Coronary computed tomography angiography-based assessment of vascular inflammation in patients with obstructive sleep apnoea and coronary artery disease.

Background: Obstructive sleep apnoea (OSA) is associated with increased coronary artery disease (CAD) plaque burden, but the role of vascular inflammation in this relationship is unclear. Coronary computed tomography angiography (CTA) enables surrogate assessment of systemic inflammation via subcutaneous adipose tissue attenuation (SCAT-a), and of coronary inflammation via epicardial adipose tissue volume and attenuation (EAT-v and EAT-a) and pericoronary adipose tissue attenuation (PCAT-a). We investigated whether patients with severe OSA and high plaque burden have increased vascular inflammation. Methods: Patients with overnight polysomnography within ≤12 months of coronary CTA were included. Severe OSA was classified as apnoea/hypopnoea index (AHI) >30. High plaque burden was defined as a CT-adapted Leaman score (CT-LeSc) ≥8.3. Patients with both severe OSA and high plaque burden were defined as 'Group 1', all other patients were classified as 'Group 2'. ScAT, PCAT and EAT attenuation and volume were assessed on semi-automated software. Results: A total of 91 patients were studied (59.3±11.1 years). Severe OSA was associated with high plaque burden (P=0.02). AHI correlated with CT-LeSc (r=0.24, P=0.023). Group 1 had lower EAT-a and PCAT-a compared to Group 2 (EAT-a: -87.6 vs. -84.0 HU, P=0.011; PCAT-a: -90.4 vs. -83.4 HU, P<0.01). However, among patients with low plaque burden, EAT-a was higher in the presence of severe OSA versus mild-moderate OSA (-80.3 vs. -84.0 HU, P=0.020). On multivariable analysis, severe OSA and high plaque burden associated with EAT-a (P<0.02), and severe OSA and high plaque burden (P<0.01) and hypertension (P<0.01) associated with PCAT-a. Conclusions: EAT and PCAT attenuation are decreased in patients with severe OSA and high plaque burden, but EAT attenuation was increased in patients with severe OSA and low plaque burden. These divergent results suggest vascular inflammation may be increased in OSA independent of CAD, but larger studies are required to validate these findings.

A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease.

OBJECTIVE: Individual studies of peripheral artery disease (PAD) have indicated that gender discrepancies exist in the symptoms, functional status, and treatment usage. It remains uncertain whether these discrepancies result in different long-term outcomes. We examined the potential gender differences in mortality and major adverse cardiovascular events (MACE) in patients with symptomatic PAD. METHODS: The PubMed and Embase databases were searched for studies from 2000 to January 2019. After a review of 13,582 citations, 14 articles were analyzed. The reported age-adjusted hazard ratios (HRs) for gender differences in mortality and MACE were included in the meta-analysis. The mortality outcomes were stratified according to the clinical presentation and study context. RESULTS: Male gender was associated with a greater risk of all-cause mortality (HR, 1.13; 95% confidence interval [CI], 1.10-1.16; P < .001) and MACE (HR, 1.10; 95% CI, 1.06-1.14; P < .001). In a stratified analysis, male gender was associated with a higher mortality risk for patients presenting with either critical limb ischemia (HR, 1.08; 95% CI, 1.05-1.10; P < .001) or mixed clinical presentations (HR, 1.16; 95% CI, 1.11-1.21; P < .001) but not for those with intermittent claudication (HR, 1.13; 95% CI, 0.98-1.30; P = .09). Elevated mortality risk was evident after revascularization (HR, 1.11; 95% CI, 1.04-1.19; P = .003), hospitalization (HR, 1.15; 95% CI, 1.08-1.22; P < .001), and amputation (HR, 1.09; 95% CI, 1.08-1.10; P < .001), although not in outpatient clinics (HR, 1.13; 95% CI, 0.97-1.32; P = .13), in men compared with women. CONCLUSIONS: Greater mortality and MACE rates in men with PAD occurred despite other accepted gender disparities. The mechanisms underlying these gender differences in the outcomes for PAD patients require further investigation.

Epicardial adipose tissue is associated with extent of pneumonia and adverse outcomes in patients with COVID-19.

