Anoop Shah

Global association of air pollution and heart failure: a systematic review and meta-analysis

Summary Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality. Methods Five databases were searched for studies investigating the association between daily increases in gaseous (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate (diameter <2·5 μm [PM2·5] or <10 μm [PM10]) air pollutants, and heart failure hospitalisations or heart failure mortality. We used a random-effects model to derive overall risk estimates per pollutant. Findings Of 1146 identified articles, 195 were reviewed in-depth with 35 satisfying inclusion criteria. Heart failure hospitalisation or death was associated with increases in carbon monoxide (3·52% per 1 part per million; 95% CI 2·52–4·54), sulphur dioxide (2·36% per 10 parts per billion; 1·35–3·38), and nitrogen dioxide (1·70% per 10 parts per billion; 1·25–2·16), but not ozone (0·46% per 10 parts per billion; −0·10 to 1·02) concentrations. Increases in particulate matter concentration were associated with heart failure hospitalisation or death (PM2·5 2·12% per 10 μg/m3, 95% CI 1·42–2·82; PM10 1·63% per 10 μg/m3, 95% CI 1·20–2·07). Strongest associations were seen on the day of exposure, with more persistent effects for PM2·5. In the USA, we estimate that a mean reduction in PM2·5 of 3·9 μg/m3 would prevent 7978 heart failure hospitalisations and save a third of a billion US dollars a year. Interpretation Air pollution has a close temporal association with heart failure hospitalisation and heart failure mortality. Although more studies from developing nations are required, air pollution is a pervasive public health issue with major cardiovascular and health economic consequences, and it should remain a key target for global health policy. Funding British Heart Foundation.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

BACKGROUND The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). METHODS In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. FINDINGS In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001). INTERPRETATION (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. FUNDING Chief Scientist Office Scotland and British Heart Foundation.

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.

High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study.

Objective To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary syndrome. Design Prospective cohort study. Setting Regional cardiac centre, United Kingdom. Participants Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care. Main outcome measure Diagnosis of myocardial infarction. Results The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 for both). At 12 months, women with undisclosed increases in troponin concentration (17-49 ng/L) and those with myocardial infarction (≥50 ng/L) had the highest rate of death or reinfarction compared with women without (≤16 ng/L) myocardial infarction (25%, 24%, and 4%, respectively; P<0.001). Conclusions Although having little effect in men, a high sensitivity troponin assay with sex specific diagnostic thresholds may double the diagnosis of myocardial infarction in women and identify those at high risk of reinfarction and death. Whether use of sex specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention.

High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study

Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers. Funding British Heart Foundation and Chief Scientist Office (Scotland).

Short term exposure to air pollution and stroke: systematic review and meta-analysis

Objective To review the evidence for the short term association between air pollution and stroke. Design Systematic review and meta-analysis of observational studies Data sources Medline, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science searched to January 2014 with no language restrictions. Eligibility criteria Studies investigating the short term associations (up to lag of seven days) between daily increases in gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate matter (<2.5 µm or <10 µm diameter (PM2.5 and PM10)), and admission to hospital for stroke or mortality. Main outcome measures Admission to hospital and mortality from stroke. Results From 2748 articles, 238 were reviewed in depth with 103 satisfying our inclusion criteria and 94 contributing to our meta-estimates. This provided a total of 6.2 million events across 28 countries. Admission to hospital for stroke or mortality from stroke was associated with an increase in concentrations of carbon monoxide (relative risk 1.015 per 1 ppm, 95% confidence interval 1.004 to 1.026), sulphur dioxide (1.019 per 10 ppb, 1.011 to 1.027), and nitrogen dioxide (1.014 per 10 ppb, 1.009 to 1.019). Increases in PM2.5 and PM10 concentration were also associated with admission and mortality (1.011 per 10 μg/m3 (1.011 to 1.012) and 1.003 per 10 µg/m3 (1.002 to 1.004), respectively). The weakest association was seen with ozone (1.001 per 10 ppb, 1.000 to 1.002). Strongest associations were observed on the day of exposure with more persistent effects observed for PM2·5. Conclusion Gaseous and particulate air pollutants have a marked and close temporal association with admissions to hospital for stroke or mortality from stroke. Public and environmental health policies to reduce air pollution could reduce the burden of stroke. Systematic review registration PROSPERO-CRD42014009225.

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

Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.

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High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis.

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Left Ventricular Hypertrophy with Strain and Aortic Stenosis

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)