Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension

Background: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. Methods: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. Results: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. Conclusion: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. Methods: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEi EDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. Results: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEi EDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEi EDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEi EDV were independent predictors of RV remodelling index. Conclusions: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT03217240

A relative resistance of T cells to dexamethasone in bipolar disorder

Objective: A relative resistance of immune cells to steroids has been established in patients with major depression (MD). In this study, we investigated the in vitro responsiveness of T cells to dexamethasone (DEX) of patients with bipolar disorder (BD).Methods: T cells of outpatients with DSM-IV BD (n = 54) and of healthy control subjects (HC; n = 29) were isolated, cultured and stimulated with phytohemagglutinin (PHA) for 72 h. The suppressive effect of graded concentrations of DEX (5 x 10(-9)-10(-5) M) on PHA-induced CD25 (IL-2R) expression was measured by fluorescence-activated cell sorting (FACS) analysis. Data were correlated to the T-cell activation status in the peripheral blood of the same patients and to their diagnosis, current mood state, ultradian cycling pattern and current use of medication, including lithium.Results: T cells of patients with BD were less sensitive to DEX-induced suppressive effects as compared with T cells of HC. These data were particularly evident at 10(-7) M DEX (mean % suppression +/- SEM BD: 18.9% +/- 3.5 versus HC: 35.8% +/- 4.7, p = 0.001). We found no correlations of this relative in vitro DEX resistance of T cells neither with the previously mentioned clinical characteristics nor with the actual activation status of the T cells in the BD patients.Conclusion: A relative T-cell resistance to steroids, as has been observed in MD previously, may be a trait phenomenon of BD, independent of mood state.</p

A relative resistance of T cells to dexamethasone in bipolar disorder

Objective: A relative resistance of immune cells to steroids has been established in patients with major depression (MD). In this study, we investigated the in vitro responsiveness of T cells to dexamethasone (DEX) of patients with bipolar disorder (BD). Methods: T cells of outpatients with DSM-IV BD (n = 54) and of healthy control subjects (HC; n = 29) were isolated, cultured and stimulated with phytohemagglutinin (PHA) for 72 h. The suppressive effect of graded concentrations of DEX (5 x 10(-9)-10(-5) M) on PHA-induced CD25 (IL-2R) expression was measured by fluorescence-activated cell sorting (FACS) analysis. Data were correlated to the T-cell activation status in the peripheral blood of the same patients and to their diagnosis, current mood state, ultradian cycling pattern and current use of medication, including lithium. Results: T cells of patients with BD were less sensitive to DEX-induced suppressive effects as compared with T cells of HC. These data were particularly evident at 10(-7) M DEX (mean % suppression +/- SEM BD: 18.9% +/- 3.5 versus HC: 35.8% +/- 4.7, p = 0.001). We found no correlations of this relative in vitro DEX resistance of T cells neither with the previously mentioned clinical characteristics nor with the actual activation status of the T cells in the BD patients. Conclusion: A relative T-cell resistance to steroids, as has been observed in MD previously, may be a trait phenomenon of BD, independent of mood state

Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects

Abstract Background Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. Methods We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. Results Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = − 0.355 for LV and − 0.318 for RV), and KEiEDV E/A ratio (r = − 0.475 for LV and − 0.504 for RV) decreased significantly, with age. Conclusion These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www.clinicaltrials.gov . Unique identifier: NCT03217240