Changes In Extracellular Volume Research Articles

#2464 Association of vascular access flow and volume status on fistula arm by bio-impedance analysis

Abstract Background and Aims Multi-frequency bio-impedance is a tool of body composition measure and can monitor changes in extracellular volume during dialysis. Arterio-venous fistulae (AVF) could potentially affect fluid retention in the arm. We investigated whether multi-frequency bio-impedance could defect AVF stenosis or association of AVF with fluid retention in the AVF arm. Method We measured the extracellular water (ECF) and total body water (TBW) in AVF arm following hemodialysis by multi-frequency bio-impedance (Inbody S10®) using an eight-electrode contact technique. We measured AVF or AVG flow by transonic ultrasonography using an ultrasound dilution technology (HD 03®) in hemodialysis. Results Total 82 patients (male 38 patients : female 44 patients) were enrolled. The causes of ESRD were DM : non-DM = 38 : 44. The mean age of patients was 54.89 ± 13.21 years. The ECW/TBW ration of fistula arm was a significantly higher than the ECW/TBW ration of non-fistula arm (0.389 ± 0.010 vs. 0.382 ± 0.001; p<0.05). The ECW/TBW ration of fistula arm was a significantly negative correlation with access flow level (mL/min) on fistula (p<0.05). The 5kHz reactance of fistula arm was a significantly positive correlation with access flow level (mL/min) on fistula (p<0.05). The 5kHz Phase Angle of fistula arm was a significantly positive correlation with access flow level (mL/min) on fistula (p<0.05). Conclusion Absolute and also relative extracellular fluid volumes are increased in the fistula arm of hemodialysis. We thought that extracellular fluid volumes in the fistula arm were associated with access flow level (mL/min) and/or relative fistula stenosis. We suggest that multi-frequency bio-impedance can be a useful assistant tool of vascular access flow measure.

Extracellular volume fraction can predict the treatment response and survival outcome of colorectal cancer liver metastases

ObjectiveTo assess the prognostic value of pre- and post-therapeutic changes in extracellular volume (ECV) fraction of liver metastases (LMs) for treatment response (TR) and survival outcomes in colorectal cancer liver metastases (CRLM). Methods186 LMs were confirmed by pathology or follow-up (Training: 130; Test: 56). We analyzed the changes in ECV fraction of LMs before and after 2 cycles of chemotherapy combined with bevacizumab. After 12 cycles, we evaluated the TR on LMs based on the RECIST v1.1. Relative changes in ECV fraction and Hounsfield Units (HU), defined as ΔECV and ΔHU, were associated with progression-free survival (PFS), overall survival (OS), and TR. We identified TR predictors with multivariate logistic regression and PFS, OS risk factors with COX analysis. Results186 LMs were classified as TR lesions (TR+: 84) and non-TR lesions (TR-:102). ΔECV, ΔHUA-E, and texture could distinguish the TR of LMs in training and test set (P < 0.05). ΔECV [Odds ratio (OR): 1.03; 95% Confidence interval (CI): 1.02–1.05, P < 0.01] was an independent predictor of TR-. Area under the curve (AUC), sensitivity and specificity of TR model in training and test set were 0.87, 0.84, 90.14%, 90.32%, 72.88%, 64.00%, respectively. High CRD_score indicates that patients have shorter PFS [Hazard ratio (HR): 2.01; 95%CI: 1.02–3.98, P = 0.045)] and OS (HR: 1.89, 95%CI: 1.04–3.42, P = 0.038). ConclusionΔECV can be used as an independent predictor of TR of CRLM chemotherapy combined with bevacizumab.

CT Images in Follicular Lymphoma: Changes after Treatment Are Predictive of Cardiac Toxicity in Patients Treated with Anthracycline-Based or R-B Regimens

The aim of this study is to evaluate changes in epicardial adipose tissue (EAT) and cardiac extracellular volume (ECV) in patients with follicular lymphoma (FL) treated with R-CHOP-like regimens or R-bendamustine. We included 80 patients with FL between the ages of 60 and 80 and, using computed tomography (CT) performed at onset and at the end of treatment, we assessed changes in EAT by measuring tissue density at the level of the cardiac apex, anterior interventricular sulcus and posterior interventricular sulcus of the heart. EAT is known to be associated with metabolic syndrome, increased calcium in the coronary arteries and therefore increased risk of coronary artery disease. We also evaluated changes in ECV, which can be used as an early imaging marker of cardiac fibrosis and thus myocardial damage. The R-CHOP-like regimen was associated with lower EAT values (p &lt; 0.001), indicative of a less active metabolism and more adipose tissue, and an increase in ECV (p &lt; 0.001). Furthermore, in patients treated with anthracyclines and steroids (R-CHOP-like) there is a greater decrease in ejection fraction (EF p &lt; 0.001) than in the R-B group. EAT and ECV may represent early biomarkers of cardiological damage, and this may be considered, to our knowledge, the first study investigating radiological and cardiological parameters in patients with FL.

Myocardial structural and functional changes in cardiac amyloidosis - insights from a prospective observational patient registry

Abstract Background Within the last decade, cardiac amyloidosis (CA) has been acknowledged as a significant cause of heart failure and patients who are affected face a dismal prognosis, especially in later stages of the disease. The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time and its' impact on prognosis are lacking. Objectives We aimed to investigate the progression of ECV and its prognostic impact in CA patients. Methods Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification were performed in consecutive CA patients. Results Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%. During a median follow-up period of 12 months, ECV increased significantly in all cohorts (48.0% to 50.5%, p&amp;lt;0.001; 49.0% to 50.5%, p&amp;lt;0.001; 42.6% to 50.6%, p = 0.026). Separate analyses for treatment-naïve (n = 14) and treated (n = 66) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (5.5% versus 2.7%, p = 0.035). Survival analyses demonstrated that median change of ECV was an independent (adjusted for troponin t and NT-proBNP) predictor of outcome in all CA cohorts [total: hazard ratio (HR): 1.114, 95% confidence-interval (CI): 1.045 – 1.189, p&amp;lt;0.001; ATTR: HR: 1.099, 95% CI: 1.014 – 1.192, p = 0.022; AL: HR: 1.142, 95% CI: 1.006 – 1.297, p = 0.040]. Conclusions The present study demonstrates that ECV, quantified by CMR T1 mapping, increases significantly in CA patients over the course of 12 months. While ECV increased, irrespective of amyloid type our analyses showed the highest increase among untreated ATTR patients. Moreover, the change of ECV was an independent predictor of adverse outcomes in AL, as well as ATTR patients emphasizing the usefulness of CMR T1 mapping in the management of CA patients.Figure 1.Dot PlotsFigure 2.Kaplan Meier Curves

