR) due to infective endocarditis can progress rapidly from the hemodynamically stable patient to pulmonary edema and cardiogenic shock. We sought to identify patients at risk of decompensation where emergent surgery should be undertaken. METHODS: We identified 90 patients with acute severe AR from the echocardiography laboratory database. Baseline clinical, hemodynamic (heart rate (HR) and blood pressure (BP)), and echocardiographic data including mitral filling, premature mitral valve closure (PMVC), and diastolic mitral regurgitation (DMR) were identified. The primary endpoint was subsequent development of pulmonary edema or severe hemodynamic instability. RESULTS: Patients who met the primary endpoint had a higher HR (98.5 bpm vs 80.5 bpm), lower diastolic BP (54 mm Hg vs 61.5 mm Hg), higher mitral E-wave velocity (113 cm/s vs 83 cm/s), higher E/e' ratio (12.4 vs 8), higher proportion of DMR (27.8% vs 7.4%), and PMVC (25% vs 9.3%) than patients who did not meet the endpoint. The proportion of patients with the primary endpoint increased as HR increased ((≤81 bpm) 3/30 (10%), (81-94 bpm) 11/31 (35.5%), (≥94 bpm) 22/29 (75.9%), P < .0001) and as the diastolic BP reduced ((≤54 mm Hg) 19/31 (61.3%), (54-63 mm Hg) 12/31 (38.7%), (≥63 mm Hg) 5/28 (17.9%), P = .003). Independent predictors were a higher HR (OR 1.08 (95% CI 1.04-1.13) P = .0003) and DMR (OR 4.71 (95% CI 1.23-18.09), P = .02). CONCLUSION: Decompensation in acute severe AR is common. Independent predictors of decompensation are increasing HR(≥94 bpm) and the presence of DMR. Those with these adverse markers should be considered for emergent surgery.


Subject(s)
Aortic Valve Insufficiency , Endocarditis, Bacterial , Mitral Valve Insufficiency , Aortic Valve Insufficiency/complications , Aortic Valve Insufficiency/diagnostic imaging , Echocardiography , Humans , Mitral Valve
16.
J Thromb Haemost ; 19(5): 1236-1249, 2021 05.
Article in English | MEDLINE | ID: mdl-33587817

ABSTRACT

BACKGROUND: Megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable from hematopoietic stem cells (HSCs), bypassing intermediate progenitors. They mature within the adult bone marrow and release platelets into the circulation. Until now, there have been no transcriptional studies of primary human bone marrow MKs. OBJECTIVES: To characterize MKs and HSCs from human bone marrow using single-cell RNA sequencing, to investigate MK lineage commitment, maturation steps, and thrombopoiesis. RESULTS: We show that MKs at different levels of polyploidization exhibit distinct transcriptional states. Although high levels of platelet-specific gene expression occur in the lower ploidy classes, as polyploidization increases, gene expression is redirected toward translation and posttranslational processing transcriptional programs, in preparation for thrombopoiesis. Our findings are in keeping with studies of MK ultrastructure and supersede evidence generated using in vitro cultured MKs. Additionally, by analyzing transcriptional signatures of a single HSC, we identify two MK-biased HSC subpopulations exhibiting unique differentiation kinetics. We show that human bone marrow MKs originate from these HSC subpopulations, supporting the notion that they display priming for MK differentiation. Finally, to investigate transcriptional changes in MKs associated with stress thrombopoiesis, we analyzed bone marrow MKs from individuals with recent myocardial infarction and found a specific gene expression signature. Our data support the modulation of MK differentiation in this thrombotic state. CONCLUSIONS: Here, we use single-cell sequencing for the first time to characterize the human bone marrow MK transcriptome at different levels of polyploidization and investigate their differentiation from the HSC.


Subject(s)
Megakaryocytes , Thrombopoiesis , Blood Platelets , Bone Marrow , Cell Differentiation , Humans , Thrombopoiesis/genetics
17.
Front Cardiovasc Med ; 8: 795195, 2021.
Article in English | MEDLINE | ID: mdl-35004905

ABSTRACT

Coronary artery bypass graft (CABG) surgery effectively relieves symptoms and improves outcomes. However, patients undergoing CABG surgery typically have advanced coronary atherosclerotic disease and remain at high risk for symptom recurrence and adverse events. Functional non-invasive testing for ischaemia is commonly used as a gatekeeper for invasive coronary and graft angiography, and for guiding subsequent revascularisation decisions. However, performing and interpreting non-invasive ischaemia testing in patients post CABG is challenging, irrespective of the imaging modality used. Multiple factors including advanced multi-vessel native vessel disease, variability in coronary hemodynamics post-surgery, differences in graft lengths and vasomotor properties, and complex myocardial scar morphology are only some of the pathophysiological mechanisms that complicate ischaemia evaluation in this patient population. Systematic assessment of the impact of these challenges in relation to each imaging modality may help optimize diagnostic test selection by incorporating clinical information and individual patient characteristics. At the same time, recent technological advances in cardiac imaging including improvements in image quality, wider availability of quantitative techniques for measuring myocardial blood flow and the introduction of artificial intelligence-based approaches for image analysis offer the opportunity to re-evaluate the value of ischaemia testing, providing new insights into the pathophysiological processes that determine outcomes in this patient population.

