Atrial fibrillation incidence, prevalence, predictors, and adverse outcomes in acute coronary syndromes: A pooled analysis of data from 8 million patients.

OBJECTIVE: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute coronary syndromes (ACS). METHODS: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through August 23, 2020. Random-effects meta-analysis method was used to pool estimates. RESULTS: We included 109 studies reporting data from a pooled population of 8 239 364 patients. The prevalence rates were 5.8% for pre-existing AF, 7.3% for newly diagnosed AF, and 11.3% for prevalent (total) AF, in patients with ACS. Predictors of newly diagnosed AF included age (per year increase) (adjusted odds ratio [aOR]: 1.05), C-reactive protein (aOR: 1.49), left atrial (LA) diameter (aOR: 1.08), LA dilatation (aOR: 2.32), left ventricular ejection fraction <40% (aOR: 1.82), hypertension (aOR: 1.87), and Killip ˃ 1 (aOR: 1.85), p < .01 in all analyzes. Newly diagnosed AF was associated with an increased risk of acute heart failure (adjusted hazard ratio [aHR]: 3.20), acute kidney injury (aHR: 3.09), re-infarction (aHR: 1.96), stroke (aHR: 2.15), major bleeding (aHR: 2.93), and mortality (aHR: 1.80) in the short term; and with an increased risk of heart failure (aHR: 2.21), stroke (aHR: 1.75), mortality (aHR: 1.67), CV mortality (aHR: 2.09), sudden cardiac death (aHR: 1.53), and a composite of major adverse cardiovascular events (aHR: 1.54) in the long term (beyond 1 month), p < .05 in all analyzes. CONCLUSION: One in nine patients with ACS has AF, with a high proportion of newly diagnosed AF. AF, in particular newly diagnosed AF, is associated with poor short-term and long-term outcomes in patients with ACS.

Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. METHODS: In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity. RESULTS: A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans. CONCLUSIONS: Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter)2 × APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis <30%) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10-3mmHg-1 at the AA, 4.08 ± 1.80·10-3mmHg-1 at the PDA, and 4.42 ± 1.67·10-3mmHg-1 at the DDA. All levels of distensibility correlated with resting CBF (R2 = 0.350-0.373, P < 0.05), hyperemic CBF (R2 = 0.453-0.464, P < 0.01), and CFVR (R2 = 0.442-0.511, P < 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction.NEW & NOTEWORTHY Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.

The predictive capabilities of a novel cardiovascular magnetic resonance derived marker of cardiopulmonary reserve on established prognostic surrogate markers in patients with pulmonary vascular disease: results of a longitudinal pilot study.

BACKGROUND: No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease. METHODS AND RESULTS: Twenty participants with confirmed (n = 14) or at high risk (n = 6) for PAH underwent cardiovascular magnetic resonance (CMR) at baseline and after ~6 months of guideline-appropriate management. Ten PAH participants underwent RHC within 48 h of each CMR. RHC (mean pulmonary arterial pressure, mPAP; pulmonary vascular resistance index, PVRI; cardiac index, CI) and phase-contrast CMR (mean pulmonary arterial blood flow velocity, meanPAvel) measurements were taken at rest and during continuous adenosine infusion (70/140/210 mcg/kg/min). Initial meanPAvel's (rest and hyperemic) were correlated with validated surrogate prognostic parameters (CMR: RV ejection fraction, RVEF; RV end systolic volume indexed, RVESVI; RHC: PVRI, CI; biomarker: NT-pro brain natriuretic peptide, NTpBNP; clinical: 6-min walk distance, 6MWD), a measure of pulmonary arterial stiffness (elastic modulus) and volumetric estimation of RV ventriculoarterial (VA) coupling. Changes in meanPAvel's were correlated with changes in comparator parameters over time. At initial assessment, meanPAvel at rest correlated significantly with PVRI (inversely), CI (positively) and elastic modulus (inversely) (R 2 > 0.37,P < 0.05 for all), whereas meanPAvel at peak hyperemia correlated significantly with PVRI, RVEF, RVESVI, 6MWD, elastic modulus and VA coupling (R 2 > 0.30,P < 0.05 for all). Neither resting or hyperemia-derived meanPAvel correlated with NTpBNP levels. Initial meanPAvel at rest correlated significantly with RVEF, RVESVI, CI and VA coupling at follow up assessment (R 2 > 0.2,P < 0.05 for all) and initial meanPAvel at peak hyperemia correlated with RVEF, RVESVI, PVRI and VA coupling (R 2 > 0.37,P < 0.05 for all). Change in meanPAvel at rest over time did not show statistically significant correlation with change in prognostic parameters, while change in meanPAvel at peak hyperemia did show a significant relationship with ΔRVEF, ΔRVESVI, ΔNTpBNP and ΔCI (R 2 > 0.24,P < 0.05 for all). CONCLUSION: MeanPAvel during peak hyperemia correlated with invasive, non-invasive and clinical prognostic parameters at different time points. Further studies with predefined clinical endpoints are required to evaluated if this novel tool is a marker of disease progression in patients with pulmonary vascular disease.

The Impact of Arteriovenous Fistulae for Hemodialysis on the Cardiovascular System.

An arteriovenous fistula (AVF) is critical for the provision of optimal chronic hemodialysis. Its creation causes significant hemodynamic alterations in cardiovascular parameters, and can result in progressive left and right heart failure. Despite successful kidney transplantation, many patients retain a functional AVF indefinitely, which may contribute to ongoing adverse cardiovascular outcomes. A similar high risk:benefit ratio may exist in peritoneal dialysis patients with "backup" AVF.

Characterisation of Myocardial Injury via T1 Mapping in Early Reperfused Myocardial Infarction and its Relationship with Global and Regional Diastolic Dysfunction.

BACKGROUND: Cardiovascular magnetic resonance (CMR) advances in imaging techniques, permits the ability to accurately characterise tissue injury post myocardial infarction. Pre-contrast T1 mapping enables this through measurement of pre-contrast T1 relaxation times. We investigate the relationship between T1 characterisation of myocardial injury with global and regional diastolic function. METHODS: Revascularised acute myocardial infarction patients with normal left ventricular (LV) systolic function on TTE were assessed by 1.5T CMR. Acute regional diastolic wall motion abnormalities, global diastolic function measurements, acute segmental damage fraction with LGE and mean segmental pre-contrast T1 values were assessed on matching short axis slices. RESULTS: Forty-four patients were analysed. Mean LVEF was 62.1±9.4%. No difference between NSTEMI (22/44) and STEMI in mean pre-contrast T1 values of infarcted (1025.0±109.2 vs 1011.0±81.6ms, p=0.70), adjacent (948.3±45.3 vs 941.1±46.6ms, p=0.70) and remote (888.8±52.8 vs 881.2±54.5ms, p=0.66) segments was detected. There was no correlation between pre-contrast T1 of infarcted segments with global diastolic dysfunction (E/A, r2=0.216, p=0.06; S/D, r2=0.243, p=0.053; E/E', r2=0.240, p=0.072), but there was significantly positive, moderate correlation with circumferential diastolic strain rate, (r2=0.579, p<0.01) with excellent agreement and reproducibility. CONCLUSION: Cardiac magnetic resonance evaluation of pre-contrast T1 values revealed no difference between NSTEMI and STEMI patients in terms of tissue characterisation post-myocardial infarction. However, pre-contrast T1 of infarcted tissue is significantly correlated with regional diastolic circumferential strain rate.

Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction.

BACKGROUND AIMS: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). METHODS: Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 10(6) cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. RESULTS: Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. CONCLUSIONS: Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.

Magnetic resonance-derived circumferential strain provides a superior and incremental assessment of improvement in contractile function in patients early after ST-segment elevation myocardial infarction.

BACKGROUND: We evaluate whether circumferential strain derived from grid-tagged CMR is a better method for assessing improvement in segmental contractile function after STEMI compared to late gadolinium enhancement (LGE). METHODS: STEMI patients post primary PCI underwent baseline CMR (day 3) and follow-up (day 90). Cine, grid-tagged and LGE images were acquired. Baseline LGE infarct hyperenhancement was categorised as ≤25 %, 26-50 %, 51-75 % and >75 % hyperenhancement. The segmental baseline circumferential strain (CS) and circumferential strain rate (CSR) were calculated from grid-tagged images. Segments demonstrating an improvement in wall motion of ≥1 grade compared to baseline were regarded as having improved segmental contractile-function. RESULTS: Forty-five patients (aged 58 ± 12 years) and 179 infarct segments were analysed. A baseline CS cutoff of -5 % had sensitivity of 89 % and specificity of 70 % for detection of improvement in segmental-contractile-function. On receiver-operating characteristic analysis for predicting improvement in contractile function, AUC for baseline CS (0.82) compared favourably to LGE hyperenhancement (0.68), MVO (0.67) and baseline-CSR (0.74). On comparison of AUCs, baseline CS was superior to LGE hyperenhancement and MVO in predicting improvement in contractile function (P < 0.001). On multivariate-analysis, baseline CS was the independent predictor of improvement in segmental contractile function (P < 0.001). CONCLUSION: Grid-tagged CMR-derived baseline CS is a superior predictor of improvement in segmental contractile function, providing incremental value when added to LGE hyperenhancement and MVO following STEMI. KEY POINTS: Baseline CS predicts contractile function recovery better than LGE and MVO following STEMI. Baseline CS predicts contractile function recovery better than baseline CSR following STEMI. Baseline CS provides incremental value to LGE and MVO following STEMI.

Beneficial cardiovascular remodeling following arterio-venous fistula ligation post-renal transplantation: a longitudinal magnetic resonance imaging study.

Despite improvements in survival following renal transplantation, high rates of cardiovascular morbidity and mortality remain. Persistence of arterio-venous fistulae (AVF) may contribute to maladaptive cardiovascular remodeling and poor health outcomes in this cohort. Utilizing recent advances in cardiovascular magnetic resonance imaging (CMR), we prospectively evaluated alterations in cardiac and vascular structure and function six months after elective ligation of AVF, following stable, successful renal transplantation. Eighteen subjects underwent CMR evaluation of cardiac structure and function, aortic distensibility and endothelial function prior to AVF ligation and at six months. At follow-up, while left ventricular ejection fraction was unchanged, mean cardiac output decreased by 15.6% (9.6 ± 2.9 L/min vs. 8.1 ± 2.3 L/min, p = 0.004) and left ventricular mass had regressed by 10% (166 ± 56 g vs. 149 ± 51 g, p = 0.0001). Significant improvements were also noted in right ventricular and biatrial structure and function. Aortic distensibility was unchanged at follow-up, but endothelial dependent vasodilatation had improved (2.5 ± 6.5% vs. 8.0 ± 5.9%, p = 0.04). Elective AVF ligation following successful renal transplantation is associated with improvements in left ventricular mass, right ventricular, and biatrial structure and function. Further randomized studies are warranted to determine the potential clinical improvement following AVF ligation in this cohort.

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial.

AIMS: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN(™) multi-electrode system. METHODS AND RESULTS: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). CONCLUSION: Renal sympathetic denervation, using the EnligHTN multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN system delivers a promising therapy for the treatment of drug-resistant hypertension.

Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease.

BACKGROUND: Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD). METHODS AND RESULTS: Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group; this effect was maintained at three months (21±9% increase from baseline; P<0.01). A significant decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group (P<0.01). There was no correlation between endothelial function and platelet function testing in the clopidogrel therapy group. CONCLUSION: Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity.

Tandem lesions associate with angiographic progression of coronary artery stenoses.

Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56-73) and the median interval between angiograms was 2.1 years (IQR 1.2-3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04-4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21-2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.

Impact of timing and dose of mesenchymal stromal cell therapy in a preclinical model of acute myocardial infarction.

BACKGROUND: Although mesenchymal stem/stromal cells (MSC) have shown therapeutic promise after myocardial infarction (MI), the impact of cell dose and timing of intervention remains uncertain. We compared immediate and deferred administration of 2 doses of MSC in a rat model of MI. METHODS AND RESULTS: Sprague-Dawley rats were used. Allogeneic prospectively isolated MSC ("low" dose 1 × 10(6) or "high" dose 2 × 10(6) cells) were delivered by transepicardial injection immediately after MI ("early-low," "early-high"), or 1 week later ("late-low," "late-high"). Control subjects received cryopreservant solution alone. Left ventricular dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance. All 4 MSC-treatment cohorts demonstrated higher EF than control animals 4 weeks after MI (P values <.01 to <.0001), with function most preserved in the early-high group (absolute reduction in EF from baseline: control 39.1 ± 1.7%, early-low 26.5 ± 3.2%, early-high 7.9 ± 2.6%, late-low 19.6 ± 3.5%, late-high 17.9 ± 4.0%). Cell treatment also attenuated left ventricular dilatation and fibrosis and augmented left ventricular mass, systolic wall thickening (SWT), and microvascular density. Although early intervention selectively increased SWT and vascular density in the infarct territory, delayed treatment caused greater benefit in remote (noninfarct) myocardium. All outcomes demonstrated dose dependence for early MSC treatment, but not for later cell administration. CONCLUSIONS: The nature and magnitude of benefit from MSC after acute MI is strongly influenced by timing of cell delivery, with dose dependence most evident for early intervention. These novel insights have potential implications for cell therapy after MI in human patients.

Coronary ß2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.

AIMS: The interaction between coronary ß(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary ß(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. METHODS AND RESULTS: In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 µg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 µg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 µg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 µg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 µg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.

'Bushfire Season' in Australia: Determinants of Increases in Risk of Acute Coronary Syndromes and Takotsubo Syndrome.

BACKGROUND: Climate change has resulted in an increase in ambient temperatures during the summer months as well as an increase in risk of associated air pollution and of potentially disastrous bushfires throughout much of the world. The increasingly frequent combination of elevated summer temperatures and bushfires may be associated with acute increases in risks of cardiovascular events, but this relationship remains unstudied. We evaluated the individual and cumulative impacts of daily fluctuations in temperature, fine particulate matter of less than 2.5 µm (PM2.5) pollution and presence of bushfires on incidence of acute coronary syndromes and Takotsubo syndrome. METHODS: From November 1, 2019, to February 28, 2020, all admissions with acute coronary syndromes or Takotsubo syndrome to South Australian tertiary public hospitals were evaluated. Univariate and combined associations were sought among each of 1) maximal daily temperature, 2) PM2.5 concentrations, and 3) presence of active bushfires within 200 km of the hospitals concerned. RESULTS: A total of 504 patients with acute coronary syndromes and 35 with Takotsubo syndrome were studied. In isolation, increasing temperature was associated (rs = 0.26, P = .005) with increased incidence of acute coronary syndromes, while there were similar, but nonsignificant correlations for PM2.5 and presence of bushfires. Combinations of all these risk factors were also associated with a doubling of risk of acute coronary syndromes. No significant associations were found for Takotsubo syndrome. CONCLUSION: The combination of high temperatures, presence of bushfires and associated elevation of atmospheric PM2.5 concentrations represents a substantially increased risk for precipitation of acute coronary syndromes; this risk should be factored into health care planning including public education and acute hospital preparedness.

Trends in myocardial infarction and coronary revascularisation procedures in Australia, 1993-2017.

OBJECTIVE: Prior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI hospitalisations and coronary procedures in Australia and their associated economic burden. METHODS: The primary outcome measure was the incidence and time trends of total MI, ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) hospitalisations from 1993 to 2017. The incidence and time trends of coronary procedures were additionally collected, alongside MI hospitalisation costs. RESULTS: Adjusted for population changes, annual MI incidence increased from 216.2 cases per 100 000 to a peak of 270.4 in 2007 with subsequent decline to 218.7 in 2017. Similarly, NSTEMI incidence increased from 68.0 cases per 100 000 in 1993 to a peak of 192.6 in 2007 with subsequent decline to 162.6 in 2017. STEMI incidence decreased from 148.3 cases per 100 000 in 1993 to 56.2 in 2017. Across the study period, there were annual increases in MI hospitalisations of 0.7% and NSTEMI hospitalisations of 5.6%, and an annual decrease in STEMI hospitalisations of 4.8%. Angiography and percutaneous coronary intervention increased by 3.4% and 3.3% annually, respectively, while coronary artery bypass graft surgery declined by 2.2% annually. MI hospitalisation costs increased by 100% over the study period, despite a decreased average length of stay by 45%. CONCLUSIONS: The rising incidence of MI hospitalisations appear to have stabilised in Australia. Despite this, associated healthcare expenditure remains significant, suggesting a need for continual implementation of public health policies and preventative strategies.