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1.
Diabetes Obes Metab ; 23(8): 1806-1822, 2021 08.
Article in English | MEDLINE | ID: mdl-33830637

ABSTRACT

AIM: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes. METHODS: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference -0.54 mg/L [-0.75, -0.34]; standard mean difference [SMD] -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. CONCLUSIONS: There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Biomarkers , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/therapeutic use , Inflammation/drug therapy , Male , Middle Aged , Oxidative Stress , Randomized Controlled Trials as Topic
2.
Catheter Cardiovasc Interv ; 88(3): 340-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26527101

ABSTRACT

OBJECTIVES: To determine the incidence, characteristics, and outcomes associated with geographical miss (GM) of plaque. BACKGROUND: GM describes plaques that are incompletely covered following stenting, with GM thought to be associated with worse clinical outcomes. However, the incidence and characteristics of intravascular ultrasound (IVUS)-defined GM plaques have never been studied and the relationship between GM with both short and long-term clinical events is unknown. METHODS: One hundred and seventy patients with stable angina (n = 100) or myocardial infarction (MI) (n = 70) underwent virtual-histology IVUS (VH-IVUS) prior to, and following, percutaneous coronary intervention (PCI). GM was defined as three consecutive uncovered VH frames, either proximal or distal to the stented segment with plaque burden >40%. MACE was defined as a composite of death, myocardial infarction, unplanned revascularization, or hospitalization for angina. RESULTS: In total, 245 plaques underwent PCI with 80 (32.7%) displaying evidence of GM (69 patients). GM was associated with increased plaque volume (p < 0.001), % necrotic core, and dense calcium (both p < 0.001) and VH-defined thin-cap fibroatheroma (VH-TCFA) (p = 0.01). GM was not associated with increased periprocedural MI (p = 0.15) or inflammatory cytokine release. At follow-up, 42 MACE occurred in 28 patients (median 1,115 days). MACE was attributable to 8/80 (10%) plaques with and 7/165 (4.2%) plaques without GM (log-rank p = 0.11). GM was associated with increased MACE in patients presenting with MI (p = 0.015), but not for those with stable angina (p = 0.94). CONCLUSIONS: GM is common after PCI and associated with more vulnerable plaque composition/subtype. GM may confer a worse prognosis in patients undergoing PCI for MI. © 2015 Wiley Periodicals, Inc.


Subject(s)
Angina, Stable/therapy , Coronary Artery Disease/therapy , Coronary Vessels , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , Plaque, Atherosclerotic , Aged , Angina, Stable/diagnostic imaging , Angina, Stable/mortality , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Vessels/diagnostic imaging , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality , Patient Readmission , Percutaneous Coronary Intervention/instrumentation , Prospective Studies , Risk Factors , Rupture, Spontaneous , Stents , Time Factors , Treatment Outcome , Ultrasonography, Interventional
3.
Circulation ; 128(7): 702-12, 2013 Aug 13.
Article in English | MEDLINE | ID: mdl-23841983

ABSTRACT

BACKGROUND: Mitochondrial DNA (mtDNA) damage occurs in both circulating cells and the vessel wall in human atherosclerosis. However, it is unclear whether mtDNA damage directly promotes atherogenesis or is a consequence of tissue damage, which cell types are involved, and whether its effects are mediated only through reactive oxygen species. METHODS AND RESULTS: mtDNA damage occurred early in the vessel wall in apolipoprotein E-null (ApoE(-/-)) mice, before significant atherosclerosis developed. mtDNA defects were also identified in circulating monocytes and liver and were associated with mitochondrial dysfunction. To determine whether mtDNA damage directly promotes atherosclerosis, we studied ApoE(-/-) mice deficient for mitochondrial polymerase-γ proofreading activity (polG(-/-)/ApoE(-/-)). polG(-/-)/ApoE(-/-) mice showed extensive mtDNA damage and defects in oxidative phosphorylation but no increase in reactive oxygen species. polG(-/-)/ApoE(-/-) mice showed increased atherosclerosis, associated with impaired proliferation and apoptosis of vascular smooth muscle cells, and hyperlipidemia. Transplantation with polG(-/-)/ApoE(-/-) bone marrow increased the features of plaque vulnerability, and polG(-/-)/ApoE(-/-) monocytes showed increased apoptosis and inflammatory cytokine release. To examine mtDNA damage in human atherosclerosis, we assessed mtDNA adducts in plaques and in leukocytes from patients who had undergone virtual histology intravascular ultrasound characterization of coronary plaques. Human atherosclerotic plaques showed increased mtDNA damage compared with normal vessels; in contrast, leukocyte mtDNA damage was associated with higher-risk plaques but not plaque burden. CONCLUSIONS: We show that mtDNA damage in vessel wall and circulating cells is widespread and causative and indicates higher risk in atherosclerosis. Protection against mtDNA damage and improvement of mitochondrial function are potential areas for new therapeutics.


