Mustafa Zakkar

Dr. Mustafa Zakkar


Research Focus & Metrics

Academic Career Length

11Years (2016-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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6 March 2023 in Cells
Verified
Journal Article
Open access
PDF file
Georgia R. LaytonGeorgia R. Layton
Georgia R. Layton
SLShameem S Ladak
Shameem S Ladak
RARiccardo Giuseppe Abbasciano
Riccardo Giuseppe Abbasciano
Liam Wallace McQueenLiam Wallace McQueen
Liam Wallace McQueen
SGSarah J George
Sarah J George
MZMustafa Zakkar
Mustafa Zakkar
The long saphenous vein is the most used conduit in cardiac surgery, but its long-term patency is limited by vein graft disease (VGD). Endothelial dysfunction is a key driver of VGD; its aetiology is multi-factorial. However emerging evidence identifies vein conduit harvest technique and preservation fluids as causal in their onset and propagation. This study aims to comprehensively review published data on the relationship between preservation solutions, endothelial cell integrity and function, and VGD in human saphenous veins harvested for CABG. The review was registered with PROSPERO (CRD42022358828). Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until August 2022. Papers were evaluated in line with registered inclusion and exclusion criteria. Searches identified 13 prospective, controlled studies for inclusion in the analysis. All studies used saline as a control solution. Intervention solutions included heparinised whole blood and saline, DuraGraft, TiProtec, EuroCollins, University of Wisconsin (UoW), buffered, cardioplegic and Pyruvate solutions. Most studies demonstrated that normal saline appears to have negative effects on venous endothelium and the most effective preservation solutions identified in this review were TiProtec and DuraGraft. The most used preservation solutions in the UK are heparinised saline or autologous whole blood. There is substantial heterogeneity both in practice and reporting of trials evaluating vein graft preservation solutions, and the quality of existing evidence is low. There is an unmet need for high quality trials evaluating the potential for these interventions to improve long-term patency in venous bypass grafts.

18 July 2023 in European Journal of Cardio-Thoracic Surgery
Verified
Journal Article
Open access
PDF file
DFDaniel P Fudulu
Daniel P Fudulu
Georgia R. LaytonGeorgia R. Layton
Georgia R. Layton
BNBao Nguyen
Bao Nguyen
SSShubhra Sinha
Shubhra Sinha
ADArnaldo Dimagli
Arnaldo Dimagli
MZMustafa Zakkar
Mustafa Zakkar
Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05–1.30], P = 0.005 and OR 1.15, 95% CI [1.02–1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68–0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78–0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.

13 January 2025 in Cells
Verified
Journal Article
Open access
PDF file
Georgia R. LaytonGeorgia R. Layton
Georgia R. Layton
IAIbrahim Antoun
Ibrahim Antoun
ACAlice Copperwheat
Alice Copperwheat
ZKZaidhan Latif Khan
Zaidhan Latif Khan
SBSanjay S. Bhandari
Sanjay S. Bhandari
MZMustafa Zakkar
Mustafa Zakkar
Osteopontin (OPN) is a sialylated phosphoprotein highly expressed in atherosclerosis and upregulated in settings of both acute and chronic inflammation. It is hypothesised that plasma levels of OPN may correlate with the presence of coronary artery disease, “CAD”. This offers potential as a point-of-care testing biomarker for early diagnosis, disease monitoring, and prognosis. This review evaluates the current literature on the association between plasma OPN levels and coronary artery disease and what is currently known to support its potential as a biomarker for future practice. Electronic searches of MEDLINE and EMBASE databases were undertaken from inception until July 2024. Thirty-three studies met the inclusion criteria. All studies were observational, with gross heterogeneity in methods used to analyse the association of plasma OPN with clinical characteristics. They included case series, case–control, cross-sectional, and cohort study designs. OPN has been linked to higher cardiovascular risk and unfavourable cardiovascular outcomes. However, the evidence regarding the direct assessment of CAD severity using tools like the SYNTAX or TIMI scores, which focus on anatomical complexity and risk factors, is less definitive. This suggests that OPN may be a more precise reflection of the inflammatory processes and atherosclerotic activity contributing to unfavourable outcomes rather than a direct indicator of the anatomical severity of CAD itself. Consequently, OPN is increasingly perceived as a marker of a poor prognosis rather than a tool for assessing the severity of coronary artery lesions.

1 November 2016 in Journal of Thoracic Disease
Verified
Journal Article
Open access
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PCPierpaolo Chivasso
Pierpaolo Chivasso
GGGustavo A. Guida
Gustavo A. Guida
DFDaniel Fudulu
Daniel Fudulu
DBDomenico Bruno
Domenico Bruno
RMRoberto Marsico
Roberto Marsico
GAGianni Angelini
Gianni Angelini
The superiority of either off-pump (OPCAB) or on-pump (ONCAB) coronary artery bypass grafting (CABG) remains unclear despite a large body of literature evidence comparing the two approaches. The potential advantages of avoiding cardiopulmonary bypass (CPB), minimizing aortic manipulation and maintaining pulsatile flow may be associated with reduced inflammatory responses and embolic events. Numerous studies compared OPCAB with ONCAB and the cumulative data have been presented in meta-analyses of both randomized and observational studies. Although there is an abundance of data with respect to the operative morbidity and mortality and the short-term outcomes associated with these two strategies, not much is known about how they impact long-term survival and recurrence of myocardial ischaemic events. Recent studies and meta-analyses have focused on long-term survival and major secondary outcomes in OPCAB vs. ONCAB within the general population. Significant limitations in methodology, however, have raised concerns about the strength of several randomized trials with restrictive inclusion criteria that reduced the populations to those at low risk only, thus creating result bias. Here, we present a review of the best available evidence with a focus on long-term outcomes.

27 May 2022 in Perfusion
Verified
Journal Article
Open access
OFOluwatomini Fashina
Oluwatomini Fashina
RARiccardo G Abbasciano
Riccardo G Abbasciano
Liam Wallace McQueenLiam Wallace McQueen
Liam Wallace McQueen
SLShameem Ladak
Shameem Ladak
SGSarah J George
Sarah J George
MZMustafa Zakkar
Mustafa Zakkar
Coronary artery bypass grafting remains the treatment of choice for a large cohort of patients with significant coronary disease. Despite the increased use of arterial grafts, the long saphenous vein remains the most commonly used conduit. Long-term graft patency continues to be the Achilles heel of saphenous vein grafts. This is due to the development of intimal hyperplasia, a chronic inflammatory disease that results in the narrowing and occlusion of a significant number of vein grafts. Research models for intimal hyperplasia are essential for a better understanding of pathophysiological processes of this condition. Large animal models resemble human anatomical structures and have been used as a surrogate to study disease development and prevention over the years. In this paper, we systematically review all published studies that utilized large animal models of vein graft disease with a focus on the type of model and any therapeutic intervention, specifically the use of external stents/mesh.

7 March 2024 in Frontiers in Cardiovascular Medicine
Verified
Journal Article
Open access
RAR. G. Abbasciano
R. G. Abbasciano
GLG. R. Layton
G. R. Layton
STS. Torre
S. Torre
NAN. Abbaker
N. Abbaker
ACA. Copperwheat
A. Copperwheat
AVA. Viviano
A. Viviano
Objective: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive methods to assess the functional significance of intermediate severity coronary lesions. Both indexes have been extensively validated in clinical trials in guiding revascularisation in patients with stable ischaemic heart disease undergoing percutaneous coronary intervention (PCI) with improved clinical outcomes. However, the role of these tools in coronary artery bypass grafting (CABG) is less clear.Methods: A meta-analysis of randomised trials and observational studies was carried out to help in determining the optimal strategy for assessing lesion severity and selecting graft targets in patients undergoing CABG. Electronic searches were carried out on Embase, MEDLINE, and Web of Science. A group of four authors independently screened and then assessed the retrieved records. Cochrane's Risk of Bias and Robins-I tools were used for bias assessment. A survey was conducted among surgeons and cardiologists to describe current attitudes towards the preoperative use of functional coronary investigations in practice.Results: Clinical outcomes including mortality at 30 days, perioperative myocardial infarction, number of grafts, incidence of stroke, rate of further need for revascularisation, and patient-reported quality of life did not differ in CABG guided by functional testing from those guided by traditional angiography.The survey revealed that in half of the surgical and cardiology units functional assessment is performed in CABG patients; there is a general perception that functional testing has improved patient care and its use would clarify the role of moderate coronary lesions that often need multidisciplinary rediscussions; moderate stenosis are felt to be clinically relevant; and anatomical considerations need to be taken into account together with functional assessment.Conclusions: At present, the evidence to support the routine use of functional testing in intermediate lesions for planning CABG is currently insufficient. The pooled data currently available do not show an increased risk in mortality, myocardial injury, and stroke in the FFR/iFR-guided group. Further trials with highly selected populations are needed to clarify the best strategy.Systematic Review Registration: ClinicalTrials.gov, identifier (CRD42023414604).