Mustafa Zakkar

University of Bristol, Bristol, England, United Kingdom

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Publications (47)175.34 Total impact

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    ABSTRACT: Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/ parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions. Copyright © 2015. Published by Elsevier Inc.
    Pharmacology [?] Therapeutics 06/2015; 93. DOI:10.1016/j.pharmthera.2015.06.009 · 7.75 Impact Factor
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    ABSTRACT: The development of the cardiopulmonary bypass (CPB) revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress.
    Oxidative medicine and cellular longevity 02/2015; 2015:1-8. DOI:10.1155/2015/189863 · 3.36 Impact Factor
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    ABSTRACT: The impact of transcatheter aortic valve implantation (TAVI) on left ventricular (LV) mass regression is not well defined. We aimed to measure LV mass regression, changes in LV volumes and dimensions, as well as mitral valve function after TAVI. Eighty patients who underwent TAVI between 2008 and 2010 were studied. Echocardiographic findings before procedure and at 6- and 12-month follow-up were analyzed. Aortic valve area increased from 0.71 (0.27) cm before procedure to 1.89 (0.64) cm at 12 months (P < 0.001), which was associated with reduction in peak [80.79 (23) vs 16.9 (6.5) mm Hg, P < 0.001] and mean [47.65 (14.2) vs 8.77 (3.29) mm Hg, P < 0.001] gradients. At 1 year, there was a change in LV end-systolic volume [46.12 (36.6) to 48.96 (4.05) mL, P = 0.042] and LV mass [202.4 (92.2) to 183.6 (98.2) g, P = 0.04]. Left ventricular mass index regressed from 130.7 (28.9) to 122.1 (28.9) g/m (P = 0.01). Maximum wall thickness decreased from 1.28 (0.18) to 1.25 (0.17) cm (P < 0.001). There was no significant change in LV ejection fraction, LV end-systolic and end-diastolic diameters, as well as mitral valve regurgitation. Transcatheter aortic valve implantation is associated with significant regression of LV hypertrophy at 1 year. However, this regression was not associated with changes in LV systolic and diastolic functions, size, or changes in mitral valve regurgitation.
    Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery 01/2015; 10(1):44-7. DOI:10.1097/IMI.0000000000000122
  • Mustafa Zakkar · Gustavo Guida · Gianni D Angelini
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    ABSTRACT: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was the impact of modified ultrafiltration on adult patients undergoing cardiac surgery in terms of inflammatory and metabolic changes, blood loss and early clinical outcomes. A total of 155 papers were identified using the search as described below. Of these, six papers presented the best evidence to answer the clinical question as they reported data to reach conclusions regarding the issues of interest for this review. The author, date and country of publication, patient group, study type and weaknesses and relevant outcomes were tabulated. Modified ultrafiltration in adult patients undergoing cardiac surgery seems to attenuate the levels of inflammatory molecules associated with surgery, reduces blood loss and blood transfusion and improves cardiac output, index and systemic vascular resistance. However, this was not translated in any reduction in length of stay in intensive care unit or hospital. Most studies were single-centre prospective non-blinded trials that included a small cohort of elective coronary artery bypass grafting patients, which makes it underpowered to provide unbiased evidence regarding clinical outcomes. Properly designed and conducted prospective randomized studies are required to answer whether the beneficial effect of modified ultrafiltration on systemic inflammatory molecules associated with surgery can translate with improvement in clinical outcome. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    Interactive Cardiovascular and Thoracic Surgery 11/2014; 20(3). DOI:10.1093/icvts/ivu388 · 1.11 Impact Factor
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    ABSTRACT: Objective The c-Jun N-terminal kinase (JNK) family regulates fundamental physiological processes including apoptosis and metabolism. Although JNK2 is known to promote foam cell formation during atherosclerosis, the potential role of JNK1 is uncertain. We examined the potential influence of JNK1 and its negative regulator, MAP kinase phosphatase-1 (MKP-1), on endothelial cell (EC) injury and early lesion formation using hypercholesterolemic LDLR−/− mice. Methods and results To assess the function of JNK1 in early atherogenesis, we measured EC apoptosis and lesion formation in LDLR−/− or LDLR−/−/JNK1−/− mice exposed to a high fat diet for 6 weeks. En face staining using antibodies that recognise active, cleaved caspase-3 (apoptosis) or using Sudan IV (lipid deposition) revealed that genetic deletion of JNK1 reduced EC apoptosis and lesion formation in hypercholesterolemic mice. By contrast, although EC apoptosis was enhanced in LDLR−/−/MKP-1−/− mice compared to LDLR−/− mice, lesion formation was unaltered. Conclusion We conclude that JNK1 is required for EC apoptosis and lipid deposition during early atherogenesis. Thus pharmacological inhibitors of JNK may reduce atherosclerosis by preventing EC injury as well as by influencing foam cell formation.
    Atherosclerosis 08/2014; 235(2):613–618. DOI:10.1016/j.atherosclerosis.2014.05.950 · 3.97 Impact Factor
  • Jonathan Afoke · Carol Tan · Ian Hunt · Mustafa Zakkar
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    ABSTRACT: A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: might digital drains speed up the time to thoracic drain removal in terms of time till chest drain removal, hospital stay and overall cost? A total of 296 papers were identified as a result of the search as described below. Of these, five papers provided the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. A literature search revealed that several single-centre prospective randomized studies have shown significantly earlier removal of chest drains with digital drains ranging between 0.8 and 2.1 days sooner. However, there was heterogeneity in studies in the management protocol of chest drains in terms of the use of suction, number of drains and assessment for drain removal. Some protocols such as routinely keeping drains irrespective of the presence of air leak or drain output may have skewed results. Differences in exclusion criteria and protocols for discharging home with portable devices may have biased results. Due to heterogeneity in the management protocol of chest drains, there is conflicting evidence regarding hospital stay. The limited data on cost suggest that there may be significantly lower postoperative costs in the digital drain group. All the studies were single-centre series generally including patients with good preoperative lung function tests. Further larger studies with more robust chest drain management protocols are required especially to assess length of hospital stay, cost and whether the results are applicable to a larger patient population.
    Interactive Cardiovascular and Thoracic Surgery 04/2014; 19(1). DOI:10.1093/icvts/ivu099 · 1.11 Impact Factor
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    ABSTRACT: A 72-year-old female presented with severe ischaemic mitral regurgitation following a recent myocardial infarction. She had no significant past medical history.Pre-operative echocardiogram assessment demonstrated preserved tendinous cords of the mitral leaflets, a mitral valve annulus measuring 3.2 cm with end systolic coaptation of 0.3 cm, impaired left ventricular function with an ejection fraction of 35% and significant ventricular dilatation. Cardiac magnetic resonance imaging (MRI) showed delayed enhancement in the anterolateral, septal and lateral walls and confirmed the impairment of the left ventricle and a large aneurysmal deformation. On-table transoesophageal echo showed that the distance between the two papillary muscles was over 4 cm.We performed coronary artery bypass grafting combined with a Dor Procedure and papillary muscle approximation using a polytetrafluoroethylene (PTFE) vascular graft as a sling, without the insertion of a mitral annuloplasty ring. Postoperative echo and cardiac MRI showed improved left ventricular systolic function and reduced left ventricle volume associated with mild mitral regurgitation.We conclude that papillary muscles approximation as a method of mitral valve repair is a very effective procedure for functional ischaemic mitral regurgitation.
    Perfusion 01/2014; 29(5). DOI:10.1177/0267659114521265 · 1.08 Impact Factor
  • Mustafa Zakkar · Robin Kanagasabay · Ian Hunt
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    ABSTRACT: A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether manual closure of the bronchial stump is safer with lower failure rates than mechanical closure using a stapling device following anatomical lung resection. One hundred and twenty-nine papers were identified using the search below. Eight papers presented the best evidence to answer the clinical question as they included sufficient number of patients to reach conclusions regarding the issues of interest for this review. Complications, complication rates and operation time were included in the assessment. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. When looking at manual vs mechanical staples, it was noted that stapler failure can occur in around 4% of cases. The rate of bronchopleural fistula (BPF) development varied more in patients who underwent manual closure (1.5-12.5%) than in patients who underwent mechanical closure (1-5.7%). Although most of the studies reviewed showed no statistical differences between manual and mechanical closure in terms of BPF development, one study, however, showed that manual closure was significantly associated with lower numbers of postoperative BPF, while another study showed that mechanical closure is significantly associated with lower incidence of BPF. When looking at the role of the learning curve and training opportunities, it seems that the surgeon's inexperience when using mechanical staples can contribute to BPF development. A surgeon's experience can play a major role in the prevention of BPF development in patients having manual closure. Manual closure can provide a cheap and reliable technique when compared with costs incurred from using staplers, it is applicable in all situations and can be taught to surgeons in training with an acceptable risk. However, there is a lack of evidence to suggest that manual closure is better than mechanical stapler closure following anatomical lung resection.
