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  • 1
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    Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 31 ( 2020-11-01), p. 3638-3651
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 31 ( 2020-11-01), p. 3638-3651
    Abstract: The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR). METHODS An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy. RESULTS Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P 〈 .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient’s sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low] , 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy] , 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group ( P 〉 .12). CONCLUSION This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.19.03205
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Association of Noise Annoyance with Measured Renal Hemodynamic Changes
    S. Karger AG ; 2021
    In:  Kidney and Blood Pressure Research Vol. 46, No. 3 ( 2021), p. 323-330
    Details
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 46, No. 3 ( 2021), p. 323-330
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Chronic mental stress is recognized as a modifiable risk factor for cardiovascular disease. The aim of this study was to demonstrate that noise annoyance-induced stress is associated with changes in renal hemodynamics. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Renal hemodynamic parameters were measured using steady-state input clearance with infusion of para-aminohippuric acid and inulin in individuals with normal, high normal, and elevated blood pressure. All individuals ranked subjective annoyance due to noise in everyday life on a 7-grade Likert scale. The median of all rankings was used as a cutoff point to divide the group into noise-annoyed and non-noise-annoyed individuals. Different renal hemodynamic parameters were calculated based on the Gomez equation. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Noise-annoyed individuals ( 〈 i 〉 n 〈 /i 〉 = 58) showed lower renal plasma flow (599 ± 106 vs. 663 ± 124 mL/min, 〈 i 〉 p 〈 /i 〉 = 0.009), lower renal blood flow (1,068 ± 203 vs. 1,172 ± 225 mL/min, 〈 i 〉 p 〈 /i 〉 = 0.047), higher filtration fraction (22.7 ± 3.3 vs. 21.3 ± 3.0, 〈 i 〉 p 〈 /i 〉 = 0.012), higher renal vascular resistance (88.9 ± 25.6 vs. 75.8 ± 22.9 mm Hg/[mL/min], 〈 i 〉 p 〈 /i 〉 = 0.002), and higher resistance of afferent arteriole (2,439.5 ± 1,253.4 vs. 1,849.9 ± 1,242.0 dyn s 〈 sup 〉 −1 〈 /sup 〉 cm 〈 sup 〉 −5 〈 /sup 〉 , 〈 i 〉 p 〈 /i 〉 = 0.001) compared to non-noise-annoyed individuals ( 〈 i 〉 n 〈 /i 〉 = 55). There was no difference in measured glomerular filtration rate (133 ± 11.8 vs. 138 ± 15 mL/min, 〈 i 〉 p 〈 /i 〉 = 0.181), resistance of efferent arteriole (2,419.4 ± 472.2 vs. 2,245.8 ± 370.3 dyn s 〈 sup 〉 −1 〈 /sup 〉 cm 〈 sup 〉 −5 〈 /sup 〉 , 〈 i 〉 p 〈 /i 〉 = 0.060), and intraglomerular pressure (64.0 ± 3.1 vs. 64.6 ± 3.5 mm Hg, 〈 i 〉 p 〈 /i 〉 = 0.298) between the groups. After adjusting for age, renal plasma flow, renal blood flow, and renal vascular resistance remained significantly different between the groups, with a trend in increased afferent arteriolar resistance and filtration fraction. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In this study, noise annoyance was associated with reduced renal perfusion attributed to increased renal vascular resistance predominantly at the afferent site. Long-term consequences of this renal hemodynamic pattern due to noise annoyance need to be investigated.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    URL: Article
    DOI: 10.1159/000515527
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
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  • 3
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    Renal and intraglomerular haemodynamics in chronic heart failure with preserved and reduced ejection fraction
    Wiley ; 2021
    In:  ESC Heart Failure Vol. 8, No. 2 ( 2021-04), p. 1562-1570
    Details
    In: ESC Heart Failure, Wiley, Vol. 8, No. 2 ( 2021-04), p. 1562-1570
    Abstract: Congestive heart failure (CHF) and impaired renal function are two often co‐existing medical conditions and associated with adverse cardiovascular outcome. The aim of the current study was to assess renal and intraglomerular haemodynamics by constant infusion input clearance technique in subjects with CHF. Methods and results The group of subjects with CHF consisted of 27 individuals with HFpEF and 27 individuals with HFrEF and were compared with 31 healthy controls. Subjects underwent renal clearance examination to measure glomerular filtration rate (GFR) and renal blood and plasma flow (RBF and RPF) and to calculate intraglomerular haemodynamics such as resistances of the afferent (R A ) and efferent arterioles (R E ) as well as intraglomerular pressure ( P glom ). Measured GFR was lower in CHF subjects (68.1 ± 10.1 mL/min/1.73 m 2 ) compared with controls (83.6 ± 13.4 mL/min/1.73 m 2 , P adj   〈  0.001) as was P glom ( P adj   〈  0.001). Total renal vascular resistance (RVR) was higher in CHF subjects (87.3 ± 20.1 vs. 73.8 ± 17.1 dyn × s/cm 5 , P adj   〈  0.001) mediated by an increased resistance at the afferent site (3201 ± 1084 vs. 2181 ± 796 dyn × s/cm 5 , P adj   〈  0.001). Comparing HFpEF and HFrEF subjects, R A was higher in HFrEF subjects. The severity of CHF assessed by NT‐proBNP revealed an inverse association with renal perfusion (RPF r  = −0.421, P  = 0.002, RBF r  = −0.414, P  = 0.002) and a positive relation with RVR ( r  = 0.346, P  = 0.012) at the post‐glomerular site (R E : r  = 0.318, P  = 0.022). Conclusions Renal function assessed by measured GFR is reduced and renal vascular resistance at the preglomerular, afferent site is increased in HFpEF and, to greater extent, in HFrEF. Our data indicate a close cardiorenal interaction in CHF.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v8.2
    DOI: 10.1002/ehf2.13257
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 4
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    Effects of the sodium‐glucose cotransporter 2 inhibitor empagliflozin on vascular function in patients with chronic heart failure
    Wiley ; 2021
    In:  ESC Heart Failure Vol. 8, No. 6 ( 2021-12), p. 5327-5337
    Details
    In: ESC Heart Failure, Wiley, Vol. 8, No. 6 ( 2021-12), p. 5327-5337
    Abstract: Impairment of vascular function contributes to the progression of chronic heart failure (HF) by increasing the afterload. Treatment with selective sodium‐glucose cotransporter 2 (SGLT2) inhibitors improves the prognosis of HF, but the precise mechanisms remain unclear. The aim of this study was to analyse the effect of empagliflozin on vascular function in patients with HF. Methods and results In an investigator initiated, double‐blind, randomized, placebo‐controlled, parallel‐group, clinical study, patients with HF NYHA II‐III and an ejection fraction of 49% or less were randomized 2:1 to receive empagliflozin 10 mg once daily or placebo for 3 months. A total of 74 patients (15% female), aged 66 ± 9 years, with a mean ejection fraction of 39 ± 8% and a median NTproBNP of 558 pg/mL (IQR 219–1051 pg/mL), were included. Vascular parameters such as central systolic blood pressure (cSBP), central pulse pressure (cPP), forward (FPH), and reflected pressure pulse height (RPH) decreased under resting conditions after 1 and 3 months (1 month: cSBP −6.4 ± 8.3 mmHg, P   〈  0.001, cPP −3.0 ± 6.6 mmHg, P  = 0.004, FPH −2.5 ± 4.5 mmHg, P  = 0.001, RPH −1.6 ± 3.0 mmHg, P  = 0.001; 3 months: cSBP −4.6 ± 8.4 mmHg, P  = 0.001, cPP −3.1 ± 4.8 mmHg, P   〈  0.001, FPH −1.7 ± 3.7 mmHg, P  = 0.004, RPH −1.4 ± 2.5 mmHg, P  = 0.001) in patients treated with empagliflozin ( n  = 45). In accordance, cSBP and cPP decreased in patients with empagliflozin treatment under 24 h ambulatory conditions after 1 and 3 months (1 month: cSBP −4.8 ± 10.1 mmHg, P  = 0.003, cPP −2.0 ± 5.7 mmHg, P  = 0.026; 3 months: cSBP −4.7 ± 9.0 mmHg, P  = 0.002, cPP −2.1 ± 6.4 mmHg, P  = 0.044). In the placebo group, there was no significant change after 1 and 3 months. The decrease in cSBP under resting conditions (−5.7 ± 2.4 mmHg, P  = 0.019) after 1 month and in cSBP (−6.0 ± 2.6, P  = 0.027) as well as in pulse wave velocity (−0.5 ± 0.2 m/s, P  = 0.021) under 24 h ambulatory conditions after 3 months was greater in the empagliflozin group than in the placebo group. Conclusions We found an improvement of vascular function after treatment with empagliflozin that indicates decreased afterload of the left ventricle and may contribute to the beneficial effects of SGLT2 inhibition in HF.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v8.6
