Asymptomatic coronary artery disease in ischaemic stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke and coronary artery disease share risk factors and stroke survivors experience a high rate of cardiac events. Recent work suggests a high burden of asymptomatic coronary artery disease (CAD) in ischaemic stroke survivors. Thus, we performed this systematic review and meta-analysis to A) estimate the prevalence of CAD in ischaemic stroke survivors without known CAD and B) evaluate the association between coronary atherosclerosis and future major adverse cardiovascular events (MACE) in stroke survivors. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis according to the PRISMA statement. We included studies investigating acute ischaemic stroke or transient ischaemic attack where participants underwent anatomical assessment of all coronary arteries. For objective B) we included studies that reported an association between coronary atherosclerosis and MACE. Two reviewers used the Newcastle-Ottawa Scale to assess risk of bias. We used random-effects modelling for our analyses. RESULTS: We identified 2983 studies of which 17 were included. These studies had a total of 6862 participants between 2008 and 2022. The pooled prevalence of any coronary atherosclerosis was 66.8% (95% CI 57.2%-75.1%) with substantial heterogeneity (I2 = 95.2%). The pooled prevalence of obstructive (>50%) stenosis was 29.3% with substantial heterogeneity (I2 = 91%). High-risk coronary anatomy (triple vessel disease or left main stenosis) was found in 7.0% (95% CI 4%-12%) with high heterogeneity I2 = 72%. One study examined high-risk plaques and found a prevalence of 5.9%. Five studies reported the association of coronary atherosclerosis with future MACE. The presence of obstructive CAD confers a HR of 8.0 (95% CI 1.7-37.1, p = 0.007) for future MACE. DISCUSSION AND CONCLUSIONS: Asymptomatic CAD is common in ischaemic stroke survivors. The presence and severity of asymptomatic CAD strongly associates with the risk of future MACE. Further evaluation of the benefits of routine coronary assessment in ischaemic stroke is warranted.

Asia-Pacific Investigators and Asian Enrollment in Cardiometabolic Trials: Insights From Publications Between 2011 and 2020.

Background: A lack of geographic and racial diversity in clinical trial populations may arise from a disproportionate focus on the United States and Europe for trial leadership and conduct. Inadequate diversity may compromise the external validity to the Asia-Pacific (APAC) region, where 60% of global cardiometabolic disease exists. Objectives: This study aimed to assess the proportion and trends of Asian race participants and APAC authorship in cardiometabolic trials. Methods: We performed a systematic review of all cardiovascular, diabetes and obesity-related randomized controlled trials (phase ≥2, n = ≥100) published in these major medical journals: the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association between January 1, 2011, and December 31, 2020. Trial leadership was defined by first authorship, and any listed author was considered a trial collaborator. Temporal trends were evaluated using the Jonckheere-Terpstra proportion test and correlations using Pearson's correlation coefficient. Participant-to-prevalence ratios (PPR) were determined using Global Health Data Exchange registry data. Results: A total of 8.3% (218,613 of 2,619,710) participants identified as being of Asian race and 7.7% of total enrollment occurred in APAC. APAC lead authorship occurred in 52 of 656 (7.9%) trials and collaboration in 10.1% (1312 of 13,000 of authors), which correlated with Asian enrollment (r = 0.63 and r = 0.76, respectively). A marginal increase in the proportion of Asian race (Δ1.40% ± 6.95%/year, P = 0.003) and APAC regional (Δ1.46% ± 8.67%/year, P = 0.003) enrollment was observed; however, severe regional underrepresentation persisted (PPR <0.30). Conclusions: Despite a favorable trend over the past decade, Asian participants and authors from APAC remain significantly underrepresented in seminal cardiometabolic trials; barriers to trial conduct and leadership in this region must be addressed.

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.

Incessant myopericarditis after mRNA vaccination requiring IL-1 receptor antagonist therapy and pericardiectomy: case report.

Background: During the COVID-19 pandemic, there has been global administration of novel mRNA vaccines that are effective in reducing the burden of COVID-19. In tandem with this administration, mRNA vaccine-associated complications have been identified. One such complication is mRNA vaccine-associated pericarditis. Case summary: This is a case of a 40-year old male who developed clinical pericarditis 3 days after his first dose of the Pfizer-BioNtech mRNA COVID-19 vaccination. The diagnosis of mRNA vaccine-induced pericarditis was confirmed on cardiac magnetic imaging and was resistant to numerous lines of medical therapy. These included substantial simple and opioid-based analgaesia, colchicine, prednisolone, interleukin-1 receptor antagonist therapy (anakinra), and a ketamine infusion that were all titrated over the course of eight hospital admissions. Ultimately, surgical pericardiectomy was performed that resulted in a favourable outcome. Discussion: This case depicts an example of incessant mRNA vaccine-associated pericarditis, a known complication of the Pfizer-BioNtech mRNA COVID-19 vaccination. There is limited evidence guiding the therapy of mRNA-induced pericarditis especially when recurrent and resistant to simple analgaesia, colchicine, and steroids. Thus, this case represents a potential framework to help future cases of incessant mRNA vaccine-induced pericarditis.

Pericoronary adipose tissue attenuation on coronary computed tomography angiography associates with male sex and Indigenous Australian status.

To evaluate if Indigenous Australians have higher coronary inflammation demonstrated non-invasively using pericoronary adipose tissue attenuation on coronary computed tomography angiography (CCTA). We retrospectively obtained a cohort 54 Indigenous patients age- and sex-matched to 54 non-Indigenous controls (age: 46.5 ± 13.1 years; male: n = 66) undergoing CCTA at the Royal Darwin Hospital and Monash Medical Centre. Patient groups were defined to investigate the interaction of ethnicity and sex: Indigenous + male, Indigenous + female, control + male, control + female. Semi-automated software was used to assess pericoronary adipose tissue attenuation (PCAT-a) and volume (PCAT-v). Males had significantly higher PCAT-a (- 86.7 ± 7.8 HU vs. - 91.3 ± 7.1 HU, p = 0.003) than females. Indigenous patients had significantly higher PCAT-v (1.5 ± 0.5cm3 vs. 1.3 ± 0.4cm3, p = 0.032), but only numerically higher PCAT-a (p = 0.133) than controls. There was a significant difference in PCAT-a and PCAT-v across groups defined by Indigenous status and sex (p = 0.010 and p = 0.030, respectively). Among patients with matching CCTA contrast density, multivariable linear regression analysis showed an independent association between Indigenous status and PCAT-a. Indigenous men have increased PCAT-a in an age- and sex-matched cohort. Male sex is strongly associated with increased PCAT-a. Coronary inflammation may contribute to adverse cardiovascular outcomes in Indigenous Australians, but larger studies are required to validate these findings.

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).

Artificial intelligence-assisted quantification of COVID-19 pneumonia burden from computed tomography improves prediction of adverse outcomes over visual scoring systems.

OBJECTIVE: We aimed to evaluate the effectiveness of utilizing artificial intelligence (AI) to quantify the extent of pneumonia from chest CT scans, and to determine its ability to predict clinical deterioration or mortality in patients admitted to the hospital with COVID-19 in comparison to semi-quantitative visual scoring systems. METHODS: A deep-learning algorithm was utilized to quantify the pneumonia burden, while semi-quantitative pneumonia severity scores were estimated through visual means. The primary outcome was clinical deterioration, the composite end point including admission to the intensive care unit, need for invasive mechanical ventilation, or vasopressor therapy, as well as in-hospital death. RESULTS: The final population comprised 743 patients (mean age 65  ±â€¯ 17 years, 55% men), of whom 175 (23.5%) experienced clinical deterioration or death. The area under the receiver operating characteristic curve (AUC) for predicting the primary outcome was significantly higher for AI-assisted quantitative pneumonia burden (0.739, p = 0.021) compared with the visual lobar severity score (0.711, p < 0.001) and visual segmental severity score (0.722, p = 0.042). AI-assisted pneumonia assessment exhibited lower performance when applied for calculation of the lobar severity score (AUC of 0.723, p = 0.021). Time taken for AI-assisted quantification of pneumonia burden was lower (38 ± 10 s) compared to that of visual lobar (328 ± 54 s, p < 0.001) and segmental (698 ± 147 s, p < 0.001) severity scores. CONCLUSION: Utilizing AI-assisted quantification of pneumonia burden from chest CT scans offers a more accurate prediction of clinical deterioration in patients with COVID-19 compared to semi-quantitative severity scores, while requiring only a fraction of the analysis time. ADVANCES IN KNOWLEDGE: Quantitative pneumonia burden assessed using AI demonstrated higher performance for predicting clinical deterioration compared to current semi-quantitative scoring systems. Such an AI system has the potential to be applied for image-based triage of COVID-19 patients in clinical practice.