Subject(s)
Atherosclerosis/etiology , DNA Damage , DNA, Mitochondrial/chemistry , Mitochondria/pathology , Monocytes/pathology , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Plaque, Atherosclerotic/pathology , Adiposity , Adult , Aged , Animals , Apolipoproteins E/genetics , Apoptosis , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cells, Cultured , Cytokines/metabolism , DNA Adducts/analysis , DNA Polymerase gamma , DNA-Directed DNA Polymerase/deficiency , DNA-Directed DNA Polymerase/genetics , Electron Transport , Female , Humans , Hyperlipidemias/genetics , Leukocytes/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Mitochondria/chemistry , Mitochondria/physiology , Monocytes/metabolism , Muscle, Smooth, Vascular/metabolism , Oxygen Consumption , Radiation Chimera , Reactive Oxygen Species , Risk
4.
Article in English | MEDLINE | ID: mdl-38604832

ABSTRACT

BACKGROUND: The impact of new-onset left bundle branch block (N-LBBB) developing after Transcatheter Aortic Valve Replacement (TAVR) on cardiac function and mechanical dyssynchrony is not well defined. METHODS: We retrospectively screened all patients who underwent TAVR in our centre between Oct 2018 and Sept 2021 (n = 409). We identified 38 patients with N-LBBB post-operatively (of which 28 were persistent and 10 were transient), and 17 patients with chronic pre-existent LBBB (C-LBBB). We excluded patients requiring pacing post TAVR. For all groups, we retrospectively analysed stored echocardiograms at 3 time points: before TAVR (T0), early after TAVR (T1, 1.2 ± 1.1 days), and late follow-up (T2, 1.5 ± 0.8 years), comparing LV mass and volumes, indices of LV function (LV ejection fraction, LVEF; global longitudinal strain, GLS), and mechanical dyssynchrony indices (systolic stretch index, severity of septal flash). RESULTS: At baseline (T0), C-LBBB had worse cardiac function, and larger LV volumes and LV mass, compared with patients with N-LBBB. At T1, N-LBBB resulted in mild dyssynchrony and decreased LVEF and GLS. Dyssynchrony progressed at T2 in persistent N-LBBB but not C-LBBB. In both groups however, LVEF remained stable at T2, although individual response was variable. Patients with better LVEF at baseline demonstrated a higher proportion of developing LBBB-induced LV dysfunction at T2. Lack of improvement of LVEF immediately after TAVR predicted deteriorating LVEF at T2. In transient LBBB, cardiac function and most dyssynchrony indices returned to baseline. CONCLUSIONS: N-LBBB after TAVR results in an immediate reduction of cardiac function, in spite of only mild dyssynchrony. When LBBB persists, patients with better cardiac function before TAVR are more likely to have LBBB-induced LV dysfunction after TAVR.

