Ideal Plasma Volume Research Articles

Can Plasma Volume Determination in Cirrhosis Be Replaced by an Algorithm Using Body Weight and Hematocrit?

Patients with cirrhosis often develop hyperdynamic circulation with increased cardiac output, heart rate, and redistribution of the circulating volume with expanded plasma volume (PV). PV determination is part of the evaluation of patients with cirrhosis, but gold-standard methods are invasive, expensive, and time-consuming. Therefore, other estimations of PV would be preferable, and the aim of this study was therefore to study if PV, as assessed by a simplified algorithm based on hematocrit and weight, can replace the gold-standard method. We included 328 patients with cirrhosis who had their PV assessed by the indicator dilution technique as the gold-standard method (PVI-125). Actual PV was estimated as PVa = (1 - hematocrit)·(a + (b·body weight)). Ideal PV was estimated as PVi = c · body weight, where a, b, and c are constants. PVI-125, PVa, and PVi were 3.99 ± 1.01, 3.09 ± 0.54, and 3.01 ± 0.65 (Mean ± SD), respectively. Although PVI-125 correlated significantly with PVa (r = 0.72, p < 0.001), a Bland-Altman plot revealed wide limits of confidence. The use of simplified algorithms does not sufficiently estimate PV and cannot replace the indicator dilution technique.

The Relation of Calculated Plasma Volume Status to Sublingual Microcirculatory Blood Flow and Organ Injury.

The calculated plasma volume status (cPVS) was validated as a surrogate of intravascular filling. The aim of this study is to assess the cPVS in relation to sublingual perfusion and organ injury. Pre- and postoperative cPVS were obtained by determining the actual and ideal plasma volume levels in surgical patients. The sublingual microcirculation was assessed using SDF imaging, and we determined the De Backer score, the Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Our primary outcome was the assessment of the distribution of cPVS and its association with intraoperative sublingual microcirculation and postoperative complications. The median pre- and postoperative cPVS were -7.25% (IQR -14.29--1.88) and -0.4% (IQR -5.43-6.06), respectively (p < 0.001). The mean intraoperative administered fluid volume was 2.5 ± 2.5 L (1.14 L h-1). No statistically significant correlation was observed between the pre- or postoperative cPVS and sublingual microcirculation variables. Higher preoperative (OR = 1.04, p = 0.098) and postoperative cPVS (OR = 1.057, p = 0.029) were associated with postoperative organ injury and complications (sepsis (30%), anemia (24%), respiratory failure (13%), acute kidney injury (6%), hypotension (6%), stroke (3%)). The calculated PVS was associated with an increased risk of organ injury and complications in this cohort.

427 MUTUAL INTERDEPENDENCE OF BNP, PLASMA VOLUME, RENAL FUNCTION AND LVEF IN HEALTHY SUBJECTS

Abstract Background Natriuretic peptides play an important role in cardiovascular control, stimulating diuresis and vasodilatation and suppressing the renin-angiotensin-aldosterone system. They are also pivotal markers in diagnosis, prognosis and therapy of heart failure (HF), specially BNP and its precursor pro-hormone Nt-proBNP. .Many factors can affect BNP levels in HF patients, potentially reducing its diagnostic accuracy. The main important ones include left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR) and plasma volume (PV). Though the mutual relationship between BNP levels and these drivers is well studied in HF patients, paradoxically little is known about this relationship in physiological conditions in healthy subjects. We tried to elucidate mutual interdependence of BNP, PV, renal function and LVEF in healthy subjects. Methods A total of 200 healthy adult males underwent clinical assessment, measurement of serum levels of BNP, creatinine, uricemia, hemochrome and echocardiography for LVEF assessment. GFR was calculated according to EPI-CKD formula. PV was estimated with both the Hakim formula and the Kaplan formula. The ideal PV (iPV) i.e. the normal PV was calculated using body weight and sex: iPV (in ml) = c × body weight (in kg), where c = 39 in males and 40 in females. Results Mean levels of BP, LVEF, BNP, serum creatinine, GFR, uricemia and PV were all within the normal range. PV1 and PV2 were significantly different from each other and both differed from iPV (Friedman ANOVA; | = 28.4; df = 2; P &amp;lt;0.01 for all the comparisons). Nevertheless, the three estimates of PV were all significantly and strictly correlated to each other (Spearman correlation coefficient, Rho &amp;gt;0.82 and P&amp;lt;0.001 for all the correlations). BNP levels were positively correlated with age and inversely with both uricemia and iPV. The latter ones were positively correlated to each other. GFR was inversely correlated with both age and uricemia (but not with PV nor with BNP levels). No correlation was found between LVEF and BNP levels or PV. Conclusions In homeostatic conditions, BNP and PV are inversely correlated in healthy adult males (contrary to the positive correlation existing in HF patients due to the predominant effects of angiotensin II and aldosterone), whereas opposite correlations between uricemia and both PV (positive) and GFR (negative) exist. The positive correlation between uricemia and PV could be explained by the strict dependence of tubular reabsorption of uric acid on serum levels of sodium, which is in turn strictly related to the extracellular fluid volume. The negative correlation between uricemia and GFR can be explained by the mutual influence of these two factors, since hyperuricemia seems to be both a cause and a consequence of chronic kidney disease (CKD).

Intravascular Volume Derangement and Value of Blood Volume Analysis in Stable Ambulatory Patients with Advanced Heart Failure Supported with Left Ventricular Assist Device

<h3>Purpose</h3> Heart failure is associated with elevated filling pressures and significant volume expansion. Durable left ventricular assist devices (LVAD) have been shown to improve survival and quality of life in patients with advanced heart failure. There is strong evidence suggesting structural, neurohormonal and hemodynamic improvement after LVAD implantation. The data on normalization of plasma volume is lacking. We sought to describe blood volume parameters in stable outpatient LVAD recipients. <h3>Methods</h3> We performed blood volume analysis (BVA) on 33 stable consecutive patients supported with LVADs in the outpatient setting. All BVAs were obtained as part of routine outpatient follow up. Results of the test were provided to clinicians for ongoing patient management. BVA is clinically approved and utilizes the Iodine131-tagged albumin tracer to provide quantitative measurement of total blood volume (TBV), plasma volume (PV) and red blood cell volume (RBC). The BVA-report provides absolute values (ml) and deviation from ideal TBV, PV, and RBC. A TBV deviation ≥±8% was considered to be either an excess or deficit of volume. <h3>Results</h3> Only 9% of stable ambulatory LVAD patients had normal blood volume results. 18/33 (54%) had significant anemia, 4/33 (12%) had polycythemia. Polycythemia in all of the patients was masked on complete blood count analysis, due to significant hypervolemia. One of the patients with masked polycythemia had fatal pump thrombosis. Plasma volume abnormality was found in 75% of patients (39% were hypervolemic, 36% were hypovolemic). 6 patients had repeat BVA after medical interventions and all of them were unsuccessful in normalizing plasma volume. <h3>Conclusion</h3> BVA is useful tool in outpatient management of patients with LVADs. As with advanced heart failure, correction of clinically unsuspected and undetected derangements in intravascular volume and red blood cell volumes likely have an impact on device and patient outcomes. These deviations may be recalcitrant to correction and further investigation is ongoing. Underdiagnosed polycythemia in LVAD patients may further contribute to hemo-compatibility issues and thrombosis. Measurement and treatment of derangements of intravascular volumes likely will improve performance and survival of patients and devices.

Deviations From the Ideal Plasma Volume and Isolated Tricuspid Valve Surgery-Paving the Way for New Risk Stratification Parameters.

BackgroundCongestion and plasma volume expansion are important features of heart failure, whose prognostic significance has been investigated in a range of surgical and non-surgical settings. The aim of this study was to evaluate the value of the estimated plasma volume status (ePVS) in patients undergoing isolated tricuspid valve surgery.MethodsThis study included patients who underwent isolated tricuspid valve surgery at the Vienna General Hospital (Austria) between July 2008 and November 2018. The PVS cut-off was calculated using ROC analysis and Youden's Index.ResultsEighty eight patients (median age: 58 [IQR: 35-70] years; 44.3% male; 75.6% NYHA III/IV; median EuroSCORE II 2.65 [IQR: 1.70-5.10]; 33.0% endocarditis-related regurgitation; 60.2% isolated repair; 39.8% isolated replacement) were included in this study. Patients who died within 1 year following surgery had significantly higher baseline ePVS values than survivors (median ePVS 5.29 [IQR: −1.55-13.55] vs. −3.68 [IQR: −10.92-4.22]; p = 0.005). During a median actuarial follow-up of 3.02 (IQR: 0.36-6.80) years, patients with a preoperative ePVS ≥ −4.17 had a significantly increased mortality (log-rank p = 0.006).ConclusionsePVS is an easily obtainable risk parameter for patients undergoing isolated tricuspid valve surgery capable of predicting mid- and long-term outcomes after isolated tricuspid valve surgery.

Prognostic value of simple risk index and plasma volume status in patients with acute decompensated heart failure

Abstract Background Increased heart rate (HR) and low systolic blood pressure (SBP) are associated with adverse clinical outcomes in patients admitted for acute decompensated heart failure (ADHF), and simple risk index (SRI) based on easily assessed clinical characteristics (age, HR, and SBP) provides prognostic information. On the other hand, plasma volume (PV) expansion plays an essential role in heart failure, and PV status is has been reported to be associated with adverse outcomes in ADHF patients. However, there is no information available on the value of the combination of SRI and PV status in patients admitted for ADHF. Methods and results We studied 301 patients admitted for ADHF. At the admission, SRI was calculated as (HR x [age/10]2)/SBP. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 patients had all-cause death (ACD) and 68 patients had cardiovascular death (CVD). At multivariate Cox analysis, SRI and PV status were significantly associated with ACD and CVD, independently of the prior history of heart failure hospitalization and serum creatinine and sodium levels, after the adjustment with serum albumin level and anemia. Patients with both greater SRI (≥35.1 by ROC analysis; AUC 0.599 [0.524–0.674]) and greater PV status (≥8.1% by ROC analysis; AUC 0.625 [0.550–0.700]) had a significantly higher risk of ACD and CVD than those with either or none of them (ACD: 49% vs 27% vs 24%, p&amp;lt;0.0001, CVD: 39% vs 18% vs 15%, p&amp;lt;0.0001,respectively). Conclusion The combination of SRI and PV status might be useful for stratifying patients at risk for the total mortality and cardiovascular death in patients with ADHF. Funding Acknowledgement Type of funding sources: None.

Calculated Plasma Volume Status Is Associated With Mortality in Acute Respiratory Distress Syndrome.

This is a retrospective cohort study of subjects enrolled in four previously completed National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials, using data from the National Institutes of Health Biologic Specimen and Data Repository Information Coordinating Center repository. Study subjects included 3,165 patients with acute respiratory distress syndrome previously enrolled in National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials. The exposure variable of interest was plasma volume status, calculated as the percentage alteration of actual plasma volume calculated on the basis of weight and hematocrit using sex-specific constants. We performed Kaplan-Meier survival analysis and univariable and adjusted Cox proportional hazard models to determine the association of plasma volume status with 60-day mortality. The median age of subjects was 52 years (interquartile range, 40-63 yr). Median plasma volume status was 5.9% (interquartile range, -2.4% to 13.6%), and overall, 68% of subjects had positive plasma volume status suggesting plasma volume higher than ideal plasma volume. In adjusted models, plasma volume status greater than median was associated with 38% greater risk for mortality (hazard ratio, 1.38; 95% CI, 1.20-1.59; p < 0.001). Each interquartile range increase in plasma volume status was associated with greater mortality in adjusted models (hazard ratio, 1.24 per interquartile range increase; 95% CI, 1.13-1.36; p < 0.001). Plasma volume status greater than median was associated with fewer ventilator-free days (18 vs 19 d; p = 0.0026) and ICU-free days (15 vs 17 d; p = 0.0001). Plasma volume status is independently associated with mortality, ICU-free days, and ventilator-free days among subjects with acute respiratory distress syndrome. Plasma volume status could be considered for risk-stratification and to direct therapy, particularly fluid management.

