Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Insertable Biosensors: Combining Implanted Sensing Materials with Wearable Monitors.

Insertable biosensor systems are medical diagnostic devices with two primary components: an implantable biosensor within the body and a wearable monitor that can remotely interrogate the biosensor from outside the body. Because the biosensor does not require a physical connection to the electronic monitor, insertable biosensor systems promise improved patient comfort, reduced inflammation and infection risk, and extended operational lifetimes relative to established percutaneous biosensor systems. However, the lack of physical connection also presents technical challenges that have necessitated new innovations in developing sensing chemistries, transduction methods, and communication modalities. In this review, we discuss the key developments that have made insertables a promising option for longitudinal biometric monitoring and highlight the essential needs and existing development challenges to realizing the next generation of insertables for extended-use diagnostic and prognostic devices.

Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Relationship between coronary volume, myocardial mass, and post-PCI fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) carries prognostic information. Yet, myocardial mass subtended by a stenosis influences FFR. We hypothesized that a smaller coronary lumen volume and a large myocardial mass might be associated with lower post-PCI FFR. AIM: We sought to assess the relationship between vessel volume, myocardial mass, and post-PCI FFR. METHODS: This was a subanalysis with an international prospective study of patients with significant lesions (FFR ≤ 0.80) undergoing PCI. Territory-specific myocardial mass was calculated from coronary computed tomography angiography (CCTA) using the Voronoi's algorithm. Vessel volume was extracted from quantitative CCTA analysis. Resting full-cycle ratio (RFR) and FFR were measured before and after PCI. We assessed the association between coronary lumen volume (V) and its related myocardial mass (M), and the percent of total myocardial mass (%M) with post-PCI FFR. RESULTS: We studied 120 patients (123 vessels: 94 left anterior descending arteries, 13 left Circumflex arteries, 16 right coronary arteries). Mean vessel-specific mass was 61 ± 23.1 g (%M 39.6 ± 11.7%). The mean post-PCI FFR was 0.88 ± 0.06 FFR units. Post-PCI FFR values were lower in vessels subtending higher mass (0.87 ± 0.05 vs. 0.89 ± 0.07, p = 0.047), and with lower V/M ratio (0.87 ± 0.06 vs. 0.89 ± 0.07, p = 0.02). V/M ratio correlated significantly with post-PCI RFR and FFR (RFR r = 0.37, 95% CI: 0.21-0.52, p < 0.001 and FFR r = 0.41, 95% CI: 0.26-0.55, p < 0.001). CONCLUSION: Post-PCI RFR and FFR are associated with the subtended myocardial mass and the coronary volume to mass ratio. Vessels with higher mass and lower V/M ratio have lower post-PCI RFR and FFR.

Evaluation of an artificial intelligence coronary artery calcium scoring model from computed tomography.

OBJECTIVES: Coronary artery calcium (CAC) scores derived from computed tomography (CT) scans are used for cardiovascular risk stratification. Artificial intelligence (AI) can assist in CAC quantification and potentially reduce the time required for human analysis. This study aimed to develop and evaluate a fully automated model that identifies and quantifies CAC. METHODS: Fully convolutional neural networks for automated CAC scoring were developed and trained on 2439 cardiac CT scans and validated using 771 scans. The model was tested on an independent set of 1849 cardiac CT scans. Agatston CAC scores were further categorised into five risk categories (0, 1-10, 11-100, 101-400, and > 400). Automated scores were compared to the manual reference standard (level 3 expert readers). RESULTS: Of 1849 scans used for model testing (mean age 55.7 ± 10.5 years, 49% males), the automated model detected the presence of CAC in 867 (47%) scans compared with 815 (44%) by human readers (p = 0.09). CAC scores from the model correlated very strongly with the manual score (Spearman's r = 0.90, 95% confidence interval [CI] 0.89-0.91, p < 0.001 and intraclass correlation coefficient = 0.98, 95% CI 0.98-0.99, p < 0.001). The model classified 1646 (89%) into the same risk category as human observers. The Bland-Altman analysis demonstrated little difference (1.69, 95% limits of agreement: -41.22, 44.60) and there was almost excellent agreement (Cohen's κ = 0.90, 95% CI 0.88-0.91, p < 0.001). Model analysis time was 13.1 ± 3.2 s/scan. CONCLUSIONS: This artificial intelligence-based fully automated CAC scoring model shows high accuracy and low analysis times. Its potential to optimise clinical workflow efficiency and patient outcomes requires evaluation. KEY POINTS: • Coronary artery calcium (CAC) scores are traditionally assessed using cardiac computed tomography and require manual input by human operators to identify calcified lesions. • A novel artificial intelligence (AI)-based model for fully automated CAC scoring was developed and tested on an independent dataset of computed tomography scans, showing very high levels of correlation and agreement with manual measurements as a reference standard. • AI has the potential to assist in the identification and quantification of CAC, thereby reducing the time required for human analysis.