18.
Europace ; 23(1): 104-112, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33083830

ABSTRACT

AIMS: Optimum timing of pacemaker implantation following cardiac surgery is a clinical challenge. European and American guidelines recommend observation, to assess recovery of atrioventricular block (AVB) (up to 7 days) and sinus node (5 days to weeks) after cardiac surgery. This study aims to determine rates of cardiac implantable electronic devices (CIEDs) implants post-surgery at a high-volume tertiary centre over 3 years. Implant timing, patient characteristics and outcomes at 6 months including pacemaker utilization were assessed. METHODS AND RESULTS: All cardiac operations (n = 5950) were screened for CIED implantation following surgery, during the same admission, from 2015 to 2018. Data collection included patient, operative, and device characteristics; pacing utilization and complications at 6 months. A total of 250 (4.2%) implants occurred; 232 (3.9%) for bradycardia. Advanced age, infective endocarditis, left ventricle systolic impairment, and valve surgery were independent predictors for CIED implants (P < 0.0001). Relative risk (RR) of CIED implants and proportion of AVB increased with valve numbers operated (single-triple) vs. non-valve surgery: RR 5.4 (95% CI 3.9-7.6)-21.0 (11.4-38.9) CIEDs. Follow-up pacing utilization data were available in 91%. Significant utilization occurred in 82% and underutilization (<1% A and V paced) in 18%. There were no significant differences comparing utilization rates in early (≤day 5 post-operatively) vs. late implants (P = 0.55). CONCLUSION: Multi-valve surgery has a particularly high incidence of CIED implants (14.9% double, 25.6% triple valve). Age, left ventricle systolic impairment, endocarditis, and valve surgery were independent predictors of CIED implants. Device underutilization was infrequent and uninfluenced by implant timing. Early implantation (≤5 days) should be considered in AVB post-multi-valve surgery.


Subject(s)
Cardiac Surgical Procedures , Defibrillators, Implantable , Pacemaker, Artificial , Cardiac Surgical Procedures/adverse effects , Defibrillators, Implantable/adverse effects , Electronics , Humans , Pacemaker, Artificial/adverse effects , Retrospective Studies , Risk Factors , Treatment Outcome
19.
Heart Lung Circ ; 30(6): 854-860, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33279409

ABSTRACT

AIM: The mortality of patients with infective endocarditis (IE) is high. The management of patients with large vegetations is controversial. This study sought to investigate the association of vegetation size on outcomes including valve destruction, embolism and mortality. METHODS AND RESULTS: One hundred and forty-two (142) patients with definite IE and transoesophageal echocardiography (TEE) imaging available for analysis were identified and data retrospectively reviewed. Vegetation length, width and area were measured. Severe valve destruction was defined as the composite of one or more of severe valve regurgitation, abscess, pseudoaneurysm, perforation or fistula. Associations with 6-month mortality were identified by Cox regression analysis. Eighty (80) (56.3%) patients had evidence of valve destruction on TEE. Vegetation length ≥10 mm and vegetation area ≥50 mm2 were significantly associated with increased risk of valve destruction, (both odds ratio OR 1.21, p=0.03 and p=0.02 respectively). Thirty-nine (39) (72.2%) patients who had an embolic event, did so prior initiation of antibiotics. Six (6)-month mortality was 18.3%. In the surgically managed group, vegetation size was not associated with mortality. In the medically managed group, vegetation area (mm2) was associated with increased mortality (HR 1.01, p<0.01) along with age (HR 1.06, p=0.03). CONCLUSION: Vegetation length ≥10 mm or area ≥50 mm2 are associated with increased risk of valve destruction. Vegetation size may also predict mortality in medically managed but not surgically managed patients with IE. Further studies to evaluate whether surgery in patients with large vegetation size improves outcomes is warranted.


Subject(s)
Embolism , Endocarditis, Bacterial , Endocarditis , Heart Valve Diseases , Embolism/diagnostic imaging , Embolism/mortality , Endocarditis/diagnostic imaging , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/mortality , Heart Valve Diseases/diagnostic imaging , Humans , Retrospective Studies
20.
Interact Cardiovasc Thorac Surg ; 31(4): 483-485, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32791519

ABSTRACT

The coronavirus 2019 (COVID-19) pandemic has disrupted patient care across the NHS. Following the suspension of elective surgery, priority was placed in providing urgent and emergency surgery for patients with no alternative treatment. We aim to assess the outcomes of patients undergoing cardiac surgery who have COVID-19 infection diagnosed in the early postoperative period. We identified 9 patients who developed COVID-19 infection following cardiac surgery. These patients had a significant length of hospital stay and extremely poor outcomes with mortality of 44%. In conclusion, the outcome of cardiac surgical patients who contracted COVID-19 infection perioperatively is extremely poor. In order to offer cardiac surgery, units must implement rigorous protocols aimed at maintaining a COVID-19 protective environment to minimize additional life-threatening complications related to this virus infection.


Subject(s)
Betacoronavirus , Cardiac Surgical Procedures/methods , Coronavirus Infections/epidemiology , Elective Surgical Procedures/methods , Heart Diseases/surgery , Pandemics , Pneumonia, Viral/epidemiology , Adult , Aged , COVID-19 , Comorbidity , Female , Heart Diseases/epidemiology , Humans , Length of Stay , Male , Middle Aged , Postoperative Period , SARS-CoV-2 , Time Factors , Young Adult
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