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BACKGROUND: The increased diuresis after sodium-glucose cotransporter 2 inhibitor (SGLT2i) was associated with a reduction of the estimated plasma volume (ePV) in type 2 diabetic patients. HYPOTHESIS: We hypothesized that the early effect of SGLT2i on ePV may be monitored by the change of biomarkers of hemoconcentration. PATIENTS AND METHODS: We analyzed the early- and long-term effect of SGLT2i empagliflozin on the ePV as assessed by biomarkers of hemoconcentration in a nondiabetic patient with heart failure and reduced ejection fraction (HFrEF) and a nondiabetic patient with heart failure and preserved ejection fraction (HFpEF). The ePV was calculated from hemoglobin and hematocrit levels by Duarte formula and ePV change was calculated by Strauss formula. RESULTS: The ePV change was -22.56% between baseline and 1 month, and -37.60% between baseline and 12 months follow-up in a patient with HFrEF, and -6.18% and -16.40% in a patient with HFpEF, respectively. CONCLUSION: The early effect of SGLT2i on ePV in patients with heart failure may be monitored by biomarkers of hemoconcentration.

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Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease characterized by hypotensive shock, anasarca, hemoconcentration, and hypoalbuminemia. Despite the life-threatening course of the disease, no treatment strategy has been established. A 68-year-old man presented with hypotensive shock following a prodrome. Based on the characteristic blood test findings, ISCLS was suspected. The patient was resuscitated by administering massive amounts of fluids and inotropic and vasopressor agents. After his blood pressure had stabilized, renal replacement therapy (RRT) was promptly initiated to facilitate the removal of excess fluid, despite the presence of urine output. Typically, ISCLS has three phases: prodromal, leak, and post-leak. Diuresis should be promptly induced during the transition from the leak phase to the post-leak phase to avoid fatal complications such as pulmonary edema. We propose that in patients with ISCLS, early introduction of RRT is recommended if indicated.

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Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.

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Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77 dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

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Systemic Capillary Leak Syndrome (SCLS) is a rare disease that causes severe distributive shock provoked by infection or vaccination. SCLS is clinically diagnosed by a triad of distributive shock, paradoxical hemoconcentration, and hypoalbuminemia. SCLS associated with coronavirus disease (COVID-19) in adults has not been reported yet in Japan. Case 1: A 61-year-old woman with fever, sore throat, headache, and muscle pain was admitted to our emergency department with suspected COVID-19. She had been diagnosed with SCLS 3 years earlier. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and polymerase chain reaction (PCR) tests were negative at admission. She went into shock in the emergency department and was treated for septic shock. The following day, the SARS-CoV-2 PCR test was positive. She did not respond to fluid resuscitation and catecholamine and finally died. Case 2: A 58-year-old man was admitted to our hospital for de-saturation due to COVID-19. He got into shock on day 3. SCLS was suspected, and 5 g of intravenous immunoglobulin and 5% albumin were administered for sepsis treatment. He responded to the aggressive fluid therapy within 48 h and was finally discharged. COVID-19 can trigger SCLS, and early recognition of SCLS is crucial for survival. Primary care physicians should consider SCLS when they observe distributive shock and paradoxical hemoconcentration deviations from the natural course of COVID-19.

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Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

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Systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare and potentially lethal condition characterized by hypotension, hemoconcentration, and hypoalbuminemia; however, the cause of SCLS is still uncertain. We present the case of a 62-year-old male with flu-like symptoms who presented to the emergency department with shock. Initial evaluation revealed hemoconcentration, hypoalbuminemia, acute kidney failure, and positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite aggressive fluid resuscitation, the shock persisted, and the patient's condition deteriorated. After ruling out ischemia and septic shock, the patient was diagnosed with coronavirus disease 2019 (COVID-19)-associated SCLS. Treatment with remdesivir and intravenous immunoglobulin (IVIG), along with the restoration of intravascular volume, led to the gradual improvement of the patient's condition. The patient experienced pulmonary edema, which was managed by correcting the fluid balance through continuous hemodiafiltration. Eventually, the patient recovered without any residual organ complications. SCLS is often misdiagnosed because of its rarity and non-specific symptoms. Accurate diagnosis and understanding of the disease's pathophysiology are crucial for effective management. This report contributes to the existing literature by presenting a case of COVID-19-associated SCLS and emphasizes the need for further research on its occurrence and outcomes.

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The hemoconcentration effect for middle weight solutes in hemodialysis is corrected by oversimplified methods based on hematocrit changes or distribution volume variations. Here we implemented a variable volume dual pool kinetic model targeted at obtaining a precise correction factor equation for extracellularly distributed solutes based on relevant kinetic parameters such as the ultrafiltration to dry weight ratio UF/DW, the dialyzer clearance, Kd, the intercompartment mass-transfer coefficient, Kc, and the central compartment to extracellular volume ratio, α. More than 300,000 solutions of the model were computed, performing a sweep among physiological values of the proposed kinetic parameters, resulting in a linear regression denoted by the expression fcorr = 1.0707 - 5.2246 (UF/DW) - 0.0005 Kd - 0.0004 Kc - 0.0007 α, with an excellent coefficient of determination R2 = 0.983. The presented fcorr provides a substantial extension of the currently implemented methods to estimate the hemoconcentration factor for middle and high molecular weight extracellular distributed solutes in hemodialysis.

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BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease characterized by recurrent episodes of acute life-threatening attacks of shock, hemoconcentration, and hypoalbuminemia. Increase in capillary permeability results in reversible plasma movement into the interstitial spaces followed by appearance of related symptoms or complications, including renal failure. This condition can be potentially life-threatening; however, it is easily misdiagnosed. CASE PRESENTATION: A 47-year-old man with no previous medical history presented to the emergency department after experiencing general weakness and abdominal pain. He developed hypovolemic shock within 3 h of presentation and initial laboratory tests showed hemoconcentration, hypoalbuminemia and acute kidney injury. Following vigorous fluid therapy and supportive care, the patient recovered, but a similar episode recurred after 4 months without any specific trigger. Based on the combined clinical manifestations and laboratory findings of both the attacks, he was diagnosed with ISCLS. Symptomatic relief was achieved via oxygen supplementation and massive volume replacement using normal saline and the patient was prescribed bambuterol 10 mg and theophylline 400 mg once-a-day. He was discharged from the hospital on day 5 of hospitalization. Thereafter, the patient has been followed for 5 years without any symptoms or recurrence of ISCLS even in the situation of COVID-19 infection. CONCLUSIONS: ISCLS is an extremely infrequent and commonly misdiagnosed disease. However, early diagnosis, treatment and prophylaxis through accumulated clinical data can prevent ISCLS recurrence and the development of related fatal complications. Therefore, clinicians need to be well aware of the variety of clinical characteristics and treatment options of this disease.

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BACKGROUND: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)_the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023). CONCLUSION: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.

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Idiopathic systemic capillary leak syndrome (ISCLS) is a rare condition caused by the extravasation of intravascular fluids and proteins into the interstitial space due to increased vascular endothelium permeability. It is characterized by episodes of hypotension, hypoalbuminemia, and hemoconcentration with generalized edema. Its etiopathogenesis is unknown. However, it is associated with monoclonal gammopathy in more than 80% of cases. There is currently no targeted treatment, and the approach during a crisis is supportive, mainly to control blood pressure, maintain perfusion of vital organs, and prevent complications, such as acute pulmonary edema and organ failure due to ischemia, which are the primary causes of death. We present the case of a 72-year-old man with generalized edema and pleural, pericardial, and peritoneal effusions whose laboratory results showed hypoalbuminemia, hypoproteinemia, and immunoglobulin G kappa monoclonal gammopathy. Other etiologies for severe hypoalbuminemia with anasarca were excluded after an exhaustive complementary study, leading to the diagnosis of ISCLS associated with monoclonal gammopathy. The patient showed progressive clinical improvement with albumin and diuretic therapy. However, they were readmitted to the hospital due to hypotension with multiorgan dysfunction and died a few hours later.

