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From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events: JACC State-of-the-Art Review.
It has been believed that most acute coronary events result from the rupture of mildly stenotic plaques, based on studies in which angiographic information was available from many months to years before the event. However, serial studies in which angiographic data were available from the past as also within 1 to 3 months of myocardial infarction have clarified that nonobstructive lesions progressively enlarged relatively rapidly before the acute event occurred. Noninvasive computed tomography angiography imaging data have confirmed that lesions that did not progress voluminously over time rarely led to events, regardless of the extent of luminal stenosis or baseline high-risk plaque morphology. Therefore, plaque progression could be proposed as a necessary step between early, uncomplicated atherosclerosis and plaque rupture. On the other hand, it has been convincingly demonstrated that intensive lipid-lowering therapy (to a low-density lipoprotein cholesterol level of <70 mg/dl) halts plaque progression. Given the current ability to noninvasively detect the presence of early atherosclerosis, the importance of plaque progression in the pathogenesis of myocardial infarction, and the efficacy of maximum lipid-lowering therapy, it has been suggested that plaque progression is a modifiable step in the evolution of atherosclerotic plaque. A personalized approach based on the detection of early atherosclerosis can trigger the necessary treatment to prevent plaque progression and hence plaque instability. Therefore, this approach can redefine the traditional paradigm of primary and secondary prevention based on population-derived risk estimates and can potentially improve long-term outcomes.
Role of computed tomography cardiac angiography in acute chest pain syndromes.
Use of CT coronary angiography (CTCA) to evaluate chest pain has rapidly increased over the recent years. While its utility in the diagnosis of coronary artery disease in stable chest pain syndromes is clear and is strongly endorsed by international guidelines, the role of CTCA in the acute setting is less certain. In the low-risk setting, CTCA has been shown to be accurate, safe and efficient but inherent low rates of adverse events in this population and the advent of high-sensitivity troponin testing have left little room for CTCA to show any short-term clinical benefit.In higher-risk populations, CTCA has potential to fulfil a gatekeeper role to invasive angiography. The high negative predictive value of CTCA is maintained while also identifying non-obstructive coronary disease and alternative diagnoses in the substantial group of patients presenting with chest pain who do not have type 1 myocardial infarction. For those with obstructive coronary disease, CTCA provides accurate assessment of stenosis severity, characterisation of high-risk plaque and findings associated with perivascular inflammation. This may allow more appropriate selection of patients to proceed to invasive management with no disadvantage in outcomes and can provide a more comprehensive risk stratification to guide both acute and long-term management than routine invasive angiography.
The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis.
VEGF-A activity is tightly regulated by ligand and receptor availability. Here we investigate the physiological function of heterodimers between VEGF receptor-1 (VEGFR-1; Flt-1) and VEGFR-2 (KDR; Flk-1) (VEGFR(1-2)) in endothelial cells with a synthetic ligand that binds specifically to VEGFR(1-2). The dimeric ligand comprises one VEGFR-2-specific monomer (VEGF-E) and a VEGFR-1-specific monomer (PlGF-1). Here we show that VEGFR(1-2) activation mediates VEGFR phosphorylation, endothelial cell migration, sustained in vitro tube formation and vasorelaxation via the nitric oxide pathway. VEGFR(1-2) activation does not mediate proliferation or elicit endothelial tissue factor production, confirming that these functions are controlled by VEGFR-2 homodimers. We further demonstrate that activation of VEGFR(1-2) inhibits VEGF-A-induced prostacyclin release, phosphorylation of ERK1/2 MAP kinase and mobilization of intracellular calcium from primary endothelial cells. These findings indicate that VEGFR-1 subunits modulate VEGF activity predominantly by forming heterodimer receptors with VEGFR-2 subunits and such heterodimers regulate endothelial cell homeostasis.
Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.
BACKGROUND: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology. METHODS AND RESULTS: Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle-induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein. CONCLUSIONS: These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies.