    DOI: 10.1002/ehf2.13622
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 5
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    Abstract 12882: Renal Hemodynamics in Chronic Heart Failure With Preserved and Reduced Ejection Fraction
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: Chronic heart failure (CHF) and impaired renal function are two co-existing medical conditions and known to be associated with adverse outcome. The cardiorenal interaction has not yet been analyzed thoroughly. The aim of this study was to assess renal and intraglomerular hemodynamics by constant infusion input clearance technique in subjects with CHF compared to healthy controls. Methods: This was a cross-sectional observational study including 85 subjects. The group of subjects with CHF consisted of 27 individuals with HFpEF and 27 individuals with HFrEF, who were compared to 31 controls. All subjects underwent renal clearance examination to determine measured -not estimated- glomerular filtration rate (GFR), renal blood and plasma flow (RBF, RPF) and to calculate renal hemodynamic parameters such as filtration fraction (FF), renal vascular resistance (RVR), intraglomerular pressure (P glom ) and resistances of the afferent (R A ) and efferent arterioles (R E ). Results: GFR was lower in subjects with CHF (88.6±13.1ml/min/1.73m 2 ) compared to controls (108.6±17. ml/min/1.73m 2 ) after adjustment for age and BP (p adj =0.037). There were no significant differences regarding RPF, RBF, FF, RVR, P glom , R A as well as R E after adjustment for age and BP. Similarly, there were no significant differences regarding renal hemodynamic parameters between HFpEF and HFrEF subjects. Bivariate correlation analysis in the group of subjects with CHF revealed an inverse association between NT-proBNP and RPF (R=-0.421, p=0.002), RBF (R=-0.414, p=0.002) and a positive association with FF (R=0.324, p=0.019), RVR (R=0.346, p=0.012) and R E (R=0.318, p=0.022). Conclusions: The findings of this study indicate that in CHF renal function is slightly reduced even though renal perfusion is preserved. With progressive severity of CHF as indicated by increasing NT-proBNP, renal vascular resistance in particular at the postglomerular side increases. Our data are in accordance with neuroendocrine activation in CHF since vasoconstriction at the postglomerular site points towards angiotensin II as mediator. The association between NT-proBNP and renal hemodynamics documents a close cardiorenal interaction in CHF.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.12882
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
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    Change of renal function after short-term use of cardioprotective agents in patients with type 2 diabetes is not accurately assessed by the change of estimated glomerular filtration rate: an observational study
    Springer Science and Business Media LLC ; 2022
    In:  Diabetology & Metabolic Syndrome Vol. 14, No. 1 ( 2022-12)
    Details
    In: Diabetology & Metabolic Syndrome, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-12)