Biodegradable nanofiber-based piezoelectric transducer.

Piezoelectric materials, a type of "smart" material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA [poly(l-lactic acid)] nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood-brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.

A Glucose Biosensor Based on Phosphorescence Lifetime Sensing and a Thermoresponsive Membrane.

The adoption of existing continuous glucose monitors (CGMs) is limited by user burden. Herein, a design for a glucose biosensor with the potential for subcutaneous implantation, without the need for a transcutaneous probe or affixed transmitter, is presented. The design is based on the combination of an enzyme-driven phosphorescence lifetime-based glucose-sensing assay and a thermoresponsive membrane anticipated to reduce biofouling. The metalloporphyrin, Pd meso-tetra(sulfophenyl)-tetrabenzoporphyrin ([PdPh4 (SO3 Na)4 TBP]3 , HULK) as well as glucose oxidase (GOx) are successfully incorporated into the UV-cured double network (DN) membranes by leveraging electrostatic interactions and covalent conjugation, respectively. The oxygen-sensitive metalloporphyrin is incorporated at different levels within the DN membranes. These HULK-containing membranes retain the desired thermosensitivity, as well as glucose diffusivity and primary optical properties of the metalloporphyrin. After subsequently modifying the membranes with GOx, glucose-sensing experiments reveal that membranes prepared with the lowest GOx level exhibit the expected increase in phosphorescent lifetime for glucose concentrations up to 200 mg dL-1 . For membranes prepared with relatively higher GOx, oxygen-limited behavior is considered the source of diminished sensitivity at higher glucose levels. This proof-of-concept study demonstrates the promising potential of a biosensor design integrating a specific optical biosensing chemistry into a thermoresponsive hydrogel membrane.

Right ventricular end-diastolic volume and outcomes in exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Right ventricular (RV) volumes are crucial outcome determinants in pulmonary diseases. Little is known about the associations of RV volumes during hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to ascertain associations of RV end-diastolic volume indexed to body surface area (RVEDVI) during hospitalized AECOPD and its relationship with mortality in long-term follow-up. METHODS: This is a prospective observational cohort study (December 2013-November 2019, ACTRN12617001562369) using dynamic retrospective ECG-gated computed tomography during hospitalized AECOPD. RVEDVI was defined as normal or high using Framingham Offspring Cohort values. Cox regression determined the prognostic relevance of RVEDVI for death. RESULTS: A total of 148 participants (70 ± 10 years [mean ± SD], 88 [59%] men) were included, of whom 75 (51%) had high RVEDVI. This was associated with more frequent hospital admissions in the 12 months before admission (52/75 [69%] vs. 38/73 [52%], p = 0.04) and higher breathlessness (modified Medical Research Council score, 2.9 ± 1.3 vs. 2.4 ± 1.2, p = 0.007). During follow-up, high RVEDVI was associated with greater mortality (log-rank p = 0.001). In univariable Cox regression, increasing RVEDVI was associated with higher mortality (hazard ratio [HR]: 1.02 per ml/m2 ; 95% CI: 1.01, 1.03; p = 0.001). In multivariable Cox regression, RVEDVI was independently associated with mortality (HR: 1.01 per ml/m2 ; 95% CI: 1.00, 1.03; p = 0.050) at a borderline significance level. Adding RVEDVI to three COPD mortality prediction systems improved model fit (pooled chi-square test [BODE: p = 0.05, ADO: p = 0.04, DOSE: p = 0.02]). CONCLUSION: In patients with hospitalized AECOPD, higher RV end-diastolic volume was associated with worse acute clinical parameters and greater mortality.

Do 'pathologic' cardiac murmurs in adolescents identify structural heart disease? An evaluation of 15 141 active adolescents for conditions that put them at risk of sudden cardiac death.

OBJECTIVES: We assessed whether the presence and character of a cardiac murmur in adolescents were associated with structural heart disease that confers risk of sudden cardiac death (SCD). METHODS: We performed a retrospective analysis of 15 141 adolescents age 12-19 who underwent a heart screen with history, physical examination and ECG. Participants with any screening abnormality underwent an echocardiogram for the assessment of structural heart disease. Murmurs were classified as physiological or pathological according to standard clinical criteria, and participants with murmurs were compared with a comparison group without murmurs. The primary outcome was echocardiogram-detected structural heart disease associated with SCD. RESULTS: 905 participants with a cardiac murmur (mean age 15.8; 58% male) and 4333 participants without a murmur (comparison group; mean age 15.8; 55% male) had an echocardiogram to detect structural heart disease. 743 (82%) murmurs were described as physiological and 162 (18%) as pathological. Twenty-five (2.8%) participants with murmurs and 61 (1.4%) participants without murmurs had structural heart disease. Three (0.3%) participants in the murmur group were diagnosed with hypertrophic cardiomyopathy (HCM) which was the only identified condition associated with SCD. Two participants with HCM had physiological murmurs, one had a pathological murmur, and all three had an abnormal ECG. The most common minor structural heart disease was bicuspid aortic valve in both the murmur (7; 0.8%) and comparison (20; 0.5%) groups. The positive predictive value of physiological versus pathological murmurs for identifying any structural heart disease was 2.4% versus 4.3% (p=0.21), respectively. The positive predictive value of having any murmur versus no murmur for identifying structural heart disease was 2.8% versus 1.4% (p=0.003), respectively. CONCLUSIONS: In adolescents, the traditional classification of cardiac murmurs as 'physiologic' or 'pathologic' does not differentiate for structural heart disease that puts individuals at risk for SCD. We recommend ECG evaluation in all patients with a cardiac murmur found during preparticipation screening to increase detection of HCM.

Diagnostic Performance of CT-Derived Fractional Flow Reserve in Australian Patients Referred for Invasive Coronary Angiography.

BACKGROUND: Non-invasive computed tomography (CT)-derived fractional flow reserve (FFRCT) is computed from standard coronary CT angiography (CTA) datasets and provides accurate vessel-specific ischaemia assessment of coronary artery disease (CAD). To date, the technique and its diagnostic performance has not been verified in the Australian clinical context. The aim of this study was to describe and compare the diagnostic performance of FFRCT and CTA for the detection of vessel-specific ischaemia as determined by invasive fractional flow reserve (FFR) in the Australian patient population. METHODS: One-hundred-and-nine patients (219 vessels) referred for clinically mandated invasive angiography were retrospectively assessed. Each patient underwent research mandated CTA and FFRCT within 3 months of invasive angiography and invasive FFR assessment. Independent core laboratory assessments were made to determine visual CTA stenosis, FFRCT and invasive FFR values. FFRCT values were matched with the corresponding invasive FFR measurement taken at the given wire position. Visual CTA stenosis ≥50%, FFRCT values ≤0.8 and invasive FFR values ≤0.8 were considered significant for ischaemia. RESULTS: Per vessel accuracy, sensitivity, specificity, positive predictive value and negative predictive value of FFRCT were 80.4%, 80.0%, 80.6%, 64.9% and 90.0% respectively. Corresponding values for CTA were 75.1%, 87.1%, 69.2%, 58.1% and 91.7% respectively. In receiver operating characteristic curve analysis, FFRCT demonstrated superior area under the curve (AUC) compared with CTA in both per vessel (0.87 vs 0.77, p=0.004) and per patient analysis (0.86 vs 0.74, p=0.011). Per vessel AUC of combined CTA and FFRCT was superior to CTA alone (0.89 vs 0.77, p<0.0001). CONCLUSION: In this cohort of Australian patients, the diagnostic performance of FFRCT was found to be comparable to existing international literature, with demonstrated improvement in performance compared with CTA alone for the detection of vessel-specific ischaemia.

Contemporary Evidence-Based Diagnosis and Management of Severe Coronary Artery Calcification.

Percutaneous treatment of heavily calcified coronary lesions remains a challenge for interventional cardiologists with increased risk of incomplete lesion preparation, suboptimal stent deployment, procedural complications, and a higher rate of acute and late stent failure. Adequate lesion preparation through calcium modification is crucial in optimising procedural outcomes. Several calcium modification devices and techniques exist, with rotational atherectomy the predominant treatment for severely calcified lesions. Novel technologies such as intravascular lithotripsy are now available and show promise as a less technical and highly effective approach for calcium modification. Emerging evidence also emphasises the value of detailed characterisation of calcification severity and distribution especially with intracoronary imaging for appropriate device selection and individualised treatment strategy. This review aims to provide an overview of the non-invasive and invasive evaluation of coronary calcification, discuss calcium modification techniques and propose an algorithm for the management of calcified coronary lesions.

Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring.