AIM: We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ±â€¯16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death. RESULTS: In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (ß = 10.6, p = 0.005) and EAT attenuation (ß = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1-13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 [95% CI 1.8-14.1] per doubling p = 0.011) and EAT attenuation (OR 3.4 [95% CI 1.5-7.5] per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4-4.6, p = 0.002), chronic lung disease (OR 1.3 [95% CI 1.1-1.7], p = 0.011), and history of heart failure (OR 3.5 [95% 1.1-8.2], p = 0.037). CONCLUSIONS: EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification.

Ethnic differences in coronary anatomy, left ventricular mass and CT-derived fractional flow reserve.

BACKGROUND: Studies have observed higher incidence of cardiovascular mortality in South Asians (SA), and lower prevalence in East Asians (EA), compared with Caucasians. These observations are not entirely explained by ethnic differences in cardiovascular risk factors and mechanistic factors such as variations in cardiac anatomy and physiology may play a role. This study compared ethnic differences in CT-assessed left ventricular (LV) mass, coronary anatomy and non-invasive fractional flow reserve (FFRCT). METHODS: Three-hundred symptomatic patients (age 59 ± 7.9, male 51%) underwent clinically-mandated CT-coronary-angiography (CTA) were matched for age, gender, BMI and diabetes (100 each ethnicity). Assessment of coronary stenosis, luminal dimensions and vessel dominance was performed by independent observers. LV mass, coronary luminal volume and FFRCT were quantified by blinded core-laboratory. A sub-analysis was performed on patients (n = 187) with normal/minimal disease (0-25% stenosis). RESULTS: Stenosis severity was comparable across ethnic groups. EA demonstrated less left-dominant circulation (2%) compared with SA (8.2%) and Caucasians (10.1%). SA compared with EA and Caucasians demonstrated smallest indexed LV mass, coronary luminal volumes and dimensions. EA compared with Caucasians had comparable indexed LV mass, coronary luminal dimensions and highest luminal volumes. The latter was driven by higher prevalence of right-dominance including larger and longer right posterior left ventricular artery. FFRCT in the left anterior descending artery (LAD) was lowest in SA (0.87) compared with EA (0.89; P = 0.009) and Caucasians (0.89; P < 0.001), with no difference in other vessels. All observed differences were consistent in patients with minimal disease. CONCLUSION: This single-centre study identified significant ethnic differences in CT-assessed LV mass, coronary anatomy and LAD FFRCT. These hypotheses generating results may provide a mechanistic explanation for ethnic differences in cardiovascular outcomes and require validation in larger cohorts.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound.

BACKGROUND: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Application of the DILEMMA score to improve lesion selection for invasive physiological assessment.

OBJECTIVES: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment. BACKGROUND: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR). METHODS: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values. RESULTS: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77-0.90) and 0.82 (0.75-0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%). CONCLUSIONS: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment.

Association between socioeconomic status and incident atrial fibrillation.

BACKGROUND: Low socioeconomic status is associated with cardiovascular diseases, and an association with atrial fibrillation (AF) could guide screening. AIM: To investigate if indices of advantage/disadvantage (IAD), index of education/occupation (IEO) and index of economic resources were associated with incident AF, independent of risk factors and cardiac function. METHODS: We studied community-based participants aged ≥65 years with AF risk factors (n = 379, age 70 ± 4 years, 45% men). The CHARGE-AF score (a well validated AF risk score) was used to assess 5-year risk of developing AF. Participants also had baseline echocardiograms. IAD, IEO and index of economic resources were obtained from the 2011 Socio-Economic Indexes for Areas score, in which higher decile ranks indicate more advantaged areas. Patients were followed up for incident AF (median 21 (range 5-31) months), with AF diagnosed by clinical review, including 12-lead electrocardiogram (ECG), as well as single-lead portable ECG monitoring used to record 60 s ECG tracings five times/day for 1 week. Cox proportional hazards models were used to assess the association between socioeconomic status and incident AF. RESULTS: Subjects with AF (n = 50, 13%) were more likely to be male (64 vs 42%, P = 0.003) and had higher CHARGE-AF score (median 7.1% (5.2-12.8%) vs 5.3% (3.3-8.6%), P < 0.001). Areas with lower socioeconomic status (IAD and IEO) had a higher risk of incident AF independent of LV function and CHARGE-AF score (hazard ratio for IAD 1.16, 95% confidence interval 1.05-1.29, P = 0.005 and hazard ratio for IEO 1.18, 95% confidence interval 1.07-1.30, P = 0.001). CONCLUSION: Regional socioeconomic status is associated with risk of incident AF, independent of LV function and clinical risk. This association might permit better regional targeting of prevention.

Smart watches for heart rate assessment in atrial arrhythmias.

BACKGROUND: Despite studies demonstrating the accuracy of smart watches (SW) and wearable heart rate (HR) monitors in sinus rhythm, no data exists regarding their utility in arrhythmias. METHODS: 102 hospitalized patients were evaluated at rest using continuous electrocardiogram (ECG) monitoring with concomitant SW-HR (FitBit, FB, Apple Watch, AW) for 30 min. RESULTS: Across all devices, 38,616 HR values were recorded. Sinus rhythm cohort demonstrated strong agreement for both devices with a low bias (FB & AW Bias = 1 beat). In atrial arrhythmias, AW demonstrated a stronger correlation than FB (AW rs = 0.83, FB rs = 0.56, both p < 0.01) with a lower bias (Bias AW = -5 beats, FB = -18 beats). Atrial flutter demonstrated strongest agreement in both devices with a mean bias <1 beat. However, in AF, there was significant HR underestimation (Bias FB = -28 beats, AW-8 beats) with wide limits of agreement. Despite HR underestimation in AF, when SW recorded HR ≥ 100 in arrhythmias, 98% of values were within ±10-beats of ECG-HR. CONCLUSIONS: SW demonstrate strong agreement for HR estimation in sinus rhythm and atrial flutter but underestimates HR in AF. Tachycardic episodes recorded at rest on a SW may be suggestive of an underlying atrial tachyarrhythmia and warrant further clinical evaluation. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) ACTRN: 12616001374459.

Diagnostic accuracy of ASLA score (a novel CT angiographic index) and aggregate plaque volume in the assessment of functional significance of coronary stenosis.

BACKGROUND: Visual assessment of diameter-stenosis on Computed Tomography Coronary Angiography (CTCA) lacks specificity to determine functional significance of coronary artery stenosis. Percent-aggregate plaque volume (%APV) and ASLA score, which incorporates Area of Stenosis, Lesion length, and area of myocardium subtended estimated by APPROACH score (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) have been described to predict lesion specific ischaemia in focal lesions with intermediate stenosis. METHODS AND RESULTS: Included were 81 patients (mean age 64.7 ±â€¯9 years, 62% male; 94 vessels) who underwent 320- detector-row CTCA, invasive coronary angiography and fractional-flow-reserve (FFR). We examined vessels with wide range of diameter stenosis (mid to severe) and with multiple lesions. Invasive FFR of ≤0.8 was considered functionally significant. The first 54 patients (62 vessels) formed the derivation cohort. ASLA score was the best predictor of FFR ≤ 0.8 (AUC 0.83, p < 0.001) compared to %APV (0.72), CT >50% (0.76), APPROACH score (0.79), area-stenosis (0.73), diameter-stenosis (0.74), minimum-luminal-diameter (0.74), minimal-luminal-area (0.72), and lesion-length (0.67). ASLA score and not %APV, provided incremental predictive value when added to CT > 50 [(NRI 0.71, p = 0.005) vs. (NRI 0.01, p = 0.96)]. In the validation cohort of 27 patients (32 vessels), the ASLA score (AUC 0.85) was again a better predictor of FFR ≤ 0.8 compared to %APV (0.71), CT > 50% (0.66) and other CT indices. The AUC of ASLA score was superior to CTCA>50% (p = 0.001). CONCLUSION: ASLA score is a novel predictor of functional significance of coronary stenosis and adds incremental predictive value to CT > 50 but %APV did not.

Statins in adult patients with HIV: Protocol for a systematic review and network meta-analysis.

BACKGROUND: Patients with HIV have been found to suffer from lipid abnormalities, including elevated levels of total and LDL-cholesterol as well as triglyceride levels. Abnormal lipid levels are associated with an increased risk of developing cardiovascular diseases, which are significant causes of mortality among the general population. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of statins classes on HIV patients. METHODS: Randomized clinical trials (RCTs) and observational studies published in English up to 31 December 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will all-cause mortality, new event of acute myocardial infarction, stroke (hemorrhagic and ischemic), hospitalization for acute coronary syndrome and urgent revascularization procedures and cardiovascular mortality. Secondary outcomes will be assessment of the differences in change of total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein (HDL-C). Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of statins that reduce cardiovascular mortality in HIV patients. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. RESULTS AND CONCLUSION: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The evidence will determine which combination of interventions are most promising for current practice and further investigation. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42017072996).

The evolving role of cardiac magnetic resonance imaging in the assessment of cardiovascular disease.

BACKGROUND: Imaging of the heart is important in the diagnosis and follow-up of a broad range of cardiac pathology. The authors discuss the growing role of cardiac magnetic resonance imaging (CMR) in cardiology practice and its relevance to primary healthcare. OBJECTIVE: In this article we discuss the advantages of CMR over other imaging modalities, and give a brief description of the common CMR techniques and cardiac pathologies where CMR is especially useful. DISCUSSION: CMR provides specific advantages over other cardiac imaging modalities when evaluating pathology in congenital heart disease, cardiac masses, cardiomyopathies, and in some aspects of ischaemic and valvular heart diseases. The strength of CMR in these pathologies includes its precise ana-tomical delineation of structures, characterisation of myocardial tissue, and accurate, reproducible measurements of blood volume and flow. CMR is used in inpatient and outpatient settings, and is available primarily in major hospitals.

Feasibility of exercise stress echocardiography for cardiac risk assessment in chronic kidney disease patients prior to renal transplantation.

BACKGROUND: Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population. METHODS: Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220-age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP). RESULTS: Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate-control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate-control medication. There were 97% of ESE completed to physiologic endpoints. CONCLUSION: In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9-in-10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.

Invasive assessment of the coronary microcirculation in the catheter laboratory.

Historically much of our understanding of the coronary circulation has been centered towards the epicardial vessels. However, recent work has highlighted the importance of the coronary microcirculation across a broad spectrum of clinical conditions in influencing patient outcomes. Therefore an ability to measure microvascular function is most valuable. While evaluation of the epicardial coronary circulation is widely understood, interrogation of the coronary microcirculation is more complex. Many methods are available to assess the integrity of the microcirculation in the catheter laboratory. This review will discuss the physiology of the coronary microcirculation and evaluate the utility of available invasive techniques.

Comparison of diagnostic accuracy of combined assessment using adenosine stress computed tomography perfusion + computed tomography angiography with transluminal attenuation gradient + computed tomography angiography against invasive fractional flow reserve.

OBJECTIVES: The goal of this study was to compare the diagnostic accuracy of combined computed tomography perfusion (CTP) + computed tomography angiography (CTA), transluminal attenuation gradient by 320-detector row computed tomography (TAG320) + CTA, and CTP + TAG320 + CTA (multidetector computed tomography-integrated protocol [MDCT-IP]) assessment in predicting significant fractional flow reserve (FFR). BACKGROUND: CTA has limited specificity for predicting functionally significant stenoses. Novel CT techniques, including adenosine stress CTP and TAG320, may improve the diagnostic accuracy of CTA. METHODS: CTA, CTP, and TAG320 were assessed using 320-detector row MDCT. Patients who underwent CTA, CTP, and FFR assessment on invasive coronary angiography were included. CTP was assessed using the visual perfusion assessment. TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. A TAG320 cutoff value of -15.1 HU/10 mm as previously described was defined as significant. Functionally significant coronary stenosis was defined as FFR ≤0.8. RESULTS: The cohort included 75 patients (age 64.1 ± 10.8 years, 52 men) and 44 (35%) FFR-significant vessels. In 127 vessels, CTA predicted FFR-significant stenosis with 89% sensitivity and 65% specificity compared with MDCT-IP, which showed 88% sensitivity and 83% specificity. In 97 vessels in which the results of all techniques were available, TAG320 + CTA (area under the curve [AUC] = 0.844) and CTP + CTA (AUC = 0.845) had comparable per-vessel diagnostic accuracy (p = 0.98). The diagnostic accuracy of MDCT-IP (AUC = 0.91) was superior to TAG320 + CTA or CTP + CTA (p = 0.01). CONCLUSIONS: In vessels without significant calcification or artefact, TAG320 + CTA and CTP + CTA provide comparable diagnostic accuracy for functional assessment of coronary artery stenosis. MDCT-IP may provide the best diagnostic accuracy for functional assessment of coronary artery stenosis.