Leiner, Tim

Fetal cardiovascular magnetic resonance imaging (MRI) has emerged as a complementary modality for prenatal imaging in suspected congenital heart disease. Ongoing technical improvements extend the potential clinical value of fetal cardiovascular MRI. Ascertaining equivocal prenatal diagnostics obtained with ultrasonography allows for appropriate parental counseling and planning of postnatal surgery. This work summarizes current acquisition techniques and clinical applications of fetal cardiovascular MRI in the prenatal diagnosis and follow‐up of fetuses with congenital heart disease.Level of Evidence3Technical EfficacyStage 3

Abstract Background Incorporation of CT-derived fractional flow reserve (CT-FFR) enhances the precision of Coronary CT Angiography (CCTA) to detect hemodynamically significant coronary artery disease (CAD). However, the financial consequences remain unclear. Purpose Our objective is to assess the economic implications of CT-FFR in the Dutch Healthcare system. Methods This retrospective, single-center cost effectiveness analysis includes patient data of a previously published study assessing the impact of routine CT-FFR availability on clinical management. We collected medical resource use for both diagnostic and therapeutic cardiovascular care with a follow-up duration of 1 year. Costs of CT-FFR analysis were set at €1000, its current price for Dutch hospitals. Median total costs at were compared using the Wilcoxon rank sum test, including a sensitivity analysis in which cost estimations (without registered maximum tariffs) were increased or decreased with 10%. Results A total of 360 patients, classified as having low to intermediate risk of CAD, were enrolled in the study – 224 in the CCTA group and 136 in the CT-FFR group. In addition to undergoing more (invasive) diagnostic testing and revascularization procedures over the studied period, patients in the CCTA-group had more outpatient clinic consultations (p<0.001), presented more frequently to the emergency department (p=0.035) and spend more nights in the hospital (p=0.11). Median costs were €3.347 (IQR €1.066 – €4.862) in the CCTA-group and €1.436 (IQR €1.362 - €3.943) in the CT-FFR group (p=0.091). Increasing cost estimation with 10% revealed a median of €3.431 in the CCTA-group versus €1.479 in the CT-FFR group (p=0.078), decreasing with 10% showed median costs of €3.263 in the CCTA-group and €1.392 in the CT-FFR group (p=0.118). In our sample, CT-FFR guided care would have been significantly cheaper than CCTA-guided care at or below a market price of €770. Conclusion Despite the significant reduction in additional diagnostic testing and hospital visits in the CT-FFR group, CT-FFR guided care was not cheaper than CCTA-guided care at its current market price of €1.000. Economic cost-effectiveness would have occurred from a price of €770 per analysis. The large difference between medians suggests that the lack of significance might partially be attributed to insufficient power in this relatively small sample size. Additionally, this study did not account for costs associated with loss of productivity and quality of life. However, less additional diagnostic testing, less revascularization procedures and less hospital consultations and admissions leads to reduction in hospital resource consumption and patient burden, which is an important advantage of CT-FFR as the number of referred patients increases yearly.

Abstract Objectives To perform a systematic review and meta-analysis on diagnostic accuracy and other outcomes of coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (CT-FFR) in candidates for trans-catheter aortic valve implantation (TAVI). Background Screening for obstructive coronary artery disease (CAD) with CCTA during TAVI work-up could prevent unnecessary invasive coronary angiography (ICA). This becomes increasingly relevant as the TAVI-population grows. CT-FFR improves CCTA accuracy in chest pain patients, but its reliability is unknown in the TAVI-population. Methods Pubmed, Embase and Web of Science were searched for studies regarding CCTA and/or CT-FFR in TAVI-candidates. Primary endpoint was correct identification and rule-out of obstructive CAD. Results were pooled in a meta-analysis. Results Twenty-four of the 29 included articles were part of the meta-analysis, reporting results for CCTA and CT-FFR in 3.494 and 797 patients respectively. Reference standard was anatomical severity of CAD in most studies. At patient-level, pooled CCTA sensitivity was 94.3% and specificity 74.8%. CT-FFR sensitivity was 91.5% and specificity 60.3% with strong variation between studies. CCTA correctly ruled out CAD in 52% of all patients, but 42% of positive CCTAs were false positives. CT-FFR correctly ruled out CAD in 47% of all patients included in this meta-analysis, but showed better accuracy than CCTA in studies that compared both. In these studies, sensitivity of CCTA versus CT-FFR was 70.7% versus 79.0% and specificity was 64.4% versus 92.9%. Conclusions Negative CCTA effectively rules-out CAD in the TAVI-population. Adding CCTA to TAVI work-up could lead to significant reduction in pre-TAVI ICA procedures, but the proportion of false-positives remains high. In studies performing a direct comparison, CT-FFR performed better than CCTA. This is not reflected in the CT-FFR meta-analysis. Therefore, diagnostic accuracy of CT-FFR and added value over CCTA in the TAVI-population remains unclear. Further research regarding validation and reliability is warranted.Meta-analysis of CCTA and CT-FFR

