Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume

Background Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. Methods Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). Results Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to − 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (− 2 ± 7%). Conclusions CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV. Graphical abstract

Comparison of the effects of adenosine, isoproterenol and their combinations on pulmonary transit time in rats using contrast echocardiography

Aims: To compare the effects of adenosine (Ade), isoproterenol (Iso) and their combinations on pulmonary transit time (PTT) in rats using contrast echocardiography.Material and methods: Thirty-two adult Sprague Dawley (SD) rats were divided into four groups (n=8) according the medicines of tail-intravenous injection: Group 1, control; Group 2, Ade; Group 3, Iso; Group 4, Ade+Iso. They all underwent conventional echocardiography and contrast echocardiography with measurements of PTT.Results: With Ade injection, OnsetRV-OnsetLV PTT (PTT1), PeakRV-PeakLV PTT (PTT2) and OnsetRV-PeakLV PPT (PTT3) decreased and PTT3 had the largest decreased percentage, with the highest performance in differentiating the Ade group from the control group [the area under receiver operating characteristic curve (AUC), sensitivity and Youden’s index was maximal]. With Iso injection, PTT1, PTT2 and PTT1 all increased and PTT1 had the largest increased percentage, with the highest performance in differentiating the Iso group from the control group (AUC, sensitivity and Youden’s index was maximal). With a combination injection of Ade and Iso, the PTT values were similar to the control group and no PTT coulddifferentiate the Ade+Iso group from the control group.Conclusions: Ade or/and Iso exerted distinct effects on PTT. These findings remind us that it is a necessary to consider the effects of medicine (especially cardiopulmonary vasoactive drugs) on the PTT values. At the same time, it provides the basis for the clinical transformation of consecutive Iso/Ade treatment from the perspective of pulmonary circulation.

Comparison of the prognostic value of stress and rest pulmonary transit time estimation using myocardial perfusion CMR

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship Background Pulmonary transit time (PTT) is a quantitative biomarker of cardiopulmonary status. Rest PTT was previously shown to predict outcomes in specific disease models, but clinical adoption is hindered but challenges in data acquisition. Whether evaluation of PTT during stress encodes incremental prognostic information has not been previously investigated as scale. Objectives To compare the prognostic value of stress and rest PTT derived from a fully automated, in-line method of estimation using perfusion CMR, in a large patient cohort. Methods A retrospective two-center study of patients referred clinically for adenosine stress myocardial perfusion assessment using CMR. Analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically, allowing the in-line estimation of both rest and stress PTT. Association with major adverse cardiovascular events (MACE) was evaluated. MACE was defined as a composite outcome of myocardial infarction, stroke, heart failure admission and ventricular tachycardia or appropriate ICD treatment (including ICD shock and/or anti-tachycardia pacing). Results 985 patients (67% male, median age 62 years (IQR 52,71)) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR 54-69). Median stress PTT was shorter than rest PTT 6.2 (IQR 5.1, 7.7) seconds versus 7.7 (IQR, 6.4, 9.2) seconds. Stress and rest PTT were highly correlated (r = 0.69; p < 0.001). Stress PTT also correlated with LVEF (r=-0.37), stress MBF (r=-0.31), LVEDVi (r = 0.24), LA area index (r = 0.32) (p < 0.001 for all). Over a median follow-up period of 28.6 (IQR, 22.6 35,7) months, MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both rest and stress PTT, independently predicted MACE, but not all-cause mortality. For every 1xSD (2.39s) increase in rest PTT the adjusted hazard ratio (HR) for MACE was 1.43 (95% CI 1.10-1.85, p = 0.007). The hazard ratio for one standard deviation (2.64s) increase in stress PTT was 1.34 (95% CI 1.048-1.723; p = 0.020) after adjusting for age, LVEF, hypertension, diabetes, sex and presence of LGE Conclusions In this 2-center study of 985 patients, we deploy a fully automated method of PTT estimation using perfusion mapping with CMR and show that both stress and rest PTT are independently associated with adverse cardiovascular outcomes. In this patient cohort, there is no clear incremental prognostic value of stress PTT, over its evaluation during rest. Figure 1. Stress and Rest Pulmonary Transit Time estimation using myocardial perfusion CMR Figure 2. Event-free survival curves for major adverse cardiovascular events (Heart failure hospitalization, myocardial infarction, stroke and ventricular tachycardia/ICD treatment) according to mean rest PTT (8.05seconds) and mean stress PTT (6.7seconds). Log-rank for both p < 0.05

Prognostic value of pulmonary transit time by cardiac magnetic resonance in patients with heart failure with preserved ejection fraction

