Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study.

BACKGROUND: Methods for accurate quantification of lung fluid in heart failure (HF) are needed. Dynamic contrast-enhanced (DCE)-MRI may be an appropriate modality. PURPOSE: DCE-MRI evaluation of fraction of fluid volume in the interstitial lung space (ve ) and vascular permeability (Ktrans ). STUDY TYPE: Prospective, single-center method validation. POPULATION: Seventeen evaluable healthy volunteers (HVs), 12 participants with HF, and 3 with acute decompensated HF (ADHF). FIELD STRENGTH/SEQUENCE: T1 mapping (spoiled gradient echo variable flip angle acquisition) followed by dynamic series (three-dimensional spoiled gradient-recalled echo acquisitions [constant echo time, repetition time, and flip angle at 1.5 T]). ASSESSMENT: Three whole-chest scans were acquired: baseline (Session 1), 1-week later (Session 2), following exercise (Session 3). Extended Tofts model quantified ve and Ktrans (voxel-wise basis); total lung median measures were extracted and fitted via repeat measure analysis of variance (ANOVA) model. Patient tolerability of the scanning protocol was assessed. STATISTICAL TESTS: This was constructed as an experimental medicine study. PRIMARY ENDPOINTS: Ktrans and ve at baseline (HV vs. HF), change in Ktrans and ve following exercise, and following lung congestion resolution (ADHF). Ktrans and ve were fitted separately using ANOVA. Secondary endpoint: repeatability, that is, within-participant variability in ve and Ktrans between sessions (coefficient of variation estimated via mixed effects model). RESULTS: There was no significant difference in mean Ktrans between HF and HV (P ≤ 0.17): 0.2216 minutes-1 and 0.2353 minutes-1 (Session 1), 0.2044 minutes-1 and 0.2567 minutes-1 (Session 2), 0.1841 minutes-1 and 0.2108 minutes-1 (Session 3), respectively. ve was greater in the HF group (all scans, P ≤ 0.02). Results were repeatable between Sessions 1 and 2; mean values for HF and HV were 0.4946 and 0.3346 (Session 1), 0.4353 and 0.3205 (Session 2), respectively. There was minimal difference in Ktrans or ve between scans for participants with ADHF (small population precluded significance testing). Scanning was well tolerated. DATA CONCLUSION: While no differences were detected in Ktrans , ve was greater in chronic HF patients vs. HV, augmented beyond plasma and intracellular volume. DCE-MRI is a valuable diagnostic and physiologic tool to evaluate changes in fluid volume in the interstitial lung space associated with symptomatic HF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Role of Vascular Adaptation in Determining Systolic Blood Pressure in Young Adults.

Background Two individuals can have a similar pulse pressure (PP) but different levels of systolic blood pressure (SBP), although the underlying mechanisms have not been described. We hypothesized that, for a given level of PP, differences in SBP relate to peripheral vascular resistance (PVR); and we tested this hypothesis in a large cohort of healthy young adults. Methods and Results Demographic, biochemical, and hemodynamic data from 3103 subjects were available for the current analyses. In both men and women, for a given level of PP, higher SBP was associated with significantly higher body weight, body mass index, heart rate, and PVR (P<0.05 versus those with lower BP for all comparisons). Moreover, stratifying individuals by quartiles of PP and PVR revealed a stepwise increase in SBP from the lowest to highest quartile for each variable, with the highest SBP occurring in those in the highest quartile of both PP and PVR (P<0.001 for overall trend for both sexes). PVR was also increased with increasing tertile of minimum forearm vascular resistance, in both men (P=0.002) and women (P=0.03). Conclusions Increased PVR, mediated in part through altered resistance vessel structure, strongly associates with the elevation of SBP for a given level of PP in young adults. An impaired ability to adapt PVR appropriately to a given level of PP may be an important mechanism underlying elevated SBP in young adults.

Evaluation of inert gas rebreathing for determination of cardiac output: influence of age, gender and body size.

The aim of this study was to evaluate an inert gas rebreathing method (Innocor) for measurement of cardiac output and related haemodynamic variables and to provide robust normative data describing the influence of age, gender and body size on these variables. Four separate studies were conducted: measurement repeatability (study 1, n = 45); postural change (study 2, n = 40); response to submaximal cycling exercise (study 3, n = 20); and the influence of age, gender and body size (study 4, n = 1400). Repeated measurements of cardiac output, stroke volume and heart rate were similar, with low mean (±SD) differences (0.26 ± 0.53 L/min, 0 ± 11 mL and 2 ± 6beats/min, respectively). In addition, cardiac output and stroke volume both declined progressively from supine to seated and standing positions (P < 0.001 for both) and there was a stepwise increase in both parameters moving from rest to submaximal exercise (P < 0.001 for both). In study 4, there was a significant age-related decline in cardiac output and stroke volume in males and females, which remained significant after adjusting for body surface area (BSA, P < 0.001 for all comparisons). Both parameters were also significantly higher in those with high body mass index (BMI; P < 0.01 versus those with normal BMI for all comparisons), although indexing cardiac output and stroke volume to BSA reversed these trends. Inert gas rebreathing using the Innocor device provides repeatable measurements of cardiac output and related indices, which are sensitive to the effects of acute physiological manoeuvres. Moreover, inert gas rebreathing is a suitable technique for examining chronic influences such as age, gender and body size on key haemodynamic components of the arterial blood pressure.

Feeling the pressure: (patho) physiological mechanisms of weight gain and weight loss in humans.

Obesity is an ongoing global epidemic and has adverse consequences for cardiovascular health. Obesity is often associated with hypertension, which is, itself, a common condition and an important cause of morbidity and mortality worldwide. Although animal models of obesity have provided extensive data on the links between obesity and hypertension, a greater understanding of the pathways linking obesity and hypertension in humans is likely to assist translation of animal data, and may, itself, identify important treatment strategies. Ultimately, this could have a substantial impact on human health, both at an individual and population level. The current review will focus specifically on studies of experimental weight gain and weight loss in humans and the following key areas, which are strongly related to blood pressure: cardiovascular function, autonomic nervous system function, metabolic function and the impact of cardiorespiratory fitness.

Mechanisms underlying elevated SBP differ with adiposity in young adults: the Enigma study.

OBJECTIVES: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults. METHOD: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex. RESULTS: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals. CONCLUSION: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP.