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Background The linkage of primary care, hospital and other health registry data is a global goal, and a consent-based approach is often used. Understanding the attitudes of why participants take part is important, yet little is known about reasons for non-participation. The ATHENA COVID-19 feasibility study investigated: 1) health outcomes of people diagnosed with COVID-19 in Queensland, Australia through primary care health data linkage using consent, and 2) created a cohort of patients willing to be re-contacted in future to participate in clinical trials. This report describes the characteristics of participants declining to participate and reasons for non-consent. Methods Patients diagnosed with COVID-19 from January 1st, 2020, to December 31st, 2020, were invited to consent to having their primary healthcare data extracted from their GP into a Queensland Health database and linked to other data sets for ethically approved research. Patients were also asked to consent to future recontact for participation in clinical trials. Outcome measures were proportions of patients consenting to data extraction, permission to recontact, and reason for consent decline. Results 996 participants were approached and 853(86%) reached a consent decision. 581(69%), 623(73%) and 567(67%) consented to data extraction, recontact, or both, respectively. Mean (range) age of consenters and non-consenters were 50.6(range) and 46.1(range) years, respectively. Adjusting for age, gender and remoteness, older participants were more likely to consent than younger (aOR 1.02, 95%CI 1.01 to 1.03). The least socio-economically disadvantaged were more likely to consent than the most disadvantaged (aOR 2.20, 95% 1.33 to 3.64). There was no difference in consent proportions regarding gender or living in more remote regions. The main reasons for non-consent were ‘not interested in research’ (37%), ‘concerns about privacy’ (15%), ‘not registered with a GP’ (8%) and ‘too busy/no time’ (7%). ‘No reason’ was given in 20%. Conclusion Younger participants and the more socio-economically deprived are more likely to non-consent to primary care data linkage. Lack of patient interest in research, time required to participate and privacy concerns, were the most common reasons cited for non-consent. Future health care data linkage studies addressing these issues may prove helpful. Trial registration details: not applicable

Objective/background: Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. Methods: Twenty-two men with small diameter AAAs (36 ± 5 mm; mean age 74 ± 6 years) and 22 healthy adults (mean age 72 ± 5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. Results: At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). Conclusion: High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.

Background: To date, there are limited Australian data on characteristics of people diagnosed with COVID-19 and on how these characteristics relate to outcomes. The ATHENA COVID-19 Study was established to describe health outcomes and investigate predictors of outcomes for all people diagnosed with COVID-19 in Queensland by linking COVID-19 notification, hospital, general practice and death registry data. This paper reports on the establishment and first findings for the ATHENA COVID-19 Study. Methods: Part 1 of the ATHENA COVID-19 Study used Notifiable Conditions System data from 1 January 2020 to 31 December 2020, linked to: Emergency Department Collection data for the same period; Queensland Health Admitted Patient Data Collections (from 1 January 2010 to 30 January 2021); and Deaths Registrations data (from 1 January 2020 to 17 January 2021). Results: To 31 December 2020, a total of 1,254 people had been diagnosed with SARS-CoV-2 infection in Queensland: half were female (49.8%); two-thirds (67.7%) were aged 20–59 years; and there was an over-representation of people living in less-disadvantaged areas. More than half of people diagnosed (57.6%) presented to an ED; 21.2% were admitted to hospital as an inpatient (median length of stay 11 days); 1.4% were admitted to an intensive care unit (82.4% of these required ventilation); and there were six deaths. Analysis of factors associated with these outcomes was limited due to small case numbers: people living in less-disadvantaged areas had a lower risk of being admitted to hospital (test for trend, p < 0.001), while those living in more remote areas were less likely than people living in major cities to present to an ED (test for trend: p=0.007), which may reflect differential health care access rather than health outcomes per se. Increasing age (test for trend, p < 0.001) and being a current/recent smoker (age-sex-adjusted relative risk: 1.61; 95% confidence interval: 1.00, 2.61) were associated with a higher risk of being admitted to hospital. Conclusion: Despite uncertainty in our estimates due to small numbers, our findings are consistent with what is known about COVID-19. Our findings reinforce the value of linking multiple data sources to enhance reporting of outcomes for people diagnosed with COVID-19 and provide a platform for longer term follow-up.

Stress echocardiography is an established cardiac imaging modality for the detection and quantification of severity of coronary artery disease. In recent years, there has also been an increasing use of stress echocardiography in the assessment of non-ischaemic cardiac disease given its ability to assess functional capacity and haemodynamic changes with exercise which can help guide therapy and inform prognosis. The emerging use of strain, myocardial contrast and three-dimensional (3D) echocardiography further assists in improving diagnostic accuracy particularly in patients with coronary artery disease. This paper summarises the protocols, indications and clinical applications of stress echocardiography in both ischaemic and non-ischaemic cardiac disease.

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.

ObjectivesTo describe (1) absolute cardiovascular disease risk (ACVDR) scores in patients presenting to hospital with acute coronary syndrome (ACS) and (2) proportions of these patients on guideline-recommended pharmacotherapy according to their ACVDR score.DesignCross-sectional study.SettingSingle-site tertiary centre hospital, Queensland, Australia over a 12-month period.ParticipantsPatients >18 years of age presenting to hospital with ACS due to coronary artery disease (CAD) confirmed by angiography.Primary and secondary outcome measuresProportion of patients without prior history of CVD with a high ACVDR score, and of patients with a prior history of CVD, who are on guideline-recommended pharmacotherapy.Results527 ACS patients were included of whom the mean age was 63 years and 75% were male. Overall, 66% (350) had no prior CVD and 34% (177) patients had prior CVD.In patients with no prior CVD, the proportions of patients with low, intermediate and high CVD risk scores were 41%, 24% and 36%. In the no prior CVD, high-risk patient group, 48% were on no preventative pharmacotherapy, 32% on single pharmacotherapy and 20% patients on complete guideline-recommended pharmacotherapy. In the prior CVD group, 7% patients were on no pharmacotherapy, 40% on incomplete pharmacotherapy and 53% were on complete guideline-recommended pharmacotherapy.ConclusionThis study adds to the evidence on implementation gaps in guideline-recommended management of ACVDR, showing that a large proportion of patients presenting with ACS due to CAD were at high risk of developing CVD prior to the event and most were not on guideline-recommended treatment. A significant proportion of these events are likely to have been preventable, and therefore, increased assessment and appropriate treatment of ACVDR in primary care is needed to reduce the incidence of CVD events in the population.

