Publications by authors named "Rakesh Uppal"

48 Publications

Fifty years of the pericardial valve: Long-term results in the aortic position.

J Card Surg 2021 May 12. Epub 2021 May 12.

Barts Heart Centre, St Bartholomew's Hospital, London, UK.

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.
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http://dx.doi.org/10.1111/jocs.15604DOI Listing
May 2021

Neuroprotective strategies in acute aortic dissection: an analysis of the UK National Adult Cardiac Surgical Audit.

Eur J Cardiothorac Surg 2021 May 8. Epub 2021 May 8.

South Tees Hospitals NHS Trust, Middlesbrough, UK.

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.
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http://dx.doi.org/10.1093/ejcts/ezab192DOI Listing
May 2021

Clinical and echocardiographic predictors of decompensation in acute severe aortic regurgitation due to infective endocarditis.

Echocardiography 2021 Apr 12;38(4):590-595. Epub 2021 Mar 12.

Echocardiography Laboratory, St Bartholomew's Hospital, London, UK.

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.
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http://dx.doi.org/10.1111/echo.15028DOI Listing
April 2021

Transcriptional characterization of human megakaryocyte polyploidization and lineage commitment.

J Thromb Haemost 2021 05 29;19(5):1236-1249. Epub 2021 Mar 29.

Department of Hematology, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1111/jth.15271DOI Listing
May 2021

Association of Vegetation Size With Valve Destruction, Embolism and Mortality.

Heart Lung Circ 2021 Jun 3;30(6):854-860. Epub 2020 Dec 3.

Echocardiography Laboratory, Barts Heart Centre, St Bartholomew's Hospital, London, UK; Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital, London, UK; William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address:

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 mm 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 (mm) 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 mm 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.
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http://dx.doi.org/10.1016/j.hlc.2020.10.028DOI Listing
June 2021

Post-operative cardiac implantable electronic devices in patients undergoing cardiac surgery: a contemporary experience.

Europace 2021 Jan;23(1):104-112

Cardiac Research Department, Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, 1 St Martin's Le Grand, West Smithfield, London EC1A 7BE, UK.

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.
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http://dx.doi.org/10.1093/europace/euaa241DOI Listing
January 2021

Outcomes of patients diagnosed with COVID-19 in the early postoperative period following cardiac surgery.

Interact Cardiovasc Thorac Surg 2020 10;31(4):483-485

Department of Cardiothoracic Surgery, St Bartholomew's Hospital, London, UK.

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.
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http://dx.doi.org/10.1093/icvts/ivaa143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454553PMC
October 2020

A nationwide survey of UK cardiac surgeons' view on clinical decision making during the coronavirus disease 2019 (COVID-19) pandemic.

J Thorac Cardiovasc Surg 2020 10 19;160(4):968-973. Epub 2020 May 19.

South Tees Hospitals NHS Trust, Middlesbrough, United Kingdom.

Background: No firm recommendations are currently available to guide decision making for patients requiring cardiac surgery during the coronavirus disease 2019 (COVID-19) pandemic. Systematic appraisal of senior surgeons' consensus can be used to generate interim recommendations until data from clinical observations become available. Hence, we aimed to collect and quantitatively appraise nationwide UK consultants' opinions on clinical decision making for patients requiring cardiac surgery during the COVID-19 pandemic.

Methods: We E-mailed a Web-based questionnaire to all consultant cardiac surgeons through the Society for Cardiothoracic Surgery in Great Britain and Ireland mailing list on the April 17, 2020, and we predetermined to close the survey on the April 21, 2020. This survey was primarily designed to gather information on UK surgeons' opinions using 12 items. Strong consensus was predefined as an opinion shared by at least 60% of responding consultants.