    Abstract: After initiating cardioprotective agents, a fall of estimated glomerular filtration rate (eGFR) has been reported in several studies. Our goal was to evaluate the accuracy of change of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR in patients with type 2 diabetes (T2D) after short-term pharmacological intervention with angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, gliptin or sodium-glucose cotransporter-2 inhibitor. Methods We analyzed 190 patients with T2D in the early stage of the disease, having no overt renal impairment by CKD-EPI equation. In each patient, we measured GFR (mGFR) by applying the constant infusion input clearance technique with sinistrin (Inutest; Fresenius, Linz, Austria) at baseline and after short-term (4–12 weeks) pharmacological intervention with cardioprotective agents (ramipril, telmisartan, linagliptin, metformin, empagliflozin) that potentially lead to an alteration of renal function. Simultaneously, a standardized analysis of serum creatinine was performed and eGFR was estimated by the CKD-EPI equation. Results Average mGFR was 111 ± 20 ml/min/1.73m 2 , whereas eGFR was lower with 93 ± 13 ml/min/1.73m 2 . The ratio eGFR/mGFR in relation to mGFR was almost curvilinear, showing an underestimation of renal function by eGFR in the upper normal range. At baseline only 80 patients (42%) lay within ± 10% of mGFR and the concordance correlation coefficient (CCC) was extremely low (− 0.07). After short-term pharmacological intervention changes in eGFR and mGFR correlated with each other (r = 0.286, p  〈  0.001). For example, for a given mGFR of 111 ml/min/1.73m 2 , a change of mGFR by ± 10% corresponded to ± 11 ml/min/1.73m 2 , but the confidence interval of eGFR was 25 ml/min/1.73m 2 . The CCC was low (0.22). Conclusion The agreement between eGFR by CKD-EPI and mGFR is modest and the change of renal function after short-term pharmacological intervention is not accurately and precisely reflected by the change of eGFR in patients with T2D in the early stage of their disease.
    Type of Medium: Online Resource
    ISSN: 1758-5996
    URL: Article
    DOI: 10.1186/s13098-022-00874-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2518786-7
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  • 7
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    Detection of Changes in Renal Blood Flow Using Arterial Spin Labeling MRI
    S. Karger AG ; 2021
    In:  American Journal of Nephrology Vol. 52, No. 1 ( 2021), p. 69-75
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 52, No. 1 ( 2021), p. 69-75
    Abstract: Background: Alteration in kidney perfusion is an early marker of renal damage. The purpose of this study was to evaluate if changes in renal blood flow (RBF) could be detected using MRI with arterial spin labeling (ASL) technique. Methods: RBF as assessed by cortical (CRBF), medullary, and total renal blood flow (TRBF) were measured by MRI with arterial spin labeling (ASL-MRI) using flow-sensitive alternating inversion recovery true fast imaging with steady-state precession sequence. In 11 normotensive healthy individuals (NT) and 11 hypertensive patients (HT), RBF was measured at baseline and after both feet were covered with cold ice packs (cold pressor test) that activates the sympathetic nervous system. In another experiment, RBF was measured in 10 patients with CKD before and after a pharmacological intervention. We compared RBF measurements between the 3 study populations. Results: A significant reduction in CRBF (p = 0.042) and a trend in TRBF (p = 0.053) were observed in response to the activation of the sympathetic nervous system. A trend toward reduction of CRBF (p = 0.051) and TRBF (p = 0.059) has been detected after pharmacological intervention. TRBF was significantly lower in patients with HT and CKD patients compared to NT individuals (NT vs. HT, p = 0.014; NT vs. CKD, p = 0.004). TRBF was lower in patients with CKD compared to HT (p = 0.047). Conclusion: Our data indicate that both acute and short-term changes in RBF could be detected using ASL-MRI. We were able to detect differences in RBF between healthy and diseased individuals by needing only small sample size per group. Thus, ASL-MRI offers an advantage in conducting clinical trials compared to other technologies.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000513665
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
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  • 8
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    Abstract 13827: Sleep Quality Improved After Intensified Blood Pressure Lowering Therapy
