Difference In Extracellular Volume Research Articles

Overall fibrosis content rather than regional differences in extracellular volume alters ventricular conduction in aortic stenosis patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation program under the ERA-NET co-fund action No. 680969 with ANR (ERA-CVD SICVALVES) and Agence Nationale de la Recherche Background Extracellular volume (ECV) determined by magnetic resonance imaging (MRI) is considered a marker of myocardial fibrosis and a predictor of mortality. In addition to diffuse fibrosis, aortic stenosis (AS) patients present increased ECV. However, the impact of regional ECV differences on ventricular conduction in AS patients has not been assessed. Purpose To investigate regional ECV differences in AS patients and to determine their impact on ventricular conduction. Methods MRI was performed in 22 AS patients (11 males, 11 females) before and 3 months after aortic valve replacement (AVR). Regional differences in ECV were determined between mid-ventricular and basal planes. To investigate the impact of these differences on conduction, a computational model of ventricular tissue (9x1x1 cm) was developed with human fiber orientation and transmural/apicobasal electrophysiology. The model was divided in two regions (Fig 1A), each representing tissue with different ECV. Extracellular conductivities (GE) in each region were adjusted to the patient with the highest difference in ECV between the planes (male 75y, post-AVR, ECV mid 25.5%, ECV base 31.3%) so that GE was 26.4% less for ECV of 31.3% compared to 25.5%. A model with uniform ECV of 25.5% was used as a control. The models were paced from the apical face with a S1-S2 protocol (S1: 750 ms, n=10, S2: 700-350 ms, n=1). To compare the results to conduction slowing from diffuse myocardial fibrosis, the simulations were repeated with an additional GE reduction by 40% in both regions to mimic conduction delays observed in fibrotic hearts. Ventricular conduction was compared between the models by analyzing conduction velocity (CV) measured between two points at the endocardium (Fig 1A, blue dots) and the occurrence of abnormalities in the form of non-uniform conduction, and/or conduction block after S2 (Fig 1B). Results Significantly higher ECV was found in the basal plane of AS patients when compared to the mid-ventricular plane before and after AVR (Fig 2), with the largest ECV found after AVR (mid-ventricular: p=0.0021; basal: p=0.0048). No sex-specific differences were found. The model representing the patient with the largest regional ECV difference showed slightly lower CV than the model with uniform ECV (92.9 vs. 96.0 cm/s, S2=500 ms). By contrast, myocardial fibrosis had a larger impact on CV slowing (92.9 vs. 79.2 cm/s, S2=500 ms, patient model, Fig 1C). Conduction block and non-uniform conduction occurred at comparable cycle lengths for all models (Fig 1D). Conclusion Regional differences in ECV were found in the ventricles of AS patients, but computer simulations suggest that these differences have a minimal effect on ventricular conduction when compared to diffuse fibrosis. Although the results suggest a limited electrophysiological relevance, additional studies are necessary to investigate whether these ECV differences have a more significant impact on cardiac mechanics.

Automated Dual-energy Computed Tomography-based Extracellular Volume Estimation for Myocardial Characterization in Patients With Ischemic and Nonischemic Cardiomyopathy.

We aimed to validate and test a prototype algorithm for automated dual-energy computed tomography (DECT)-based myocardial extracellular volume (ECV) assessment in patients with various cardiomyopathies. This retrospective study included healthy subjects (n=9; 61±10 y) and patients with cardiomyopathy (n=109, including a validation cohort n=60; 68±9 y; and a test cohort n=49; 69±11 y), who had previously undergone cardiac DECT. Myocardial ECV was calculated using a prototype-based fully automated algorithm and compared with manual assessment. Receiver-operating characteristic analysis was performed to test the algorithm's ability to distinguish healthy subjects and patients with cardiomyopathy. The fully automated method led to a significant reduction of postprocessing time compared with manual assessment (2.2±0.4 min and 9.4±0.7 min, respectively, P <0.001). There was no significant difference in ECV between the automated and manual methods ( P =0.088). The automated method showed moderate correlation and agreement with the manual technique ( r =0.68, intraclass correlation coefficient=0.66). ECV was significantly higher in patients with cardiomyopathy compared with healthy subjects, regardless of the method used ( P <0.001). In the test cohort, the automated method yielded an area under the curve of 0.98 for identifying patients with cardiomyopathies. Automated ECV estimation based on DECT showed moderate agreement with the manual method and matched with previously reported ECV values for healthy volunteers and patients with cardiomyopathy. The automatically derived ECV demonstrated an excellent diagnostic performance to discriminate between healthy and diseased myocardium, suggesting that it could be an effective initial screening tool while significantly reducing the time of assessment.

