Lung ultrasound as tool to evaluate fluid accumulation in dialysis patients

Background: Volume overload is the main mechanism of BP elevation in end-stage kidney disease (ESKD) patients undergoing hemodialysis or peritoneal dialysis and has been linked to adverse outcomes and increased mortality in this population. Summary: This review discusses current knowledge on lung ultrasound as a tool for detection of extracellular volume overload through evaluation of extravascular lung water content. We describe the principles of lung US, the main protocols to apply it in clinical practice, and accumulated data evidence regarding its associations with cardiovascular events and mortality. We also summarize available evidence on the effect of lung-ultrasound guided volume management strategies on BP control, echocardiographic parameters and major outcomes in patients undergoing dialysis. Key Messages: Among interventions attempting to reduce the burden of cardiovascular disease in ESKD, effective management of volume overload represents an unmet clinical need. Assessment of hydration status by lung-ultrasound is a cheap, easy to employ and real-time technique that can offer accurate dry weight assessment leading to several clinical benefits.

Cardiac involvement in cystic fibrosis evaluated using cardiopulmonary magnetic resonance

Cystic fibrosis (CF) transmembrane conductance regulator is expressed in myocardium, but cardiac involvement in CF remains poorly understood. The recent development of a combined cardiopulmonary magnetic resonance imaging technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. The aim of this study was to investigate myocardial manifestations in adults with CF, both in a stable state and during an acute respiratory exacerbation, and to investigate the relationship between cardiac and pulmonary disease. Healthy adult volunteers (n = 12) and adults with CF (n = 10) were studied using a multiparametric cardiopulmonary magnetic resonance protocol. CF patients were scanned during an acute respiratory exacerbation and re-scanned when stable. Stable CF was associated with left ventricular dilatation and hypertrophy (LVH; left ventricular mass: CF 59 ± 9 g/m2 vs. control 50 ± 8 g/m2; p = 0.028). LVH was predominantly driven by extracellular myocardial matrix expansion (extracellular matrix mass: CF 27.5 ± 3.4 g vs. control 23.6 ± 5.2 g; p = 0.006; extracellular volume [ECV]: CF 27.6 [24.7–29.8]% vs. control 24.8 [22.9–26.0]%; p = 0.030). Acute CF was associated with an acute reduction in left ventricular function (ejection fraction: acute 57 ± 3% vs. stable 61 ± 5%; p = 0.025) and there was a suggestion of myocardial oedema. Myocardial oedema severity was strongly associated with the severity of airflow limitation (r = − 0.726, p = 0.017). Multiparametric cardiopulmonary magnetic resonance technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. Stable CF is associated with adverse myocardial remodelling, including left ventricular systolic dilatation and hypertrophy, driven by myocardial fibrosis. CF exacerbation is associated with acute myocardial contractile dysfunction. There is also a suggestion of myocardial oedema in the acute period which is related to pulmonary disease severity.

Clinical impact of personalized sodium prescriptions in hemodialysis

Dialysate sodium prescription is often standardized. In some patients, this can be hypernatremic compared to serum sodium, causing a positive sodium balance at the end of treatment that will contribute to increased extracellular volume and interdialytic weight gain. A prospective study was carried out to monitor and compare the clinical implications between different prescriptions of sodium dialysate (isonatremic versus hyponatremic hemodialysis). For that purpose, we included hemodialysis patients in treatment for at least 9 months. The individual sodium setpoint was determined through the median of pre-dialysis sodium measurements, carried out for 6 treatments. The prescribed dialysate sodium was equal to the setpoint (isonatremic period) for 4 weeks and then 2 meq/L inferior to the setpoint (hyponatremic period) for another 4 weeks. The main outcome was interdialytic weight gain. Secondary outcomes were ultrafiltration rate, blood pressure at the beginning of treatment, intradialytic complications, and qualitative assessment of symptoms. Twenty patients were included. Pre-dialysis serum sodium assessments in both periods tended to be patient specific with a stable value. The interdialytic weight gain was lower in the hyponatremic period (1.83±0.50 kg versus 2.04±0.58 kg) but without statistical significance (p value=0.387). The same trend was found in mean ultrafiltration and blood pressure. Dialysis complications were low in both periods. The percentage of cramps and hypotension requiring intervention was higher in the hyponatremic period with no statistically significant differences. Concerning thirst, there was a symptomatic improvement with sodium customization. This improvement was even more significant in the hyponatremic period. This study allowed us to reinforce the existence of a “sodium setpoint” for each patient and the importance of an individualized dialysis prescription. Our results suggest the safety of using isonatremic hemodialysis with improving patients’ symptoms. Regarding hyponatremic hemodialysis, despite being beneficial, it seemed to be associated with a higher number of complications.

Myocardial Parametric Mapping by Cardiac Magnetic Resonance Imaging in Pediatric Cardiology and Congenital Heart Disease

Parametric mapping, that is, a pixel-wise map of magnetic relaxation parameters, expands the diagnostic potential of cardiac magnetic resonance by enabling quantification of myocardial tissue-specific magnetic relaxation on an absolute scale. Parametric mapping includes T 1 mapping (native and postcontrast), T 2 and T 2 * mapping, and extracellular volume measurements. The myocardial composition is altered in various disease states affecting its inherent magnetic properties and thus the myocardial relaxation times that can be directly quantified using parametric mapping. Parametric mapping helps in the diagnosis of nonfocal disease states and allows for longitudinal disease monitoring, evaluating therapeutic response (as in Thalassemia patients with iron overload undergoing chelation), and risk-stratification of certain diseases. In this review article, we describe various mapping techniques and their clinical utility in congenital heart disease. We will also review the available literature on normative values in children, the strengths, and weaknesses of these techniques. This review provides a starting point for pediatric cardiologists to understand and implement parametric mapping in their practice.

Changes of Cardiac Magnetic Resonance T1 and ECV Values in Healthy Adults of Different Gender and Age

purposeThe correlation between T1 and ECV value and myocardial fibrosis has been confirmed. In healthy adult, many disease may change T1 and ECV value. The purpose of this reseach is to clarify the T1 mapping and extracellular volume (ECV) value of healthy adults in 3 Tesla (T) magnetic resonance imaging (MRI), and to study the relationship between the values with age and gender.Methods We recruited 87 healthy adult subjects (mean age 38 ± 11 years; 61% were females) for cardiac magnetic resonance examination at 3T MRI. The left ventricular function parameters were obtained from functional imaging. T1 mapping was performed using an improved Look-Locker reversal recovery sequence after motion correction. resultsUnder 3T field strength, T1 value of the myocardium of healthy adults was 1,261 ± 52, and the ECV value was 28.3% ± 2.9%. T1 value and ECV values of female myocardium were higher than those of males (1,274 ± 56 vs. 1,241 ± 40, P = 0.003; 29.6% ± 2.6% vs. 26.2% ± 2.1%, P < 0.001). Only gender (Beta = 0.311, P = 0.003) was independently related to the native T1 mapping of left ventricular myocardium, while gender (Beta = 0.572, P < 0.001) and age (Beta = 0.501, P = 0.003) were related to the ECV value of left ventricular myocardium. T1 value (P = 0.002) and ECV value (P = 0.013) increased significantly from the base to the apex. There were significant differences in the T1 and ECV value between each segment (P < 0.001) in the base of the left ventricle. Significant differences were observed between the middle segments of T1 value (P = 0.001) but not between the middle of the ECV value of each segment (P = 0.068). Lastly, there was no statistical difference between each segment in the apical of the T1 (P = 0.756) and ECV value (P = 0.344).ConclusionsUnder 3T MRI, the T1 value of the myocardium of healthy adults was 1,261 ± 52, and the ECV value was 28.3% ± 2.9%. T1 and ECV values of females were significantly higher than those of males. The ECV values of males increased with age, while T1 value in males and T1 and ECV values in females had no significant relationship with age.