Impairments in skeletal muscle microvascular function are frequently reported in patients with various cardiometabolic conditions for which older age is a risk factor. Whether aging per se predisposes the skeletal muscle to microvascular dysfunction is unclear. We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. Test–retest reliability of CEU perfusion parameters was also assessed. Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: (a) 5‐min of thigh‐cuff occlusion, and (b) 5‐min of submaximal intermittent isometric plantar‐flexion exercise (400 N) using CEU. Whole‐leg blood flow was measured using strain‐gauge plethysmography. Repeated measures were obtained with a 15‐min interval, and averaged responses were used for comparisons between age groups. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05). The overall level of agreement between the test–retest measures of calf muscle perfusion was excellent for measurements taken at rest (intraclass correlation coefficient [ICC] 0.85), and in response to cuff occlusion (ICC 0.89) and exercise (ICC 0.95). Our findings suggest that healthy aging does not affect muscle perfusion responses to cuff‐occlusion and submaximal leg exercise. CEU muscle perfusion parameters measured in response to these provocation tests are highly reproducible in both young and older adults., We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05).

New Findings: What is the central question of the study? Cuff-occlusion duration may influence contrast-enhanced ultrasound (CEUS) assessments of skeletal muscle microvascular blood flow responsiveness: what are the effects of 1, 3 and 5 min cuff-occlusion on the magnitude and reliability of calf muscle microvascular blood flow responsiveness in older adults? What is the main finding and its importance? Calf muscle microvascular blood flow responsiveness was enhanced following 5 min cuff-occlusion compared with 1 min. The reliability of post-occlusion CEUS measurements was also improved following 5 min occlusion. The use of a standardized 5 min occlusion period should therefore be considered in future studies and clinical practice. Abstract: Contrast-enhanced ultrasound (CEUS) is increasingly used in assessments of skeletal muscle microvascular blood flow responsiveness. In response to limb cuff-occlusion, some studies have reported significant impairments in CEUS measurements of microvascular blood flow in older adults with cardiovascular or metabolic disease, whereas others have failed to detect significant between-group differences, which has brought the reliability of the technique into question. In the absence of a standardized CEUS protocol, there is variance in the duration of cuff-occlusion used, which is likely to influence post-occlusion measurements of muscle microvascular blood flow. We aimed to determine the effect of cuff-occlusion duration by comparing the magnitude and reliability of CEUS measurements of calf muscle microvascular blood flow responsiveness in older adults (n = 15, 67 ± 11 years) following 1, 3 and 5 min occlusion periods. Microvascular blood flow (= microvascular volume × microvascular velocity) within the calf muscle was measured using real-time destruction–replenishment CEUS. Measurements were made following thigh cuff-occlusion (200 mmHg) periods of 1, 3 and 5 min in a random order. Microvascular blood flow was higher following 3 min (3.71 ± 1.46 aU s−1) and 5 min (3.47 ± 1.48 aU s−1) compared with 1 min (2.42 ± 1.27 aU s−1, P = 0.002), which corresponded with higher microvascular volumes after 3 and 5 min compared with 1 min. Reliability was good following 5 min (intraclass correlation coefficient (ICC) 0.49) compared with poor following 1 min (ICC 0.34) and 3 min (ICC 0.35). This study demonstrates that the magnitude and reliability of calf muscle microvascular responsiveness is enhanced using a 5 min cuff-occlusion protocol compared with 1 min in older adults.

BackgroundIncomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion.MethodsThe MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length.ResultsExperiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02).ConclusionsPresence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this.

BACKGROUND: Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation. METHODS: 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay. RESULTS: Mean (±SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β=0.05, 95% CI: 0.02, 0.08, P=0.007), hs-CRP (β=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (β=1.03, CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (β=-0.87, CI: -1.44, -0.30, P=0.003), BMI (β=-0.11, CI: -0.21, -0.01, P=0.033), and LDL (β=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model. CONCLUSION: Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation.

Cardiovascular disease is associated with increased risk for cognitive decline and dementia, but it is unclear whether this risk varies across disease states or occurs in the absence of symptomatic stroke. To examine the evidence of increased risk for cognitive decline and dementia following non-stroke cardiovascular disease we conducted two independent meta-analyses in accordance with PRISMA guidelines. The first review examined cardiovascular diagnoses (atrial fibrillation, congestive heart failure, periphery artery disease and myocardial infarction) while the second review assessed the impact of atherosclerotic burden (as indicated by degree of stenosis, calcification score, plaque morphology or number of plaques). Studies eligible for review longitudinally assessed risk for clinically significant cognitive decline and/or dementia and excluded stroke and cognitive impairment at baseline. Summary statistics were computed via the inverse variance weighted method, utilising Cox Proportional Hazards data (Hazard Ratios, HR). Both atrial fibrillation (n = 5, HR = 1.26, 95% CI [1.12, 1.43]) and severe atherosclerosis (n = 4, HR = 1.59, 95% CI [1.12, 2.26]) emerged as significant risk factors for cognitive decline and/or dementia. A small set of studies reviewed, insufficient for meta-analysis, examining congestive heart failure, peripheral artery disease and myocardial infarction suggested that these conditions may also be associated with an increased risk of cognitive decline/dementia. In the absence of stroke, patients with atrial fibrillation or generalised atherosclerosis are at heightened risk for cognitive deterioration. Nonetheless, this paper highlights the need for methodologically rigorous and prospective investigation of the relationship between CVD and dementia.