No signs of diffuse myocardial fibrosis by T1 mapping in male elite endurance athletes

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital Rikshospitalet, Department of Cardiology, Oslo, Norway. Background/Introduction: Observational data indicating increased prevalence of focal myocardial fibrosis in endurance athletes have raised concerns regarding the potential detrimental cardiac consequences of long-term athleticism. Cumulative exercise and competitive exposure has been associated with focal myocardial fibrosis visualised as late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Reports of higher extracellular volume (ECV) in the remote myocardium of athletes with LGE have suggested that this fibrotic process may affect the entire myocardium. However, detailed data on exercise exposure and possible associations with diffuse myocardial fibrosis in endurance athletes are scarce. Purpose Our aim was to investigate the association between cumulative exercise exposure and diffuse myocardial fibrosis in male elite endurance athletes. Methods In this cross-sectional observational study we evaluated 27 healthy adult male elite endurance athletes age 41 ± 9 years and 16 healthy controls age 41 ± 12 years. All subjects underwent 3 T CMR including LGE and T1 mapping. The athletes detailed their exercise history from 12 years of age in a structured interview. Results Athletes had lower resting heart rate, enlarged cardiac chambers and increased left ventricular mass compared to controls, in accordance with the athlete’s heart phenotype (table 1). In contrast to what would have been expected in diffuse myocardial fibrosis, athletes had shorter native T1 time than controls (1214 ± 24 vs. 1268 ± 48 ms, p &amp;lt; 0.001). The native T1 time fell with increasing yearly exercise dose, accumulated exercise duration and accumulated exercise dose (r=-0.46, -0.51 and -0.53, p &amp;lt; 0.05 for all). In a stepwise multiple linear regression model, only the accumulated exercise dose was independently associated with native T1 time as shown in figure 1 (r = 0.53, p = 0.01). There was no clear difference in ECV between athletes and controls (22.5 ± 3.1 vs. 23.8 ± 2.0 %, p = 0.16), indicating that increased left ventricular mass in the athletes was balanced without disproportionate extracellular expansion. There was no association between exercise exposure and ECV. LGE was observed in 5 (19 %) of the athletes and none of the controls (p = 0.14). There was no difference in native T1 time (1220 ± 4 vs. 1212 ± 27 ms, p = 0.56) or ECV (22.0 ± 1.2 vs. 22.7 ± 3.4 %, p = 0.69) between athletes with or without LGE. Conclusion(s): We did not observe signs of diffuse myocardial fibrosis in healthy elite endurance athletes. These results indicate that diffuse myocardial fibrosis is not highly prevalent in healthy athletes with extreme exercise exposure. Abstract Figure. Abstract Figure.