Results: A total of 86 consultant surgeons undertook the survey. All UK cardiac units were represented by at least 1 consultant. Strong consensus was achieved for the following key questions: (1) before any hospital admission for cardiac surgery, nasopharyngeal swab, polymerase chain reaction, and computed tomography of the chest should be performed; (2) the use of full personal protective equipment should to be adopted in every case by the theater team regardless of the patient's COVID-19 status; (3) the risk of COVID-19 exposure for patients undergoing heart surgery should be considered moderate to high and likely to increase mortality if it occurs; and (4) cardiac procedures should be decided based on a rapidly convened multidisciplinary team discussion for every patient. The majority believed that both aortic and mitral surgery should be considered in selected cases. The role of coronary artery bypass graft surgery during the pandemic was controversial.

Conclusions: In this unprecedented pandemic period, this survey provides information for generating interim recommendations until data from clinical observations become available.
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http://dx.doi.org/10.1016/j.jtcvs.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235560PMC
October 2020

Size and dissection: what is the relation?

Indian J Thorac Cardiovasc Surg 2019 Jun 9;35(Suppl 2):72-78. Epub 2018 Jul 9.

Department of Cardiac Surgery, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE UK.

Thoracic aortic aneurysm is a complex disease. The consequences of such silent and indolent disease include acute aortic syndrome if not recognized early and treated appropriately. Aortic aneurysm size was a reliable clinical marker to aid clinical intervention; however, aneurysm growth is variable and is influenced by many factors such as age, presence of connective tissue disorders, genetic disorders, hypertension, inflammatory conditions of the aorta, autoimmune diseases, smoking, and history of previous cardiac surgery. Therefore, aortic size became a non-specific disease surrogate and prediction tool on outcome and intervention. In this review article, we examined the current literature for evidence about aneurysm size and its relation to type A aortic dissection.
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http://dx.doi.org/10.1007/s12055-018-0687-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525749PMC
June 2019

On-site fabrication of Bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure.

Biomaterials 2019 07 16;209:41-53. Epub 2019 Apr 16.

William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom. Electronic address:

Mesenchymal stromal/stem cell (MSC)-based therapy is a promising approach for the treatment of heart failure. However, current MSC-delivery methods result in poor donor cell engraftment, limiting the therapeutic efficacy. To address this issue, we introduce here a novel technique, epicardial placement of bi-layered, adhesive dressings incorporating MSCs (MSC-dressing), which can be easily fabricated from a fibrin sealant film and MSC suspension at the site of treatment. The inner layer of the MSC dressing, an MSC-fibrin complex, promptly and firmly adheres to the heart surface without sutures or extra glues. We revealed that fibrin improves the potential of integrated MSCs through amplifying their tissue-repair abilities and activating the Akt/PI3K self-protection pathway. Outer collagen-sheets protect the MSC-fibrin complex from abrasion by surrounding tissues and also facilitates easy handling. As such, the MSC-dressing technique not only improves initial retention and subsequent maintenance of donor MSCs but also augment MSC's reparative functions. As a result, this technique results in enhanced cardiac function recovery with improved myocardial tissue repair in a rat ischemic cardiomyopathy model, compared to the current method. Dose-dependent therapeutic effects by this therapy is also exhibited. This user-friendly, highly-effective bioengineering technique will contribute to future success of MSC-based therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2019.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527869PMC
July 2019

Echocardiography in Patients With Infective Endocarditis and the Impact of Diagnostic Delays on Clinical Outcomes.

Am J Cardiol 2018 08 11;122(4):650-655. Epub 2018 May 11.

Echocardiography Laboratory, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom. Electronic address:

Infective endocarditis (IE) is associated with high mortality and morbidity. The aim of this study was to investigate the impact of timing of echocardiography on IE complications. We studied 151 consecutive patients with definite IE. Valve destruction was defined as ≥1 of severe regurgitation, cardiac abscess, or fistula. A definitive echocardiogram was the first echocardiogram (transthoracic (TTE) or Transesophageal (TEE)) which identified pathology consistent with IE and further echocardiography was not required for the diagnosis. TTE and TEE were performed within 4 days of admission in 62% and 15% patients respectively. Definitive echocardiography was achieved with TTE in 60% patients and required additional TEE in 40% patients. Significantly more in-patient embolic events occurred when definitive echocardiography was performed late (≥4 days) compared with early (<4 days) (40% vs 14%, p = 0.043). A significantly greater proportion of patients who underwent late definitive echocardiography (≥4 days) required valve surgery (73% vs 56%, p = 0.04). Time to definitive echocardiography (odds ratio [OR] 1.015, p = 0.011), male gender (OR 1.254, p = 0.005) and age (OR 0.992, p = 0.002) were predictors of severe valve destruction. Late definitive echocardiography (OR 1.166, p=0.035) was a predictor of in-patient embolism. In conclusion, time to definitive echocardiography is an important predictor of valve destruction, embolic events, and subsequent valve surgery. Pathways to reduce delays to echocardiography are required in patients with suspected IE.
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http://dx.doi.org/10.1016/j.amjcard.2018.04.039DOI Listing
August 2018

Fibrin Glue-aided, Instant Epicardial Placement Enhances the Efficacy of Mesenchymal Stromal Cell-Based Therapy for Heart Failure.

Sci Rep 2018 06 21;8(1):9448. Epub 2018 Jun 21.

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Transplantation of mesenchymal stromal cells (MSCs) is a promising new therapy for heart failure. However, the current cell delivery routes result in poor donor cell engraftment. We therefore explored the role of fibrin glue (FG)-aided, instant epicardial placement to enhance the efficacy of MSC-based therapy in a rat ischemic cardiomyopathy model. We identified a feasible and reproducible method to instantly produce a FG-MSC complex directly on the heart surface. This complex exhibited prompt, firm adhesion to the heart, markedly improving initial retention of donor MSCs compared to intramyocardial injection. In addition, maintenance of retained MSCs was enhanced using this method, together contributing the increased donor cell presence. Such increased donor cell quantity using the FG-aided technique led to further improved cardiac function in association with augmented histological myocardial repair, which correlated with upregulation of tissue repair-related genes. We identified that the epicardial layer was eliminated shortly after FG-aided epicardial placement of MSCs, facilitating permeation of the donor MSC's secretome into the myocardium enabling myocardial repair. These data indicate that FG-aided, on-site, instant epicardial placement enhances MSC engraftment, promoting the efficacy of MSC-based therapy for heart failure. Further development of this accessible, advanced MSC-therapy is justified.
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http://dx.doi.org/10.1038/s41598-018-27881-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013428PMC
June 2018

Decoding the volume-outcome relationship in Type A aortic dissection.

Gen Thorac Cardiovasc Surg 2019 Jan 12;67(1):32-36. Epub 2018 May 12.

Department of Cardiac Surgery, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK.

Over the past few decades, the advents in monitoring, imaging, diagnostics, and implementation of multidisciplinary team approach in Type A aortic dissection surgery resulted in improved surgical outcomes. One other factor that needed to be targeted and carefully analyzed was the volume-outcome relationship on hospital and surgeon level in the settings of Type A dissection. This surely sprung form reports which indicated that supercenters providing aortic services with concentrated expert and expertise were performing better than smaller centers. We dwell in this article on the body of evidence to support concentration of experts and the effect of this organization on volume, referral, and outcome in Type A aortic dissection.
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http://dx.doi.org/10.1007/s11748-018-0939-5DOI Listing
January 2019

A Completely Epicardial Biventricular Defibrillator for a Pacing Dependent Patient With No Superior Central Venous Access.

JACC Clin Electrophysiol 2018 02 19;4(2):277-279. Epub 2018 Feb 19.

Bart's Heart Centre, St. Bartholomew's Hospital, Bart's Health National Health Service Trust, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jacep.2017.11.006DOI Listing
February 2018

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

Biomaterials 2018 Feb 31;154:12-23. Epub 2017 Oct 31.

William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biomaterials.2017.10.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768325PMC
February 2018

Is there a role for biomarkers in thoracic aortic aneurysm disease?

Gen Thorac Cardiovasc Surg 2019 Jan 28;67(1):12-19. Epub 2017 Oct 28.

