Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

An association between Dasatinib, elevated left atrial pressure and pleural effusion.

BACKGROUND: Tyrosine kinase inhibitors (TKI), such as Dasatinib, are effective in the treatment of chronic myeloid leukemia (CML) but associated with development of pleural effusions (PE). The relationship between haemodynamic parameters identified on transthoracic echocardiogram (TTE) such as elevated estimated left atrial pressure (LAP), and PE development is unknown. This study aims to describe associations between Dasatinib, elevated LAP and PE. METHODS: This was a retrospective study of 71 CML patients who underwent TTE during treatment with various TKIs. Descriptive analysis was performed to identify associations between TKI use, PE and elevated LAP on TTE. Multivariate logistic regression was performed to identify predictors of elevated LAP. RESULTS: There were 36 patients treated with Dasatinib, 15 Nilotinib, and 20 Imatinib. Those treated with Dasatinib had higher rates of elevated LAP (44% vs 7% Nilotinib vs 10% Imatinib, p < 0.01) and PE (39% vs 7% vs 0%, p < 0.01). In the 15 patients who developed PE, 14 (93%) patients were treated with Dasatinib. Patients with PE had higher rates of elevated LAP (67% vs 16%, p < 0.01). Nineteen (26.8%) patients in the entire cohort had elevated LAP. After multivariate adjustment, Dasatinib (OR 33.50, 95% CI = 4.99-224.73, p < 0.01) and age (OR 1.12, 95% CI = 1.04-1.20, p < 0.01) were associated with elevated LAP. CONCLUSIONS: Among patients with CML, there was an association between Dasatinib use, PE and elevated LAP on TTE. These findings are hypothesis generating and further studies are required to evaluate the utility of elevated LAP on TTE as a novel marker for prediction and surveillance of PE.

Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. METHOD: A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. RESULTS: Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. CONCLUSIONS: History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Electrocardiogram Changes Following Intravenous Bisphosphonate Infusion: A Systematic Review and Meta-Analysis.

Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients receiving bisphosphonates; however, uncertainty remains as to whether electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting electrocardiogram (ECG) findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE from inception until January 14, 2023, for studies reporting ECG parameters after intravenous bisphosphonate infusion. We excluded studies that only reported atrial fibrillation. Study quality was assessed using the Newcastle-Ottawa scale. Continuous data were meta-analyzed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95% CIs). We found 1083 unique records, of which 11 met our inclusion and exclusion criteria. Studies had a low to low/moderate risk of bias. Six prospective cohort studies were included in the meta-analysis. Five studies used zoledronic acid, whereas one study used pamidronate. Most studies (n = 4) were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases, and one study in children with osteoporosis secondary to cerebral palsy. Study populations ranged from n = 15 to n = 116. Heart rate-corrected QT (QTc) was significantly longer post-infusion (SMD = 0.46 ms [95% CI 0.80 to 0.11]; n = 67 patients, k = 2 studies, τ2 = 0). There were no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc, QTc (maximum), QTc (minimum), and QTc dispersion. The correlation between pre- and post-infusion QTc was not significant (p = 0.93). Overall, there is a weak association between intravenous bisphosphonate infusion and a QTc interval prolongation. However, there is insufficient evidence to support an association between intravenous bisphosphonate and any ECG variable changes, which may precipitate atrial fibrillation. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Blood pressure surveillance in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) are cancer therapies that have been associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood pressure (BP) measurements are routinely performed during day oncology center visits for administration of ICI therapy but are often not assessed temporally to screen and monitor hypertension, which could independently increase the risk of ASCVD in cancer survivorship. This study reports the feasibility of using serial BP measurements from routine visits to day oncology center to diagnose and monitor hypertension control in cancer patients receiving ICIs.

Breast arterial calcification and epicardial adipose tissue volume, but not density are independently associated with cardiovascular risk.

BACKGROUND: Mammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT. METHODS: Single-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders. RESULTS: Among 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26-18.49), p < 0.001, EATv OR 1.02 (1.01-1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39-13), p = 0.01; EATv OR 1.01 (1.0-1.03), p = 0.04). CONCLUSION: BAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors.

Systematic review and meta-analysis of the clinical characteristics and outcomes of spontanous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an uncommon, non-iatrogenic, non-atherosclerotic cause of acute coronary syndrome. A lack of large prospective cohort studies and randomised controlled trials means that important questions about clinical characteristics and outcomes of patients with SCAD are yet to be fully answered. METHOD: A literature search of PUBMED, EMBASE and SCOPUS was undertaken up to and including the 23rd January 2020. Studies reporting any cohort of 10 or more SCAD patients presenting with acute coronary syndrome, with appropriate clinical follow-up data were included in the analysis. Incidences of major adverse cardiovascular events (MACE), myocardial infarction and SCAD recurrence were meta-analysed using Poisson regression. RESULTS: 19 studies, totalling p=2,172 patients, were included in the analysis. There was significant heterogeneity across the studies in all baseline characteristics and clinical outcomes. Prevalence of traditional cardiovascular risk factors was low; however, hypertension had a prevalence of 45% (95% CI; [35-54]) and fibromuscular dysplasia (FMD) was present in 68% (95% CI; [61-74]). Across all cohorts, the incidence of MACE in patients with SCAD was 7.80 per 100 person years (n=19, p=2172, 95% CI; [4.50-13.54]) and SCAD recurrence was 5.49 per 100 person years (n=13, p=1408, 95% CI; [3.75-8.02]). CONCLUSIONS: This meta-analysis confirms that SCAD is not an inconsequential cause of acute coronary syndrome and heralds the need for further prospective research to identify predictors of recurrent events and therapies to prevent them.

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.

The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study.

Epicardial adipose tissue (EAT) is associated with cardiovascular risk. The longitudinal change in EAT volume (EATv) and density (EATd), and potential modulators of these parameters, has not been described. We prospectively recruited 90 patients with non-obstructive coronary atherosclerosis on baseline computed tomography coronary angiography (CTCA) performed for suspected coronary artery disease to undergo a repeat research CTCA. EATv in millilitres (mL) and EATd in Hounsfield units (HU) were analysed and multivariable regression analysis controlling for traditional cardiovascular risk factors (CVRF) performed to assess for any predictors of change. Secondary analysis was performed based on statin therapy. The median duration between CTCA was 4.3years. Mean EATv increased at follow-up (72 ± 33 mL to 89 ± 43 mL, p < 0.001) and mean EATd decreased (baseline -76 ± 6 HU vs. -86 ± 5 HU, p < 0.001). There were no associations between baseline variables of body mass index, age, sex, hypertension, hyperlipidaemia, diabetes or smoking on change in EATv or EATd. No difference in baseline, follow-up or delta EATv or EATd was seen in patients with (60%) or without baseline statin therapy. In this select group of patients, EATv consistently increased and EATd consistently decreased at long-term follow-up and these changes were independent of CVRF, age and statin use. Together with the knowledge of strong associations between EAT and cardiac disease, these findings may suggest that EAT is an independent parameter rather than a surrogate for cardiovascular risk.

Off- vs. On-Pump Coronary Artery Bypass Grafting Long-Term Survival is Driven by Incompleteness of Revascularisation.

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG. METHODS: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation. RESULTS: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke. CONCLUSIONS: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up. STUDY REGISTRATION: CRD42018102019 (PROSPERO).

The utility of coronary computed tomography angiography in elderly patients.

BACKGROUND: Coronary computed tomography angiography (CCTA) is often avoided in elderly patients due to a presumption that a high proportion of patients will have heavily calcified plaque limiting an accurate assessment. We sought to assess the image quality, luminal stenosis and utility of CCTA in elderly patients with suspected coronary artery disease (CAD) and stable chest pain. METHODS: Retrospective analysis of elderly patients (> 75 years) who underwent 320-detector row CCTA between 2012-2017 at MonashHeart. The CCTA was analysed for degree maximal coronary stenosis by CAD-RADS classification, image quality by a 5-point Likert score (1-poor, 2-adequate, 3-good, 4-very good, 5-excellent) and presence of artefact limiting interpretability. RESULTS: 1011 elderly patients (62% females, 78.8 ± 3.3 years) were studied. Cardiovascular risk factor prevalence included: hypertension (65%), hyperlipidaemia (48%), diabetes (19%) and smoking (21%). The CCTA was evaluable in 68% of patients which included 52% with non-obstructive CAD (< 50% stenosis), 48% with obstructive CAD (> 50%) stenosis. Mean Likert score was 3.1 ± 0.6 corresponding to good image quality. Of the 323 (32%) of patients with a non-interpretable CCTA, 80% were due to calcified plaque and 20% due to motion artefact. Male gender (P = 0.009), age (P = 0.02), excess motion (P < 0.01) and diabetes mellitus (P = 0.03) were associated with non-interpretable CCTA. CONCLUSION: Although CCTA is a feasible non-invasive tool for assessment of elderly patients with stable chest pain, clinicians should still be cautious about referring elderly patients for CCTA. Patients who are male, diabetic and >78 years of age are significantly less likely to have interpretable scans.

Pre-operative Bariatric Clinic Attendance Is a Predictor of Post-operative Clinic Attendance and Weight Loss Outcomes.

AIM: Our primary aim was to determine whether non-attendance at pre-operative clinics were associated with non-attendance at post-operative clinics and its influence on weight loss. We also sought to examine the relationship between gender, ethnicity and post-operative clinic attendance with respect to weight loss post-bariatric surgery. METHODS: A retrospective audit was performed for patients undertaking the bariatric surgery program at the Auckland City Hospital between 2013 and 2016. RESULTS: One hundred and eighty-four patients completed our program, with a mean age of 46.1 years. Mean weight at commencement was 133.3 kg, with a BMI of 47.4. At 2 years follow-up (n = 143), excess weight loss was 70.8% following RYGB and 68.0% following LSG (p = 0.5743). More patients attended all pre-operative than post-operative clinics (67.4% vs 37.5% p = < 0.001). One pre-operative clinic non-attendance was associated with less weight loss at 2 years and it increases the risk of missing at least 50% of post-operative clinics with a risk ratio of 2.73, p = 0.005. Non-attendance of at least 50% of post-operative clinics was also associated with less weight loss at 2 years (33.4 kg vs 44.3 kg, p = 0.040). Although Maori and Pacific Islanders more frequently missed > 50% of post-operative clinics, weight loss was similar between European, Maori and Pacific Islander populations (2-year weight loss 44.2 kg vs 40.74 kg vs 44.1 kg, respectively, p = 0.8192). CONCLUSION: Pre-operative clinic non-attendance helps predict post-operative clinic non-attendance. Missing any pre-operative clinics and at least 50% of scheduled post-operative clinics is associated with poorer weight loss outcomes.

Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function.

Background Epicardial adipose tissue ( EAT ) is in immediate apposition to the underlying myocardium and, therefore, has the potential to influence myocardial systolic and diastolic function or myocardial geometry, through paracrine or compressive mechanical effects. We aimed to review the association between volumetric EAT and markers of myocardial function and geometry. Methods and Results PubMed, Medline, and Embase were searched from inception to May 2018. Studies were included only if complete EAT volume or mass was reported and related to a measure of myocardial function and/or geometry. Meta-analysis and meta-regression were used to evaluate the weighted mean difference of EAT in patients with and without diastolic dysfunction. Heterogeneity of data reporting precluded meta-analysis for systolic and geometric associations. In the 22 studies included in the analysis, there was a significant correlation with increasing EAT and presence of diastolic dysfunction and mean e' (average mitral annular tissue Doppler velocity) and E/e' (early inflow / annular velocity ratio) but not E/A (ratio of peak early (E) and late (A) transmitral inflow velocities), independent of adiposity measures. There was a greater EAT in patients with diastolic dysfunction (weighted mean difference, 24.43 mL; 95% confidence interval, 18.5-30.4 mL; P<0.001), and meta-regression confirmed the association of increasing EAT with diastolic dysfunction ( P=0.001). Reported associations of increasing EAT with increasing left ventricular mass and the inverse correlation of EAT with left ventricular ejection fraction were inconsistent, and not independent from other adiposity measures. Conclusions EAT is associated with diastolic function, independent of other influential variables. EAT is an effect modifier for chamber size but not systolic function.

Drug eluting versus bare metal stents for percutaneous coronary intervention of saphenous vein graft lesions: An updated meta-analysis of randomized controlled trials.

BACKGROUND/PURPOSE: Percutaneous coronary intervention (PCI) is the preferred strategy for treatment of saphenous vein graft (SVG) disease. However, there remains ongoing debate on whether drug-eluting stents (DES) or bare-metal stents (BMS) should be used during SVG-PCI. METHODS/MATERIALS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing DES and BMS for SVG-PCI. The primary end point was major adverse cardiac events (MACE), defined as composite of all-cause death, myocardial infarction (MI) or repeat revascularization. Secondary end points included individual MACE components, cardiac death and stent thrombosis (ST). RESULTS: Six RCTs including 1582 patients (50% receiving DES) met inclusion criteria. MACE occurred in 31% (244/797) patients receiving DES and 36% (281/785) patients receiving BMS (median follow-up, 12-35 months). There was no significant difference in MACE between DES and BMS (Odds Ratio (OR) 0.62, 95%CI 0.36-1.09, p = 0.10, I2 = 77%). However, for individual components of MACE, DES was associated with a significant reduction in repeat revascularization (OR 0.53, 95%CI 0.29-0.97, p = 0.04, I2 = 73%). There was no difference in all-cause death (OR 1.30, 95%CI 0.77-2.20, p = 0.33, I2 = 40%), MI (OR 0.68, 95%CI 0.38-1.25, p = 0.22, I2 = 56%), cardiac death (OR 1.08, 95%CI 0.45-2.64, p = 0.86, I2 = 42%) or ST (OR 0.89, 95%CI 0.37-2.17, p = 0.80, I2 = 35%) between stents. CONCLUSIONS: Although there was no significant difference in MACE, DES is associated with a reduction in repeat revascularization compared with BMS in pooled randomized trials for SVG-PCI. The high occurrence of MACE in both stent platforms highlights the need for novel therapeutic approaches to improve clinical outcomes following SVG intervention. SUMMARY: We performed a meta-analysis of randomized controlled trials comparing DES and BMS for SVG-PCI. There was no significant difference in MACE between DES and BMS. However, for individual components of MACE, DES was associated with a significant reduction in repeat revascularization. The high occurrence of MACE in both stent platforms highlights the need for novel therapeutic approaches to improve clinical outcomes following SVG intervention.

Association of Epicardial Adipose Tissue and High-Risk Plaque Characteristics: A Systematic Review and Meta-Analysis.

BACKGROUND: Epicardial adipose tissue (EAT) is hypothesized to alter atherosclerotic plaque composition, with potential development of high-risk plaque (HRP). EAT can be measured by volumetric assessment (EAT-v) or linear thickness (EAT-t). We performed a systematic review and random-effects meta-analysis to assess the association of EAT with HRP and whether this association is dependent on the measurement method used. METHODS AND RESULTS: Electronic databases were systematically searched up to October 2016. Studies reporting HRP by computed tomography or intracoronary imaging and studies measuring EAT-v or EAT-t were included. Odds ratios were extracted from multivariable models reporting the association of EAT with HRP and described as pooled estimates with 95% confidence intervals (CIs). Analysis was stratified by EAT measurement method. Nine studies (n=3772 patients) were included with 7 measuring EAT-v and 2 measuring EAT-t. Increasing EAT was significantly associated with the presence of HRP (odds ratio: 1.26 [95% CI, 1.11-1.43]; P<0.001). Patients with HRP had higher EAT-v than those without (weighted mean difference: 28.3 mL [95% CI, 18.8-37.8 mL]; P<0.001). EAT-v was associated with HRP (odds ratio: 1.19 [95% CI, 1.06-1.33]; P<0.001); however, EAT-t was not (odds ratio: 3.09 [95% CI, 0.56-17]; P=0.2). Estimates remained significant when adjusted for small-study effect bias (odds ratio: 1.13 [95% CI, 1.03-1.28]; P=0.04). CONCLUSIONS: Increasing EAT is associated with the presence of HRP, and patients with HRP have higher quantified EAT-v. The association of EAT-v with HRP is significant compared with EAT-t; however, a larger scale study is still required, and further evaluation is needed to assess whether EAT may be a potential therapeutic target for novel pharmaceutical agents. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/. Unique identifier: CRD42017055473.

Optical Coherence Tomography Guided Percutaneous Coronary Intervention.

Optical coherence tomography (OCT) is an increasingly available intracoronary imaging modality that provides high-resolution imaging of coronary arteries. Its fundamental reliance on the emission and reflection of light enables rapid data acquisition without compromise of image resolution. As such, OCT can inform operators planning percutaneous coronary intervention (PCI) by accurately defining luminal geometry and detailing plaque composition. Following PCI, OCT imaging delivers a thorough assessment of the treated arterial segment and can identify specific features not always visible on alternate imaging modalities, including stent edge-related dissection, plaque tissue prolapse, incomplete stent apposition and the presence of intra-coronary thrombus. Clinical trials highlight that procedural strategy is frequently altered based on OCT findings, while concerns over final stent dimensions have been mitigated through use of a sizing protocol based on external elastic lamina dimensions in the reference arterial segment. Randomised trials are now warranted to definitively ascertain whether OCT-guidance improves clinical outcomes when utilised during PCI.

Impact of heart rate on diagnostic accuracy of second generation 320-detector computed tomography coronary angiography.

OBJECTIVE: To assess the impact of elevated heart rate (HR) on the diagnostic accuracy and image quality of second-generation 320-detector computed tomography coronary angiography (320-CTCA). METHODS: Consecutive patients with suspected coronary disease referred for invasive coronary angiography (ICA) were prospectively recruited and underwent 320-CTCA. Pre-scan beta-blockers were administered if native HR>80 bpm and post-scan cohorts stratified by traditional (HR ≤60 bpm) and elevated HR (61-80 bpm). A wider phase window was used for the elevated HR group (30-80%). 320-CTCA and ICA were analyzed by independent readers blinded to other data. Significant disease was defined as ≥50% visual stenosis on ICA. Uninterpretable segments by 320-CTCA were considered to be significant on an intention-to-diagnose principle. Image quality was assessed by 5-point Likert score. RESULTS: Of 107 patients studied (1,662 segments), there was no significant difference in sensitivity, specificity, positive and negative predictive value between patients with HR ≤60 bpm (n=55) vs. HR 61-80 bpm (n=52): 97%, 88%, 95%, 94% vs. 100%, 88%, 95%, 100%; Receiver operator characteristic-area under the curve 0.93 vs. 0.94, P=0.82). Overall per-patient diagnostic accuracy was 96% in both groups with no significant difference in interpretable segments (Likert ≥2) or median radiation dose (2.4 mSv vs. 2.7 mSv, P=0.35). Only 4/1,662 (0.2%) segments were uninterpretable by motion artefact in the whole cohort. CONCLUSIONS: In patients with HR >60 and up to 80bpm, second generation 320-CTCA provides comparably adequate diagnostic accuracy to HR ≤60 without significantly impacting upon overall segmental evaluability.

Epicardial adipose tissue and myocardial ischemia assessed by computed tomography perfusion imaging and invasive fractional flow reserve.

BACKGROUND: Epicardial adipose tissue (EAT) is a metabolically active fat depot that is associated with incident coronary artery disease (CAD) and major adverse cardiovascular events. The relationship between EAT and myocardial ischemia remains unclear. This study investigated the relationship between EAT volume and the presence of perfusion defects on myocardial computed tomographic perfusion imaging (CTP) and functional stenoses on invasive fractional flow-reserve (FFR). METHODS: Data were obtained from a previous prospective cross-sectional study in patients with suspected CAD. Patients underwent combined coronary computed tomography angiography (coronary CTA) and CTP followed by invasive coronary angiogram (ICA) and FFR within 14 days. FFR was performed in all major epicardial vessels unless they were angiographically smooth or occluded, with a threshold of <0.8 considered significant. EAT volume was quantified semi-automatically on coronary CTA. RESULTS: There were 38 patients included for analysis, mean age 62.5 ± 10.0 years, 68.4% male. Median EAT volume was 82.8 mL (interquartile range (IQR) 49.3 mL). FFR was interrogated in 73/114 (64%) vessels. There was no difference in EAT volumes in patients with and without CTP defects (84.4 mL, IQR: 35.6 mL vs 81.1 mL, IQR: 53.1 mL, p = 0.7). There was also no difference in EAT volumes in patients with and without FFR-significant vessels (86.5 mL IQR: 36.6 mL vs 79.1 mL IQR: 54.5 mL, p = 0.7) and no difference when analysed by number of CTP positive territories or FFR-significant vessels (p = 0.4 and p = 0.8 respectively). CONCLUSION: This study demonstrated no observable relationship between EAT volume and perfusion defects on myocardial CT perfusion imaging or functional stenosis on invasive FFR.