Myocardial functional and structural abnormalities after adjuvant radiotherapy for breast cancer. Relation to cardiac radiation exposure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Funds Pierre Masure, Alphonse and Marie Walckiers &amp; De Winter-Vermant, by King Baudouin Foundation Background Radiation therapy (RXT) is a keystone in breast cancer (BC) treatment which allows to reduce risk of local recurrence and cancer related mortality. Yet these benefits may be offset by increases in cardiovascular mortality due to late radiation induced cardiotoxicity. Indeed, prior works in patients exposed to high cardiac radiation dose demonstrated development of diffuse and focal myocardial fibrosis by cMR. However, whether such effects may also occur after contemporary BC-RXT with lower cardiac dose exposure, has not yet been evaluated. Purpose To evaluate the long-term cardiac safety of contemporary RXT for BC, we sought to estimate the prevalence of cardiac functional and structural focal and myocardial abnormalities in BC survivors treated by RXT 10 years earlier, in direct relation to measured local radiation dose exposure. Methods In a prospective cross-sectional study, we studied 27 women (mean age 62 ± 7 years) treated with adjuvant RXT but without chemotherapy for a first left (n= 12) or right sided (n= 15) BC between 2009 and 2011, which had no history of coronary artery or cardiac disease and compared them to 20 age matched (64 ± 10 years) healthy female controls (without history of BC or RXT). All subjects underwent 3T cMR to measure LV volumes, function, global longitudinal (GLS), circumferential (GRS) and radial strains (GRS) as well as extracellular volume (ECV) and late gadolinium enhancement (LGE). Functional and structural abnormalities in women with BC were compared to healthy controls. We also compared abnormalities among patients with left vs right BC and related them to mean heart radiation dose measured at the time of RXT (Figure). Results Mean cardiac radiation exposure in BC survivors was 1.87 ± 1.7 Gy (range 0-7.9 Gy). Exposure was significantly (p &amp;lt; 0.001) higher in left (3.3 ± 0.66 Gy) than in right (0.84 ± 0.65 Gy) sided BC. Indexed LV mass was slightly lower in BC patients than in controls (46 ± 6 vs 51 ± 9 g/m2, p = 0.03), whereas indexed end-diastolic (66 ± 11 vs 66 ± 12 ml/m2, p = NS) and end-systolic volumes (25 ± 8 vs 24 ± 7 ml/m2, p = NS) were similar. Also, LV ejection fraction (63 ± 6 vs 64 ± 6, p = NS), GLS (-14.7 ± 1.9 vs -15.5 ± 1.8, p = NS), GCS (-20.0 ± 3.6 vs -19.3 ± 5.9, p = NS) and GRS (40.9 ± 10.7 vs 37.0 ± 9.0, p = NS) were not statistically different in BC survivors than in controls. No patient presented LGE, and ECV was similar in BC patients exposed to RXT (28.3 ± 2.8) than in controls (29.3 ± 2.4, p = 0.58). Also, no differences in ECV between left and right sided BC and no statistical correlation between ECV and mean heart dose (r = 0.01, p = NS) was observed. Conclusions In this preliminary work, patients with BC treated by adjuvant RXT 10 years ago, presented no significant structural or functional abnormalities in relation to cardiac dose exposure nor in comparison to healthy controls. This suggests that current RXT protocols for BC are safe without long-term functional or morphological cardiac side effects.

Effect of image quality on myocardial extracellular volume quantification using cardiac computed tomography: a phantom study.

The image quality directly affects the accuracy of computed tomography (CT) extracellular volume (ECV) quantification. To investigate the effects of image quality and acquisition protocol on the accuracy of ECV quantification. One-volume scans were performed on a 320-row multidetector CT volume scanner using a multi-energy CT phantom. To simulate the blood pool and myocardium, solid rods representing blood and soft tissue were used in precontrast CT. Moreover, the solid rods including different iodine concentrations were used in postcontrast CT. The tube voltage was set at 120 kVp, and the tube current was changed from 750 mA (100% dose) to 190 mA (25% dose). All images underwent full- and half-scan reconstructions based on model-based iterative reconstruction. The ECV was calculated from the CT numbers between pre- and postcontrast. The mean ECV with full- and half-scan reconstructions at the central portion was 0.275 at 100% scan dose to 0.271 at 25% scan dose and 0.276 at 100% scan dose to 0.269 at 25% scan dose. Compared with that in the 100% scan dose, the variation in each ECV increased with decreasing radiation dose. The ECV at the center of the image along the z-axis had lower variation than that at outer portion of the images. On the reconstruction algorithm, there was no statistical difference in ECVs with full- and half-scan reconstructions. For stable ECV quantifications, excessive radiation dose reduction may be inappropriate, and it is better to consider the variations in ECV values depending on the slice location.

Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients

BackgroundPeople living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.Materials and methodsIn the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.ResultsThe ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p < 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p < 0.001), were positively and strongly associated with ECV values. Differences in ECV (p < 0.001) were also observed regarding the duration of cART exposure (< 5 years, 5–10 years and > 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084).ConclusionsHIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.