Calculated Plasma Volume Status Is Associated with Adverse Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation

Background: Calculated plasma volume status (PVS) reflects volume overload based on the deviation of the estimated plasma volume (ePV) from the ideal plasma volume (iPV). Calculated PVS is associated with prognosis in the context of heart failure. This single-center study investigated the prognostic impact of PVS in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: A total of 859 TAVI patients had been prospectively enrolled in an observational study and were included in the analysis. An optimal cutoff for PVS of −5.4% was determined by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization within 1 year after TAVI. Results: A total of 324 patients had a PVS < −5.4% (no congestion), while 535 patients showed a PVS ≥ −5.4% (congestion). The primary endpoint occurred more frequently in patients with a PVS ≥ −5.4% compared to patients with PVS < −5.4% (22.6% vs. 13.0%, p < 0.001). After multivariable adjustment, PVS was confirmed as a significant predictor of the primary endpoint (HR 1.53, 95% CI 1.05–2.22, p = 0.026). Conclusions: Elevated PVS, as a marker of subclinical congestion, is significantly associated with all-cause mortality and heart failure hospitalization within 1 year after TAVI.

Effect of Empagliflozin Versus Placebo on Plasma Volume Status in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus.

IntroductionPlasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF).MethodsThe EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (1:1) to receive 10 mg empagliflozin or a placebo (once daily), 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24.ResultsOverall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9 years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24 weeks (− 2.2 vs. + 0.1 kg, P < 0.001, and − 5.1 vs. − 0.3%, P < 0.001, respectively). Decreased PVS, defined as a change in PVS of < − 4.5%, was associated with the administration of empagliflozin (odds ratio 2.61, 95% confidence interval 1.11–6.15, P = 0.028). N-terminal pro b-type natriuretic peptide levels decreased in both the empagliflozin and placebo groups (1028.7–370.3 pg/mL, P < 0.001, and 1270.6–673.7 pg/mL, P < 0.01, respectively).ConclusionEmpagliflozin reduced the body weight and PVS. Early SGLT2 inhibitor administration in patients with AMI, CHF, and T2DM can therefore be effective in reducing the body weight and PVS.Trial RegistrationUMIN 000030158.

Impact of plasma volume status on mortality following left ventricular assist device implantation.

Worsening systemic congestion is often the central trigger of hospitalization in patients with heart failure. However, accurate assessment of congestion is challenging. The prognostic impact of systemic congestion following durable continuous-flow left ventricular assist device (LVAD) implantation remains unknown. Consecutive patients who received durable continuous-flow LVAD implantation between January 2014 and June 2017 and were followed for 1year were included. The association of preoperative plasma volume status, which was calculated using patients' body weight and hematocrit and expressed as a deviation from ideal plasma volume, with 1-year mortality following LVAD implantation was investigated. In total, 186 patients (median 57years and 138 males) were included. Baseline plasma volume status was -30.1% (-37.1%, -19.4%) on median. Eighty-eight patients (47%) had higher plasma volume status (>-29.8%), and their 1-year survival was significantly lower than those without (67% vs. 87%, P=.001). High plasma volume status was an independent predictor of 1-year death with an adjusted hazard ratio of 4.52 (95% confidence interval 1.52-13.5). Baseline systemic congestion, as defined by the high plasma volume status, was associated with higher mortality following durable continuous-flow LVAD implantation. The implication of improving preoperative plasma volume remains an area of needed investigation.

Abstract 13625: Effect of Empagliflozin versus Placebo on Plasma Volume Status in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the Embody Trial