Department of Cardiac Surgery, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK.

Thoracic aortic aneurysm (TAA) represents a major cause of mortality and morbidity in Western countries. The natural history of TAA is indolent, with patients usually being asymptomatic until a catastrophic event such as rupture or dissection ensues. As such, early diagnosis is crucial and the search is ongoing for a biomarker that can indicate the presence of TAA with sufficient accuracy to act as a screening tool. To date, no such marker has been developed for the diagnosis of non-familial or 'sporadic' TAA. However, our increased understanding of the pathogenesis of both familial and sporadic TAA has suggested potential candidates for diagnostic biomarkers. Many markers/pathways have been shown to have differential activity levels or expression in the aortic tissue of TAA. However, priority is given to markers that have shown differential levels in blood plasma, as blood tests represent the easiest route for mass screening for TAA. This review aims to evaluate the efficacy of clinical tests already in use in diagnosing TAA, explore novel proposed biomarkers and identify key areas of future interest.
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http://dx.doi.org/10.1007/s11748-017-0855-0DOI Listing
January 2019

Is ministernotomy superior to right anterior minithoracotomy in minimally invasive aortic valve replacement?

Interact Cardiovasc Thorac Surg 2017 11;25(5):818-821

Department of Cardiothoracic Surgery, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London, UK.

A best evidence topic was constructed according to a structured protocol. The question addressed was whether, in patients undergoing minimally invasive aortic valve replacement (AVR), right anterior thoracotomy (RT) or mini-sternotomy (MS) was superior in terms of postoperative outcome? A total of 840 publications were found using the reported search. Of these, 6 represented the best available evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In all, except 1 study, the primary outcome was early mortality, ranging from in-hospital mortality to 90 days postoperatively. The remaining study was a cost-benefit analysis. Four studies were non-randomized observational studies, one of which was multicentre. Two were meta-analyses of studies comparing minithoracotomy or MS with conventional sternotomy for AVR, rather than direct comparisons of the 2 minimal access techniques. We conclude that there is a lack of high-quality evidence comparing RT and MS for minimally invasive AVR, with no randomized controlled trials to date. The available evidence shows no difference in early mortality between RT and MS for surgical AVR. In studies that directly compared RT and MS, RT was found to be associated with reduced length of hospital stay, despite longer cardiopulmonary bypass times and cross-clamp times. One study reported groin complications (10.8%) with the RT group, where peripheral cannulation was used, while the other 5 studies did not comment on groin complications associated with peripheral cannulation. In the only cost-benefit analysis, RT was found to carry considerably more cost than MS over and above conventional AVR.
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http://dx.doi.org/10.1093/icvts/ivx241DOI Listing
November 2017

A systematic review and meta-analysis of mechanical vs biological composite aortic root replacement, early and 1-year results.

Gen Thorac Cardiovasc Surg 2019 Jan 10;67(1):70-76. Epub 2017 Oct 10.

Department of Cardiac Surgery, Barts Heart Centre, St. Bartholomew's Hospital, London, EC1A 7BE, UK.

Objective: Composite aortic root replacement is a standard procedure for various aortic root pathologies. This systematic review was set to identify the postoperative outcomes for composite mechanical root replacement (mCRR) compared to composite biological root replacement (bCRR).

Methods: We systematically reviewed four major databases for all papers assessing outcomes in composite root replacement. Articles selected were chosen by two reviewers. Amongst our inclusion and exclusion criteria, all pediatric populations were excluded as were studies with a cohort less than 50 patients.

Results: We identified seven studies that conformed to our inclusion criteria and incorporated 2240 patients. In-hospital mortality was higher but non-significant in the mechanical group (6.1 vs 4.2% respectively). There was no significant difference demonstrated in the risk of in-hospital stroke, late stroke and re-operation in either groups. Additionally, there was no significant difference in: endocarditis, 1-year mortality, 5-year mortality, mean cardiopulmonary or aortic cross-clamp time.