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.

Pericoronary Adipose Tissue as a Marker of Cardiovascular Risk: JACC Review Topic of the Week.

Vascular inflammation is a key driver in atherosclerotic progression and plaque rupture. Recent evidence has shown that coronary computed tomography provides a noninvasive method of quantifying coronary inflammation by mapping changes in pericoronary adipose tissue (PCAT) radiodensity, which are associated with cardiovascular diseases. However, there are significant knowledge gaps in the performance and measurement of PCAT that complicate its interpretation. In this review the authors aim to summarize the role of PCAT in cardiac imaging and explore the clinical implications and applicability as a novel biomarker of cardiovascular risk, as well as to discuss its limitations and potential pitfalls.

Cardiac adverse events in bisphosphonate and teriparatide users: An international pharmacovigilance study.

BACKGROUND: Cardiovascular effects of osteoporosis medications have recently been highlighted. Although oral and intravenous bisphosphonates are assumed to have similar cardiovascular safety, few head-to-head comparisons exist. The cardiovascular safety of teriparatide is unknown. Aim We conducted a pharmacovigilance safety study of cardiac events using real-life adverse event reports from alendronate, zoledronic acid and teriparatide users. METHODS: Adverse drug reactions were obtained from Vigibase, a WHO database of individual case safety reports (ICSRs) from 130 countries (1967-2020). ISCRs for atrial fibrillation (AF), angina pectoris, arteriosclerosis coronary artery (ACA), cardiac arrhythmias, coronary artery disease (CAD), thromboembolic events (TE), ischaemic heart disease (IHD), torsade de pointes/QT prolongation (TDP) associated with alendronate, zoledronic acid and teriparatide use were extracted. Data were included in a disproportionality analysis where the lower end of the 95 % credibility interval for the information component (IC025), showing a statistical association when >0. Head-to-head comparisons of ISCRs were estimated by age-adjusted odds ratios and 95 % confidence intervals. RESULTS: 465 episodes of angina, 287 ACA, 13,385 arrhythmias, 792 CAD, 6743 TE, 3264 IHD, 1037 myocardial infarcts, and 3714 TDP events were recorded across 50,365 alendronate, 52,436 zoledronic acid and 137,629 teriparatide users. There was a significant association between alendronate and zoledronate with all outcomes except MI. Teriparatide use was associated with AF, arrythmias and angina only. In head-to-head comparisons, teriparatide use was associated with fewer ACA and CAD events than alendronate and fewer ACA than zoledronic acid. DISCUSSION: Osteoporosis medication use is associated with adverse cardiac events, except for MI, and these appear to be more common with oral and intravenous bisphosphonates than teriparatide. Our data do not support differential effects of oral and intravenous bisphosphonates on cardiac events. Mechanisms whereby teriparatide may be cardio-protective warrant further investigation.

Rapid quantification of COVID-19 pneumonia burden from computed tomography with convolutional long short-term memory networks.