    Interactive Cardiovascular and Thoracic Surgery 12/2013; 18(4). DOI:10.1093/icvts/ivt502 · 1.11 Impact Factor
  • Alessandro Viviano · Robin Kanagasabay · Mustafa Zakkar
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    ABSTRACT: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation (POAF) in adult cardiac surgery? A total of 70 papers were identified using the search as described below. Of these, eight were identified to provide best evidence to answer the clinical question. These papers consisted of well-designed, double-blinded randomized control trials (RCTs) or meta-analysis of RCTs that presented sufficient data to reach conclusions regarding the issues of interest for this review. Postoperative atrial fibrillation occurrence, outcomes and complications were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. Literature search showed that the prophylactic use of hydrocortisone (100 mg/day, 4 days) can reduce the incidence of POAF to 30%, compared with 48% in the control group (P = 0.004). One gram of methylprednisolone before surgery followed by 4 mg of dexamethasone every 6 h for 1 day after surgery was also associated with a significant reduction in POAF (21 vs 51%; P = 0.003). Moreover, a single dose of dexamethasone (0.6 mg/kg) can significantly diminish POAF (18.95 vs 32.3%; P = 0.027). The changes in POAF appeared greatest in patients receiving intermediate doses of corticosteroid (50-210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236-2850 mg) dosing resulted in blunted effects. Similarly, a moderate dose of hydrocortisone (200-1000 mg/day) is as effective as high (1001-10 000 mg/day) and very high doses (10 000 mg/day). Although the optimal dose, dosing interval and duration of therapy are unclear, meta-analysis suggests that a single dose can be as effective as multiple doses. No statistically significant complications associated with the use of corticosteroids were reported in any of the studies. We conclude that a single prophylactic moderate dose of corticosteroid (50-210 mg of dexamethasone equivalent or 200-1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality.
    Interactive Cardiovascular and Thoracic Surgery 11/2013; 18(2). DOI:10.1093/icvts/ivt486 · 1.11 Impact Factor
  • Interactive Cardiovascular and Thoracic Surgery 09/2013; 17(suppl 2):S126-S126. DOI:10.1093/icvts/ivt372.234 · 1.11 Impact Factor
  • M. Zakkar · C. Tan · I. Hunt
    Interactive Cardiovascular and Thoracic Surgery 09/2013; 17(suppl 2):S79-S79. DOI:10.1093/icvts/ivt372.45 · 1.11 Impact Factor
  • Mustafa Zakkar · Stephanie Frazer · Ian Hunt
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    ABSTRACT: A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether gabapentin, a commonly prescribed neuropathic analgesic and anticonvulsant, is safe and beneficial in patients with post-thoracotomy pain following thoracic surgery. Seventeen papers were identified using the search described below, and five papers presented the best evidence to reach conclusions regarding the issues of interest for this review. Side effects and complications as well as evidence of benefit, typically using various pain-scoring systems, were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. The systematic review of two randomized controlled trials (RCTs) demonstrated that the use of a single dose gabapentin does not reduce pain scores or the need for epidural or morphine immediately in hospital following thoracic surgery. One double-blinded RCT used multiple doses of gabapentin perioperatively and showed that oral gabapentin administered preoperatively and during the first 2 days postoperatively, in conjunction with patient controlled analgesia morphine, provides effective analgesia in thoracic surgery with a consequent improvement in postoperative pulmonary function and less morphine consumption. One prospective clinical study comparing a 2-month course of gabapentin with naproxen sodium for chronic post thoracotomy pain following surgery showed significant improvement in both the visual analogue scale (VAS) score and the Leeds assessment of neuropathic symptoms and signs (LANSS) at 60 days in the gabapentin (P = 0.001). One prospective study of out-patients with chronic pain (>4 weeks since thoracotomy performed) suggested that gabapentin is effective, safe and well tolerated when used for persistent postoperative and post-traumatic pain in thoracic surgery patients. We conclude that there is no evidence to support the role of a single preoperative oral dose of gabapentin in reducing pain scores or opioid consumption following thoracic surgery. Multiple dosing regimens may be beneficial in reducing acute and chronic pain; however, more robust randomized control studies are needed.
    Interactive Cardiovascular and Thoracic Surgery 07/2013; 17(4). DOI:10.1093/icvts/ivt301 · 1.11 Impact Factor
  • M Zakkar · R Kanagasabay
    Annals of The Royal College of Surgeons of England 07/2013; 95(5):380. DOI:10.1308/003588413X13629960046877m · 1.22 Impact Factor
  • M Zakkar · R Kanagasabay
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    ABSTRACT: Glucocorticoids can play a pivotal role in modulating different immune responses. The role of glucocorticoids in cardiac surgery is still controversial as many surgeons are concerned about the potential side effects.In this review, we looked at the role of glucocorticoid administration in modulating postoperative inflammatory responses, atrial fibrillation (AF) and intimal hyperplasia and whether glucocorticoid use is associated with a significant increase in undesirable postoperative complication.
    Perfusion 05/2013; 28(5). DOI:10.1177/0267659113488433 · 1.08 Impact Factor
  • Jonathan Afoke · Carol Tan · Ian Hunt · Mustafa Zakkar
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    ABSTRACT: A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Is sub-lobar resection equivalent to lobectomy in terms of operative morbidity and mortality, long-term survival and disease recurrence in patients with peripheral carcinoid lung cancer? A total of 342 papers were identified using the search as described below. Of these, 10 papers presented the best evidence to answer the clinical question as they presented sufficient data to reach conclusions regarding the issues of interest for this review. Long-term survival, disease recurrence and operative morbidity were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. A literature search showed that there is a good prognosis after resection of lung carcinoid with the 10-year disease-free survival rate ranging between 77 and 94%, and suggested that sub-lobar resection of a typical carcinoid did not compromise the long-term survival. The proportion of peripheral tumours ranged between 22.6 and 100% and the proportion of patients with a preoperative diagnosis of carcinoid ranged between 51.9 and 86.7%, with many series not providing either or both of these data. As a result, a lobectomy or greater resection was necessary on anatomical or diagnostic grounds and led to a low number of sub-lobar resections. Owing to the high heterogeneity within and between series and small numbers of cases included, it is difficult to draw conclusions on disease recurrence and postoperative morbidity. All studies available retrospectively compared heterogeneous groups of non-matched group of patients, which can bias the outcomes reported. There is a lack of comprehensive randomized studies to compare a lobectomy or greater resection and sub-lobar resection. We conclude that there is little objective evidence to show the equivalence or superiority of lobectomy over sub-lobar resection.
    Interactive Cardiovascular and Thoracic Surgery 03/2013; 16(6). DOI:10.1093/icvts/ivt067 · 1.11 Impact Factor
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    M Zakkar · I Hunt
    Annals of The Royal College of Surgeons of England 01/2013; 95(1):75. DOI:10.1308/003588413X13511609957056d · 1.22 Impact Factor
  • Mustafa Zakkar · Robin Kanagasabay
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2012; 43(4). DOI:10.1093/ejcts/ezs540 · 2.81 Impact Factor
  • Mustafa Zakkar · Ian Hunt
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2012; 43(3). DOI:10.1093/ejcts/ezs525 · 2.81 Impact Factor
  • Mustafa Zakkar · Ian Hunt
    The Annals of thoracic surgery 07/2012; 94(1):337; author reply 337-8. DOI:10.1016/j.athoracsur.2012.01.033 · 3.65 Impact Factor
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    ABSTRACT: An 81-year-old woman with recurrent episodes of dizzy spells was found to have a mass in the right atrium on transthoracic echocardiography. The patient underwent successful surgery to excise the mass, which was arising from the anterior leaflet of the tricuspid valve. Histology showed a papillary fibroelastoma. Although management is still controversial when such tumours are found incidentally in asymptomatic patients, surgery may be considered, especially if the tumour is large, due to the high risk of embolism.
    Perfusion 12/2011; 27(2):156-9. DOI:10.1177/0267659111431124 · 1.08 Impact Factor

Publication Stats

591 Citations
175.34 Total Impact Points

Institutions

  • 2015
    • University of Bristol
      • School of Physiology and Pharmacology
      Bristol, England, United Kingdom
  • 2011–2015
    • St George's, University of London
      Londinium, England, United Kingdom
  • 2007–2014
    • Imperial College London
      Londinium, England, United Kingdom
  • 2013
    • St George's Healthcare NHS Trust
      Londinium, England, United Kingdom
    • South London Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2010
    • Imperial College Healthcare NHS Trust
      • Division of Cardiology Cardiothoracic and Thoracic Surgery
      London, ENG, United Kingdom
  • 2008
    • National Heart Institute
      New Dilli, NCT, India