Conclusions: Composite mechanical root offers no superiority to composite biological root. There is a significant increase in the perioperative bleeding amongst composite mechanical root cohort. There is a need for further randomized control trail to assess the efficacy of either methods.
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http://dx.doi.org/10.1007/s11748-017-0845-2DOI Listing
January 2019

Aortic Valve Replacement: Are We Spoiled for Choice?

Semin Thorac Cardiovasc Surg 2017 Autumn;29(3):265-272. Epub 2017 Aug 18.

Department of Cardiothoracic Surgery, St Bartholomew's Hospital, London, UK.

Management of aortic valve disease and, in particular, aortic valve stenosis has evolved through the course of time from medical management and balloon valvuloplasty to the presumed gold-standard surgical intervention. However, with the advent of surgical innovation, intra- and postoperative patients monitoring, understanding of hemodynamic dysfunction, and choices of prosthesis, conventional surgical aortic valve replacements are currently being challenged in particular in moderate- and high-risk patients. Although the long-term results and survival are not robustly available, the durability of the new prosthesis, repair, and the freedom from reoperation remain debatable. In this review, we aim to highlight the surgical innovation attained, choices of aortic valve prosthesis, and also dwell on the current evidence, practice, and trend steered to managing patients with aortic valve stenosis.
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http://dx.doi.org/10.1053/j.semtcvs.2017.08.003DOI Listing
December 2017

Is endoscopic long saphenous vein harvesting equivalent to open harvesting technique in terms of graft patency?

Interact Cardiovasc Thorac Surg 2017 08;25(2):323-326

Department of Cardiothoracic Surgery, Barts Heart Centre, St. Bartholomew's Hospital, London, UK.

A best evidence topic was written according to a structured protocol. The question addressed was whether endoscopic vein harvesting (EVH) is equivalent to open vein harvesting in terms of graft patency for patients undergoing coronary artery bypass surgery. A total of 417 articles were found using the reported search, of which 4 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these articles are tabulated. Reported outcomes were vein graft failure or patency on coronary angiography or computed tomography angiography at early, mid and long-term follow-up. Of the non-randomized studies reviewed, those with greater patient numbers and longer follow-up periods showed reduced patency rates in the EVH group. Two small early randomized controlled trials demonstrated equivalent patency rates at up to 6 months follow-up. However, a more recent randomized controlled trial showed reduced patency with EVH in 63 patients at a median follow-up of 6.3 years. We conclude that high-quality evidence for the effects of harvesting method on vein graft patency is lacking, with no large randomized trials performed to date. The current evidence suggests that although rates of vein graft failure seem to be similar within the first 6 months following surgery, EVH is associated with reduced graft patency from 12 months onwards.
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http://dx.doi.org/10.1093/icvts/ivx049DOI Listing
August 2017

Incidental finding of anomalous circumflex coronary artery from right coronary sinus prior to aortic valve surgery.

BMJ Case Rep 2017 Mar 31;2017. Epub 2017 Mar 31.

Department of Cardiothoracic Surgery, Barts Heart Centre, St Bartholomew's Hospital, London, UK.

Anomalous origin of the left circumflex (Cx) artery is a common and mostly benign coronary artery anomaly. We report the case of a man aged 52 years who presented to his local hospital with progressive breathlessness on exertion and syncopal episodes. His admission transthoracic echocardiography (TTE) showed bicuspid aortic valve, severe aortic stenosis with a valve area of 0.5 cm and his left ventricular ejection fraction (LVEF) was 27%. His coronary angiogram showed normal coronary arteries but anomalous origin of the Cx artery from the right coronary. He underwent elective bioprosthetic aortic valve replacement. His postoperative recovery was uneventful and he was discharged on day 5 postoperatively. His TTE postoperatively showed well-seated aortic valve, improved LVEF to 51%. We here report a case of incidental finding of anomalous Cx artery arising from the right coronary while the patient is being worked up for aortic valve replacement for congenital bicuspid aortic valve.
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http://dx.doi.org/10.1136/bcr-2017-219265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388007PMC
March 2017

Acute type A aortic dissection in the United Kingdom: Surgeon volume-outcome relation.