5.
Article in English | MEDLINE | ID: mdl-38971662

ABSTRACT

BACKGROUND: Optical coherence tomography (OCT) is used widely to guide stent placement, identify higher-risk plaques, and assess mechanisms of drug efficacy. However, a range of common artifacts can prevent accurate plaque classification and measurements, and limit usable frames in research studies. We determined whether pre-processing OCT images corrects artifacts and improves plaque classification. METHODS: We examined both ex-vivo and clinical trial OCT pullbacks for artifacts that prevented accurate tissue identification and/or plaque measurements. We developed Fourier transform-based software that reconstructed images free of common OCT artifacts, and compared corrected and uncorrected images. RESULTS: 48 % of OCT frames contained image artifacts, with 62 % of artifacts over or within lesions, preventing accurate measurement in 12 % frames. Pre-processing corrected >70 % of all artifacts, including thrombus, macrophage shadows, inadequate flushing, and gas bubbles. True tissue reconstruction was achieved in 63 % frames that would otherwise prevent accurate clinical measurements. Artifact correction was non-destructive and retained anatomical lumen and plaque parameters. Correction improved accuracy of plaque classification compared against histology and retained accurate assessment of higher-risk features. Correction also changed plaque classification and prevented artifact-related measurement errors in a clinical study, and reduced unmeasurable frames to <5 % ex-vivo and ~1 % in-vivo. CONCLUSIONS: Fourier transform-based pre-processing corrects a wide range of common OCT artifacts, improving identification of higher-risk features and plaque classification, and allowing more of the whole dataset to be used for clinical decision-making and in research. Pre-processing can augment OCT image analysis systems both for stent optimization and in natural history or drug studies.

6.
Int J Cardiol ; 377: 104-111, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36764610

ABSTRACT

AIM: To assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. METHOD: We conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012-2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. RESULTS: Overall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmol/L, but 81% had blood pressure < 140/80 (current ESC targets). Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmol/mol. Only 51% & 27% of the patients had LDL-C levels <1.8 &1.4 mmol/L (2016 & 2019 guidelines recommendations respectively), and 55% & 34% had non-HDL-C levels <2.6 & 2.2 mmol/L (2016 & 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. CONCLUSION: Achievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.


Subject(s)
Cardiology , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Percutaneous Coronary Intervention , Female , Humans , Cholesterol, LDL , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/chemically induced , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Secondary Prevention , Glycated Hemoglobin , Risk Factors , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol , Cohort Studies , Heart Disease Risk Factors
7.
Br J Radiol ; 96(1152): 20230296, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37747290

ABSTRACT

OBJECTIVE: Vascular and bleeding complications after transcatheter aortic valve implantation (TAVI) are common and lead to increased morbidity and mortality. Analysis of plaque at the arterial access site may improve prediction of complications. METHODS: We investigated the association between demographic and procedural risk factors for Valve Academic Research Consortium (VARC-3) vascular complications in patients undergoing transfemoral TAVI with use of a vascular closure device (ProGlide® or MANTA®) in this retrospective cohort study. The ability of pre-procedure femoral CT angiography to predict complications was investigated including a novel method of quantifying plaque composition of the common femoral artery using plaque maps created with patient specific X-ray attenuation cut-offs. RESULTS: 23 vascular complications occurred in the 299 patients in the study group (7.7%). There were no demographic risk factors associated with vascular complications and no statistical difference between use of closure device (ProGlide® vs MANTA®) and vascular complications. Vascular complications after TAVI were associated with sheath size (OR 1.36, 95% CI 1.08-1.76, P 0.01) and strongly associated with CT-derived necrotic core volume in the common femoral artery of the procedural side (OR 17.49, 95% CI 1.21-226.60, P 0.03). CONCLUSION: Plaque map analysis of the common femoral artery by CT angiography reveals patients with greater necrotic core are at increased risk of VARC-3 vascular complications. ADVANCES IN KNOWLEDGE: The novel measurement of necrotic core volume in the common femoral artery on the procedural side by CT analysis was associated with post-TAVI vascular complications, which can be used to highlight increased risk.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Femoral Artery/diagnostic imaging , Femoral Artery/surgery , Retrospective Studies , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Tomography, X-Ray Computed , Treatment Outcome , Aortic Valve
8.
Br J Radiol ; 96(1147): 20220982, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37183910