A standardised method for cardiovascular risk stratification in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors is lacking. We report an algorithm for risk stratification applicable to all patients commencing tyrosine kinase inhibitor therapy based on age, prior cardiovascular disease and Framingham Risk Score, incorporating coronary artery calcium scoring in patients at intermediate Framingham Risk Score risk. Of 88 patients retrospectively studied, major adverse cardiovascular event rates in our study-defined low-, intermediate- and high-risk categories were 0%, 10% and 19% respectively. Of nine patients down-classified from intermediate to low risk on the basis of coronary artery calcium scoring, none went on to experience a major adverse cardiovascular event.

Computational Fluid Dynamics in Intracranial Atherosclerosis - Lessons from Cardiology: A Review of CFD in Intracranial Atherosclerosis.

BACKGROUND: Intracranial atherosclerosis is a common cause of stroke with a high recurrence rate. Haemodynamically significant lesions are associated with a particularly high risk of recurrence. Computational fluid dynamics (CFD) is a tool that has been investigated to identify haemodynamically significant lesions. CFD in the intracranial vasculature benefits from the precedent set by cardiology, where CFD is an established clinical tool. This precedent is particularly important in CFD as models are very heterogenous. There are many decisions-points in the model-creation process, usually involving a trade-off between computational expense and accuracy. OBJECTIVES: This study aimed to review published CFD models in intracranial atherosclerosis and compare them to those used in cardiology. METHODS: A systematic search for all published computational fluid dynamics models applied to intracranial atherosclerosis was performed. Each study was analysed as regards to the different steps in creating a fluid dynamics model and findings were compared with established cardiology CFD models. RESULTS AND CONCLUSION: 38 papers were screened and 12 were included in the final analysis. There were important differences between coronary and intracranial atherosclerosis models in the following areas: area of interest segmented, use of transient models vs steady-state models, boundary conditions, methods for solving the fluid dynamics equations and validation. These differences may be high-yield areas to explore for future research.

Fractional Flow Reserve following Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.

CT-Derived Fractional Flow Reserve (CT-FFR) in the Evaluation of Coronary Artery Disease.

Fractional flow reserve derived from coronary computed tomography enables anatomical and haemodynamic assessment of coronary artery disease in a single non-invasive test. Its diagnostic performance has been established against invasive fractional flow reserve in multi-centre trials, and a growing body of evidence has demonstrated its utility in predicting clinical outcomes. The purpose of this article is to describe the physiological principles, review its diagnostic performance, and describe the role of this technology in a real world clinical application.

Prognostic Value and Risk Continuum of Noninvasive Fractional Flow Reserve Derived from Coronary CT Angiography.

Background Coronary CT angiography with noninvasive fractional flow reserve (FFR) predicts lesion-specific ischemia when compared with invasive FFR. The longer term prognostic value of CT-derived FFR (FFRCT) is unknown. Purpose To determine the prognostic value of FFRCT when compared with coronary CT angiography and describe the relationship of the numeric value of FFRCT with outcomes. Materials and Methods This prospective subanalysis of the NXT study (Clinicaltrials.gov: NCT01757678) evaluated participants suspected of having stable coronary artery disease who were referred for invasive angiography and who underwent FFR, coronary CT angiography, and FFRCT. The incidence of the composite primary end point of death, myocardial infarction, and any revascularization and the composite secondary end point of major adverse cardiac events (MACE: cardiac death, myocardial infarction, unplanned revascularization) were compared for an FFRCT of 0.8 or less versus stenosis of 50% or greater on coronary CT angiograms, with treating physicians blinded to the FFRCT result. Results Long-term outcomes were obtained in 206 individuals (age, 64 years ± 9.5), including 64% men. At median follow-up of 4.7 years, there were no cardiac deaths or myocardial infarctions in participants with normal FFRCT. The incidence of the primary end point was more frequent in participants with positive FFRCT compared with clinically significant stenosis at coronary CT angiography (73.4% [80 of 109] vs 48.7% [91 of 187], respectively; P < .001), with the majority of outcomes being planned revascularization. Corresponding hazard ratios (HRs) were 9.2 (95% confidence interval [CI]: 5.1, 17; P < .001) for FFRCT and 5.9 (95% CI: 1.5, 24; P = .01) for coronary CT angiography. FFRCT was a superior predictor compared with coronary CT angiography for primary end point (C-index FFRCT, 0.76 vs coronary CT angiography, 0.54; P < .001) and MACE (FFRCT, 0.71 vs coronary CT angiography, 0.52; P = .001). Frequency of MACE was higher in participants with positive FFRCT compared with coronary CT angiography (15.6% [17 of 109] vs 10.2% [19 of 187], respectively; P = .02), driven by unplanned revascularization. MACE HR was 5.5 (95% CI: 1.6, 19; P = .006) for FFRCT and 2.0 (95% CI: 0.3, 14; P = .46) for coronary CT angiography. Each 0.05-unit FFRCT reduction was independently associated with greater incidence of primary end point (HR, 1.7; 95% CI: 1.4, 1.9; P < .001) and MACE (HR, 1.4; 95% CI: 1.1, 1.8; P < .001). Conclusion In stable patients referred for invasive angiography, a CT-derived fractional flow reserve (FFRCT) value of 0.8 or less was a predictor of long-term outcomes driven by planned and unplanned revascularization and was superior to clinically significant stenosis on coronary CT angiograms. Additionally, the numeric value of FFRCT was an independent predictor of outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dennie and Rubens in this issue.