J Thorac Cardiovasc Surg 2017 08 14;154(2):398-406.e1. Epub 2017 Feb 14.

Aortic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

Objectives: Surgery for acute type A aortic dissection (ATAD) carries a high risk of operative mortality. We examined the surgeon volume-outcome relation with respect to in-hospital mortality for patients presenting with this pathology in the United Kingdom.

Method: Between April 2007 and March 2013, 1550 ATAD procedures were identified from the National Institute for Cardiovascular Outcomes Research database. A total of 249 responsible consultant cardiac surgeons from the United Kingdom recorded 1 or more of these procedures in their surgical activity over this period. We describe the patient population and mortality rates, focusing on the relationship between surgeon volume and in-hospital mortality.

Results: The mean annual volume of procedures per surgeon during the 6-year period ranged from 1 to 6.6. The overall in-hospital mortality rate was 18.3% (283/1550). A mortality improvement at the 95% level was observed with a risk-adjusted mean annual volume >4.5. Surgeons with a mean annual volume <4 over the study period had significantly higher in-hospital mortality rates in comparison with surgeons with a mean annual volume ≥4 (19.3% vs 12.6%; P = .015).

Conclusions: Patients with ATAD who are operated on by lower-volume surgeons experience higher levels of in-hospital mortality. Directing these patients to higher-volume surgeons may be a strategy to reduce in-hospital mortality.
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http://dx.doi.org/10.1016/j.jtcvs.2017.02.015DOI Listing
August 2017

A 72-year-old male with recurrent syncope.

Heart 2017 05 21;103(10):800. Epub 2016 Dec 21.

Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital, London, UK.

Clinical Introduction: A 72-year-old patient presented with recurrent syncope 1 year after a myocardial infarction. Two recent falls resulted in fractures to the femur. Serial troponins were negative and ECG demonstrated fixed inferior ST-segment elevation and pathological Q waves. A Holter monitor recorded non-sustained ventricular tachycardia. A subsequent echocardiogram was abnormal, and further investigation with a three-dimensional (3D) cardiac CT coronary angiogram was performed (figure 1).

Question: What is the most likely diagnosis? Cardiac tumourHypertrophic obstructive cardiomyopathyVentricular aneurysmVentricular diverticulum heartjnl;103/10/800/HEARTJNL2016309670F1F1HEARTJNL2016309670F1Figure 1Cardiac CT coronary angiogram-three-dimensional reconstruction.
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http://dx.doi.org/10.1136/heartjnl-2016-309670DOI Listing
May 2017

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation.

Cell Stem Cell 2016 12 17;19(6):808-822. Epub 2016 Nov 17.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbrücken, Germany; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, 1090 Vienna, Austria. Electronic address:

Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood. We also observed lineage-specific DNA methylation between myeloid and lymphoid progenitors, characterized immature multi-lymphoid progenitors, and detected progressive DNA methylation differences in maturing megakaryocytes. We linked these patterns to gene expression, histone modifications, and chromatin accessibility, and we used machine learning to derive a model of human hematopoietic differentiation directly from DNA methylation data. Our results contribute to a better understanding of human hematopoietic stem cell differentiation and provide a framework for studying blood-linked diseases.
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http://dx.doi.org/10.1016/j.stem.2016.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145815PMC
December 2016

Quality of life after mitral valve intervention.

Interact Cardiovasc Thorac Surg 2017 02;24(2):265-272

Department of Surgery and Cancer, Imperial College London, London, UK.