Tracking multi-organ treatment response in systemic AL amyloidosis with cardiac magnetic resonance derived extracellular volume mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Systemic light-chain (AL) amyloidosis commonly involves the liver, spleen and heart. Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has demonstrated accuracy in measuring cardiac, hepatic and splenic amyloid infiltration. Purpose We sought to: (1) assess the association between baseline multi-organ ECVs and prognosis (2) assess the multi-organ response to treatment using ECV mapping, and (3) assess the association between multi-organ treatment response and prognosis. Methods We identified 351 patients with a confirmed diagnosis of systemic AL amyloidosis who underwent baseline serum amyloid P component (SAP) scintigraphy and CMR at diagnosis, of which 171 had follow-up imaging. We also recruited 20 healthy volunteers who underwent CMR with ECV mapping, without corresponding SAP scintigraphy, to allow calculation of the ECV normal ranges. Results At diagnosis, ECV mapping demonstrated that 304(86.7%) had cardiac involvement, 114(32.5%) significant hepatic involvement and 147(41.9%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial: HR=1.05,95CI%[1.03–1.07],P&amp;lt;0.001; liver: HR=1.03,95%CI[1.01–1.05],P&amp;lt;0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R=0.751,P&amp;lt;0.001; R=0.765,P&amp;lt;0.001, respectively). Serial multi-organ ECV measurements accurately tracked treatment response as validated against serial SAP scintigraphy (the current reference standard). Multi-organ ECV regression was observed as early as 6-months in patients with a good haematological response (liver=15%, spleen=15%, heart=5%). The remaining patients with a good haematological response had stable liver and spleen ECVs, but 20% had cardiac progression. By 12-months more patients with a good haematological response demonstrated cardiac regression (liver=30%, spleen=36%, heart=32%), and this trend was maintained at 24-months. Multi-variable analysis adjusting for haematological response, change in myocardial, liver and spleen ECV demonstrated that haematological response, change in myocardial ECV (HR=1.11, 95%CI[1.02–1.19], P=0.011) and liver ECV (HR=1.06, 95%CI[1.01–1.11], P=0.015) remained independent predictors of prognosis at 6-months. Conclusions Multi-organ ECV quantification accurately tracks treatment response, and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. A good haematological response alone is likely to induce visceral organ stabilisation/regression, but may not be sufficient to induce myocardial stabilisation/regression. Liver and myocardial ECV at diagnosis and changes in ECV at 6-months independently predict mortality. ECV mapping offers a comprehensive multi-organ assessment of treatment response and accurate prognostication.

ABSENT VASOREACTIVE RESPONSE TO HIGH SODIUM INTAKE COINCIDES WITH SALT SENSITIVITY IN CKD PATIENTS

Objective: Chronic kidney disease (CKD) patients are advised to limit salt intake, because of its detrimental effects on blood pressure (BP) and albuminuria. The salt-sensitive BP response in CKD is classically attributed to impaired renal ability to excrete sodium (Na+) resulting in fluid overload. Yet, BP sensitivity to salt is also linked to vasodysfuction, and may even be fluid independent. We aimed to investigate which factor contributes to BP sensitivity to salt in CKD. Design and method: In this randomized crossover study, CKD patients (KDIGO stage G2-3A, proteinuria &gt;0.5 g/d) and healthy controls (HC) followed a 7-day low sodium diet (LSD, &lt;50mmol/d) and high sodium diet (HSD, &gt;200mmol/d), respectively. After each diet, assessment of the hemodynamic profile included daytime BP (Mobil-O-Graph) and cardiac output (CO) measurements (using NexfinTM), by which SVR was calculated accordingly. Extracellular fluid volume (ECV) change was assessed with multi-frequency body impedance spectroscopy (FHCresenius). Results: We included 16 HC (median age 36.0 yrs) and 8 CKD patients (median age 49.5 yrs, and median (IQR) proteinuria 0.6 (0.5-1.1) g/d and plasma creatinine 144 (103 - 167) μmol/l. Dietary salt intervention was successful with median difference in urine Na+ excretion of 242.2 vs 224.6 mmol/day in HC and CKD respectively (p = 0.74). After HSD, the median (IQR) change in systolic BP of patients with CKD was 14 mmHg (4 - 18; p = 0.04), while systolic BP change (4 mmHg (-3 - 8)) in HC was not significant (Fig 1A). After HSD, we observed a significant ECV expansion in both CKD and HC subjects (Fig 1B), but no effect on CO. No associations between HSD-induced BP changes and both ECV and CO were found. Systolic BP increase was correlated with SVR decline in HC, but not in CKD patients (Fig 1C). Conclusions: In contrast to healthy persons, BP salt sensitivity in CKD does not associate with vasodilation. Regarding the absence of differences with ECV and CO between healthy and CKD persons, our data indicate that the incapacity for vasodilation might explain salt sensitivity in CKD.

Management of Intermittent Hemodialysis in the Critically Ill Patient.

Intermittent hemodialysis remains a cornerstone of extracorporeal KRT in the intensive care unit, either as a first-line therapy for AKI or a second-line therapy when patients transition from a continuous or prolonged intermittent therapy. Intermittent hemodialysis is usually provided 3 days per week in this setting on the basis that no clinical benefits have been demonstrated with more frequent hemodialysis. This should not detract from the importance of continually assessing and refining the hemodialysis prescription (including the need for extra treatments) according to dynamic changes in extracellular volume and other parameters, and ensuring that an adequate dose of hemodialysis is being delivered to the patient. Compared with other KRT modalities, the cardinal challenge encountered during intermittent hemodialysis is hemodynamic instability. This phenomenon occurs when reductions in intravascular volume, as a consequence of ultrafiltration and/or osmotic shifts, outpace compensatory plasma refilling from the extravascular space. Myocardial stunning, triggered by intermittent hemodialysis, and independent of ultrafiltration, may also contribute. The hemodynamic effect of intermittent hemodialysis is likely magnified in patients who are critically ill due to an inability to mount sufficient compensatory physiologic responses in the context of multiorgan dysfunction. Of the many interventions that have undergone testing to mitigate hemodynamic instability related to KRT, the best evidence exists for cooling the dialysate and raising the dialysate sodium concentration. Unfortunately, the evidence supporting routine use of these and other interventions is weak owing to poor study quality and limited sample sizes. Intermittent hemodialysis will continue to be an important and commonly used KRT modality for AKI in patients with critical illness, especially in jurisdictions where resources are limited. There is an urgent need to harmonize the definition of hemodynamic instability related to KRT in clinical trials and robustly test strategies to combat it in this vulnerable patient population.

Progression, regression and redefining the treatment response – cardiac magnetic resonance with T1 and extracellular volume mapping in cardiac light-chain amyloidosis

Abstract Background The presence and severity of cardiac involvement in AL amyloidosis is the main driver of prognosis [1]; patients with symptomatic heart failure frequently die within 6 months [1] but median survival has nearly doubled over the past decade, mainly due to significant improvements in chemotherapy. The haematological response to chemotherapy is principally evaluated with serial measurements of serum-free light-chains (FLC) [2]. The cardiac response to chemotherapy is assessed through changes in serum concentrations of brain natriuretic peptides (including NT-proBNP) and echocardiographic parameters [3–5]. Neither are able to directly measure cardiac amyloid burden. Cardiovascular magnetic resonance (CMR) with extra-cellular volume (ECV) mapping can measure the extent cardiac amyloid infiltration [6]. Aims We investigated the ability of CMR to: 1) measure changes in response to chemotherapy; 2) assess the correlation between haematological response (HMR) and changes in cardiac amyloid; 3) assess the association between changes in cardiac amyloid and prognosis over and above existing predictors. Methods In total, 176 patients with cardiac light-chain amyloidosis treated with chemotherapy were assessed with FLC, NT-proBNP and CMR with ECV mapping at baseline (before chemotherapy), 6-months, 12-months &amp; 24-months after commencing chemotherapy. Haematological response was categorized by reductions in FLC as: complete response (CR), very good partial response (VGPR), partial response (PR) or no response (NR). CMR response was categorized by changes in ECV as: progression (≥0.05 increase), stable (&amp;lt;0.05 change) or regression (≥0.05 decrease). Results A progressive increase in patients achieving either CR or VGPR was observed at each time point (61% of patients at 6-months, 71% at 12-months and 80% at 24-months). At 6-months, CMR regression was observed in 3% (all had either CR or VGPR) and progression in 32% (61% had either PR or NR; 39% had either CR or VGPR). At 1-year, CMR regression was observed in 22% (all had either CR or VGPR); progression in 22% (63% had either PR or NR; 37% had either CR or VGPR). At 2-years, CMR regression was observed in 38% (all had CR/VGPR); progression in 14% (80% had either PR or NR; 20% had either CR or VGPR). During follow-up (40±15 months), 36 (25%) patients died. CMR response at 6-months predicted death (progression HR 3.821; 95% CI 1.950–7.487; p&amp;lt;0.001) and remained independently associated with prognosis after adjusting for haematological response, NT-proBNP and longitudinal strain on echocardiography (p&amp;lt;0.01). Conclusions CMR demonstrates that cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR, highlighting the need for deep haematological response. Changes in amyloid burden (ECV) predict outcomes after adjusting for known predictors, showing the crucial role of CMR in redefining treatment response. Funding Acknowledgement Type of funding sources: Foundation.