Coexisting chronic obstructive pulmonary disease and cardiovascular disease in clinical practice: a diagnostic and therapeutic challenge.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist but combined disease is often not recognised. Since symptoms overlap significantly, it is common for patients' presentations to be attributed to one disease alone, and for the other to be overlooked. The effect of COPD and CVD goes beyond the shared risk factors of smoking and advancing age. The presence of COPD adversely affects cardiac disease and vice versa. In comparison to individuals with one disease alone, those with both conditions have a higher mortality rate, experience more frequent exacerbations with more hospitalisations and have worse quality of life. More patients with mild and moderate COPD die from CVD than from COPD, and there is a higher rate of arrhythmias, particularly atrial fibrillation. Accurate and timely diagnosis is therefore crucial. Retrospective evidence indicates that individuals with COPD and CVD may have better outcomes with appropriate CVD pharmacotherapy, yet robust prospective evidence is lacking. Inhaled medications for patients with stable COPD improve quality of life and reduce exacerbations, but there is limited evidence that they reduce mortality. A low threshold for investigation and treatment of CVD in COPD and COPD in CVD is essential.

Apelin-36 Modulates Blood Glucose and Body Weight Independently of Canonical APJ Receptor Signaling.

Apelin-36 was discovered as the endogenous ligand for the previously orphan receptor APJ. Apelin-36 has been linked to two major types of biological activities: cardiovascular (stimulation of cardiac contractility and suppression of blood pressure) and metabolic (improving glucose homeostasis and lowering body weight). It has been assumed that both of these activities are modulated through APJ. Here, we demonstrate that the metabolic activity of apelin-36 can be separated from canonical APJ activation. We developed a series of apelin-36 variants in which evolutionarily conserved residues were mutated, and evaluated their ability to modulate glucose homeostasis and body weight in chronic mouse models. We found that apelin-36(L28A) retains full metabolic activity, but is 100-fold impaired in its ability to activate APJ. In contrast to its full metabolic activity, apelin-36(L28A) lost the ability to suppress blood pressure in spontaneously hypertensive rats (SHR). We took advantage of these findings to develop a longer-acting variant of apelin-36 that could modulate glucose homeostasis without impacting blood pressure (or activating APJ). Apelin-36-[L28C(30kDa-PEG)] is 10,000-fold less potent than apelin-36 at activating the APJ receptor but retains its ability to significantly lower blood glucose and improve glucose tolerance in diet-induced obese mice. Apelin-36-[L28C(30kDa-PEG)] provides a starting point for the development of diabetes therapeutics that are devoid of the blood pressure effects associated with canonical APJ activation.

Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors.

Several BCR-ABL1 tyrosine kinase inhibitors (TKIs) are approved for the first-line treatment of chronic phase chronic myeloid leukaemia (CML). Disease control is achieved in the vast majority of patients and disease-specific survival is excellent. Consequently, there is now emphasis on managing comorbidities and minimising treatment-related toxicity. Second-generation TKIs have cardiovascular risks that are greater than with imatinib treatment, but these risks must be balanced against the superior CML responses encountered with more potent TKIs. Cardiovascular risk should be assessed at baseline using a locally validated model based on the Framingham risk equation. Clinicians involved in the care of CML patients should be aware of the vascular complications of TKIs and manage cardiovascular risk factors early to mitigate treatment-related risks. Reversible risk factors, such as dyslipidaemia, smoking, diabetes and hypertension, should be addressed. We summarise the available data on cardiovascular complications in CML patients treated with TKIs. Using the latest evidence and collective expert opinion, we provide practical advice for clinicians to assess, stratify and manage cardiovascular risk in people with CML receiving TKI therapy.