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Insufficient and poor sleep on a chronic basis raises blood pressure (BP), the risk of hypertension and cardiovascular disease which in turn further leads to sleep disturbances.In a prospective observational study we tested the hypothesis whether intensification of antihypertensive therapy improves sleep quality Patients with arterial hypertension on multiple drug medication were followed for 3 months if according to the physician‘s perception BP control was insufficient or patients profit from simplification of drug therapy. Intensification of antihypertensive therapy consisted of switching from multiple pills per day to a single pill combination. Office BP readings and out-of-BP measurements were monitored. The abbreviated PITTSBURGH SLEEP INVENTORY (PSQI) was applied to assess sleep duration and quality Results: In 229 patients (mean age 65 years, 62 % were males) office BP decreased from 158 ± 15/92 ± 8 to 132 ± 10/87 ± 8 mmHg (both p 〈 0.001). In parallel, sleep quality improved in 45 % and remained equal/worse in 53 % (p 〈 0.001) after 3 months In patients whose sleep quality improved (N=95) office BP dropped from 160±15/94±10 to 131±8.6/80±7 mmHg (both p 〈 0.001), whereas in patients with equal or worse sleep quality (N=119) BP fell only from 156±15/90±5 to 133±10/80±8 mmHg (both p 〈 0.001). BP fall was significantly greater in those with improved sleep quality as opposed to those with equal/worse sleep quality after 3 months of therapy (4.98±1.5/2.71±0.94 mmHg, p 〈 0.001 and p=0.005, respectively). Change in out-office systolic BP measurements was greater in those with improved as opposed to those with equal/worse sleep quality (5.80±1.9 mmHg, p=0.003). Thus, intensification of antihypertensive treatment by using single pill combination resulted in significant fall in BP accompanied by an improvement in sleep quality. Abstract Sleep quality improved after intensified blood pressure lowering therapy.docx
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13827
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 9
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    Abstract 12895: Tissue Sodium Content Increases With Severity of Chronic Heart Failure
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: Heart failure is strongly linked to renal sodium and water retention as well as intravascular and interstitial fluid shifts. Experimental studies demonstrated a non-osmotic sodium storage, bound to proteoglycans, in the extravascular space. New sodium magnetic resonance imaging ( 23 Na-MRI) enables us to quantify tissue (muscle and skin) sodium content in a reliable and accurate way. Hypothesis: We hypothesised that the increase of tissue sodium content is dependent on the severity of chronic heart failure (CHF). Methods: We investigated patients with stable CHF before initiating treatment with an SGLT2-inhibitor within a prospective, placebo-controlled study. We here report the baseline data of 64 patients with CHF, defined as patients with reduced (HFrEF) or mid-range ejection fraction (HFmEF). In each patient, tissue sodium content of the lower leg was assessed non-invasively by a clinical 3.0T 23 Na-MRI. The median NT-proBNP plasma level at baseline was 493.3pg/ml (IQR: 225.8-1122.0pg/ml) and was used as cut off value of CHF severity. Results: Our patients (men: n=54) were 66.9±8.9 years old and had NYHA class II-III; mean muscle sodium content was 19.1±3.8mmol/l and mean skin sodium content was 22.5±5.9mmol/l. Our reference for young healthy subjects are 18.7±2.0 mmol/l for muscle sodium content and 19.6±3.1 mmol/l for skin sodium content. Patients with CHF and NT-proBNP levels above the median showed higher muscle (20.2±3.5 vs 17.9±3.7mmol/l, p=0.008) and skin sodium content (24.1±6.8 vs 20.8±4.4mmol/l, p=0.005) than patients with CHF and NT-proBNP levels below the median. No difference in plasma sodium levels between the two groups (138.0±3.7 vs 138.8±2.1mmol/l, p=0.527) was observed, but patients with NT-proBNP levels above the median had lower urinary sodium excretion over 24 hours (167.0±78.8 vs 172.3±63.4mmol/l, p=0.009). Age was different in the two groups (69.88±8.2 vs 63.8±8.7, p 〈 0.001) with no difference in gender. The number of diagnosed coronary heart disease was similar in the two groups (62.5% vs 59.4%, p=0.802). Conclusion: Concluding, tissue sodium content in patients with stable CHF as assessed by 23 Na-MRI increases with the severity of CHF. A decrease of tissue sodium content might be a future therapeutic goal.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.12895