BACKGROUND: An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2-2.6 microm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles. RESULTS: The particle size distribution was unaltered by the concentrator over the size range 0.2-2.6 microm, with an average enrichment factor during this study of approximately 5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition. CONCLUSION: These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2-2.6 microm after passage through the VACES concentration instrumentation.
Deep learning estimation of three-dimensional left atrial shape from two-chamber and four-chamber cardiac long axis views.
AIMS: Left atrial volume is commonly estimated using the bi-plane area-length method from two-chamber (2CH) and four-chamber (4CH) long axes views. However, this can be inaccurate due to a violation of geometric assumptions. We aimed to develop a deep learning neural network to infer 3D left atrial shape, volume and surface area from 2CH and 4CH views. METHODS AND RESULTS: A 3D UNet was trained and tested using 2CH and 4CH segmentations generated from 3D coronary computed tomography angiography (CCTA) segmentations (n = 1700, with 1400/100/200 cases for training/validating/testing). An independent test dataset from another institution was also evaluated, using cardiac magnetic resonance (CMR) 2CH and 4CH segmentations as input and 3D CCTA segmentations as the ground truth (n = 20). For the 200 test cases generated from CCTA, the network achieved a mean Dice score value of 93.7%, showing excellent 3D shape reconstruction from two views compared with the 3D segmentation Dice of 97.4%. The network also showed significantly lower mean absolute error values of 3.5 mL/4.9 cm2 for LA volume/surface area respectively compared to the area-length method errors of 13.0 mL/34.1 cm2 respectively (P < 0.05 for both). For the independent CMR test set, the network achieved accurate 3D shape estimation (mean Dice score value of 87.4%), and a mean absolute error values of 6.0 mL/5.7 cm2 for left atrial volume/surface area respectively, significantly less than the area-length method errors of 14.2 mL/19.3 cm2 respectively (P < 0.05 for both). CONCLUSIONS: Compared to the bi-plane area-length method, the network showed higher accuracy and robustness for both volume and surface area.
Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology.
OBJECTIVES: With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively. BACKGROUND: The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation. METHODS: We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0). RESULTS: Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498). CONCLUSIONS: 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).
Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E(-/-) mice.
Glutathione is a vital intracellular antioxidant. The enzymes involved in its synthesis and utilisation are tightly regulated, but the importance of glutathione regulation in atherogenesis is poorly understood. Here, we establish that glutathione is severely (approximately 80%) depleted very early (10 weeks) in the atheroma-prone aortic arch of male apoprotein E-deficient (Apo-E(-/-)) mice compared to age-matched wild-type controls. Importantly, this event pre-empts lipid peroxidation and detectable atheroma by several months. Depletion of glutathione was associated with excessive oxidant burden and reduced transcription and activity of the rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine ligase, together with the glutathione-dependent antioxidant enzyme, glutathione peroxidase. Depletion via reduced synthesis of glutathione precedes lipid peroxidation and atherogenesis in Apo-E(-/-) mice. We suggest that glutathione deficiency is central to the failure of the intracellular antioxidant defences and is causally implicated in the pathogenesis of atherosclerosis. Modification of the glutathione pathway may present a novel and important therapeutic target in the prevention and treatment of atherosclerosis.
miR-96 and miR-183 differentially regulate neonatal and adult postinfarct neovascularization.
Following myocardial infarction (MI), the adult heart has minimal regenerative potential. Conversely, the neonatal heart can undergo extensive regeneration, and neovascularization capacity was hypothesized to contribute to this difference. Here, we demonstrate the higher angiogenic potential of neonatal compared with adult mouse cardiac endothelial cells (MCECs) in vitro and use this difference to identify candidate microRNAs (miRs) regulating cardiac angiogenesis after MI. miR expression profiling revealed miR-96 and miR-183 upregulation in adult compared with neonatal MCECs. Their overexpression decreased the angiogenic potential of neonatal MCECs in vitro and prevented scar resolution and neovascularization in neonatal mice after MI. Inversely, their inhibition improved the angiogenic potential of adult MCECs, and miR-96/miR-183-KO mice had increased peri-infarct neovascularization. In silico analyses identified anillin (ANLN) as a direct target of miR-96 and miR-183. In agreement, Anln expression declined following their overexpression and increased after their inhibition in vitro. Moreover, ANLN expression inversely correlated with miR-96 expression and age in cardiac ECs of cardiovascular patients. In vivo, ANLN+ vessels were enriched in the peri-infarct area of miR-96/miR-183-KO mice. These findings identify miR-96 and miR-183 as regulators of neovascularization following MI and miR-regulated genes, such as anillin, as potential therapeutic targets for cardiovascular disease.
Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions.
BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 microg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05). CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease.
BACKGROUND: Reliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity. OBJECTIVES: This study assessed whether 18F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification. METHODS: Patients with known coronary artery disease underwent 18F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA). RESULTS: In a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary 18F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p 1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction. CONCLUSIONS: In patients with established coronary artery disease, 18F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.
Incidence, Microbiology, and Outcomes in Patients Hospitalized With Infective Endocarditis.
BACKGROUND: Despite improvements in management, infective endocarditis remains associated with high mortality and morbidity. We describe temporal changes in the incidence, microbiology, and outcomes of infective endocarditis and the effect of changes in national antibiotic prophylaxis guidelines on incident infective endocarditis. METHODS: Using a Scotland-wide, individual-level linkage approach, all patients hospitalized with infective endocarditis from 1990 to 2014 were identified and linked to national microbiology, prescribing, and morbidity and mortality datasets. Linked data were used to evaluate trends in the crude and age- and sex-adjusted incidence and outcomes of infective endocarditis hospitalizations. From 2008, microbiology data and associated outcomes adjusted for patient demographics and comorbidity were also analyzed. An interrupted time series analysis was performed to evaluate incidence before and after changes to national antibiotic prophylaxis guidelines. RESULTS: There were 7638 hospitalizations (65±17 years, 51% females) with infective endocarditis. The estimated crude hospitalization rate increased from 5.3/100 000 (95% CI, 4.8-5.9) to 8.6/100 000 (95% CI, 8.1-9.1) between 1990 and 1995 but remained stable thereafter. There was no change in crude incidence following the 2008 change in antibiotic prophylaxis guidelines (relative risk of change 1.06 [95% CI, 0.94-1.20]). The incidence rate in patients >80 years of age doubled from 1990 to 2014 (17.7/100 000 [95% CI, 13.4-23.3] to 37.9/100 000 [95% CI, 31.5-45.5]). The predicted 1-year age- and comorbidity-adjusted case fatality rate for a 65-year-old patient decreased in women (27.3% [95% CI, 24.6-30.2] to 23.7% [95% CI, 21.1-26.6]) and men (30.7% [95% CI, 27.7-33.8] to 26.8% [95% CI, 24.0-29.7]) from 1990 to 2014. Blood culture data were available from 2008 (n=2267/7638, 30%), with positive blood cultures recorded in 42% (950/2267). Staphylococcus (403/950, 42.4%) and streptococcus (337/950, 35.5%) species were most common. Staphylococcus aureus and enterococcus had the highest 1-year mortality (adjusted odds ratio 4.34 [95% CI, 3.12-6.05] and 3.41 [95% CI, 2.04-5.70], respectively). CONCLUSIONS: Despite changes in antibiotic prophylaxis guidelines, the crude incidence of infective endocarditis has remained stable. However, the incidence rate has doubled in the elderly. Positive blood cultures were observed in less than half of patients, with Staphylococcus aureus and enterococcus bacteremia associated with worse outcomes.
Inhaled Nanoparticles Accumulate at Sites of Vascular Disease.
The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.
Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome.