Cardiac magnetic resonance and B-natriuretic peptide are superior prognostic tools to guideline-based echocardiography in asymptomatic patients with chronic severe aortic regurgitation

Abstract Background The optimal timing of intervention in patients with chronic aortic regurgitation (AR) is currently based on patient symptoms and echocardiography derived parameters. The sensitivity of this approach is suboptimal and late operation often results in irreversible myocardial damage. Purpose To determine the prognostic value of novel parameters in asymptomatic patients with chronic severe AR in optimal timing of aortic valve surgery. Methods Consecutive patients with chronic severe AR not indicated for surgery per the current guidelines were studied in a prospective design in 5 centers. Baseline examination consisted of B-natriuretic peptide (BNP) measurement, comprehensive echocardiography (ECHO) including 3-dimensional (3D) study with vena contracta area (VCA), and complex magnetic resonance (MRI) including regurgitant volume (RV), regurgitant fraction (RF), global myocardial work efficiency (GWE) and extracellular volume (ECV); all analyzed in core lab. All patients were followed every 6 months and the endpoint was disease progression defined as an indication for surgery. The perioperative myocardial biopsy was performed in all surgically treated patients for histological myocardial fibrosis quantification. Results In total, 129 patients were enrolled between 2015 and 2019, the endpoint occurred in 35 patients during a mean follow-up of 1044 days. Baseline clinical data did not differ between patients with disease progression (surgical group) and stable patients. Baseline BNP levels were higher in the surgical group (63 vs. 20, P&amp;lt;0.01) and a cut-off value of 30.4 ng/L was predictive of disease progression with AUC 0.75. None of the standard ECHO parameters of left ventricular (LV) size and function was predictive of the endpoint. Novel ECHO parameter 3D VCA was higher in the surgical group (32 vs. 26 mm2, P=0.037). All MRI parameters of LV size and function were predictive of disease progression (all P&amp;lt;0.02), except LV ejection fraction. MRI-derived RV (57 vs. 37 ml, P&amp;lt;0.01) and RF (46 vs. 34%, P&amp;lt;0.01) were identified as the strongest independent predictors of surgery. There was no difference in ECV between the surgical group and stable patients (24 vs. 24, P=0.81) despite a good correlation with histological quantification of myocardial fibrosis. Conclusions Standard ECHO parameters cannot reliably predict the need for surgery in asymptomatic aortic regurgitation patients. Baseline BNP levels above 30.4 ng/L predict disease progression. Novel imaging parameters – ECHO-derived 3D VCA and MRI-derived parameters of LV size and AR severity might be useful in optimal timing determination. Imaging markers and myocardial histology Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

Quantitative Assessment of Extracellular Volume in Doxorubicin-Induced Liver Injury in Beagle Models by Equilibrium Computed Tomography.

The purpose of this study was to determine whether liver extracellular volume (ECV) measured using equilibrium computed tomography (EQ-CT) can be used to quantitatively assess doxorubicin-induced liver injury (DILI). The ethical approval was obtained from the Institutional Animal Care and Use Committee regulations. Thirteen dogs administered with doxorubicin for 0 to 24 weeks were imaged by contrast-enhanced EQ-CT. The dogs were divided into 3 groups: the baseline (13 dogs), 16-week (10 dogs), and 24-week (7 dogs) groups. Pathological analysis of the liver was performed using hematoxylin-eosin and Masson staining. Liver ECV uptake was calculated for each group and correlated with the histopathological and serological findings of hepatic fibrosis (hyaluronic acid and procollagen type III). In the baseline group, the median ECVs of the right and left liver lobes were 21.78% (interquartile range [IQR], 16.78%-26.68%) and 20.91% (IQR, 16.39%-24.07%), respectively. In the 16- and 24-week groups, the median ECVs of these 2 liver lobes were 28.18% (IQR, 20.56%-34.61%) and 25.96% (IQR, 14.07%-41.38%) and 29.71% (IQR, 27.19%-35.25%) and 29.22% (IQR, 22.62%-38.67%), respectively. There were no significant differences in ECV between the left and right lobes in the 3 groups (P < 0.05). Both the 16- and 24-week groups showed significantly higher ECV than did the primary group (P = 0.001-0.0006). However, there were no significant differences in ECV between the 16-week group and 24-week group (P = 0.412). There was a positive correlation between the serum index and edema due to the inflammation and necrosis associated with DILI (R = 0.6534, R = 0.7129). Extracellular volume measured by EQ-CT imaging can accurately predict the potential DILI through the quantification of ECV changes.

CMR Tissue Characterization in Patients with HFmrEF.