Purpose: Quantitative lung measures derived from computed tomography (CT) have been demonstrated to improve prognostication in coronavirus disease 2019 (COVID-19) patients but are not part of clinical routine because the required manual segmentation of lung lesions is prohibitively time consuming. We aim to automatically segment ground-glass opacities and high opacities (comprising consolidation and pleural effusion). Approach: We propose a new fully automated deep-learning framework for fast multi-class segmentation of lung lesions in COVID-19 pneumonia from both contrast and non-contrast CT images using convolutional long short-term memory (ConvLSTM) networks. Utilizing the expert annotations, model training was performed using five-fold cross-validation to segment COVID-19 lesions. The performance of the method was evaluated on CT datasets from 197 patients with a positive reverse transcription polymerase chain reaction test result for SARS-CoV-2, 68 unseen test cases, and 695 independent controls. Results: Strong agreement between expert manual and automatic segmentation was obtained for lung lesions with a Dice score of 0.89 ± 0.07 ; excellent correlations of 0.93 and 0.98 for ground-glass opacity (GGO) and high opacity volumes, respectively, were obtained. In the external testing set of 68 patients, we observed a Dice score of 0.89 ± 0.06 as well as excellent correlations of 0.99 and 0.98 for GGO and high opacity volumes, respectively. Computations for a CT scan comprising 120 slices were performed under 3 s on a computer equipped with an NVIDIA TITAN RTX GPU. Diagnostically, the automated quantification of the lung burden % discriminate COVID-19 patients from controls with an area under the receiver operating curve of 0.96 (0.95-0.98). Conclusions: Our method allows for the rapid fully automated quantitative measurement of the pneumonia burden from CT, which can be used to rapidly assess the severity of COVID-19 pneumonia on chest CT.

Quantitative plaque characterisation and association with acute coronary syndrome on medium to long term follow up: insights from computed tomography coronary angiography.

Background: Computed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up. Methods: Retrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP; <56 HU), very-low-attenuation-plaque (vLAP; <30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up. Results: A total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (-) patients and patients with no plaques (20.5% vs. 1.6% vs. 0.4%, log-rank test P<0.001). ACS was more frequent in HRP (+)/OS (+) patients (20.7%) compared to HRP (+)/OS (-) patients (8.6%), HRP (-)/OS (+) patients (1.8%) and HRP (-)/OS (-) patients (1.0%). OS, cross-sectional plaque area (PA) and the presence of vLAP identified those HRP lesions that were more likely to cause future ACS. Cross-sectional LAP area (<56 HU) in HRP lesions added incremental prognostic value to OS in predicting ACS (P=0.008). Conclusions: The presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS.

Prognostic Value of Exercise Capacity in Kidney Transplant Candidates.

Background Exercise stress testing for cardiovascular assessment in kidney transplant candidates has been shown to be a feasible alternative to pharmacologic methods. Exercise stress testing allows the additional assessment of exercise capacity, which may have prognostic value for long-term cardiovascular outcomes in pre-transplant recipients. This study aimed to evaluate the prognostic value of exercise capacity on long-term cardiovascular outcomes in kidney transplant candidates. Methods and Results We retrospectively evaluated exercise capacity in 898 consecutive kidney transplant candidates between 2013 and 2020 who underwent symptom-limited exercise stress echocardiography for pre-transplant cardiovascular assessment. Exercise capacity was measured by age- and sex-predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events, defined as cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazard multivariable modeling was performed to define major adverse cardiovascular events predictors with transplantation treated as a time-varying covariate. A total of 429 patients (48%) achieved predicted METs. During follow-up, 93 (10%) developed major adverse cardiovascular events and 525 (58%) underwent transplantation. Achievement of predicted METs was independently associated with reduced major adverse cardiovascular events (hazard ratio [HR] 0.49; [95% CI 0.29-0.82], P=0.007), as was transplantation (HR, 0.52; [95% CI 0.30-0.91], P=0.02). Patients achieving predicted METs on pre-transplant exercise stress echocardiography had favorable outcomes that were independent (HR, 0.78; [95% CI 0.32-1.92], P=0.59) and of similar magnitude to subsequent transplantation (HR, 0.97; [95% CI 0.42-2.25], P=0.95). Conclusions Achievement of predicted METs on pre-transplant exercise stress echocardiography confers excellent prognosis independent of and of similar magnitude to subsequent kidney transplantation. Future studies should assess the benefit on exercise training in this population.