Background: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been evaluated recently as a prognostic marker of patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor affect the improvement of heart failure and PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. A total of one hundred and five patients were randomized (1:1) to receive once-daily 10 mg empagliflozin or placebo 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients were included in the subgroup analysis set (64.3±10.9 years, male 80.2%, and 46 in the empagliflozin group and 50 in the placebo group). The empagliflozin group showed significant decreases in body weight, systolic blood pressure, and PVS compared with the placebo group at 24 weeks (-2.2 vs. +0.1 kg, P=0.0007; -6.6 vs. +3.5 mmHg, P=0.003; and -5.1 vs. -0.3%, P=0.0006; respectively). Decreased of PVS, defined as change of PVS &lt; -4.5 % was associated with received empagliflozin (odds ratio, 2.61; 95% confidence interval, 1.11 - 6.15; P=0.028). On the other hand, NT-Pro BNP levels significantly decreased in the empagliflozin group and placebo group (1028.7 to 370.3 pg/ml, P=0.0001 and 1270.6 to 673.7 pg/ml, P=0.006, respectively). Conclusion: Empagliflozin reduced not only body weight but also PVS. These results suggested that early SGLT2 inhibitor administration in patients with AMI, CHF and T2DM could be effective to reduce body weight and PVS.

Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention

Abstract Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention. Objective Contrast-induced nephropathy (CIN) remains a common complication of coronary procedure and increases poor outcomes, especially in patients with heart failure. Plasma volume expansion relates to worsening prognosis of heart failure. We hypothesised that calculated plasma volume status (PVS) might provide predictive utility for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention (PCI). Methods We enrolled 441 patients with heart failure undergoing PCI from 2012 to 2018. Pre-procedural PVS was calculated by comparing actual plasma volume (aPV) derived from the Hakim formula to ideal plasma volume (iPV). CIN was defined as an absolute SCr increase ≥0.5 mg/dl within 72h of contrast medium exposure. We assessed the association between PVS and risk of contrast-induced nephropathy in patients with heart failure undergoing elective PCI. Results In 441 patients, 28 (6.3%) patients developed CIN. The median pre-procedural PVS was −0.02 (−0.09–0.05). The best cutoff value of PVS for predicting CIN was 0.04 with 64.5% sensitivity and 75.5% specificity according to the ROC analysis (C statistic = 0.718; 95% CI: 0.674–0.760),of which predictive value is similar to NT-proBNP (C statistics 0.721 vs. 0.773, P=0.355). After adjusting for potential confounding risk factors, multivariable analysis demonstrated that PVS &amp;gt;0.04 (OR=3.142, 95% CI: 1.185–8.332, P&amp;lt;0.05) and NT-proBNP &amp;gt;4518pg/ml (OR=7.591, 95% CI: 2.886–19.968, P&amp;lt;0.05)were strong independent predictors of CIN. Conclusion Pre-procedural PVS is an independent risk factor for predicting CIN markedly, of which predictive value is comparable to BNP and also independent of BNP. The best cutoff point of PVS for predicting CIN was 0.04. ROC for PVS and NT-proBNP to predict CIN Funding Acknowledgement Type of funding source: None

P4552The prognostic impact of worsening and improved renal function in acute decompensated heart failure with and without plasma volume expansion

Abstract Background Recent studies showed that both worsening renal function (WRF) and improved renal function (IRF) during hospitalization are associated with poor prognosis in patients with acute decompensate heart failure (ADHF). On the other hand, plasma volume (PV) expansion plays an essential role in ADHF. However, there is little information about the difference of prognostic impact of WRF and IRF in ADHF patients, relating to PV status (PVS). Methods We prospectively studied 348 patients admitted for ADHF. PVS was defined as follows: actual PV = (1 - hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females); and PVS = [(actual PV - ideal PV)/ideal PV] × 100 (%). WRF and IRF were defined as an increase and a decrease in serum creatinine of ≥0.3 mg/dl from admission to discharge, respectively. The endpoint was readmission for worsening heart failure (WHF) within 1 year. Result Median PVS was 6.7% (IQR: −4.1%–16.7%). 43 and 21 patients had WHF in groups with high PVS (PVS ≥ median) and low PVS (PVS &gt; median), respectively. In high PVS group, multivariate Cox analysis showed that IRF was independently and significantly associated with WHF (p=0.016, HR: 2.4 [1.2–4.8]), but WRF was not (p=0.55, HR: 0.7 [0.3–2.1]). On the other hand, in low PVS group, WRF was independently associated with WHF (p=0.035, HR: 3.0 [1.1–8.1]), but IRF was not (p=0.27, HR: 2.1 [0.6–8.0]). Kaplan-Meier analysis revealed that only patients with IRF had a significantly higher risk of WHF than those with stable renal function (SRF) in high PVS group, while patients with WRF had a significantly higher risk of WHF than those with SRF in low PVS group. Worsening heart failure-free rate curves Conclusion In ADHF patients with PV expansion, IRF during hospitalization could predict poor outcomes, but WRF could not. On the other hand, in ADHF patients without PV expansion, not IRF but WRF could predict poor outcomes. PVS guided-therapy may be considered in secondary prevention for WHF.