Empagliflozin Reduces Renal Hyperfiltration in Response to Uninephrectomy, but Is Not Nephroprotective in UNx/DOCA/Salt Mouse Models

Large-scale clinical outcome studies demonstrated the efficacy of SGLT2 inhibitors in patients with type II diabetes. Besides their therapeutic efficacy in diabetes, significant renoprotection was observed in non-diabetic patients with chronic kidney disease (CKD), suggesting the existence of glucose-independent beneficial effects of SGLT2 inhibitors. However, the relevant mechanisms by which SGLT2 inhibition delays the progression of renal injury are still largely unknown and speculative. Previous studies showed that SGLT2 inhibitors reduce diabetic hyperfiltration, which is likely a key element in renoprotection. In line with this hypothesis, this study aimed to investigate the nephroprotective effects of the SGLT2 inhibitor empagliflozin (EMPA) in different mouse models with non-diabetic hyperfiltration and progressing CKD to identify the underlying diabetes-independent cellular mechanisms. Non-diabetic hyperfiltration was induced by unilateral nephrectomy (UNx). Since UNx alone does not result in renal damage, renal disease models with varying degrees of glomerular damage and albuminuria were generated by combining UNx with high NaCl diets ± deoxycorticosterone acetate (DOCA) in different mouse strains with and without genetic predisposition for glomerular injury. Renal parameters (GFR, albuminuria, urine volume) were monitored for 4–6 weeks. Application of EMPA via the drinking water resulted in sufficient EMPA plasma concentration and caused glucosuria, diuresis and in some models renal hypertrophy. EMPA had no effect on GFR in untreated wildtype animals, but significantly reduced hyperfiltration after UNx by 36%. In contrast, EMPA did not reduce UNx induced hyperfiltration in any of our kidney disease models, regardless of their degree of glomerular damage caused by DOCA/salt treatment. Consistent with the lack of reduction in glomerular hyperfiltration, EMPA-treated animals developed albuminuria and renal fibrosis to a similar extent as H2O control animals. Taken together, the data clearly indicate that blockade of SGLT2 has the potential to reduce non-diabetic hyperfiltration in otherwise untreated mice. However, no effects on hyperfiltration or progression of renal injury were observed in hypervolemic kidney disease models, suggesting that high salt intake and extracellular volume might attenuate the protective effects of SGLT2 blockers.

The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Myocardial Fibrosis in Young and Veteran Athletes: Insights From a Meta-Analysis

Background: Cardiac magnetic resonance (CMR) combined with late gadolinium enhancement (LGE) has revealed a non-negligible increased incidence of myocardial fibrosis (MF) in athletes compared to healthy sedentary controls.Objective: The aim of this systematic research and meta-analysis is to investigate and present our perspective regarding CMR indices in athletes compared to sedentary controls, including T1 values, myocardial extracellular volume (ECV) and positive LGE indicative of non-specific fibrosis, also to discuss the differences between young and veteran athletes.Methods: The protocol included searching, up to October 2021, of MEDLINE, EMBASE, SPORTDiscus, Web of Science and Cochrane databases for original studies assessing fibrosis via CMR in athletes. A mean age of 40 years differentiated studies' athletic populations to veteran and young.Results: The research yielded 14 studies including in total 1,312 individuals. There was a statistically significant difference in LGE fibrosis between the 118/759 athletes and 16/553 controls (Z = 5.2, P &lt; 0.001, I2 = 0%, PI = 0.45). Notably, LGE fibrosis differed significantly between 546 (14.6%) veteran and 140 (25.7%) young athletes (P = 0.002). At 1.5T, T1 values differed between 117 athletes and 48 controls (P &lt; 0.0001). A statistically significant difference was also shown at 3T (110 athletes vs. 41 controls, P = 0.0004), as well as when pooling both 1.5T and 3T populations (P &lt; 0.00001). Mean ECV showed no statistically significant difference between these groups.Conclusions: Based on currently available data, we reported that overall LGE based non-specific fibrosis and T1 values differ between athletes and sedentary controls, in contrast to ECV values. Age of athletes seems to have impact on the incidence of MF. Future prospective studies should focus on the investigation of the underlying pathophysiological mechanisms.

Myocardial extracellular volume fraction quantification based on T1 mapping at 3 T: quality optimization by contour-based registration and segmental analysis

Background Myocardial extracellular volume fraction (ECV) assessment can be affected by various technical and subject-related factors. Purpose To evaluate the role of contour-based registration in quantification of ECV and investigate normal segment-based myocardial ECV values at 3T. Material and Methods Pre- and post-contrast T1 mapping images of the left ventricular basal, mid-cavity, and apical slices were obtained in 26 healthy volunteers. ECV maps were generated using motion correction with and without contour-based registration. The image quality of all ECV maps was evaluated by a 4-point scale. Slices were dichotomized according to the occurrence of misregistration in the source data. Contour-registered ECVs and standard ECVs were compared within each subgroup using analysis of variance for repeated measurements and generalized linear mixed models. Results In all three slices, higher quality of ECV maps were found using contour-registered method than using standard method. Standard ECVs were statistically different from contour-registered ECVs in global (26.8% ± 2.8% vs. 25.8% ± 2.4%; P = 0.001), mid-cavity (25.4% ± 3.1% vs. 24.3% ± 2.5%; P = 0.016), and apical slices (28.7% ± 4.1% vs. 27.2% ± 3.4%; P = 0.010). In the misregistration subgroups, contour-registered ECVs were lower with smaller SDs (basal: 25.2% ± 1.8% vs. 26.7% ± 2.6%; P = 0.038; mid-cavity: 24.4% ± 2.3% vs. 26.8% ± 3.1%; P = 0.012; apical: 27.5% ± 3.6% vs. 29.7% ± 4.5%; P = 0.016). Apical (27.2% ± 3.4%) and basal-septal ECVs (25.6% ± 2.6%) were statistically higher than mid-cavity ECV (24.3% ± 2.5%; both P < 0.001). Conclusion Contour-based registration can optimize image quality and improve the precision of ECV quantification in cases demonstrating ventricular misregistration among source images.

Evaluation of Extracellular Volume by Computed Tomography is Useful for Prediction of Prognosis in Dilated Cardiomyopathy

Purpose: Dilated cardiomyopathy (DCM) is commonly encountered in daily clinical practice, and screening for coronary artery disease and other cardiomyopathies is necessary for its diagnosis. Cardiac CT is useful for the screening of coronary artery stenosis, and extracellular volume fraction (ECV) analysis by CT has become available using new specific software. Here, we evaluated the utility of ECV analysis using cardiac CT to predict patient prognosis in cases with DCM. Methods: We analyzed 70 cases with DCM and coronary computed tomography (CT) with available late-phase images. We evaluated the ECV of the left ventricular myocardium (LVM) using commercially available software (Ziostation 2, Ziosoft Inc, Japan). Results: ECV on LVM was 34.5±4.9%. Major adverse cardiac events (MACE) occurred in 20 cases (29%). ECV of the LVM on CT and the presence of significant valvular disease were significantly higher in cases with MACE than in those without (37.6±5.9 vs 33.2±3.9% and 55% vs 24%, P=0.0057 and P=0.013). LVEF was significantly lower in cases with MACE than in those without (22.3±7.6 vs 30.8±11.8%, P=0.0008). The best cut-off value of ECV on LVM for prediction of MACE was 32.7% based on receiver operating characteristics analysis. Cases with ECV ≥32.7% had significantly higher MACE based on Kaplan-Meier analysis (P=0.012). Only ECV on LVM was an independent predictor of MACE based on a Cox proportional hazards model (P=0.028). Conclusion: Evaluation of ECV on LVM by CT is useful for predicting MACE in patients with DCM.