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Background: Capillary leak is the hallmark of development of severe dengue. A rise in haematocrit has been a major warning sign in WHO guidelines. Postural hypotension, which could reflect the intravascular volume reduction in capillary leak has been noted as warning sign in CDC and Pan American Health Organisation guidelines. We evaluated the diagnostic accuracy of postural hypotension as a marker of development of severe dengue. Methods: 150 patients admitted with dengue fever were recruited in this prospective observational study. Diagnostic accuracy of conventional warning signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and postural hypotension was evaluated. Results: 23 (15.3%) subjects developed severe dengue. Multiple logistic regression analysis showed that ascites/pleural effusion and postural fall in systolic blood pressure of >10.33% had odds ratio of 5.024(95%CI:1.11 - 22.75) and 11.369 (95% CI:2.27 - 56.87), respectively. Other parameters did not reach statistical significance. Sensitivity and specificity of ascites/pleural effusion were 82.6% and 88.2% for development of severe dengue whereas postural fall in systolic blood pressure had sensitivity and specificity of 87% and 82.7%. Conclusions: These findings present a strong case for including postural hypotension as a warning sign in patients with dengue fever, especially in resource limited settings.

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Several cases of capillary leak syndrome (CLS) related to COVID-19 or vaccination against SARS-CoV-2 have been described in the literature. We present a case of a 42-year-old, previously healthy male, presenting with a mild form of COVID-19, who suddenly developed severe shock with hypotension and severe hemoconcentration within hours of admission to the hospital. Volume resuscitation was not effective, increasing hemoglobin (198 g/L on admission, 222 g/L 9 h later) suggested fluid leak into peripheral tissues. After cardiac arrest, the patient was resuscitated and connected to extracorporeal membrane oxygenation, but died shortly afterwards due to refractory heart failure. Retrospective investigation of blood samples confirmed diagnosis of CLS by progressive hypoalbuminemia (40 g/L on admission, 14 g/L 19 h later) and monoclonal gammopathy kappa (4.7 g/L). Patient's CLS was triggered by COVID-19, either a first attack of idiopathic CLS called Clarkson's disease or a COVID-19-induced secondary CLS.

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Idiopathic systemic capillary leak syndrome (SCLS) is characterized by an increased capillary hyperpermeability with subsequent hemoconcentration, hypoproteinemia, and hypovolemia. Patients present with diffuse swelling, weight gain, low blood pressure, and shock. We present our case of idiopathic SCLS in a 50-year-old man presenting with prodromal flu-like illness associated with shock that was complicated by compartment syndrome requiring four limb fasciotomies, disseminated intravascular coagulation, acute kidney injury requiring dialysis, and cardiac arrest.

