National Trends in Coronary Artery Disease Imaging: Associations With Health Care Outcomes and Costs.

BACKGROUND: In 2016, the National Institute for Health and Care Excellence Clinical Guideline Number 95 ("Chest pain of recent onset") (CG95) recommended coronary computed tomography angiography (CCTA) as the first-line test for possible angina. OBJECTIVES: The purpose of this study was to determine the impact of temporal trends in imaging use on outcomes for coronary artery disease (CAD) following the CG95 recommendations. METHODS: Investigations from 2012 to 2018 were extracted from a national database and linked to hospital admission and mortality registries. Growth rates were adjusted for population size, with image modality use, cardiovascular hospital admissions, and mortality compared using Kendall's rank correlation. The impact of CG95 was assessed using an interrupted time-series analysis. RESULTS: A total of 1,909,314 investigations for CAD were performed, with an annualized per capita growth of 4.8%. Costs were £0.35 million/100,000 population/year with an increase of 2.8%/year mirroring inflation (2.5%/year). CG95 was associated with a rise in CCTA (exp[ß]: 1.10; 95% CI: 1.03-1.18), no change in myocardial perfusion imaging, and a potential modest fall (exp[ß]: 0.997; 95% CI: 0.993-1.00]) in invasive coronary angiography. There was an apparent trend between computed tomography angiography growth and invasive catheter angiography reduction across regions (Kendall Tau: -0.19; P = 0.08). CCTA growth was associated with a reduction in cardiovascular mortality (Kendall Tau: -0.21; P = 0.045), and ischemic heart disease deaths (Kendall Tau: -0.22; P = 0.042), with an apparent trend with reduced all-cause mortality (Kendall Tau: -0.19; P = 0.07). CONCLUSIONS: Imaging investigations for CAD are increasing. Greater regional increases in CCTA were associated with fewer hospitalizations for myocardial infarction and a more rapid decline in CAD mortality.

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.

Assessment of Oxygen Supply-Demand Imbalance and Outcomes Among Patients With Type 2 Myocardial Infarction: A Secondary Analysis of the High-STEACS Cluster Randomized Clinical Trial.

Importance: Type 2 myocardial infarction occurs owing to multiple factors associated with myocardial oxygen supply-demand imbalance, which may confer different risks of adverse outcomes. Objective: To evaluate the prevalence and outcomes of different factors associated with oxygen supply-demand imbalance among patients with type 2 myocardial infarction. Design, Setting, and Participants: In this secondary analysis of a stepped-wedge, cluster randomized clinical trial conducted at 10 secondary and tertiary care hospitals in Scotland, 6096 patients with an adjudicated diagnosis of type 1 or type 2 myocardial infarction from June 10, 2013, to March 3, 2016, were identified, and the findings were reported on August 28, 2018. The trial enrolled consecutive patients with suspected acute coronary syndrome. The diagnosis of myocardial infarction was adjudicated according to the Fourth Universal Definition of Myocardial Infarction and the primary factor associated with oxygen supply-demand imbalance in type 2 myocardial infarction was defined. This secondary analysis was not prespecified. Statistical analysis was performed from July 7 to 30, 2020. Intervention: Implementation of a high-sensitivity cardiac troponin I assay. Main Outcomes and Measures: All-cause death at 1 year according to the factors associated with oxygen supply-demand imbalance among patients with type 2 myocardial infarction. Results: Of 6096 patients (2602 women [43%]; median age, 70 years [IQR, 58-80 years]), 4981 patients had type 1 myocardial infarction, and 1115 patients had type 2 myocardial infarction. The most common factor associated with oxygen supply-demand imbalance was tachyarrhythmia (616 of 1115 [55%]), followed by hypoxemia (219 of 1115 [20%]), anemia (95 of 1115 [9%]), hypotension (89 of 1115 [8%]), severe hypertension (61 of 1115 [5%]), and coronary mechanisms (35 of 1115 [3%]). At 1 year, all-cause mortality occurred for 15% of patients (720 of 4981) with type 1 myocardial infarction and 23% of patients (285 of 1115) with type 2 myocardial infarction. Compared with patients with type 1 myocardial infarction, those with type 2 myocardial infarction owing to hypoxemia (adjusted odds ratio [aOR], 2.35; 95% CI, 1.72-3.18) and anemia (aOR, 1.83; 95% CI, 1.14-2.88) were at greatest risk of death, whereas those with type 2 myocardial infarction owing to tachyarrhythmia (aOR, 0.83; 95% CI, 0.65-1.06) or coronary mechanisms (aOR, 1.07; 95% CI, 0.17-3.86) were at similar risk of death as patients with type 1 myocardial infarction. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, mortality after type 2 myocardial infarction was associated with the underlying etiologic factor associated with oxygen supply-demand imbalance. Most type 2 myocardial infarctions were associated with tachyarrhythmia, with better prognosis, whereas hypoxemia and anemia accounted for one-third of cases, with double the mortality of type 1 myocardial infarction. These differential outcomes should be considered by clinicians when determining which cases need to be managed if patient outcomes are to improve. Trial Registration: ClinicalTrials.gov Identifier: NCT01852123.