We performed real-time myocardial contrast echocardiography on a patient with cardiac amyloidosis and previous normal coronary angiography presenting with atypical chest pain to assess myocardial blood flow reserve (MBFR). Myocardial contrast echocardiography was performed and flash microbubble destruction and replenishment analysis was used to calculate myocardial blood flow. Dipyridamole was used to achieve hyperemia. MBFR was derived from the ratio of peak myocardial blood flow at hyperemia and rest. The results show a marked reduction in MBFR in our patient. Previous reports of luminal obstruction of intramyocardial rather than epicardial vessels by amyloid deposition may be causing microvascular dysfunction.

Objectives The Manchester Acute Coronary Syndromes (MACS) decision rule has been shown to be a powerful diagnostic tool in emergency department (ED) patients with suspected acute coronary syndromes (ACS). It has the potential to improve system efficiency by identifying patients suitable for discharge after a single blood draw for high-sensitivity troponin and heart-type fatty acid–binding protein (h-FABP) analysis at presentation to the ED. The objective was to externally validate the MACS decision rule and establish its diagnostic accuracy as a discharge tool in a new set of prospectively recruited ED patients. Methods In this preplanned analysis of a prospectively recruited single-center cohort, consecutive ED patients ≥18 years with suspected ACS were included. Testing for h-FABP and high-sensitivity troponin T was undertaken on serum drawn on arrival, and any clinical features required to calculate the MACS rule were recorded. The primary outcome was major adverse cardiac events (MACE) within 30 days (acute myocardial infarction [AMI], death, or revascularization). The secondary outcome was AMI alone, adjudicated using 6-hour troponin results. Results Of the 782 participants included, 78 (10.0%) developed MACE and 61 (7.8%) had an AMI. Of participants, 133 (17.0%) were identified as “very low risk” and therefore suitable for immediate discharge with a 0% incidence of MACE or AMI. Of remaining patients, 314 (40.2%) were “low risk,” 320 (40.9%) were “moderate risk,” and 15 (1.9%) were “high risk,” with incidences of MACE of 2.2, 19.7, and 53.3%, respectively. The sensitivity was 100% (95% confidence interval [CI] = 95.4% to 100%) for MACE at 30 days and 100% (95% CI = 94.1% to 100%) for AMI. The area under the receiver operating characteristic curve was 0.87 (95% CI = 0.83 to 0.91) for the MACS rule in the prediction of MACE. Conclusions In this prospectively recruited cohort of ED patients with suspected ACS, the MACS decision rule identifies a significant proportion of patients who are suitable for immediate discharge after a single blood draw at presentation, with a very low risk of MACE at 30 days. This study externally validates previous findings that the MACS rule is a powerful diagnostic tool in this setting. A randomized controlled trial to establish the utility of the rule in an everyday clinical setting is justified.

ObjectivesTo describe general practitioners’ (GPs’) absolute cardiovascular disease risk (ACVDR) self-reported assessment practices and their relationship to knowledge, attitudes and beliefs about ACVDR.DesignCross-sectional survey with opportunistic sampling (October–December 2017).SettingSunshine Coast region, Queensland, Australia.Participants111 GPs responded to the survey.Primary and secondary outcome measuresProportion of GPs reporting a high (≥80%) versus moderate (60%–79%)/low (ResultsOf the 111 respondents, 78% reported using the Australian ACVDR calculator; 45% reported high, 25% moderate and 30% low ACVDR assessment rates; >85% reported knowing how to use ACVDR assessment tools, believed assessment valuable and were comfortable with providing guideline-recommended treatment. Around half believed patients understood the concept of high risk and were willing to adopt recommendations. High assessment rates (vs moderate/low) were less likely among older GPs (≥45 vs ≤34 years, age-adjusted and sex-adjusted OR (aOR) 0.36, 95% CI 0.12 to 0.97). Those who answered knowledge-based questions about the guidelines incorrectly had lower assessment rates, including those who answered questions on patient eligibility (aOR 0.13, 95% CI 0.02 to 1.11). A high assessment rate was more likely among GPs who believed there was sufficient time to do the assessment (aOR 3.79, 95% CI 1.23 to 11.61) and that their patients were willing to undertake lifestyle modification (aOR 2.29, 95% CI 1.02 to 5.15). Over 75% of GPs agreed better patient education, nurse-led assessment and computer-reminder prompts would enable higher assessment rates.ConclusionsAlthough the majority of GPs report using the ACVDR calculator when undertaking a CVD risk assessment, there is a need to increase the actual proportion of eligible patients undergoing ACVDR assessment. This may be achieved by improving GP assessment practices such as GP and patient knowledge of CVD risk, providing sufficient time and nurse-led assessment.

Objective Epicardial fat (EF) is metabolically active adipose tissue positioned between the epicardial surface of the heart and the pericardium. We investigated whether there is a relationship between EF and Coronary Microvascular Dysfunction (CMD) in patients presenting with chest pain and unobstructed coronary arteries. Materials and Methods This study recruited patients referred to cardiology clinics for assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Myocardial blood flow reserve (MBFR) was assessed using myocardial contrast echocardiography. Epicardial fat volume (EFV) was measured by tracing serial slices on CTA with corresponding Hounsfield units of −195 to −45. Results We recruited 134 participants with a mean age of 59.2 (9.8) years. CMD was present in 54 (40%) patients, and the measured mean EFV was 128 mm3 (96, 168). Fortythree patients (32%) had a coronary artery calcium score (CACS) of 0, 64 (48%) had a CACS of 1–100, 18 (13%) had a CACS of 101–400, and 9 (7%) had a CACS >400. Univariate regression analysis showed that EFV and MBFR had a correlation coefficient of R=−0.22, with a significant regression slope (β=−0.002, p=0.012). Multivariable linear regression analysis using MBFR as a continuous outcome variable revealed age (β=−0.012, p=0.011) and CACS (β=−0.003, p=0.023) to be associated with MBFR. EFV was not associated with MBFR (β=−0.0007, p=0.538). Model repetition with MBFR as a dichotomous variable (MBFR ≥2 or

Increased arterial stiffness is observed with ageing and in individuals with low cardiorespiratory fitness ( $$\dot {V}$$ O2peak), and associated with cardiovascular risk. Following an exercise bout, transient arterial stiffness reductions offer short-term benefit, but may depend on exercise intensity. This study assessed the effects of exercise intensity on post-exercise arterial stiffness in older adults with varying fitness levels. Fifty-one older adults (72 ± 5 years) were stratified into fitness tertiles ( $$\dot {V}$$ O2peak: low-, 22.3 ± 3.1; mid-, 27.5 ± 2.4 and high-fit 36.3 ± 6.5 mL kg−1 min−1). In a randomised order, participants underwent control (no-exercise), moderate-intensity continuous exercise (40% of peak power output; PPO), and higher-intensity interval exercise (70% of PPO) protocols. Pulse wave velocity (PWV), augmentation index (AIx75) and reflection magnitude (RM) were assessed at rest and during 90 min of recovery following each protocol. After control, delta PWV increased over time (P

A 69-year old man presented with a 2-week history of back discomfort and fevers, having had bioprosthetic aortic valve replacement (AVR) for prosthetic valve infective endocarditis (PVE) 4-months ago. Past medical history included coronary artery bypass grafting in 2008, bioprosthetic AVR with root replacement for ascending aortic dissection in 2010, diabetes mellitus, and chronic renal impairment. In June 2016, he was admitted with Streptococcus mitis bacteraemia treated with 6 weeks of ceftriaxone. Transoesophageal echocardiography was negative for endocarditis and root abscess. In November 2016, the patient was admitted with heart failure secondary to new severe aortic regurgitation. Transoesophageal echocardiography showed dehiscence of the anterior leaflet of aortic valve prosthesis. Blood cultures were negative. He was commenced on vancomycin prior to re-do AVR and discharged on lifelong amoxycillin.

The vasodilatory effects of insulin may mitigate myocardial ischaemia, thus we conducted a series of experiments under hyperinsulinaemic euglycaemic conditions to determine how insulin infusion duration, insulin dose administered and type 2 diabetes (T2DM) affect myocardial blood flow reserve (MBFR

Inflammation and extracellular matrix degeneration contribute to abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of exercise intensity on circulating biomarkers of inflammation and extracellular matrix degeneration in patients with AAA and healthy older adults.Twenty patients with AAA (74 ± 6 yr) and 20 healthy males (72 ± 5 yr) completed moderate-intensity cycling at 40% peak power output, higher-intensity intervals at 70% peak power output, and control (rest) on separate days. Circulating matrix metalloproteinase-9 (MMP-9), transforming growth factor beta 1, interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were analyzed at rest and 0 to 90 min postexercise.Biomarkers at baseline were similar between groups. IL-6 responses to exercise were similar between groups, with a greater increase in ΔIL-6 after moderate-intensity compared with higher-intensity exercise (P0.001). Delta MMP-9 showed a 118-ng·mL (95% confidence interval = 23 to 214, P = 0.02) greater increase immediately after higher-intensity exercise compared with changes in control in both groups. Delta MMP-9 then decreased by 114 ng·mL (18 to 211, P = 0.02) 90 min after higher-intensity exercise compared with the changes in control. Delta TNF-α was not different between protocols in healthy adults. In patients with AAA, delta TNF-α showed a greater decrease after higher-intensity compared with moderate-intensity exercise (-6.1 pg·mL, -8.5 to -3.6, P0.001) and control (-4.9 pg·mL, -7.4 to -2.4, P0.001). IL-10 and transforming growth factor beta 1 did not change in either group.These findings suggest that a bout of higher-intensity exercise elicits a greater anti-inflammatory response compared with moderate-intensity exercise, which may be further augmented in patients with AAA. Exercise-induced reductions in biomarkers associated with AAA progression may represent a protective effect of exercise in patients with AAA.

Importance: High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain.Objective: To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome.Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017.Study Selection: Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction.Data Extraction and Synthesis: The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model.Main Outcomes and Measures: The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data.Results: Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death.Conclusions and Relevance: Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.

This review will provide an overview of supraventricular tachycardias (SVTs), their classification, diagnostic features, and management in the perioperative period of adult non-cardiac surgery. The term ‘SVT’ refers to paroxysmal tachyarrythmias that require atrial or atrioventricular (AV) nodal tissue, or both, for their initiation and maintenance. The incidence of persistent SVT is 2% before operation and 6% in the postoperative period. In non-cardiac surgery, perioperative arrhythmias are more likely to be supraventricular than ventricular in origin. Atrial arrhythmias occur most frequently 2–3 days post-surgery similar to perioperative acute coronary syndromes and are likely related to sympathetic stimulation associated with an inflammatory response. Other precipitants of SVT often associated with high sympathetic tone are summarized in Table 1. Such arrhythmias are important for the anaesthetist; in particular, atrial fibrillation (AF) is associated with haemodynamic derangement, postoperative stroke, perioperative myocardial infarction, ventricular arrhythmia, heart failure, and longer hospital stay.

Hypoglycaemia is associated with increased cardiovascular and all-cause mortality in both subjects with and without coronary artery disease (CAD) [1]. Our group recently demonstrated that insulin-induced hypoglycaemia (IIH) is associated with a 14% reduction of myocardial blood flow reserve (MBFR) compared to baseline, in both healthy subjects and those with type 1 diabetes mellitus (T1DM) [2]. Cardiac troponin is a sensitive marker of myocardial injury and higher levels have been linked to adverse outcomes in patients with ACS [3]. A new ultrasensitive cardiac troponin I (us-cTnI) has been developed which has a limit of detection of at least one order of magnitude lower below that of current commercial assays. In comparison with current generation troponin assays, us-cTnI has been shown to be more sensitive in the detection of myocardial ischaemia. Furthermore, low but elevated levels of us-cTnI in patients presenting with suspected ACS, have been linked to adverse cardiovascular outcomes and death [4]. This study investigated whether 60 min duration of symptomatic IIH and reduction in MBFR, was associated with myocardial injury as determined by a change in serum levels of us-cTnI measured immediately following hypoglycaemia, in healthy and diabetic subjects without obstructive CAD.