New advances in medical imaging technology for the evaluation of anthracycline-induced cardiotoxicity.

New advances in medical imaging technology for the evaluation of anthracycline-induced cardiotoxicity.

Cardiovascular magnetic resonance in light-chain amyloidosis to guide treatment.

To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors. In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01). Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.

Natriuretic peptides, extracellular volume, and subclinical cardiovascular changes in chronic kidney disease stages 1–3: a pilot study

Natriuretic peptide levels are elevated in persons with chronic kidney disease (CKD) stages 1–3, but it remains unclear whether this is associated with extracellular volume excess or early cardiovascular changes....

Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy

ObjectivesThe goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis. BackgroundCardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase. MethodsProspectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.4 ± 7.3 years; 47.6% male; and 48 active AL amyloidosis; age: 62.5 ± 7.4 years; 60.4% male) underwent contrast-enhanced cardiac magnetic resonance with T1 and T2 mapping and measurement of extracellular volume (ECV). By definition, serum free light-chain levels were normal for at least 1 year following successful AL therapy in the remission group and abnormal in the active group. ResultsMyocardial ECV was similarly expanded in the remission and active AL amyloidosis groups (0.488 ± 0.082 vs 0.519 ± 0.083, respectively; P = 0.15). However, myocardial T2 relaxation times (47.7 ± 3.2 ms vs 45.5 ± 3.0 ms; P = 0.008) as well as native T1 times (1,368 ms [IQR: 1,290-1,422 ms] vs 1,264 ms [IQR: 1,203-1,380 ms]; P = 0.024) were significantly higher in the remission compared to the active AL amyloidosis group. ConclusionsMyocardial ECV is substantially expanded in the active AL and remission AL cardiac amyloidosis groups, but native T1 values were higher, suggesting a different myocardial composition. There is no evidence of myocardial edema in active AL cardiac amyloidosis. Future phenotyping studies of AL cardiac amyloidosis need to consider complementary myocardial markers that define the interstitial milieu in addition to changes in extracellular volume. (Molecular Imaging of Primary Amyloid Cardiomyopathy; NCT02641145)

Association of changes in the infarct and remote zone myocardial tissue with cardiac remodeling after myocardial infarction: a T1 and T2 mapping study.

Tissue structure in the infarct and remote zone myocardium post-acute myocardial infarction (MI) may offer prognostic information concerning left ventricular remodeling. We aimed to identify or establish a relationship between adverse remodeling (AR) and changes (Δ) in T1, T2 mapping and extracellular volume (ECV) in post MI periods. Fifty-four MI patients underwent 3 Tesla CMR performed 2weeks (acute phase) and 6months post-MI. We measured T1 mapping with MOLLI sequences and T2 mapping with TrueFISP sequences. Hematocrit was quantified in scanning time. ECV was performed post-gadolinium enhancement. AR was defined as an increase of ≥ 10% in left ventricular end-diastolic volume in 6months. In the acute phase post-MI, high T2 relaxation times of the infarct and remote zone myocardium were associated with AR (OR 1.15, p = 0.023 and OR 1.54, p = 0.002, respectively). There was a decrease in T2 relaxation times of the remote zone myocardium at 6months in patients with AR (42.0 ± 4.0 vs. 39.0 ± 3.5ms, p < 0.001), while insignificant difference was found in patients without AR. Increased ΔECV (%) and decreased remote ΔT2 values were associated with AR (OR 1.04, p = 0.043 and OR 0.77, p = 0.007, respectively). The diagnostic performance analysis in predicting AR showed that acute-phase remote T2 was similar to that of remote ΔT2 (p = 0.875) but was superior to that of ΔECV (%) (ΔAUC: 0.19 ± 0.09, p = 0.038). In both acute phase and change of 6months post-MI, the T2 relaxation times in remote myocardium are independently associated with AR, and this suggests higher inflammation in the remote myocardium in the AR group than the other group, even though no significant pathophysiological difference was observed in the healing of the infarct zone between both groups.

Abstract 12139: Substance P Replacement Reduces Cardiac Fibrosis in Monkeys With Type 2 Diabetes

Introduction: Type 2 diabetes mellitus (T2DM)-associated cardiac fibrosis contributes to heart failure, especially in women. We have data showing that diabetic mice with cardiomyopathy, including cardiac fibrosis, exhibit low levels of the neuropeptide substance P (SP); and SP replacement reverses cardiac fibrosis, independent of body weight and blood glucose. To understand the potential translational significance of these findings, we sought to determine in a T2DM monkey model if replacement SP could reverse cardiac magnetic resonance (CMR) imaging and circulating markers of fibrosis, while also assessing safety of administration. Methods: Female T2DM African Green monkeys were randomized to receive SP (n=4, 0.5 mg/Kg/day S.Q. injection) or vehicle (n=3) for 10 weeks. We obtained CMR imaging and blood samples to assess left ventricular (LV) function and fibrosis by T1 map-derived extracellular volume (ECV) and circulating procollagen type I C-terminal propeptide (PICP). Hematological parameters for toxicities were also assessed. We performed a blinded paired analysis of all parameters. Results: Monkeys receiving replacement SP exhibited a decrease in ECV (Pre: 31.6 ± 5.53% vs. Post: 25.2 ± 3.3%, p=0.03), concomitant with decreased PICP levels (Pre: 5148.58 ± 1143.5 ng/mL vs. Post: 3851.1 ± 1377.5 ng/mL, p=0.01). Animals receiving vehicle showed no changes in ECV (p=0.32) or PICP (p=0.16). No changes in LV ejection fraction were observed (p=0.89). Complete blood counts, metabolic panel (ΔA1c, SP: -0.45 ± 0.59 % vs vehicle: -0.53 ± 0.61 %, p=0.43), lipids, liver and pancreatic enzymes, and inflammation markers were unchanged (p&gt;0.05 for all). Conclusion: Replacement SP reversed cardiac fibrosis in a large preclinical model of T2DM, independent of glycemic control. No organ-related toxicity was associated with replacement SP. These results strongly support a potential application for replacement SP as an antifibrotic therapy for diabetic cardiac fibrosis.

Changes in total and segmental extracellular and intracellular volumes with hypotension during hemodialysis measured with bioimpedance spectroscopy.

Bioelectrical impedance analysis (BIA) devices have been advocated to guide volume management in hemodialysis (HD) patients. We hypothesized that understanding the dynamics of fluid shifts in different body segments may provide additional insight on preventive measures to reduce the risk of intradialytic hypotension. A prospective observational study was conducted among 42 HD patients at risk of hypotension who were admitted as emergencies inpatient. A total of 191 BIA measurements were made during the 42 HD sessions, and hypotension occurred during 52 measurements (27%). The extracellular water (ECW) to intracellular water ratio (EIR) was measured in different body segments and declined significantly only in the non-access arm with increasing HD session duration (β=-0.04; 95% confidence interval (CI): -0.05 to -0.03, p<0.01). There was no significant association between EIR and hypotension with respect to the different body segments. Only pre-HD N-terminal-pro b-type natriuretic peptide was significantly associated with hypotension (β=0.20, 95% CI: 0.04 to 0.89, p=0.04). There was no association between relative blood volume monitoring change and EIR. In summary, we found that segmental BIA during HD was unable to detect or predict hypotension during dialysis. Although BIA is able to provide information about ECW and guide clinical assessment of volume in HD patients prior to dialysis, our findings did not suggest the use of serial measurements of changes in EIR in different body segments during HD provided sufficient information to predict intradialytic hypotension. Similarly, changes in EIR did not provide information on changes in plasma volume that could potentially trigger interventions to prevent or reduce intra-dialytic hypotension.

Feasibility Study on Using Dynamic Contrast Enhanced MRI to Assess the Effect of Tyrosine Kinase Inhibitor Therapy within the STAR Trial of Metastatic Renal Cell Cancer

Objective: To identify dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters predictive of early disease progression in patients with metastatic renal cell cancer (mRCC) treated with anti-angiogenic tyrosine kinase inhibitors (TKI). Methods: The study was linked to a phase II/III randomised control trial. Patients underwent DCE-MRI before, at 4- and 10-weeks after initiation of TKI. DCE-MRI parameters at each time-point were derived from a single-compartment tracer kinetic model, following semi-automated tumour segmentation by two independent readers. Primary endpoint was correlation of DCE-MRI parameters with disease progression at 6-months. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) values were calculated for parameters associated with disease progression at 6 months. Inter-observer agreement was assessed using the intraclass correlation coefficient (ICC). Results: 23 tumours in 14 patients were measurable. Three patients had disease progression at 6 months. The percentage (%) change in perfused tumour volume between baseline and 4-week DCE-MRI (p = 0.016), mean transfer constant Ktrans change (p = 0.038), and % change in extracellular volume (p = 0.009) between 4- and 10-week MRI, correlated with early disease progression (AUC 0.879 for each parameter). Inter-observer agreement was excellent for perfused tumour volume, Ktrans and extracellular volume (ICC: 0.928, 0.949, 0.910 respectively). Conclusions: Early measurement of DCE-MRI biomarkers of tumour perfusion at 4- and 10-weeks predicts disease progression at 6-months following TKI therapy in mRCC.

Reduction of extracellular volume and reverse cardiac remodeling during sacubitril/valsartan therapy assessed by cardiac magnetic resonance in patients with heart failure (REMODELING CMR-HF)

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf REMODELING HF Background/Introduction: Extracellular volume (ECV) expansion is a major determinant of cardiac remodeling in heart failure. Cardiac magnetic resonance (CMR) T1 mapping has been developed as a noninvasive technique to estimate ECV. Purpose The objective of this study is to assess the response to Sacubitril/Valsartan by measuring changes in myocardial ECV and their association with reverse cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Methods Prospective, single-center, open-label study of two hundred-four HFrEF patients underwent CMR T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence for ECV calculation, and initiated with sacubitril-valsartan treatment according to Guideline-Directed Medical Therapy. Absolute change in myocardial ECV, serum levels of procollagen type I amino-terminal peptide (PINP) and procollagen type III amino-terminal peptide (PIIINP), left ventricular end-diastolic volume index, left ventricular end-systolic volume index and left ventricle ejection fraction (LVEF) were analyzed from baseline to 12-month follow-up. Results Baseline MOLLI-ECV was 48.2% ± 2.4 in 106 patients with ischemic cardiomyopathy (ICM) and 38.7% ± 2.7 in 98 with idiopathic dilated cardiomyopathy (DCM), decreasing to 34% ± 2.4 for ICM and 29.5% ± 2.7 for DCM (P &amp;lt; 0.001), at 12 months with sacubitril-valsartan therapy. These changes were correlated with a reduction of -36 μg/L for PINP (CI 95% 78-93, P &amp;lt; 0.001), and -3.0 μg/L for PIIINP (CI 95% 73-91, P &amp;lt; 0.001), -20 ml/m² in left ventricle end-diastolic and -18 ml/m² in end-systolic volumes, and an improvement in LVEF from 29% to 36% in both groups (P &amp;lt; 0.001). Conclusions For the first time, we observe that changes in extracellular volume induced by sacubitril-valsartan therapy are related to reverse cardiac remodeling in patients with in HFrEF. These findings suggest that there may be an opportunity to decrease adverse remodeling with the use of a CMR-guided therapeutic approach aimed at decreasing fibrogenic activity and modulate the remodeling process.

Evaluation of the effectiveness of electrical muscle stimulation on human calf muscles via frequency difference electrical impedance tomography

Objectives. The human skeletal muscle responds immediately under electrical muscle stimulation (EMS), and there is an immediate physiological response in human skeletal muscle. Non-invasive quantitative analysis is at the heart of our understanding of the physiological significance of human muscle changes under EMS. Response muscle areas of human calf muscles under EMS have been detected by frequency difference electrical impedance tomography (fd-EIT). Approach. The experimental protocol consists of four parts: pre-training (pre), training (tra), post-training (post), and relaxation (relax) parts. The relaxation part has three relaxation conditions, which are massage relaxation (MR), cold pack relaxation (CR), and hot pack relaxation (HR). Main results. From the experimental results, conductivity distribution images σ p (p means protocol = pre, tra, post, or relax) are clearly reconstructed by fd-EIT as response muscle areas, which are called the M 1 response area (composed of gastrocnemius muscle) and the M 2 response area (composed of the tibialis anterior muscle, extensor digitorum longus muscle, and peroneus longus muscle). A paired samples t-test was conducted to elucidate the statistical significance of spatial-mean conductivities 〈σ p 〉 M1 and 〈σ p 〉 M2 in M 1 and M 2 with reference to the conventional extracellular water ratio β p by bioelectrical impedance analysis. Significance. From the t-test results, 〈σ p 〉 M1 and 〈σ p 〉 M2 have good correlation with β p . In the post-training part, 〈σ post 〉 and β post were significantly higher than in the pre-training part (n = 24, p < 0.001). The relax–pre difference ratios of spatial-mean conductivity Δ〈σ relax–pre 〉 and the relax–pre difference ratios of extracellular water ratio Δβ relax–pre in both MR and CR were lower; on the contrary, the Δ〈σ relax–pre 〉 and Δβ relax–pre in HR were significantly higher than those in post–pre difference ratios of spatial-mean conductivity Δ〈σ post–pre 〉 (n = 8, p < 0.05). The reason for the changes in 〈σ p 〉 M1 and 〈σ p 〉 M2 are caused by the changes in muscle extracellular volumes. In conclusion, fd-EIT satisfactorily evaluates the effectiveness of human calf muscles under EMS.

Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat

We discovered high Na+ and water content in the skin of newborn Sprague–Dawley rats, which reduced ~ 2.5-fold by 7 days of age, indicating rapid changes in extracellular volume (ECV). Equivalent changes in ECV post birth were also observed in C57Bl/6 J mice, with a fourfold reduction over 7 days, to approximately adult levels. This established the generality of increased ECV at birth. We investigated early sodium and water handling in neonates from a second rat strain, Fischer, and an Hsd11b2-knockout rat modelling the syndrome of apparent mineralocorticoid excess (SAME). Despite Hsd11b2−/− animals exhibiting lower skin Na+ and water levels than controls at birth, they retained ~ 30% higher Na+ content in their pelts at the expense of K+ thereafter. Hsd11b2−/− neonates exhibited incipient hypokalaemia from 15 days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na+ through the kidney, (56.15 ± 8.21% versus control 34.15 ± 8.23%; n = 4; P < 0.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4 weeks of age. Our data reveal that Na+ imbalance in the Hsd11b2−/− neonate leads to excess Na+ storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na+ uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na+ plays an important role in the development of SAME but, equally, may play a key physiological role at birth, supporting post-natal growth, as an innate barrier to infection or as a rudimentary kidney.

Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p&lt;0.001; and ΔLVEF 6±4 vs 0±4%, p&lt;0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction in ECV (ΔECV -1.25±1.5 vs 0.3±1.4% for EMPA vs placebo, p&lt;0.001), which demonstrates IMF regression with SGLT2i. EMPA-treated patients exhibited a reduction in PWV (ΔECV -0.6±1 vs 0.6±1.4 m/s for EMPA vs control, p&lt;0.001), which indicates amelioration of aortic stiffness with SGLT2i Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes