Publications by authors named "Diluka Premawardhana"

6 Publications

  • Page 1 of 1

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

JAMA Cardiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.

Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.

Design, Setting, And Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.

Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

Main Outcome And Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).

Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.

Conclusions And Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
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November 2021

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

Heart 2021 Sep 18;107(17):1398-1406. Epub 2021 May 18.

Department of Cardiovascular Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, Leicestershire, UK

Objective: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.

Methods: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).

Results: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.

Conclusion: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.
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September 2021

Spontaneous Coronary Artery Dissection: Insights on Rare Genetic Variation From Genome Sequencing.

Circ Genom Precis Med 2020 12 30;13(6):e003030. Epub 2020 Oct 30.

Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (A.A.B., T.R.W., S.E.H., D.P., A.A.-H., A.W., D.K., N.J.S., D.A.).

Background: Spontaneous coronary artery dissection (SCAD) occurs when an epicardial coronary artery is narrowed or occluded by an intramural hematoma. SCAD mainly affects women and is associated with pregnancy and systemic arteriopathies, particularly fibromuscular dysplasia. Variants in several genes, such as those causing connective tissue disorders, have been implicated; however, the genetic architecture is poorly understood. Here, we aim to better understand the diagnostic yield of rare variant genetic testing among a cohort of SCAD survivors and to identify genes or gene sets that have a significant enrichment of rare variants.

Methods: We sequenced a cohort of 384 SCAD survivors from the United Kingdom, alongside 13 722 UK Biobank controls and a validation cohort of 92 SCAD survivors. We performed a research diagnostic screen for pathogenic variants and exome-wide and gene-set rare variant collapsing analyses.

Results: The majority of patients within both cohorts are female, 29% of the study cohort and 14% validation cohort have a remote arteriopathy. Four cases across the 2 cohorts had a diagnosed connective tissue disorder. We identified pathogenic or likely pathogenic variants in 7 genes (, , , , , , and ) in 14/384 cases in the study cohort and in 1/92 cases in the validation cohort. In our rare variant collapsing analysis, was the highest-ranked gene, and several functionally plausible genes were enriched for rare variants, although no gene achieved study-wide statistical significance. Gene-set enrichment analysis suggested a role for additional genes involved in renal function.

Conclusions: By studying the largest sequenced cohort of SCAD survivors, we demonstrate that, based on current knowledge, only a small proportion have a pathogenic variant that could explain their disease. Our findings strengthen the overlap between SCAD and renal and connective tissue disorders, and we highlight several new genes for future validation.
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December 2020

Spontaneous Coronary Artery Dissection: Mechanisms, Diagnosis and Management.

Eur Cardiol 2020 Feb 26;15:1-8. Epub 2020 Feb 26.

Cardiology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa, Centro de Investigación en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.

Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome that usually affects young to middle-aged women. Mainly because of its low prevalence, until recently, most of the evidence on this condition was derived from case reports and small series. Over the last 5 years, more robust evidence has become available from larger retrospective and prospective cohorts of patients with SCAD. The increase in knowledge and recognition of this entity has led to the publication of expert consensus on both sides of the Atlantic. However, new data are continuously accumulating from larger cohorts of patients with SCAD, bringing new light to this little-understood condition. The aim of this article is to update the knowledge on SCAD, including new information from recent studies published since the consensus documents from the European Society of Cardiology and the American Heart Association.
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February 2020

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

Eur Heart J 2020 06;41(23):2197-2205

Department of Cardiovascular Sciences, NIHR Leicester Biomedical Research Centre, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.

Aims: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury.

Methods And Results: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass].

Conclusion: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.
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June 2020

Routine iso-osmolar contrast media use and acute kidney injury following percutaneous coronary intervention for ST elevation myocardial infarction.

Minerva Cardioangiol 2019 Oct 13;67(5):380-391. Epub 2019 Sep 13.

Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff, UK -

Background: Temporal changes in contrast-induced acute kidney injury (CI-AKI) incidence following primary percutaneous coronary intervention (PPCI) are poorly defined. Additionally, the benefits of iso-osmolar contrast media (IOCM) compared to low osmolar CM (LOCM) are uncertain.

Methods: Using data from a regional PPCI service, temporal changes in baseline risk and annual incidence of CI-AKI were studied. A CM protocol change occurred in 2013 allowing a comparison of the incidence of CI-AKI between LOCM (2012-13) and IOCM (2013-15).

Results: Between 2012 and 2015, 208 of 1310 patients experienced CI-AKI (15.9%). The Mehran AKI risk score did not change during the study period although there was an increase in the incidence of CI-AKI in later study years (P<0.001 for trend) when IOCM was used. Factors independently associated with CI-AKI were IOCM use (OR=1.96, [95% CI: 1.39-2.75]), age per year (OR=1.02, 95% CI: 1.01-1.04), baseline creatinine per µmol/L (OR=1.006, 95% CI: 1.003-1.01) and contrast volume per milliliter (OR=1.002, 95% CI: 1.001-1.004). The baseline characteristics of patients treated using IOCM (N.=783) vs. LOCM (N.=527) were similar (Mehran Score 6.6 vs. 6.9, P=0.173) but CI-AKI occurred more frequently with IOCM compared to LOCM (19.2% vs. 11.2%, P<0.001). Use of IOCM was independently associated with CI-AKI (OR=1.98, 95% CI: 1.339-2.774, P<0.001) with consistency across all sub-groups of age, gender, baseline creatinine, contrast volume, shock and diabetes. The adjusted in-hospital mortality was increased with IOCM compared to LOCM (OR=3.03, 95% CI: 1.313-6.994, P=0.009).

Conclusions: IOCM use was observed to be associated with an increased occurrence of CI-AKI, and an increase in in-hospital mortality after primary PCI.
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October 2019