Summary A papillary fibroelastoma is a rare, avascular, cardiac tumour that is often found incidentally using transthoracic echocardiography (TTE). Peripheral i.v. injection of a microbubble contrast agent is often used to characterize abnormal masses within the heart allowing further delineation of physical features, the area of attachment, and vascularity of the mass in order to differentiate the growth from a tumour or a thrombus. This case highlights a potential pitfall when assessing a cardiac tumour's vascularity using contrast TTE. A cardiac mass was identified on a TTE of a 53-year-old man and was further investigated with microbubble contrast-enhanced TTE. Contrast TTE imaging suggested a vascularized structure in the left ventricle. However, after histological examination the tumour was found to be entirely avascular. Learning points Differentiation of cardiac tumour is usually best performed with contrast echocardiography. Contrast echocardiography may not be best tool to determine if cardiac mass is vascularized. A papillary fibroelastoma can appear vascularized with contrast echocardiography due to it's frond-like structures. Physicians should be aware of this potential confusion when assessing a cardiac tumour in patients.

Endothelial dysfunction is observed in patients with abdominal aortic aneurysm (AAA), who have increased risk of cardiovascular events and mortality. This study aimed to assess the acute effects of moderate- and higher-intensity exercise on endothelial function, as assessed by flow-mediated dilation (FMD), in AAA patients (74 ± 6 yr old, n = 22) and healthy adults (72 ± 5 yr old, n = 22). Participants undertook three randomized visits, including moderate-intensity continuous exercise [40% peak power output (PPO)], higher-intensity interval exercise (70% PPO), and a no-exercise control. Brachial artery FMD was assessed at baseline and at 10 and 60 min after each condition. Baseline FMD was lower [by 1.10% (95% confidence interval: 0.72−.81), P = 0.044] in AAA patients than in healthy adults. There were no group differences in FMD responses after each condition ( P = 0.397). FMD did not change after no-exercise control but increased by 1.21% (95% confidence interval: 0.69−1.73, P < 0.001) 10 min after moderate-intensity continuous exercise in both groups and returned to baseline after 60 min. Conversely, FMD decreased by 0.93% (95% confidence interval: 0.41−1.44, P < 0.001) 10 min after higher-intensity interval exercise in both groups and remained decreased after 60 min. We found that the acute response of endothelial function to exercise is intensity-dependent and similar between AAA patients and healthy adults. Our findings provide evidence that regular exercise may improve vascular function in AAA patients, as it does in healthy adults. Improved FMD after moderate-intensity exercise may provide short-term benefit. Whether the decrease in FMD after higher-intensity exercise represents an additional risk and/or a greater stimulus for vascular adaptation remains to be elucidated. NEW & NOTEWORTHY Abdominal aortic aneurysm patients have vascular dysfunction. We observed a short-term increase in vascular function after moderate-intensity exercise. Conversely, higher-intensity exercise induced a prolonged reduction in vascular function, which may be associated with both short-term increases in cardiovascular risk and signaling for longer-term vascular adaptation in abdominal aortic aneurysm patients.

The role of insulin in the treatment of acute coronary syndrome (ACS) has been widely studied over the past 100 years. The current indication for its use in this context is the treatment of hyperglycemia, irrespective of diabetes, which is associated with adverse outcome. Initial theories proposed that glucose was beneficial in the context of myocardial ischemia and insulin was required to enable glucose cell uptake. However, studies testing this hypothesis with routine insulin administration during ACS have produced disappointing results and research interest has therefore declined. We propose that the less well known but important vasodilator effect of insulin has been overlooked by some of these studies and warrants further consideration. Previous reports have shown that hyperinsulinemic euglycaemia improves myocardial blood flow reserve. With this in mind, this review considers the role of insulin in the context of ACS from the perspective of a vasodilator rather than a metabolic modulator. We discuss the importance of time to treatment, dosage of insulin administered, problems with hypoglycaemia and insulin resistance, and how they may have affected the outcomes of the major trials. Finally, we propose new study designs that allow determination of the optimal vasodilator conditions for the use of insulin as adjunctive pharmacotherapy during myocardial ischaemia.

An 82-year-old man with previous bioprosthetic aortic valve replacement for aortic stenosis had a routine ECG (figure 1). This was thought to represent an atrial tachycardia with cycle length 280 ms and 3:1 atrioventricular response. A diagnosis of atrial flutter was made based on tachycardia cycle length, p-wave morphology and previous cardiac surgery. He had a mild left-sided tremor in keeping with known Parkinson's disease. The patient was anticoagulated and admitted electively for an electrophysiology (EP) study. In the EP laboratory, the patient had …

To the Editor: Several issues around rule-out strategies utilizing low concentrations of high-sensitivity cardiac troponin assays taken at presentation to the Emergency Department (ED)1 remain unexplored. First, large-scale analyses investigating cutoff concentrations for high-sensitivity cardiac troponin I (hs-cTnI; Abbott Architect)

Cardiorenal syndrome (CRS) is the umbrella term used to describe clinical conditions in which cardiac and renal dysfunctions coexist. Much has been written on this subject, but underlying pathophysiological mechanisms continue to be unravelled and implications for management continue to be debated. A classification system—incorporating five subtypes—has recently been proposed though it has yet to permeate into day-to-day clinical practice. CRS has garnered much attention from both the cardiological and nephrological communities since the condition is associated with significant morbidity and mortality. Renal dysfunction is highly prevalent amongst patients with heart failure and has been shown to be as powerful and independent a marker of adverse prognosis as ejection fraction. Similarly, patients with renal failure are considerably more likely to suffer cardiovascular disease than matched subjects from the general population. This paper begins by reviewing the epidemiology and classification of CRS before going on to consider the different pathological mechanisms underlying cardiorenal dysfunction. We then focus on management strategies and conclude by discussing future directions in the diagnosis and management of patients suffering with CRS.

Impaired left ventricular systolic function secondary to sepsis can occur in up to 20% of patients with septic shock. The electrocardiogram (ECG) and echocardiographic changes it produces can be very similar to those occurring during acute coronary syndromes (ACS). Myocardial contrast echocardiography (MCE) allows assessment of myocardial perfusion. This technique can be performed at the bedside of the critically unwell patient. We describe a patient presenting with septic shock secondary to pneumonia. While sedated and ventilated in the intensive care unit, the patient developed marked ECG changes, a troponin rise and widespread left ventricular wall motion abnormality. The clinical picture suggested ACS or stress cardiomyopathy was unlikely and was more in keeping with a diagnosis of sepsis-induced left ventricular systolic dysfunction. To support this, resting and flash impulse MCE was performed which revealed normal perfusion in areas of both normal and abnormal wall motion. This suggested that the cardiac presentation was more likely to be due to left ventricular impairment secondary to sepsis and ACS therapy was discontinued. Pre-discharge ECG and transthoracic echocardiogram were normal. Percutaneous coronary angiography 6 weeks later was also normal. This is the first described case of MCE being used to aid in the decision-making process in distinguishing between ACS, stress cardiomyopathy, and left ventricular systolic impairment secondary to sepsis.

Background Physicians rely upon chest pain history to make management decisions in patients with suspected acute coronary syndromes, particularly where the diagnosis is not immediately apparent through electrocardiography and troponin testing. The objective of this study was to establish the discriminatory value of "typicality of chest pain" and the effect of clinician experience, for the prediction of acute myocardial infarction and presence of significant coronary artery disease. Methods This prospective single-center observational study was undertaken in a UK General Hospital emergency department. We recruited consecutive adults with chest pain and a nondiagnostic electrocardiogram, for whom the treating physician determined that delayed troponin testing was necessary. Using their own clinical judgment, physicians recorded whether the chest pain described was typical or atypical for acute coronary syndrome. Physicians were defined as "experienced" or "novice" according to postgraduate experience. Acute myocardial infarction was adjudicated using a high-sensitivity troponin (hs-cTn) assay, whereas coronary artery disease was adjudicated angiographically. Results Overall, 912 patients had typicality of chest pain assessed, of whom 114/912 (12.5%) had an acute myocardial infarction and 157/912 (17.2%) underwent angiography. In patients undergoing angiography, 90/157 (57.3%) had hs-cTn elevation, of whom 60 (66.7%) had significant coronary artery disease. Sixty-seven of 157 (42.7%) patients had angiography without hs-cTn elevation; of these, 31 (46.2%) had significant coronary artery disease. For the diagnosis of acute myocardial infarction, chest pain typicality had an area under the curve (AUC) of 0.54 (95% confidence interval [CI], 0.49-0.60). For the prediction of significant coronary artery disease with hs-cTn elevation AUC: 0.54 (95% CI, 0.40-0.67), and without hs-cTn elevation AUC: 0.45 (95% CI, 0.31-0.59). When assessed by experienced physicians, specificity for the diagnosis of acute myocardial infarction was higher at 65.8% (95% CI, 63.1%-68.7%) vs 55.4% (95% CI, 53.9%-56.8%) for novices. Conclusions Subjective interpretation of "typicality of chest pain" is of limited discriminatory value in the assessment of suspected acute coronary syndromes, in the context of a nondiagnostic electrocardiogram. Greater clinical experience improves accuracy as a rule-in tool but does not improve overall discriminatory ability.

Objectives To establish the accuracy of emergency department (ED) nursing staff risk assessment using an established chest pain risk score alone and when incorporated with presentation high-sensitivity troponin testing as part of an accelerated diagnostic protocol (ADP). Design Prospective observational study comparing nursing and physician risk assessment using the modified Goldman (m-Goldman) score and a predefined ADP, incorporating presentation high-sensitivity troponin. Setting A UK District ED. Patients Consecutive patients, aged ≥18, with suspected cardiac chest pain and non-ischaemic ECG, for whom the treating physician determined serial troponin testing was required. Outcome measures 30-day major adverse cardiac events (MACE). Results 960 participants were recruited. 912/960 (95.0%) had m-Goldman scores recorded by physicians and 745/960 (77.6%) by nursing staff. The area under the curve of the m-Goldman score in predicting 30-day MACE was 0.647 (95% CI 0.594 to 0.700) for physicians and 0.572 (95% CI 0.510 to 0.634) for nursing staff (p=0.09). When incorporated into an ADP, sensitivity for the rule-out of MACE was 99.2% (95% CI 94.8% to 100%) and 96.7% (90.3% to 99.2%) for physicians and nurses, respectively. One patient in the physician group (0.3%) and three patients (1.1%) in the nursing group were classified as low risk yet had MACE. There was fair agreement in the identification of low-risk patients (kappa 0.31, 95% CI 0.24 to 0.38). Conclusions The diagnostic accuracy of ED nursing staff risk assessment is similar to that of ED physicians and interobserver reliability between assessor groups is fair. When incorporating high-sensitivity troponin testing, a nurse-led ADP has a miss rate of 1.1% for MACE at 30 days. Trial registration number Controlled Trials Database (ISRCTN no. 21109279).