ABSTRACT

OBJECTIVES: Ruptured carotid plaque causes stroke, but differentiating rupture-prone necrotic core from fibrous tissue with CT is limited by overlap of X-ray attenuation. We investigated the ability of CT-derived plaque maps created from ratios of plaque/contrast attenuation to identify histologically proven vulnerable plaques. METHODS: Seventy patients underwent carotid CT angiography and carotid endarterectomy. A derivation cohort of 20 patients had CT images matched with histology and carotid plaque components attenuation defined. In a validation cohort of 50 patients, CT-derived plaque maps were compared in 43 symptomatic vs 40 asymptomatic carotid plaques and accuracy detecting vulnerable plaques calculated. RESULTS: In 250 plaque areas co-registered with histology, the median attenuation (HU) of necrotic core 43(26-63), fibrous plaque 127(110-162) and calcified plaque 964 (816-1207) created significantly different ratios of plaque/contrast attenuation. CT-derived plaque maps revealed symptomatic plaques had larger necrotic core than asymptomatic (13.5%(5.9-33.3) vs 7.4%(2.3-14.3), p = 0.004) with large necrotic core predicting symptoms (area under ROC curve 0.68, p = 0.004). Twenty-four of 47 carotid plaques were histologically classified as most vulnerable (Starry-Type VI). Plaque maps revealed Type VI plaques had a greater necrotic core volume than Type IV/V plaques and a necrotic core/fibrous plaque ratio >0.5 distinguished Type VI plaques with sensitivity 75.0% (55.1-88.0) and specificity of 39.1% (22.2-59.2). CONCLUSIONS: Carotid plaque components can be differentiated by CT using a ratio of plaque/contrast attenuation. CT-derived plaque map volumes of necrotic core help distinguished the most vulnerable plaques. ADVANCES IN KNOWLEDGE: CT-derived plaque maps based on plaque/contrast attenuation may provide new markers of carotid plaque vulnerability.


Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Plaque, Atherosclerotic , Stroke , Humans , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Carotid Arteries/diagnostic imaging , Fibrosis , Tomography, X-Ray Computed/methods , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/pathology
9.
Future Cardiol ; 19(6): 353-361, 2023 05.
Article in English | MEDLINE | ID: mdl-37449460

ABSTRACT

Aim: Bifurcation-PCI is performed frequently, although without extensive evidence to back up a definitive solution for its complexity. We set out to identify factors associated with 1- and 12-month mortality after bifurcation-PCI between 2017 and 2021 in our tertiary center in Wales, UK. Results: Of 732 bifurcation PCI cases (mean age 69; 25% female), 67% were in ACS, 42% were left main PCI and 25.3% involved two-stent strategy. 30-day and 12-month mortality were 1.9 and 8.2%, respectively. Age, diabetes, smoking and renal failure are associated with mortality after bifurcation-PCI, while the choice between provisional and 2-stent strategies did not impact mortality/TLR. Conclusion: Awareness of 'real-world' outcomes of bifurcation-PCI should be used for appropriate patient selection, technique planning and procedural consent.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Female , Aged , Male , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention/methods , Coronary Angiography , Risk Factors , Treatment Outcome , Stents
10.
Clin Imaging ; 101: 69-76, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37311397

ABSTRACT

BACKGROUND: Coronary computed tomography angiography (CCTA) can identify high-risk coronary plaque types. However, the inter-observer variability for high-risk plaque features, including low attenuation plaque (LAP), positive remodelling (PR), and the Napkin-Ring sign (NRS), may reduce their utility, especially amongst less experienced readers. METHODOLOGY: In a prospective study, we compared the prevalence, location and inter-observer variability of both conventional CT-defined high-risk plaques with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using individualised X-ray attenuation cut-offs (the CT-defined thin-cap fibroatheroma - CT-TCFA) in 100 patients followed-up for 7 years. RESULTS: In total, 346 plaques were identified in all patients. Seventy-two (21%) of all plaques were classified by conventional CT parameters as high-risk (either NRS or PR and LAP combined), and 43 (12%) of plaques were considered high-risk using the novel CT-TCFA definition of (Necrotic Core/fibrous plaque ratio of >0.9). The majority (80%) of the high-risk plaques (LAP&PR, NRS and CT-TCFA) were located in the proximal and mid-LAD and RCA. The kappa co-efficient of inter-observer variability (k) for NRS was 0.4 and for PR and LAP combined 0.4. While the kappa co-efficient of inter-observer variability (k) for the new CT-TCFA definition was 0.7. During follow-up, patients with either conventional high-risk plaques or CT-TCFAs were significantly more likely to have MACE (Major adverse cardiovascular events) compared to patients without coronary plaques (p value 0.03 & 0.03, respectively). CONCLUSION: The novel CT-TCFA is associated with MACE and has improved inter-observer variability compared with current CT-defined high-risk plaques.