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We aimed to continuously determine the stroke volume (SV) and blood volume (BV) during incremental exercise to evaluate the individual SV course and to correlate both variables across different exercise intensities. Twenty-six females with heterogeneous endurance capacities performed an incremental cycle ergometer test to continuously determine the oxygen uptake (V̇O2), cardiac output (Q̇) and changes in BV. Q̇ was determined by impedance cardiography and resting cardiac dimensions by 2D echocardiography. Hemoglobin mass and BV were determined using a carbon monoxide-rebreathing method. V̇O2max ranged from 32 to 62 mL·kg-1·min-1. Q̇max and SVmax ranged from 16.4 to 31.6 L·min-1 and 90-170 mL, respectively. The SV significantly increased from rest to 40% and from 40% to 80% V̇O2max. Changes in SV from rest to 40% V̇O2max were negatively (r = -0.40, p = 0.05), between 40% and 80% positively correlated with BV (r = 0.45, p < 0.05). At each exercise intensity, the SV was significantly correlated with the BV and the cardiac dimensions, i.e., left ventricular muscle mass (LVMM) and end-diastolic diameter (LVEDD). The BV decreased by 280 ± 115 mL (5.7%, p = 0.001) until maximum exercise. We found no correlation between the changes in BV and the changes in SV between each exercise intensity. The hemoglobin concentration [Hb] increased by 0.8 ± 0.3 g·dL-1, the capillary oxygen saturation (ScO2) decreased by 4.0% (p < 0.001). As a result, the calculated arterial oxygen content significantly increased (18.5 ± 1.0 vs. 18.9 ± 1.0 mL·dL-1, p = 0.001). A 1 L higher BV at V̇O2max was associated with a higher SVmax of 16.2 mL (r = 0.63, p < 0.001) and Q̇max of 2.5 L·min-1 (r = 0.56, p < 0.01). In conclusion, the SV strongly correlates with the cardiac dimensions, which might be the result of adaptations to an increased volume load. The positive effect of a high BV on SV is particularly noticeable at high and severe intensity exercise. The theoretically expected reduction in V̇O2max due to lower SV as a consequence of reduced BV is apparently compensated by the increased arterial oxygen content due to a higher [Hb].

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BACKGROUND: Decongestion is an important goal in the management of acute heart failure. Whether the rate of decongestion is associated with mortality and cardiovascular outcomes is unknown. METHODS: Using data from 4133 patients from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we used multivariable Cox regression models to evaluate the association between rates of in-hospital change in assessments of volume overload, including b-type natriuretic peptide (BNP), N-terminal pro b-type natriuretic peptide (NT-proBNP), as well as change in hemoconcentration, with risk of all-cause mortality and a composite outcome of cardiovascular mortality or heart failure hospitalization. RESULTS: More rapid rates of in-hospital decongestion were associated with decreased risk of mortality and the composite outcome over a median 10-month follow-up. In reference to the quartile of slowest decline, the quartile with the fastest BNP and NT-proBNP decline had lower hazards of mortality (hazard rate [HR] = 0.43 [0.31, 0.59] and HR = 0.27 [0.19, 0.40], respectively) and composite outcome (HR = 0.49 [0.39, 0.60] and HR = 0.54 [0.42, 0.71], respectively). In reference to the quartile of slowest increase, the quartile with the fastest hematocrit increase had lower hazards of mortality (HR = 0.77 [0.62, 0.95]) and composite outcome (HR = 0.75 [0.64, 0.88]). Results were also consistent when models were repeated using propensity-score matching. CONCLUSIONS: Faster rates of decongestion are associated with reduced risk of mortality and a composite of cardiovascular mortality and heart failure hospitalization. It remains unknown whether more rapid decongestion provides cardiovascular benefit or whether it serves as a proxy for less treatment resistant heart failure.

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Purpose: Practical methods for detecting plasma leakage should be readily available in all areas where dengue is endemic. We compared the accuracy of measurements obtained with a handheld HemoCue® Hb 201 instrument used for hemoglobin point-of-care testing (Hb-POCT) with that of measurements of hematocrit (Ht) levels for detecting plasma leakage in dengue patients. Patients and Methods: We performed both measurements using the HemoCue® Hb201 system and microhematocrit method on EDTA blood taken from dengue patients at three time points during their hospitalization. Ascites, pleural effusion, or gallbladder thickening determined through ultrasound examinations were considered the gold standard for determining dengue hemorrhagic fever (DHF) versus dengue fever (DF). Results: Close agreement between Hb-POCT and Ht measurements was indicated by an r square value of 0.845 in a linear regression. The sensitivity results for distinguishing between DHF and DF at admission were similar for Hb-POCT (63.6%) and Ht (66.7%) (Kappa = 0.75) using the optimal cutoff point determined via ROC analysis. Delta differences (in percentage) for Hb-POCT and Ht between the highest and lowest values showed lower sensitivity (45.5% and 48.5%, respectively; Kappa 0.60) when the optimal cutoff point was applied. Recommended cutoffs of ≥20% to confirm plasma leakage provided a slightly higher sensitivity using Hb-POCT (18.2%) compared with the sensitivity obtained using Ht (15.2%) with Kappa value of 97.9%. Conclusion: Our results showed that the accuracy of Hb POCT measurements was similar and not inferior to Ht measurements for detecting plasma leakage in patients with DHF. We recommend that further evaluations are conducted to determine the optimal cutoff point given the low sensitivity associated with using ≥20% Hb-POCT or Ht increases to determine hemoconcentration.

