BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%. RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was −0.37% (95% CI, −3.59% to 2.85%; P =0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%–4.10%; P =0.92, not equivalent). CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline. REGISTRATION: URL: https://doi.org ; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2017-000896-99.

Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.

Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and ¹⁸ F-sodium fluoride ( ¹⁸ F-NaF) positron emission tomography. Participants (n=47) were imaged once with ¹⁸ F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. Results: In patients with TAVI, native aortic valves demonstrated ¹⁸ F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI ( r =0.36, P =0.023). ¹⁸ F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2–1.7] versus 1.3 [1.2–1.5], respectively; P =0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P =0.78), computed tomography (15% versus 14%, respectively; P =0.87), and positron emission tomography (15% versus 29%, respectively; P =0.09). Baseline ¹⁸ F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI ( r =0.7, P <0.001) and SAVR ( r =0.7, P <0.001). On multivariable analysis, ¹⁸ F-NaF uptake was the only predictor of peak velocity progression ( P <0.001). Conclusions: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02304276.

Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and “smart” contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque. This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology.

Inflammation affects the aortic wall through complex pathways that alter its biomechanical structure and cellular composition. Inflammatory processes that predominantly affect the intima cause occlusive disease whereas medial inflammation and degeneration cause aneurysm formation. Aortic inflammatory pathways share common metabolic features that can be localized by smart contrast agents and radiolabelled positron emission tomography (PET) tracers. 18F-Fluorodeoxyglucose (18F-FDG) is a non-specific marker of metabolism and has been widely used to study aortic inflammation in various diseased aortic states. Although useful in detecting disease, 18F-FDG has yet to demonstrate a reliable link between vessel wall disease and clinical progression. 18F-Sodium fluoride (18F-NaF) is a promising biological tracer that detects microcalcification related to active disease and cellular necrosis within the vessel wall. 18F-NaF shows a high affinity to bind to diseased arterial tissue irrespective of the underlying inflammatory process. In abdominal aortic aneurysms, 18F-NaF PET/CT predicts increased rates of growth and important clinical end-points, such as rupture or the requirement for repair. Much work remains to be done to bridge the gap between detecting aortic inflammation in at-risk individuals and predicting adverse clinical events. Novel radiotracers may hold the key to improve our understanding of vessel wall biology and how this relates to patients. Combined with established clinical and morphological assessment techniques, PET imaging promises to improve disease detection and clinical risk stratification.

Background Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying ¹⁸F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. Methods Twenty patients underwent two hybrid ¹⁸F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each ¹⁸F-NaF quantification method was compared to validated cardiovascular risk scores. Results Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. Conclusions AMA is a simple, rapid and reproducible method of quantifying global ¹⁸F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.