Subject(s)
Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography , Coronary Angiography/methods , Prospective Studies , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Predictive Value of Tests , Tomography, X-Ray Computed , Fibrosis , Chest Pain , Necrosis/pathology
11.
Clin Appl Thromb Hemost ; 29: 10760296221131563, 2023.
Article in English | MEDLINE | ID: mdl-36994631

ABSTRACT

BACKGROUND: Unfavourable clot microstructure is associated with adverse outcomes in ST elevation myocardial infarction (STEMI). We investigated the effect of comorbidities and anti-platelet treatment on clot microstructure in STEMI patients using fractal dimension (df), a novel biomarker of clot microstructure derived from the visco-elastic properties of whole blood. METHODS: Patients with STEMI (n = 187) were recruited sequentially receiving aspirin with Clopidogrel (n = 157) then Ticagrelor (n = 30). Patient characteristics and blood for rheological analysis obtained. We quantified df using sequential frequency sweep tests to obtain the phase angle of the Gel Point which is synonymous with the clot microstructure. RESULTS: Higher df was observed in males (1.755 ± 0.068) versus females (1.719 ± 0.061, p = .001), in patients with diabetes (1.786 ± 0.067 vs 1.743 ± 0.046, p < .001), hypertension (1.760 ± 0.065 vs 1.738 ± 0.069, p = .03) and previous MI (1.787 ± 0.073 vs 1.744 ± 0.066, p = .011) compared to without. Patients receiving Ticagrelor had lower df than those receiving Clopidogrel (1.708 ± 0.060 vs 1.755 ± 0.067, p < .001). Significant correlation with df was found with haematocrit (r = 0.331, p < .0001), low-density lipoprotein (LDL) (r = 0.155, p = .046) and fibrinogen (r = 0.182, p = .014). Following multiple regression analysis, diabetes, LDL, fibrinogen and haematocrit remained associated with higher df while treatment with Ticagrelor remained associated with lower df. CONCLUSIONS: The biomarker df uniquely evaluates the effect of interactions between treatment and underlying disease on clot microstructure. STEMI patients with diabetes and elevated LDL had higher df, indicating denser clot. Ticagrelor resulted in a lower df than Clopidogrel signifying a less compact clot.


Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Thrombosis , Male , Female , Humans , Ticagrelor/therapeutic use , Clopidogrel/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/etiology , Thrombosis/etiology , Biomarkers , Fibrinogen , Treatment Outcome , Percutaneous Coronary Intervention/adverse effects
12.
Arterioscler Thromb Vasc Biol ; 31(9): 2157-64, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21680897

ABSTRACT

OBJECTIVE: Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. METHODS AND RESULTS: One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01-1.53; P=0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02-1.39; P=0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1ß and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. CONCLUSIONS: Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.