The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40–50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (−15.7 ± 2.1) and GCS (−19.9 ± 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 ± 40 ms) and HFrEF (1033 ± 54 ms) compared to healthy controls (972 ± 31 ms) and HFpEF (985 ± 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 ± 3.4 ms) and HFrEF (56.0 ± 6.0 ms) compared to healthy controls (50.6 ± 2.1 ms). Differences in ECV did not reach statistical significance. HFmrEF differs from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation.

Quantification of Myocardial Extracellular Volume Fraction with Cardiac MR Imaging in Thalassemia Major.

Purpose To quantify myocardial extracellular volume (ECV) by using cardiac magnetic resonance (MR) imaging in thalassemia major and to investigate the relationship between ECV and myocardial iron overload. Materials and Methods With institutional review board approval and informed consent, 30 patients with thalassemia major (mean age ± standard deviation, 34.6 years ± 9.5) and 10 healthy control subjects (mean age, 31.5 years ± 4.4) were prospectively recruited (clinicaltrials.gov identification number NCT02090699). Nineteen patients (63.3%) had prior myocardial iron overload (defined as midseptal T2* < 20 msec on any prior cardiac MR images). Cardiac MR imaging at 1.5 T included cine steady-state free precession for ventricular function, T2* for myocardial iron quantification, and unenhanced and contrast material-enhanced T1 mapping. ECV was calculated with input of the patient's hematocrit level. Peak systolic global longitudinal strain by means of speckle tracking was assessed with same-day transthoracic echocardiography. Statistical analysis included use of the two-sample t test, Fisher exact test, and Spearman correlation. Results Unenhanced T1 values were significantly lower in patients with prior myocardial iron overload than in control subjects (850.3 ± 115.1 vs 1006.3 ± 35.4, P < .001) and correlated strongly with T2* values (r = 0.874, P < .001). Patients with prior myocardial iron overload had higher ECV than did patients without iron overload (31.3% ± 2.8 vs 28.2% ± 3.4, P = .030) and healthy control subjects (27.0% ± 3.1, P = .003). There was no difference in ECV between patients without iron overload and control subjects (P = .647). ECV correlated with lowest historical T2* (r = -0.469, P = .010) but did not correlate significantly with left ventricular ejection fraction (r = -0.216, P = .252) or global longitudinal strain (r = -0.164, P = .423). Conclusion ECV is significantly increased in thalassemia major and is associated with myocardial iron overload. These abnormalities may potentially reflect diffuse interstitial myocardial fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

BackgroundDiffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.MethodsIn a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.ResultsLate gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m2; female > 78 g/m2). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).ConclusionIn well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.

Potential reduction of interstitial myocardial fibrosis with renal denervation.

BackgroundHypertensive cardiomyopathy is characterized by myocyte hypertrophy and interstitial fibrosis. The effects of renal denervation (RD) on the heart are poorly understood. New magnetic resonance imaging techniques (extracellular volume fraction) permit the quantitative assessment of myocardial fibrosis. Our aim was to study the effects of RD on myocardial fibrosis.Methods and ResultsTwenty‐three patients with resistant hypertension undergoing RD and 5 resistant hypertensive controls were prospectively included. Cardiac magnetic resonance imaging at 1.5 T was performed before RD and at 6‐month follow‐up. Indexed left ventricular mass, septal extracellular volume fraction, and indexed absolute extracellular volume (a quantitative measure of extracellular matrix) were quantified. All data are reported as mean±SD deviation (median). Decreases in systolic (161.96±19.09 [160] versus 144.78±16.48 [143] mm Hg, P<0.0001) and diastolic (85.61±12.88 [83] versus 80.39±11.93 [81] mm Hg, P=0.018) blood pressures and in indexed left ventricular mass (41.83±10.20 [41.59] versus 37.72±7.44 [38.49] g/m1.7, P=0.001) were observed at follow‐up only in RD patients. No significant differences in extracellular volume were found (26.24±3.92% [26.06%] versus 25.74±4.53% [25.63%], P=0.605). A significant decrease in absolute extracellular volume was observed after 6 months in RD patients exclusively (10.36±2.25 [10.79] versus 9.25±2.38 [9.79] mL/m1.7, P=0.031). This effect was observed independently of blood pressure reduction.ConclusionsRD significantly decreases left ventricular mass, while extracellular volume remains stable. Our results suggest that the observed left ventricular mass decrease was due not exclusively to a reversion of myocyte hypertrophy but also to an additional reduction in collagen content, indicating interstitial myocardial fibrosis.