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PURPOSE: Hemoconcentration during acute intense exercise is intensively investigated, while the rearrangement of hematological parameters during the recovery period is less understood. The aim of our study was to understand the mechanisms of hemodilution after short-term dynamic exercise. METHODS: Twelve euhydrated male kayak athletes and 6 untrained controls were examined on a spiroergometer. In addition to the continuous recording of circulatory parameters, blood samples were taken at rest, at maximum load, and during restitution with a dense sampling frequency. Hemoglobin, hematocrit, osmolality, blood components, and core temperature were measured. RESULTS: The hemoconcentration, independently of training status, reached its maximum (athletes Δ9.59% [4.18%] vs controls Δ11.85% [2.71%]) in the first minute of the recovery period. There was a significant increase in core temperature, reducing the viscosity of blood and promoting tissue oxygenation. High cardiac output and the increased blood flow compensate for viscosity being elevated by hemoconcentration during exercise. Hemoconcentration was maintained for 7 to 10 minutes and then diluted back to baseline 30 minutes after exercise. Temporarily higher viscosity during reduced cardiac output may result in a critical hemoconcentration zone, elevating the risk of circulatory overload. Elite athletes have a faster cardiac output decrease compared with that of hemodilution, making the circulation more vulnerable. We supposed that hemodilution was guided independently by plasma- and erythrocyte-related effectors. CONCLUSIONS: After high-intensity dynamic acute exercise, hemodilution is driven by independent factors, and a critical hemoconcentration zone may be formed during the recovery period in trained elite athletes.

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RATIONALE & OBJECTIVE: Achievement of decongestion in acute heart failure (AHF) is associated with improved survival and cardiovascular outcomes but can be associated with acute declines in estimated glomerular filtration rate (eGFR). We examined whether the rate of in-hospital decongestion is associated with longer term kidney function decline. STUDY DESIGN: Post hoc analysis of trial data. SETTINGS & PARTICIPANTS: Patients with ≥2 measures of kidney function (n = 3,500) from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. EXPOSURE: In-hospital rate of change in assessments of volume overload, including B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and clinical congestion score (0-12); and rate of change in hemoconcentration including measures of hematocrit, albumin, and total protein. OUTCOME: Incident chronic kidney disease GFR category 4 or worse (chronic kidney disease [CKD] categories G4-G5; defined by a new eGFR of <30 mL/min/1.73 m2) and eGFR decline of >40%. ANALYTICAL APPROACH: Multivariable cause-specific hazards models. RESULTS: Over median 10-month follow-up period, faster decreases in volume overload and more rapid increases in hemoconcentration were associated with a decreased risk of incident CKD G4-G5 and eGFR decline of >40%. In adjusted analyses, for every 6% faster decline in BNP per week, there was a 32% lower risk of both incident CKD G4-G5 (HR, 0.68 [95% CI, 0.58-0.79]) and eGFR decline of >40% (HR, 0.68 [95% CI, 0.57-0.80]). For every 1% faster increase per week in absolute hematocrit, there was a lower risk for both incident CKD G4-G5 (HR, 0.73 [95% CI, 0.64-0.84]) and eGFR decline of >40% (HR, 0.82 [95% CI, 0.71-0.95]), with results consistent for other biomarkers. LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: These results provide reassurance that more rapid decongestion in patients with AHF does not increase the risk of adverse kidney outcomes in patients with heart failure.

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