Advancements in surgical technique and understanding of the pathophysiology of mitral valve (MV) dysfunction have led to improved outcomes. Seen as a development beyond measures of morbidity and mortality, health-related quality-of-life (HRQOL) outcome measures are becoming increasingly popular. These measures are important because complications following routine (i.e. low-risk) operations on the MV are uncommon and further markers of outcome are needed. Surgeons are increasingly operating earlier on asymptomatic patients and will need to prove that HRQOL is not impacted. Novel minimally invasive and transcatheter technologies will also need to demonstrate satisfactory HRQOL outcomes prior to widespread use. This systematic review provides an overview of all available literature detailing HRQOL in patients receiving MV interventions. In the 43 studies included, 6865 patients underwent procedures ranging from open replacement to percutaneous repair using devices such as the Mitraclip Clip Delivery System (MitraClip) (Abbott Vascular, Santa Clara, CA, USA). Most studies performed baseline HRQOL assessment, allowing postinterventional comparison. While the underlying literature had deficiencies, most studies report acceptable postintervention HRQOL that was comparable to that of matched general populations. Patient-specific (e.g. female gender, renal dysfunction) and surgical-specific factors (e.g. replacement instead of repair, elevated transmitral gradient) were identified that predispose patients to poorer long-term HRQOL outcomes. These factors are important for clinicians developing strategies to maximize their HRQOL outcomes. Future randomized studies would benefit from HRQOL measurements at specific time points to allow large-scale comparisons. Establishing a common HRQOL instrument for use in MV intervention studies may support detailed comparisons between specific techniques. Physical activity monitors, physiological biomarkers and radiological markers could also be used as innovative indicators of functional outcome.
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http://dx.doi.org/10.1093/icvts/ivw312DOI Listing
February 2017

National Survey of UK Consultant Surgeons' Opinions on Surgeon-Specific Mortality Data in Cardiothoracic Surgery.

Circ Cardiovasc Qual Outcomes 2016 07 12;9(4):414-23. Epub 2016 Jul 12.

From the Department of Surgery and Cancer, Imperial College London, London, United Kingdom (O.A.J., C.P., A.D., T.A.); Department of Cardiothoracic Surgery, St. Thomas' Hospital, London, United Kingdom (K.B.); Department of Cardiothoracic Surgery, St Bartholomew's Hospital, London, United Kingdom (R.U.); and Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, United Kingdom (D.P.T., S.W.).

Background: In the United Kingdom, cardiothoracic surgeons have led the outcome reporting revolution seen over the last 20 years. The objective of this survey was to assess cardiothoracic surgeons' opinions on the topic, with the aim of guiding future debate and policy making for all subspecialties.

Methods And Results: A questionnaire was developed using interviews with experts in the field. In January 2015, the survey was sent out to all consultant cardiothoracic surgeons in the United Kingdom (n=361). Logistic regression, bivariate correlation, and the χ(2) test were used to assess whether there was a relationship between answers and demographic variables. Free-text responses were analyzed using the grounded theory approach. The response rate was 73% (n=264). The majority of respondents (58.1% oppose, 34.1% favor, and 7.8% neither) oppose the public release of surgeon-specific mortality data and associate it with several adverse consequences. These include risk-averse behavior, gaming of data, and misinterpretation of data by the public. Despite this, the majority overwhelmingly supports publication of team-based measures of outcome. The free-text responses suggest that this is because most believe that quality of care is multifactorial and not represented by an individual's mortality rate.

Conclusions: There is evident opposition to surgeon-specific mortality data among UK cardiothoracic surgeons who associate this with several unintended consequences. Policy makers should refine their strategy behind publication of surgeon-specific mortality data and possibly consider shift toward team-based results for which there will be the required support. Stakeholder feedback and inclusive strategy should be completed before introducing major initiatives to avoid unforeseen consequences and disagreements.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.116.002749DOI Listing
July 2016

Does positron emission tomography/computed tomography aid the diagnosis of prosthetic valve infective endocarditis?

Interact Cardiovasc Thorac Surg 2016 10 31;23(4):648-52. Epub 2016 May 31.

Department of Cardiothoracic Surgery, Barts Heart Centre, St Bartholomew's Hospital, London, UK.