Increased extracellular volume and altered mechanics are associated with left ventricular hypertrophy in hypertensive heart disease, not hypertension alone

Background Study purpose To detect differences in extracellular volume (ECV) and systolic strain in hypertensive patients with LVH as compared to hypertensive patients without LVH and age-matched controls. Background: Increased ECV due to diffuse myocardial fibrosis in hypertensive patients may be an underlying mechanism contributing to increased cardiovascular risk. Moreover HTN patients with left ventricular hypertrophy (LVH) are at higher risk of cardiovascular morbidity and mortality when compared to HTN Non-LVH subjects. We compared levels of ECV and systolic strain between HTN LVH, HTN Non-LVH and control subjects.

Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure

In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

Comparison of Fluid Status in Patients Treated by Different Modalities of Peritoneal Dialysis using Multi-Frequency Bioimpedance

Patients treated by peritoneal dialysis, especially those using automatic cyclers, are frequently found to be hypervolemic. To determine whether there are significant differences between the currently available modalities of peritoneal dialysis, we analyzed whether differences in transporter status and treatment modality had a discernible effect on extracellular fluid volumes as measured by multi-frequency bioimpedance. Two hundred prevalent peritoneal dialysis patients, 48% male, mean age 54.9 yr (SD+/-15.6), were studied using multi-frequency bioimpedance following a standard peritoneal equilibration test; 63 patients were treated by CAPD, 29 by APD, 96 by CCPD and 12 by OCCPD. There were no differences in extracellular volumes, or extracellular volume adjusted for height, or as a ratio to total body water between the groups. As expected, extracellular volume adjusted for height depended upon bodyweight (r=0.412, p<0.001), sex (r=0.457, p<0.001) and systolic blood pressure (r=0.162, p=0.023), and extracellular volume to total body water related to the reciprocal of total daily peritoneal ultrafiltration losses (r=-0.0254, p=0.003) and urine output (-0.254, p=0.003). More importantly, on logistical regression analysis the ratio of extracellular fluid to total body fluid increased with falling albumin, F=21.5 p<0.001, increasing age, F=18.5 p<0.001, urine output F=6.46, p=0.014, total daily ultrafiltration, F=3.52 and protein intake p=0.003. Extracellular fluid adjusted for total body fluid was associated with CRP (males F=6.03, p=0.03, females F=4.438, p=0.04). Patients were more likely to have an expanded extracellular fluid volume if they had reduced daily fluid losses, but also with biomarkers typically associated with poor nutrition and inflammation.

Altered growth and protein turnover in rats fed sodium-deficient diets.

The effects of feeding a sodium-deficient (NaD) diet were examined in young, growing rats. All animals were fed the same diet and drank distilled water. In the control group the water contained 37 mM sodium chloride. After 2-3 wk body composition measurements were performed and epitrochlearis muscle protein synthesis and degradation rates determined. The experimental group gained only 45% of the wt and 70% of the length seen in the control group. The difference in wt gain could not be accounted for by differences in extracellular volume which averaged only 4% of body wt. Although total food intake was equivalent in both groups, urinary ammonia plus urea nitrogen excretion was higher in the experimental animals. Protein synthesis, measured as the incorporation of 14C-phenylalanine into muscle protein was significantly lower in NaD rats (56.58 versus 68.79) and (65.26 versus 83.88 nmol phenylalanine/h/g wet wt (both p less than 0.01) when incubated with or without the addition of insulin (1 mU/mL). Net protein degradation rates were unchanged. Gastrocnemius muscle RNA concentrations were also lower in NaD rats (1.09 versus 1.52 mg/g wet wt, p less than 0.001). There were no changes noted in the concentration of protein within either gastrocnemius or epitrochlearis muscles. These results suggest that in rats, the growth failure seen in sodium deficiency: 1) affects both length and wt gain; 2) is not associated with decreased nutrient intake; 3) is due to decreased rates of muscle protein synthesis without affecting net protein degradation rates; and 4) is associated with diminished muscle tissue RNA concentrations.