STUDY OBJECTIVE: We compare the ability of 5 established risk scores to identify patients with suspected acute coronary syndromes who are suitable for discharge after a modified single-presentation high-sensitivity troponin result. METHODS: This was a prospective observational study conducted in a UK district general hospital emergency department. Consecutive adults recruited with suspected acute coronary syndrome for whom attending physicians determined evaluation with serial troponin testing was required. Index tests were definitions of low risk applied to modified Goldman, Thrombolysis in Myocardial Infarction (TIMI), Global Registry of Acute Cardiac Events (GRACE), History, ECG, Age, Risk Factors, Troponin (HEART), and Vancouver Chest Pain Rule risk scores, incorporating either high-sensitivity troponin T or I results. The endpoint was acute myocardial infarction within 30 days. A test sensitivity threshold for acute myocardial infarction of 98% was chosen. Clinical utility was defined as a negative predictive value greater than or equal to 99.5% and identification of greater than 30% suitable for discharge. RESULTS: Nine hundred fifty-nine patients underwent high-sensitivity troponin T analysis and 867 underwent high-sensitivity troponin I analysis. In the high-sensitivity troponin T group, 79 of 959 (8.2%) had an acute myocardial infarction and 66 of 867 (7.6%) in the high-sensitivity troponin I group. Two risk scores (GRACE

Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of

Aims To investigate whether the vasoconstrictor isoprostane \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{F}_{2\mathrm{{\alpha}}}\) \end{document}-III (iP\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{F}_{2\mathrm{{\alpha}}}\) \end{document}-III), released during myocardial reperfusion, contributes to the low/no reflow phenomenon observed following acute myocardial infarction (AMI). Methods and results Thirteen patients undergoing primary percutaneous coronary intervention (PCI) for AMI had iP\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{F}_{2\mathrm{{\alpha}}}\) \end{document}-III measured by high-performance liquid and gas chromatography–mass spectrometry. Isoprostane \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{F}_{2\mathrm{{\alpha}}}\) \end{document}-III concentrations were significantly higher following PCI than in controls (1.5±1.3 vs.16±0.06 nM, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{

Background: Angiographic flow measurements do not define perfusion accurately at a microvascular level, so other techniques which assess flow at a tissue level are to be preferred. Objectives: To compare intravenous myocardial contrast echocardiography (MCE) with other methods of assessing microvascular reperfusion for their ability to predict left ventricular function at one month after acute myocardial infarction. Design: 15 patients underwent primary percutaneous coronary angioplasty for acute myocardial infarction, with restoration of TIMI grade 3 flow. Corrected TIMI frame count (cTFC), myocardial blush grade (MBG), and percentage ST segment resolution at 90 and 180 minutes were recorded. Baseline regional wall motion score index (WMSI) and regional contrast score index (RCSI) were obtained 12–24 hours after the procedure, with a final regional WMSI assessment at one month. Results: Mean (SD) cTFC was 27 (9.4), and ST segment resolution was 69 (22)% at 90 minutes and 77 (20)% at 180 minutes. MBG values were 0 in six patients, 2 in two, and 3 in seven. Baseline regional WMSI, RCSI, and follow up WMSI were 2.7 (0.71), 1.5 (0.71), and 1.6 (0.73), respectively. The correlation coefficient between RCSI and follow up WMSI was 0.82 (p = 0.0012). Peak CK correlated with follow up WMSI (R = 0.80). None of the other reperfusion assessment techniques correlated significantly with follow up WMSI. Multiple regression analysis showed that a perfused hypokinetic or akinetic segment was 50 times more likely to recover function than a non-perfused segment. MCE predicted segmental myocardial recovery with a sensitivity of 88%, a specificity of 74%, and positive and negative predictive values of 83% and 81%, respectively. Conclusions: MCE is currently the best and most accurate measure of reperfusion at a microvascular level and an excellent predictor of left ventricular function at one month following acute myocardial infarction.

Background: Subclinical left ventricular dysfunction(LVD) is present in up to half of individuals with type 2 diabetes mellitus(T2DM) and is associated with adverse prognosis. The development of LVD and change in global longitudinal strain(GLS) over long-term follow-up in individuals with T2DM is unknown. Methods: 102 asymptomatic individuals (age 56 ± 8yrs) with T2DM underwent clinical review, blood tests and resting echocardiography at baseline and after a follow-up over 9yrs. Participants were free of ischaemic/valvular heart disease, and had normal ejection fraction(>50%). GLS was used to identify LVD (GLS worse than -18.9%). Results: After 9.4 ± 0.7 years(median), GLS decreased from -19.2 ± 2.3% to -17.4 ± 2.8% (p < 0.001) and there were more individuals with LVD (42% to 68%, p < 0.001). Those with poorer glycaemic control at follow-up (i.e. HbA1c≥7) had significant deterioration in GLS compared to those with optimal control (p = 0.039). Independent predictors of deteriorating GLS were age, weight, HbA1c and use of statins (p < 0.05 for all). Oral antidiabetic medications (including metformin) were protective (p < 0.001). Conclusion: Subclinical LVD is common in asymptomatic individuals with T2DM and progresses over long-term follow-up. Progression of LVD is associated with poor glycaemic control, advancing age, increases in body weight nd statin use, whereas diabetes therapy was protective. Therapeutic interventions in glycaemic control may prevent progression of LVD over long-term follow-up.

Background and Aims: Insulin is a potent vasodilator which acts via the endothelial nitrous oxide pathway. Supraphysiological hyperinsulinaemic euglycaemia has been shown to increase myocardial blood flow. However the optimal dose of parenteral insulin infusion to exert maximum vasodilatory effect on the coronary microcirculation is unknown. Therefore, we investigated the relationship between myocardial blood flow reserve (MBFR), a measure of coronary microvascular function, and insulin infusion dose. Method and Results: 21 healthy volunteers (mean age 66 yrs (range 47-79)) underwent hyperinsulinaemic euglycaemic (HE) clamps for 60 minutes (8, 5, and 8 participants received 0.5, 1.5, and 3.0 mU/kg/min insulin, respectively). Baseline demographic and biochemical indices were similar across all three groups. Low-power real-time myocardial contrast echocardiography with flash impulse imaging was performed using vasodilator dipyridamole stress to quantify MBFR at baseline, and at 60 minutes after commencing the HE clamp. Mean(SD) baseline MBFR values were 2.2(0.4), 2.5(0.2), and 2.6(0.3), and post-insulin MBFR's were 2.3(0.7), 3.4(0.8), and 2.2(0.3) in the 0.5, 1.5, and 3.0 mU/kg/min dose groups, respectively. This represents an increase in MBFR of 5% and 36% in the 0.5 and 1.5 insulin dose groups, and a decrease in MBFR of 15% in the 3.0 insulin dose group (p = 0.89, 0.04, 0.04, respectively). Conclusion: We observed a non-linear dose effect of insulin infusion dose on coronary microvascular dilatation in healthy volunteers. Of the 3 insulin doses tested, 0.5mU/kg/min had no effect, 1.5mU/kg/min resulted in a 36% increase, and 3.0mU/kg/min resulted in a 15% decrease, in MBFR.