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): National Institute for Health Research Leicester Cardiovascular Biomedical Research Centre Background Quantifying pulmonary transit time (PTT) from cardiac magnetic resonance (CMR) first pass perfusion imaging is a novel technique for the evaluation of haemodynamic congestion in heart failure. Previous studies have demonstrated that PTT is prolonged in patients with heart failure with reduced ejection fraction (HFrEF) and that it provides independent prognostic information in this patient group. However, the potential diagnostic and prognostic roles of PTT assessment in patients with heart failure with preserved ejection fraction (HFpEF) remain to be established. Aim To compare PTT in healthy controls and in patients with HFpEF, and to determine the prognostic value of PTT in HFpEF. Methods In a prospective, observational study, HFpEF and age-matched control subjects underwent multi-parametric CMR at 3-Tesla, comprising quantitative left ventricular volumetric assessment using a standard steady-state free precession (SSFP) pulse sequence, and first-pass perfusion imaging at rest using a T1-weighted segmented inversion recovery gradient echo sequence (following injection of 0.04mmol/kg of contrast). PTT was calculated as the time interval between the peaks of signal intensity curves in the right and left ventricular blood pools (defined on the basal slice of the rest perfusion images). The primary endpoint was the composite of death or hospitalisation with heart failure. Results 88 HFpEF patients (age 73 ± 9 years, 51% male, EF 56.4 ± 5.6%) and 40 controls (age 73 ± 5 years, 43% male, EF 58.5 ± 4.7%) were studied. PTT was comparable in HFpEF patients (7.7 ± 3.8s) and in healthy controls (7.5 ± 1.8, p = 0.69). Normalised to cardiac cycle lengths, PTT remained comparable in HFpEF patients and healthy controls (8.5 ± 4.0 cardiac cycles versus 7.8 ± 1.6 cardiac cycles, respectively, p = 0.19). In the HFpEF group, during median follow-up of 3.4 years, there were 38 events (25 hospitalisations with heart failure, 13 deaths); a significant relationship between survival and PTT was not demonstrated (HR 1.06 [0.99,1.14] for a one-unit increase, p = 0.098). Conclusion In HFpEF, PTT is not prolonged compared with PTT in healthy subjects. Unlike in HFrEF, PTT does not appear to be diagnostically or prognostically significant in HFpEF. Figure 1: Graph showing signal intensity curves in the right (red) and left (green) ventricular blood pools Figure 2: Kaplan-Meier plot showing comparable rates of the composite endpoint in patients with PTT greater/less than median PTT (8 cardiac cycles)

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging

This methodical work describes the measurement and calculation of pulmonary blood volume in mice based on two imaging techniques namely by using magnetic particle imaging (MPI) and cardiac magnetic resonance imaging (MRI). Besides its feasibility aspects that may influence quantitative analysis are studied. Eight FVB mice underwent cardiac MRI to determine stroke volumes and anatomic MRI as morphological reference for functional MPI data. Arrival time analyses of boli of 1 µl of 1 M superparamagnetic tracer were performed by MPI. Pulmonary transit time of the bolus was determined by measurements in the right and left ventricles. Pulmonary blood volume was calculated out of stroke volume, pulmonary transit time and RR-interval length including a maximal error analysis. Cardiac stroke volume was 31.7 µl ± 2.3 µl with an ejection fraction of 71% ± 6%. A sharp contrast bolus profile was observed by MPI allowing subdividing the first pass into three distinct phases: tracer arrival in the right ventricle, pulmonary vasculature, and left ventricle. The bolus full width at half maximum was 578 ms ± 144 ms in the right ventricle and 1042 ms ± 150 ms in the left ventricle. Analysis of pulmonary transit time revealed 745 ms ± 81 ms. Mean RR-interval length was 133 ms ± 12 ms. Pulmonary blood volume resulted in 177 µl ± 27 µl with a mean maximal error limit of 27 µl. Non-invasive assessment of the pulmonary blood volume in mice was feasible. This technique can be of specific value for evaluation of pulmonary hemodynamics in mouse models of cardiac dysfunction or pulmonary disease. Pulmonary blood volume can complement cardiac functional parameters as a further hemodynamic parameter.

Pulmonary hypertension detection by computed tomography pulmonary transit time in heart failure with reduced ejection fraction

Aims To evaluate the relationships between pulmonary transit time (PTT), cardiac function, and pulmonary haemodynamics in patients with heart failure with reduced ejection fraction (HFrEF) and to explore how PTT performs in detecting pulmonary hypertension (PH). Methods and results In this prospective study, 57 patients with advanced HFrEF [49 men, 51 years ± 8, mean left ventricular (LV) ejection fraction 26% ± 8] underwent echocardiography, right heart catheterization, and cardiac computed tomography (CT). PTT was measured as the time interval between peaks of attenuation in right ventricle (RV) and LV and was compared between patients with or without PH and 15 controls. PTT was significantly longer in HFrEF patients with PH (21 s) than in those without PH (11 s) and controls (8 s) (P < 0.001) but not between patients without PH and controls (P = 0.109). PTT was positively correlated with pulmonary artery wedge pressure (PAWP) (r = 0.74), mean pulmonary artery pressure (r = 0.68), N-terminal pro-B-type natriuretic peptide (r = 0.60), mitral (r = 0.54), and tricuspid (r = 0.37) regurgitation grades, as well as with LV, RV, and left atrial volumes (r from 0.39 to 0.64) (P < 0.01). PTT was negatively correlated with cardiac index (r = −0.63) as well as with LV (r = −0.66) and RV (r = −0.74) ejection fractions. PAWP, cardiac index, mitral regurgitation grade, and RV end-diastolic volume were all independent predictors of PTT. PTT value ≥14 s best-detected PH with 91% sensitivity and 88% specificity (area under the receiver operating characteristic curve: 0.95). Conclusion In patients with HFrEF, PTT correlates with cardiac function and pulmonary haemodynamics, is determined by four independent parameters, and performs well in detecting PH.