No studies extensively compared the young adults (YA, 18–39 years), middle-aged (40–69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This ...study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent.
In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression.
A total of 6260 patients were included in this study. YA presented more often after ‘whoops’-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10 cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.46 (95% confidence interval CI: 1.22–1.74) and 3.06 (95% CI: 2.53–3.69) in the elderly population, compared with YA.
The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population.
•Young adults presented more often after ‘whoops’-surgery or reresection.•Elderly patients presented more often with grade III and larger tumours.•With increasing age, overall survival decreases and recurrence rates increases.•This could partially be explained by the imbalance in tumour/treatment variables.
Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ...ischemia in patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency department with chest pain symptoms and were referred for diagnostic invasive coronary angiography. Intravascular ultrasound virtual histology was used for the assessment of coronary plaque composition. A noncalcified plaque was defined as a combination of necrotic core and fibrofatty tissue. Quantitative flow ratio (QFR), which is a coronary angiography-based technique used to calculate fractional flow reserve without the need for hyperemia induction or for a pressure wire, was used as the reference standard for the evaluation of myocardial ischemia. Coronary artery plaques with QFR of ≤0.80 were considered abnormal—that is, ischemia-generating. In total, 149 coronary plaques were analyzed, 21 of which (14%) were considered abnormal according to QFR. The percentage of noncalcified tissue was significantly higher in plaques with abnormal QFR (38.2 ± 6.5% vs 33.1 ± 9.0%, p = 0.014). After univariable analysis, both plaque load (odds ratio OR per 1% increase 1.081, p <0.001) and the percentage of noncalcified tissue (OR per 1% increase 1.070, p = 0.020) were significantly associated with reduced QFR. However, after multivariable analysis, only plaque load remained significantly associated with abnormal QFR (OR per 1% increase 1.072, p <0.001). In conclusion, the noncalcified plaque area was significantly higher in hemodynamically significant coronary lesions than in nonsignificant lesions. Although an increase in the noncalcified plaque area was significantly associated with a reduced QFR, this association lost significance after adjustment for localized plaque load.
Currently applied methods for risk-assessment in coronary artery disease (CAD) often overestimate patients’ risk for obstructive CAD. To enhance risk estimation, assessment of coronary artery calcium ...(CAC) can be applied. In 10 % of patients presenting with stable chest pain a previous non-gated computed tomography (CT) has been performed, suitable for CAC-assessment. This study is the first to investigate the clinical utility of CAC-assessment on non-gated CT for risk-assessment of obstructive CAD in symptomatic patients.
For this analysis, all patients referred for coronary computed tomography angiography (CCTA), in whom a previous non-gated chest CT was performed were included. The extent of CAC was assessed on chest CT and ordinally scored. CAD was assessed on CCTA and obstructive CAD defined as stenosis of ≥70 %. Patients were stratified according to CAC-severity and percentages of patients with obstructive CAD were compared between the CAC groups.
In total, 170 patients of 32–88 years were included and 35 % were male. The percentage of obstructive CAD between the CAC groups differed significantly (p < 0.01). A calcium score of 0 ruled out obstructive CAD irrespective of sex, pre-test probability, type of complaints and number of risk factors with a 100 % certainty. Furthermore, a mild CAC score ruled out obstructive CAD in patients with low – intermediate PTP or non-anginal complaints with 100 % certainty.
When available, CAC on non-gated chest CT can accurately rule out obstructive CAD and can therefore function as a radiation-free and cost-free gatekeeper for additional imaging in patients presenting with stable chest pain.
Thoracic radiotherapy is one of the corner stones of HL treatment, but it is associated with increased risk of cardiovascular events. As HL is often diagnosed at a young age, long-term follow-up ...including screening for coronary artery disease (CAD) is recommended.
This study aims to evaluate the presence of coronary artery calcium score (CACS) in relation to cardiovascular events in HL patients treated with thoracic radiotherapy compared to a non-cancer control group.
Consecutive HL patients who underwent evaluation for asymptomatic CAD with coronary computed tomography angiography > 10 years after thoracic irradiation were included. The study population consisted of 97 HL patients matched to 97 non-cancer patients on gender, age, cardiovascular risk factors, and statin use.
Mean age during CT scan in the HL population was 45.5 ± 9.9 and in the non-cancer population 45.5 ± 10.3 years. CACS was elevated (defined as >0) in 49 (50.5%) HL patients and 30 (30.9%) control patients. HL survivors had an odds ratio of 2.28 95% CI: 1.22-4.28 for having a CACS > 0 compared to the matched population (
= 0.006). Prevalence of CACS > 90th percentile differed significantly: 17.1% in HL survivors vs. 4.6% in the matched population (
0.009). Non-obstructive coronary artery stenosis was more prevalent in the HL population than in the control population (45.7% vs. 28.4%, respectively,
= 0.01). During follow-up of 8.5 5.3; 9.9 years, nine HL patients experienced an event including two patients with a CACS of zero. No events occurred in the control population.