CONTEXT: Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve clinical outcomes in patients with suspected acute coronary syndrome (ACS). OBJECTIVE: To determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes. DESIGN, SETTING, AND PATIENTS: All consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, before (n = 1038; February 1-July 31, 2008, during the validation phase) and after (n = 1054; February 1-July 31, 2009, during the implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/mL with a sensitive troponin I assay were stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and ≥0.20 ng/mL). During the validation phase, only concentrations above the original diagnostic threshold of 0.20 ng/mL were reported to clinicians. MAIN OUTCOME MEASURE: Event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations. RESULTS: Plasma troponin concentrations were less than 0.05 ng/mL in 1340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P < .001) or 0.20 ng/mL or more (P = .007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; 95% confidence interval, 0.24-0.84; P = .01). CONCLUSIONS: In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.
Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction.
BACKGROUND: Effective endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium. Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial dysfunction. We therefore examined the effects of cigarette smoking on substance P-induced tPA release in vivo in humans. METHODS AND RESULTS: Blood flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent increases in blood flow and local release of plasma tPA antigen and activity (P<0.001 for all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers, increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and activity (P<0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA antigen and activity decreased by 51% and 53%, respectively. CONCLUSIONS: Cigarette smoking causes marked inhibition of substance P-induced tPA release in vivo in humans. This provides an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.
Cost-effectiveness of rapid assessment of potential ischaemic heart disease with CT coronary angiography.
OBJECTIVES: To estimate the cost-effectiveness of early CT coronary angiography (CTCA) for intermediate risk patients with suspected acute coronary syndrome (ACS), compared with standard care METHODS: We performed within-trial economic analysis using data from the RAPID-CTCA randomised trial, and long-term modelling of cost-effectiveness using secondary data sources to estimate the cost-effectiveness of early CTCA compared with standard care for patients with suspected ACS attending acute hospitals in the UK. Cost-effectiveness was estimated as the incremental cost per quality-adjusted life year (QALY) gained, and the probability of each strategy being cost-effective at varying willingness-to-pay per QALY gained. RESULTS: The within-trial analysis showed that there were no demonstrable differences in costs or QALYs between early CTCA and standard care, with point estimates suggesting higher costs (£7414 vs £6845: mean difference £569, 95% CI -£208 to £1335; p=0.1521) and lower QALYs (0.749 vs 0.758, mean difference -0.009, 95% CI -0.026 to 0.010; p=0.377) in the CTCA arm. The long-term economic analysis suggested that, on average, CTCA was slightly less effective than standard care alone with 0.025 quality-adjusted life years lost per patient treated and was more expensive with additional costs of £481 per patient treated. At a threshold of £20 000 per QALY, CTCA has 24% probability of being cost-effective. CONCLUSIONS: There are no demonstrable differences in within-trial costs and QALYs, and long-term cost-effectiveness modelling suggested higher long-term costs with CTCA and uncertain effect on long-term QALYs, making routine use of CTCA for suspected ACS unlikely to be a cost-effective use of NHS resources.
Diagnostic Strategies for the Evaluation of Chest Pain: Clinical Implications From SCOT-HEART and PROMISE.
SCOT-HEART (Scottish COmputed Tomography of the HEART) and PROMISE (PROspective Multicenter Imaging Study for Evaluation of chest pain) represent the 2 largest and most comprehensive cardiovascular imaging outcome trials in patients with stable chest pain and provide significant insights into patient diagnosis, management, and outcomes. These trials are particularly timely, given the well-recognized knowledge gaps and widespread use of noninvasive imaging. The overall goal of this review is to distill the data generated from these 2 pivotal trials to better inform the practicing clinician in the selection of noninvasive testing for stable chest pain. Similarities and differences between SCOT-HEART and PROMISE are highlighted, and clinical and practical implications are discussed. Both trials show that coronary computed tomography angiography should have a greater role in the diagnostic pathway of patients with stable chest pain.