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 10
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    Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure
    Wiley ; 2023
    In:  ESC Heart Failure Vol. 10, No. 3 ( 2023-06), p. 1635-1642
    Details
    In: ESC Heart Failure, Wiley, Vol. 10, No. 3 ( 2023-06), p. 1635-1642
    Abstract: Large outcome studies demonstrated a reduction of heart failure hospitalization or cardiovascular death in patients with chronic heart failure (CHF). The renin–angiotensin system (RAS) is a key player in fluid and sodium regulation. The classic angiotensin‐converting enzyme–angiotensin II–angiotensin‐1 receptor axis (Ang I–ACE–Ang II receptor axis) is predominantly angiotensin II (Ang‐II) induced and promotes vasoconstriction. In contrast, the angiotensin‐converting‐enzyme‐2–angiotensin‐(1‐7)–Mas axis (Mas‐axis) is mediated by the metabolites angiotensin‐1‐7 (Ang‐(1‐7)) and angtiotensin‐1‐5 (Ang‐(1‐5)) and exerts cardioprotective effects. Methods We previously investigated the effect of empagliflozin on the systemic haemodynamic in patients with stable CHF (NYHA II–III) in a randomized placebo‐controlled clinical trial ‘Analysing the Effect of Empagliflozin on Reduction of Tissue Sodium Content in Patients With Chronic Heart Failure (ELSI)’. In a post hoc analysis, we now analysed whether empagliflozin has an effect on the RAS by measuring detailed RAS profiles (LC‐MS/MS‐based approach) in 72 patients from ELSI. We compared RAS parameters after 1‐month and 3‐months treatment with empagliflozin or placebo to baseline. The secondary goal was to analyse whether the effect of empagliflozin on RAS parameters was dependent on angiotensin‐receptor‐blocking (ARB) or angiotensin‐converting‐enzyme‐inhibitor (ACEI) co‐medication. Results Empagliflozin medication induced a significant rise in Ang‐II [68.5 pmol/L (21.3–324.2) vs. 131.5 pmol/L (34.9–564.0), P  = 0.001], angiotensin‐I (Ang‐I) [78.7 pmol/L (21.5–236.6) vs. 125.9 pmol/L (52.6–512.9), P   〈  0.001], Ang‐(1‐7) [3.0 pmol/L (3.0–15.0) vs. 10.1 pmol/L (3.0–31.3), P  = 0.006], and Ang‐(1‐5) [5.4 pmol/L (2.0–22.9) vs. 9.9 pmol/L (2.8–36.4), P  = 0.004], which was not observed in the placebo group (baseline to 3‐months treatment). A significant rise in Ang‐II (206.4 pmol/L (64.2–750.6) vs. 568.2 pmol/L (164.7–1616.4), P  = 0.001), Ang‐(1‐7) (3.0 pmol/L (3.0–14.1) vs. 15.0 pmol/L (3.0–31.3), P  = 0.017), and Ang‐(1‐5) [12.2 pmol/L (3.8–46.6) vs. 36.4 pmol/L (11.1–90.7), P  = 0.001] under empagliflozin treatment was only seen in the subgroup of patients with ARB co‐medication, whereas no change of Ang‐II (16.7 pmol/L (2.0–60.8) vs. 26.4 pmol/L (10.7–63.4), P  = 0.469), Ang‐(1‐7) (6.6 pmol/L (3.0–20.7) vs. 10.5 pmol/L (3.0–50.5), P  = 0.221), and Ang‐(1‐5) (2.7 pmol/L (2.0–8.4) vs. 2.8 pmol/L (2.0–6.9), P  = 0.851) was observed in patients with empagliflozin that were on ACEI co‐medication (baseline to 3‐months treatment). Conclusions Our data indicate that empagliflozin might lead to an activation of both the Ang I–ACE–Ang II receptor axis and the Mas‐axis pathway. Activation of the Ang I–ACE–Ang II receptor axis and the protective Mas‐axis pathway after initiating treatment with empagliflozin was only seen in patients with ARB co‐medication, in contrast to co‐medication with ACEI.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v10.3
    DOI: 10.1002/ehf2.14313
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2814355-3
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