In a matched study population, HL survivors have a higher prevalence of a CACS > 0 and an increased risk of cardiovascular events after thoracic irradiation compared to a matched non-cancer control group.
Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease ...(CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD.
Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001).
In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.
Abstract Objectives Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify ...individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain. Methods We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient. Results After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis ( P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques. Conclusions In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.
Abstract
Aims
Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque ...volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET).
Methods and results
From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential 15OH2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021).
Conclusion
The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone.
Graphical Abstract
Graphical Abstract
Importance of plaque volume and composition for myocardial ischaemia.
Schematic representation of the study design and patients (left panel), the quantitative analysis of CCTA (middle panel), and the incremental predictive value of plaque volume and composition for myocardial ischaemia on PET (right panel). Images are partly derived and adjusted from Puchner et al., ‘High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial’, Journal of the American College of Cardiology, volume 64, page 687, copyright 2014, both with permission from Elsevier.
CAD, coronary artery disease; CCTA, coronary computed tomography angiography; PET, positron emission tomography.
This paper presents a readout circuit for a carbon dioxide (CO 2 ) sensor that measures the CO 2 -dependent thermal time constant of a hot-wire transducer. The readout circuit periodically heats up ...the transducer and uses a phase-domain <inline-formula> <tex-math notation="LaTeX">\Delta \Sigma </tex-math></inline-formula> modulator to digitize the phase shift of the resulting temperature transients. A single resistive transducer is used both as a heater and as a temperature sensor, thus greatly simplifying its fabrication. To extract the transducer's resistance, and hence its temperature, in the presence of large heating currents, a pair of transducers is configured as a differentially driven bridge. The transducers and the readout circuit have been implemented in a standard 0.16-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> CMOS technology, with an active area of 0.3 and 3.14 mm 2 , respectively. The sensor consumes 6.8 mW from a 1.8-V supply, of which 6.3 mW is dissipated in the transducers. A resolution of 94-ppm CO 2 is achieved in a 1.8-s measurement time, which corresponds to an energy consumption of 12 mJ per measurement, >10<inline-formula> <tex-math notation="LaTeX">\times </tex-math></inline-formula> less than prior CO 2 sensors in CMOS technology.
To enhance risk stratification in patients suspected of coronary artery disease, the assessment of coronary artery calcium (CAC) could be incorporated, especially when CAC can be readily assessed on ...previously performed non-gated chest computed tomography (CT). Guidelines recommend reporting on patients’ extent of CAC on these non-cardiac directed exams and various studies have shown the diagnostic and prognostic value. However, this method is still little applied, and no current consensus exists in clinical practice. This review aims to point out the clinical utility of different kinds of CAC assessment on non-gated CTs. It demonstrates that these scans indeed represent a merely untapped and underestimated resource for risk stratification in patients with stable chest pain or an increased risk of cardiovascular events. To our knowledge, this is the first review to describe the clinical utility of different kinds of visual CAC evaluation on non-gated unenhanced chest CT. Various methods of CAC assessment on non-gated CT are discussed and compared in terms of diagnostic and prognostic value. Furthermore, the application of these non-gated CT scans in the general practice of cardiology is discussed. The clinical utility of coronary calcium assessed on non-gated chest CT, according to the current literature, is evident. This resource of information for cardiac risk stratification needs no specific requirements for scan protocol, and is radiation-free and cost-free. However, some gaps in research remain. In conclusion, the integration of CAC on non-gated chest CT in general cardiology should be promoted and research on this method should be encouraged.
Background: Major improvements in cancer therapies have significantly contributed to increased survival rates of Hodgkin lymphoma (HL) survivors, outweighing cardiovascular side effects and the risks ...of radiation-induced heart disease. Non-invasive screening for coronary artery disease (CAD) starting five years after irradiation is recommended, as plaque development and morphology may differ in this high-risk population. Due to rapid plaque progression and a possibly higher incidence of non-calcified plaques, coronary artery calcium scoring may not be sufficient as a screening modality in HL survivors treated with thoracic radiotherapy. Case summary: A 42-year-old man with a history of HL treated with thoracic radiotherapy presented at the emergency department 20 years after cancer treatment with an ST-elevation myocardial infarction, in the absence of cardiovascular risk factors, for which primary percutaneous coronary intervention of the left anterior descending artery was performed. Four months prior to acute myocardial infarction, invasive coronary angiography only showed wall irregularities. Two years earlier, the Agatston calcium score was zero. Discussion: In HL survivors treated with thoracic radiotherapy, a calcium score of zero may not give the same warranty period for cardiac event-free survival compared to the general population. Coronary computed tomography angiography can be a proper diagnostic tool to detect CAD at an early stage after mediastinal irradiation, as performing calcium scoring may not be sufficient in this population to detect non-calcified plaques, which may show rapid progression and lead to acute coronary syndrome. Also, intensive lipid-lowering therapy should be considered in the presence of atherosclerosis in this patient population.
PDF