Subject(s)
Coronary Artery Disease/etiology , Inflammation/etiology , Leukocytes/metabolism , Plaque, Atherosclerotic/etiology , Telomere , Ultrasonography, Interventional , Cellular Senescence , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/immunology , Cytokines/metabolism , Humans , Lymphocytes/immunology , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/immunology , Risk , Risk Factors
13.
Angiology ; 73(2): 139-145, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34459224

ABSTRACT

We investigated the predictors, aetiology and long-term outcomes of acute kidney injury (AKI) following urgent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Acute kidney injury occurred in 198 (7.2%) of 2917 patients: 14.1% of AKI cases were attributed to cardiogenic shock and 5.1% were classified as atheroembolic renal disease (AERD). Significant risk factors for AKI included age (odds ratio [OR] 1.05, 95% confidence limits [CI] 1.03-1.06), diabetes (OR 1.73, 95% CI 1.20-2.47), hypertension (OR 1.43, 95% CI 1.03-2.00), heart failure (OR 3.01, 95% CI 1.58-5.57), femoral access (OR 1.50, 95% CI 1.03-2.15), cardiogenic shock (OR 2.03, 95% CI 1.19-3.37) and ST-elevation myocardial infarction (STEMI) (OR 3.89, 95% CI 2.80-5.47). One-year mortality after AERD was 44.4% and renal replacement therapy (RRT) requirement 22.2% (compared with mortality 33.3% and RRT requirement 7.4%, respectively, in all other AKI patients). Mortality at 1 year was associated with AKI (OR 4.33, 95% CI 2.89-6.43), age (OR 1.08, 95% CI 1.06-1.09), heart failure (OR 1.92, 95% CI 1.05-3.44), femoral access (OR 2.05, 95% CI 1.41-2.95) and cardiogenic shock (OR 3.63, 95% CI 2.26-5.77). Acute kidney injury after urgent PCI is strongly associated with worse outcomes. Atheroembolic renal disease has a poor outcome and a high likelihood of long-term RRT requirement.


Subject(s)
Acute Coronary Syndrome , Acute Kidney Injury , Percutaneous Coronary Intervention , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/therapy , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Contrast Media , Humans , Incidence , Percutaneous Coronary Intervention/adverse effects , Risk Factors
14.
Open Heart ; 9(2)2022 07.
Article in English | MEDLINE | ID: mdl-35790317

ABSTRACT

Automated external defibrillators (AEDs) and implantable cardioverter defibrillators (ICDs) are used to treat life-threatening arrhythmias. AEDs and ICDs use shock advice algorithms to classify ECG tracings as shockable or non-shockable rhythms in clinical practice. Machine learning algorithms have recently been assessed for shock decision classification with increasing accuracy. Outside of rhythm classification alone, they have been evaluated in diagnosis of causes of cardiac arrest, prediction of success of defibrillation and rhythm classification without the need to interrupt cardiopulmonary resuscitation. This review explores the many applications of machine learning in AEDs and ICDs. While these technologies are exciting areas of research, there remain limitations to their widespread use including high processing power, cost and the 'black-box' phenomenon.


Subject(s)
Cardiopulmonary Resuscitation , Defibrillators, Implantable , Arrhythmias, Cardiac , Artificial Intelligence , Electric Countershock/adverse effects , Humans
15.
PLoS One ; 17(2): e0264529, 2022.
Article in English | MEDLINE | ID: mdl-35213664

ABSTRACT

AIMS: To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients. METHODS & FINDINGS: A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data. CONCLUSION: Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.


Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Depression/pathology , Triglycerides/blood , Aged , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/surgery , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Percutaneous Coronary Intervention , Practice Guidelines as Topic , Retrospective Studies , Risk Factors , Sex Factors , Societies, Medical , Wales
16.
Eur J Prev Cardiol ; 28(8): 854-861, 2021 07 23.
Article in English | MEDLINE | ID: mdl-34298561

ABSTRACT

AIMS: European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients. METHODS: We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge. RESULTS: Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target. CONCLUSION: There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Percutaneous Coronary Intervention , Aftercare , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipids , Patient Discharge , Percutaneous Coronary Intervention/adverse effects , Retrospective Studies
18.
Eur Heart J Case Rep ; 4(6): 1-4, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33442598