We read with interest the paper published by Naya et al. [(1)][1], in which they suggest that global coronary flow reserve (CFR), and not coronary artery calcium, as assessed by positron emission tomographic (PET) myocardial perfusion imaging (MPI), provides significant incremental improved risk

Background and Aims: The vasodilator effect of insulin is incompletely understood. Previous insulin use in acute coronary syndrome trials have shown disappointing results. Our group has shown that hyperinsulinaemic euglycaemia increases myocardial blood flow reserve (MBFR) by 20% in healthy individuals. The time taken for hyperinsulinaemia to exert an effect on the coronary microcirculation is unknown. It is also not known whether this effect can diminish with time. This study investigated the relationship between hyperinsulinaemic clamp time on MBFR. Method & Results: Five healthy male volunteers (mean age 37 yrs (range 21-54)) underwent hyperinsulinaemic euglycaemic clamps. Low-power real-time myocardial contrast echocardiography was performed with flash impulse imaging using low-dose adenosine stress to measure MBFR at baseline. This was repeated at 30, 60, and 120 minutes after commencing insulin infusion at a fixed concentration of 1.5mU/kg/min. Mean(SD) baseline MBFR was 2.5(0.3). MBFR values at 30, 60 and 120 minutes were 3.1(0.8), 3.5(0.6), and 4.1(0.8), respectively. This represents an increase in MBFR of 24%, 40% and 64% with respect to baseline values. Mean fasting serum insulin was 2.3(1.8), 43.2(30.8), 50.6(20.9), and 45.8(21.5) mU/L, respectively. There was no significant difference between baseline and 30-minute MBFR (p=0.06). However there were significant increases in MBFR between baseline versus 60mins (p=0.009), and 60 versus 120mins (p=0.006). Conclusion: Hyperinsulinaemic euglycaemia increases MBFR significantly at 60 minutes of commencing hyperinsulinaemic clamps. This effect is maintained at 120 minutes.

IMPORTANCE: Low concentrations of high-sensitivity cardiac troponin I determined on presentation to the emergency department (ED) have been shown to have an excellent negative predictive value (NPV) for the identification of acute myocardial infarction. The sensitivity, and therefore clinical applicability, of such testing strategies is unknown.OBJECTIVE: To determine the diagnostic performance of low concentrations of high-sensitivity cardiac troponin I in patients with suspected cardiac chest pain and an electrocardiogram showing no ischemia as an indicator of acute myocardial infarction.DESIGN, SETTING, AND PARTICIPANTS: A pooled analysis of 5 international (Australia, New Zealand, and England) prospective, observational cohort studies with blinded outcome assessment and 30-day follow-up was conducted. A total of 3155 patients presenting with symptoms suggestive of cardiac ischemia were included in the analysis. Eligible patients had a nonischemic electrocardiogram determined and high-sensitivity troponin I measured at presentation. The lower limit of detection (1.2 ng/L) as well as cutoff concentrations rounded to the nearest integer for a high-sensitivity troponin I assay were used in the analysis. Recruitment was undertaken from November 1, 2007, to August 10, 2013.MAIN OUTCOMES AND MEASURES: The primary outcome was fatal or nonfatal acute myocardial infarction occurring within 30 days of ED presentation, adjudicated with serial troponin testing. The secondary outcome was the proportion of patients potentially suitable for early discharge at each cutoff concentration.RESULTS: Of the 3155 eligible patients, 1771 were male (56.1%), and mean (SD) age was 57.4 (13.3) years. Acute myocardial infarction developed in 291 individuals (9.2%). The 1.2-ng/L limit of detection gave a sensitivity of 99.0% (95% CI, 96.8%-99.7%) and an NPV of 99.5% (95% CI, 98.4%-99.9%). This cutoff level would allow for early discharge of 594 patients (18.8%). All higher rounded cutoff values had sensitivities less than 98.0%. Diagnostic performance of the limit of detection was maintained when patients were stratified by age, sex, risk factors, presence of coronary artery disease, and early presentation.CONCLUSIONS AND RELEVANCE: High-sensitivity troponin I concentrations determined at presentation to the ED that were below the limit of detection identified 18.8% of patients potentially suitable for discharge, with a high sensitivity for acute myocardial infarction. Rounded cutoff values above the limit of detection may not have the required sensitivity for clinical implementation.

Background: Clinical guidelines currently suggest that transthoracic echocardiography (TTE) be carried out in all patients with suspected endocarditis, but the use of TTE where there is a low probability of infective endocarditis has a poor diagnostic yield. This screening approach may no longer be appropriate. Objective: To examine whether clinical criteria might aid decision making with respect to the use of TTE in possible endocarditis. Design: A retrospective review of patient records. Setting: Cardiology department of a tertiary referral centre. Patients: 500 consecutive hospital inpatients referred for TTE to exclude endocarditis. Main outcome measures: Evidence of endocardial vegetations on TTE and the presence of predetermined clinical criteria that may predispose to, or be suggestive of, endocarditis. Results: Evidence of infective endocarditis was detected on echocardiography in 43 of the 500 patients (8.6%). In 239 patients (48%), vegetations and certain prespecified clinical criteria were both absent. These criteria were: vasculitic/embolic phenomena; the presence of central venous access; a recent history of injected drug use; presence of a prosthetic valve; and positive blood cultures. The collective absence of these five criteria indicated a zero probability of TTE showing evidence of endocarditis. Conclusions: The use of simple clinical criteria during the decision making process may avoid many unnecessary TTE examinations in hospital inpatients with a low probability of endocarditis.