Estimates of the global burden of cervical cancer associated with HIV.

BACKGROUND: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. METHODS: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. FINDINGS: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. INTERPRETATION: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. FUNDING: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.

Adverse health effects associated with household air pollution: a systematic review, meta-analysis, and burden estimation study.

BACKGROUND: 3 billion people worldwide rely on polluting fuels and technologies for domestic cooking and heating. We estimate the global, regional, and national health burden associated with exposure to household air pollution. METHODS: For the systematic review and meta-analysis, we systematically searched four databases for studies published from database inception to April 2, 2020, that evaluated the risk of adverse cardiorespiratory, paediatric, and maternal outcomes from exposure to household air pollution, compared with no exposure. We used a random-effects model to calculate disease-specific relative risk (RR) meta-estimates. Household air pollution exposure was defined as use of polluting fuels (coal, wood, charcoal, agricultural wastes, animal dung, or kerosene) for household cooking or heating. Temporal trends in mortality and disease burden associated with household air pollution, as measured by disability-adjusted life-years (DALYs), were estimated from 2000 to 2017 using exposure prevalence data from 183 of 193 UN member states. 95% CIs were estimated by propagating uncertainty from the RR meta-estimates, prevalence of household air pollution exposure, and disease-specific mortality and burden estimates using a simulation-based approach. This study is registered with PROSPERO, CRD42019125060. FINDINGS: 476 studies (15·5 million participants) from 123 nations (99 [80%] of which were classified as low-income and middle-income) met the inclusion criteria. Household air pollution was positively associated with asthma (RR 1·23, 95% CI 1·11-1·36), acute respiratory infection in both adults (1·53, 1·22-1·93) and children (1·39, 1·29-1·49), chronic obstructive pulmonary disease (1·70, 1·47-1·97), lung cancer (1·69, 1·44-1·98), and tuberculosis (1·26, 1·08-1·48); cerebrovascular disease (1·09, 1·04-1·14) and ischaemic heart disease (1·10, 1·09-1·11); and low birthweight (1·36, 1·19-1·55) and stillbirth (1·22, 1·06-1·41); as well as with under-5 (1·25, 1·18-1·33), respiratory (1·19, 1·18-1·20), and cardiovascular (1·07, 1·04-1·11) mortality. Household air pollution was associated with 1·8 million (95% CI 1·1-2·7) deaths and 60·9 million (34·6-93·3) DALYs in 2017, with the burden overwhelmingly experienced in low-income and middle-income countries (LMICs; 60·8 million [34·6-92·9] DALYs) compared with high-income countries (0·09 million [0·01-0·40] DALYs). From 2000, mortality associated with household air pollution had reduced by 36% (95% CI 29-43) and disease burden by 30% (25-36), with the greatest reductions observed in higher-income nations. INTERPRETATION: The burden of cardiorespiratory, paediatric, and maternal diseases associated with household air pollution has declined worldwide but remains high in the world's poorest regions. Urgent integrated health and energy strategies are needed to reduce the adverse health impact of household air pollution, especially in LMICs. FUNDING: British Heart Foundation, Wellcome Trust.

Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events. METHODS: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair. RESULTS: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]). CONCLUSION: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria.

Background Sex-specific criteria are recommended for the diagnosis of myocardial infarction, but the impact of these on presenting characteristics is unknown. Methods and Results We evaluated patient-reported symptoms in 1941 patients (39% women) with suspected acute coronary syndrome attending the emergency department in a substudy of a prospective trial. Standardized criteria defined typical and atypical presentations based on pain nature, location, radiation, and additional symptoms. Diagnosis of myocardial infarction was adjudicated using a high-sensitivity cardiac troponin I assay with sex-specific thresholds (>16 ng/L women, >34 ng/L men). Patients identified who were missed by the contemporary assay with a uniform threshold (≥50 ng/L) were reclassified by this approach. Type 1 myocardial infarction was diagnosed in 16% (184/1185) of men and 12% (90/756) of women, with 9 (5%) men and 27 (30%) women reclassified using high-sensitivity cardiac troponin I and sex-specific thresholds. Chest pain was the presenting symptom in 91% (1081/1185) of men and 92% (698/756) of women. Typical symptoms were more common in women than in men with myocardial infarction (77% [69/90] versus 59% [109/184]; P=0.007), and differences were similar in those reclassified (74% [20/27] versus 44% [4/9]; P=0.22). The presence of ≥3 typical features was associated with a positive likelihood ratio for the diagnosis of myocardial infarction in women (positive likelihood ratio, 1.18; 95% CI, 1.03-1.31) but not in men (positive likelihood ratio 1.09; 95% CI, 0.96-1.24). Conclusions Typical symptoms are more common and have greater predictive value in women than in men with myocardial infarction whether or not they are diagnosed using sex-specific criteria. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier NCT01852123.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study.

BACKGROUND: More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. FINDINGS: Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. INTERPRETATION: HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries. FUNDING: British Heart Foundation and Wellcome Trust.

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

BACKGROUND: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV. METHODS: We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV. RESULTS: In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho. CONCLUSIONS: People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease.

BACKGROUND: In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). OBJECTIVES: The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. METHODS: In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. RESULTS: Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621). CONCLUSIONS: In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

Systematic review and meta-analysis of out-of-hospital cardiac arrest and race or ethnicity: black US populations fare worse.

BACKGROUND: Several studies have reported racial/ethnic variation in out-of-hospital cardiac arrest (OOHCA) characteristics, which engendered varying conclusions. We performed a systematic review and meta-analysed the evidence for differences in OOHCA survival when considering the patient's race and/or ethnicity. METHODS: We searched Medline and EMBASE databases up to and including 1 Oct 2011 for studies investigating racial/ethnic differences in OOHCA characteristics, supplemented by manual searches of bibliographies of relevant studies. We selected studies of any relevant design that measured OOHCA characteristics and stratified them by ethnic group. Two independent reviewers extracted information on the study population, including: race and/or ethnicity, location, age and OOHCA variables as per the Utsein template. We performed a meta-analysis of the studies comparing the black and white patients. RESULTS: 1701 potentially relevant articles were identified in our systematic search. Of these, 22 articles describing original studies were reviewed after fulfilling our inclusion criteria. Although 19 studies (18 within the United States (US)) compared the black and white population, only 15 fulfilled our quality assessment criteria and were meta-analysed. Compared to white patients, black patients were less likely to receive bystander cardiopulmonary resuscitation (OR = 0.66, 95%CI = 0.55-0.78), have a witnessed arrest (OR = 0.77, 95%CI = 0.72-0.83) or have an initial ventricular fibrillation/ventricular tachycardia arrest rhythm (OR = 0.66, 95%CI = 0.58-0.76). Black patients had lower rates of survival following hospital admission (OR = 0.59, 95%CI = 0.48-0.72) and discharge (OR = 0.74, 95%CI = 0.61-0.90). CONCLUSION: Our work highlights the significant discrepancy in OOHCA characteristics and patient survival in relation to the patient's race, with the black population faring less well across all stages. Most studies compared black and white populations within the US, so research elsewhere and with other ethnic groups is needed. This review exposes an inequality that demands urgent action.