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

Abstract Purpose The aim of this study was to characterize a second‐generation wide‐detector dual‐layer spectral computed tomography (CT) system for material quantification accuracy, acquisition parameter and patient size dependencies, and tissue characterization capabilities. Methods A phantom with multiple tissue‐mimicking and material‐specific inserts was scanned with a dual‐layer spectral detector CT using different tube voltages, collimation widths, radiation dose levels, and size configurations. Accuracy of iodine density maps and virtual monoenergetic images (MonoE) were investigated. Additionally, differences between conventional and MonoE 70 keV images were calculated to evaluate acquisition parameter and patient size dependencies. To demonstrate material quantification and differentiation, liver‐mimicking inserts with adipose and iron were analyzed with a two‐base decomposition utilizing MonoE 50 and 150 keV, and root mean square error (RMSE) for adipose and iron content was reported. Results Measured inserts exhibited quantitative accuracy across a wide range of MonoE levels. MonoE 70 keV images demonstrated reduced dependence compared to conventional images for phantom size (1 vs. 27 HU) and acquisition parameters, particularly tube voltage (4 vs. 37 HU). Iodine density quantification was successful with errors ranging from ‐0.58 to 0.44 mg/mL. Similarly, inserts with different amounts of adipose and iron were differentiated, and the small deviation in values within inserts corresponded to a RMSE of 3.49 ± 1.76% and 1.67 ± 0.84 mg/mL for adipose and iron content, respectively. Conclusion The second‐generation dual‐layer CT enables acquisition of quantitatively accurate spectral data without compromises from differences in patient size and acquisition parameters.

AbstractPredicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population‐based cohort of 3525 patients with advanced cutaneous melanoma treated with anti‐PD‐1‐based therapy. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal–external cross‐validation. Included patients received anti‐PD‐1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence—all at start of ICI—, and location and type of primary melanoma, the presence of satellites and/or in‐transit metastases at primary diagnosis and sex. The over‐optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64–0.66). The range of predicted response probabilities was 7%–81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression‐free survival (20.0 vs 2.8 months; P < .001) and median overall survival (62.0 vs 8.0 months; P < .001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.

Abstract Objectives The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of Coronary CT Angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). Methods This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACE) during the one-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. Results 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA-group and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA) and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA and three (2.2%) SPECT (p&lt;0.001 for all three options). The revascularization rate after ICA was similar between groups (p=0.15). However, patients in the CCTA-group more often underwent revascularization (p=0.007). Conclusion Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after one year.Clinical decisions and follow upSignificant LAD lesion, negative FFRCT

Objective Animal data suggest that exercise during chemotherapy is cardioprotective, but clinical evidence to support this is limited. This study evaluated the effect of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity. Methods This is a follow-up study of two previously performed randomised trials in patients with breast cancer allocated to exercise during chemotherapy or non-exercise controls. Cardiac imaging parameters, including T1 mapping (native T1, extracellular volume fraction (ECV)), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), cardiorespiratory fitness, and physical activity levels, were acquired 8.5 years post-treatment. Results In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years), of whom 99% and 18% were treated with anthracyclines and trastuzumab, respectively. ECV and Native T1 were 25.3%±2.5% and 1026±51 ms in the control group, and 24.6%±2.8% and 1007±44 ms in the exercise group, respectively. LVEF was borderline normal in both groups, with an LVEF<50% prevalence of 22.5% (n=40/178) in all participants. Compared with control, native T1 was statistically significantly lower in the exercise group (β=−20.16, 95% CI −35.35 to −4.97). We found no effect of exercise on ECV (β=−0.69, 95% CI −1.62 to 0.25), LVEF (β=−1.36, 95% CI −3.45 to 0.73) or GLS (β=0.31, 95% CI −0.76 to 1.37). Higher self-reported physical activity levels during chemotherapy were significantly associated with better native T1 and ECV. Conclusions In long-term breast cancer survivors, exercise and being more physically active during chemotherapy were associated with better structural but not functional cardiac parameters. The high prevalence of cardiac dysfunction calls for additional research on cardioprotective measures, including alternative exercise regimens. Trial registration number NTR7247.