ABSTRACT

BACKGROUND: Iatrogenic right coronary artery (RCA) injury is a rare complication of tricuspid valve annuloplasty. Given that surgical intervention is increasingly favoured for tricuspid regurgitation, it is of great importance to recognize potential complications following tricuspid valve surgery. CASE SUMMARY: A 72-year-old man underwent surgical mitral and tricuspid valve repair. The early post-operative course was complicated by recurrent ventricular fibrillation episodes. Due to haemodynamic instability, a re-sternotomy and another cardiopulmonary bypass run were required. The patient subsequently underwent coronary angiography study which confirmed RCA occlusion. The occluded posterior left ventricular (PLV) branch was reopened by balloon angioplasty. However, despite multiple attempts it was not possible to pass a coronary guide wire into the posterior descending artery (PDA). An intravascular ultrasound examination revealed that the ostium of the PDA was compressed by external factors leaving a narrow slit-like appearance with no accessible lumen. Subsequently, a drug-eluting stent was placed into the PLV branch. The PDA was not accessible on repeated re-canalization attempts. The patient later successfully recovered from the right ventricular myocardial infarction. DISCUSSION: Right coronary artery occlusion should be considered as a differential diagnosis for significant rhythm disturbances and haemodynamic instability in the peri- and post-operative period following tricuspid valve annuloplasty. A low threshold for diagnostic angiography is needed to avoid potential delay in life-saving revascularization.

19.
JRSM Cardiovasc Dis ; 9: 2048004020967578, 2020.
Article in English | MEDLINE | ID: mdl-33224482

ABSTRACT

INTRODUCTION: Fractional flow reserve (FFR) improves assessment of the physiological significance of coronary lesions compared with conventional angiography. However, it is an invasive investigation. We tested the performance of a virtual FFR (1D-vFFR) using routine angiographic images and a rapidly performed reduced order computational model. METHODS: Quantitative coronary angiography (QCA) was performed in 102 with coronary lesions assessed by invasive FFR. A 1D-vFFR for each lesion was created using reduced order (one-dimensional) computational flow modelling derived from conventional angiographic images and patient specific estimates of coronary flow. The diagnostic accuracy of 1D-vFFR and QCA derived stenosis was compared against the gold standard of invasive FFR using area under the receiver operator characteristic curve (AUC). RESULTS: QCA revealed the mean coronary stenosis diameter was 44% ± 12% and lesion length 13 ± 7 mm. Following angiography calculation of the 1DvFFR took less than one minute. Coronary stenosis (QCA) had a significant but weak correlation with FFR (r = -0.2, p = 0.04) and poor diagnostic performance to identify lesions with FFR <0.80 (AUC 0.39, p = 0.09), (sensitivity - 58% and specificity - 26% at a QCA stenosis of 50%). In contrast, 1D-vFFR had a better correlation with FFR (r = 0.32, p = 0.01) and significantly better diagnostic performance (AUC 0.67, p = 0.007), (sensitivity - 92% and specificity - 29% at a 1D-vFFR of 0.7). CONCLUSIONS: 1D-vFFR improves the determination of functionally significant coronary lesions compared with conventional angiography without requiring a pressure-wire or hyperaemia induction. It is fast enough to influence immediate clinical decision-making but requires further clinical evaluation.

20.
Catheter Cardiovasc Interv ; 74(7): 1126-8, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19642199

ABSTRACT

Selective coronary angiography in severely dilated ascending aorta is technically challenging and sometimes impossible. The Terumo "five-in-six" system uses an extra long 5Fr guide catheter in a standard 6Fr guide catheter, so that the tip of the 5Fr guide catheter protrudes beyond the tip of the 6Fr catheter allowing an extra reach. This system has been used successfully to advance balloon catheters across chronic total occlusions (Takahashi et al, Catheter Cardiovasc Interv 2004;63:452-456) and stent delivery beyond proximal obstruction point (Mamas et al, Catheter Cardiovasc Interv 2008;71:358-363). We describe the successful use of this system in an atraumatic manner for selective coronary angiography in a patient with a severely dilated ascending aorta.


Subject(s)
Aorta/pathology , Cardiac Catheterization/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Aged , Aorta/surgery , Aortography , Blood Vessel Prosthesis Implantation , Coronary Artery Bypass , Coronary Artery Disease/surgery , Dilatation, Pathologic , Female , Humans
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