A best evidence topic was constructed according to a structured protocol. The question addressed was whether (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) aids the diagnosis of prosthetic valve endocarditis (PVE)? A total of 107 publications were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The reported outcome of all studies was a final diagnosis of confirmed endocarditis on follow-up. All the six studies were non-randomized, single-centre, observational studies and thus represented level 3 evidence. The diagnostic capability of PET/CT for PVE was compared with that of the modified Duke Criteria and echocardiography, and reported in terms of sensitivity, specificity and positive and negative predictive values. All studies demonstrated an increased sensitivity for the diagnosis of PVE when PET/CT was combined with the modified Duke Criteria on admission. A higher SUVmax on PET was found to be significantly associated with a confirmed diagnosis of endocarditis and an additional diagnostic benefit of PET/CT angiography over conventional PET/non-enhanced CT is reported due to improved anatomical resolution. However, PET/CT was found to be unreliable in the early postoperative period due to its inability to distinguish between infection and residual postoperative inflammatory changes. PET/CT was also found to be poor at diagnosing cases of native valve endocarditis. We conclude that PET/CT aids in the diagnosis of PVE when combined with the modified Duke Criteria on admission by increasing the diagnostic sensitivity. The diagnostic ability of PET/CT can be potentiated by the use of PET/CTA; however, its use may be unreliable in the early postoperative period or in native valve endocarditis.
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http://dx.doi.org/10.1093/icvts/ivw177DOI Listing
October 2016

The Authors Reply.

Kidney Int 2015 Nov;88(5):1195-6

William Harvey Research Institute, Queen Mary University, London, UK.

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http://dx.doi.org/10.1038/ki.2015.263DOI Listing
November 2015

Activity and outcomes for aortic valve implantations performed in England and Wales since the introduction of transcatheter aortic valve implantation.

Eur J Cardiothorac Surg 2016 Apr 13;49(4):1164-73. Epub 2015 Aug 13.

Department of Cardiothoracic Surgery, Manchester Academic Health Science Centre, University of Manchester, University Hospital of South Manchester, Manchester, UK National Institute for Cardiovascular Outcomes Research (NICOR), University College London, London, UK

Objectives: The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 2007. This study presents the subsequent national activity and outcomes for both TAVI and aortic valve replacement (AVR).

Methods: Data for all AVR and TAVI procedures between January 2006 and December 2012 in England and Wales were included. The number of procedures, patient characteristics, in-hospital and 30-day mortality, postoperative length of stay (PLOS) and survival were analysed separately for: isolated AVR; AVR + coronary artery bypass graft (CABG) surgery; AVR + other surgery and TAVI.

Results: The number of TAVIs increased from 66 in 2007 (0.8% of all implants) to 1186 in 2012 (10.9% of all implants). AVR activity also increased over the study period. TAVI patients were older and had a higher mean logistic EuroSCORE than all AVR groups. The 30-day mortality rates were 2.1% for isolated AVR, 3.9% for AVR + CABG, 7.7% for AVR + other surgery and 6.2% for TAVI. In-hospital mortality has significantly improved for all groups. The 5-year survival rates were 82.6% for isolated AVR, 81.7% for AVR + CABG, 74.5% for AVR + other surgery and 46.1% for TAVI. The median PLOS after TAVI was similar to that of isolated AVR but shorter than that of the other AVR groups.

Conclusions: Since the introduction of TAVI, there has been an increase in both TAVI and AVR activity. TAVIs now represent over 10% of all aortic valve implants. There are distinct differences between procedural groups with respect to patient risk factors. Outcomes for all procedural groups have improved, but long-term TAVI results are required before its role in the treatment of aortic stenosis can be fully defined.
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http://dx.doi.org/10.1093/ejcts/ezv270DOI Listing
April 2016

Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery.

Kidney Int 2015 Feb 30;87(2):473-81. Epub 2014 Jul 30.

1] William Harvey Research Institute, Queen Mary University, London, UK [2] NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital, London, UK [3] Department of Nephrology, Barts Health NHS Trust, London, UK.

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48 h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.
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http://dx.doi.org/10.1038/ki.2014.259DOI Listing
February 2015