P5409Plasma volume status provides the additional prognostic information to the Get With the Guidelines-Heart Failure risk score in acute decompensated heart failure patients

Abstract Background The Get with The Guidelines (GWTG) heart failure (HF) risk score was developed in the GWTG inpatient HF registry to predict in-hospital mortality and also reported to be associated with post-discharge long-term outcomes. Plasma volume (PV) expansion plays an essential role in HF. Recently, it has been reported that PV is estimated by a simple formula based on hematocrit and body weight, not using radioisotope assays, and PV status provides prognostic information in patients (pts) with acute decompensated heart failure (ADHF). However, there is no information available on the long-term prognostic value of the combination of PV status and GWTG-HF risk score in pts admitted for ADHF. Methods and results We studied 301 ADHF pts discharged with survival. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, serum levels of blood urea nitrogen and sodium, and the presence of chronic obstructive pulmonary disease. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 pts had all-cause death (ACD). At multivariate Cox analysis, GWTG-HF risk score and PV status were significantly associated with the total mortality, independently of eGFR and the prior history of heart failure hospitalization, after the adjustment with serum albumin level and anemia. Pts with both high GWTG-HF risk score (≥39 by ROC analysis; AUC 0.655 [0.586–0.724]) and greater PV status (≥8.1% by ROC analysis; AUC 0.624 [0.566–0.692]) had a significantly higher risk of ACD than those with either or none of them (58% vs 30% vs 21%, p&lt;0.0001, respectively). Conclusion PV status would provide the additional long-term prognostic information to GWTG-HF risk score in ADHF pts.

Prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction: insights from TOPCAT

Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF. We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P < 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001-1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS-risk relationship for any endpoint (P > 0.1 for all). Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization.

Plasma volume status predicts prognosis in patients with acute heart failure syndromes.

The intravascular compartment is known as the plasma volume, and the extravascular compartment represents fluid within the interstitial space. Plasma volume expansion is a major symptom of heart failure. The aim of the current study was to investigate the impact of plasma volume status on the prognosis of acute heart failure syndromes. We analyzed 1115 patients with acute heart failure syndromes who were admitted to our hospital. These patients were divided into three groups based on their plasma volume status at admission: first tertile (plasma volume status <41.9%, n = 371), second tertile (41.9%⩽ plasma volume status <49.0%, n = 372), and third tertile (49.0%⩽ plasma volume status, n = 372). Plasma volume status was defined as follows: actual plasma volume = (1 - hematocrit) × [ a + ( b × body weight)] ( a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal plasma volume = c × body weight ( c=39 in males and c=40 in females); and plasma volume status = [(actual plasma volume - ideal plasma volume)/ideal plasma volume] × 100 (%). In the Kaplan-Meier analysis, all-cause mortality, cardiac mortality and cardiac events increased progressively from the first to third tertile ( p <0.001, respectively). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, plasma volume status was an independent predictor of all-cause mortality (hazard ratio 1.429, p < 0.001), cardiac mortality (hazard ratio 1.416, p = 0.001) and cardiac events (hazard ratio 1.207, p = 0.004). Increased congestion is associated with increased morbidity and mortality in heart failure patients. Plasma volume status, which represents intravascular compartment and congestion, can identify poor prognosis in patients with acute heart failure syndromes.

Abstract 12177: Plasma Volume Status Predicts Mortality in Heart Failure Patients

Background: The intravascular compartment is known as the plasma volume (PV). PV expansion plays an essential role in heart failure (HF), and large degrees of congestion relate to morbidity and mortality. Recently, it has been reported that PV is estimated by a simple formula based on hematocrit and body weight, not using radioisotope assays. We aimed to investigate the impact of PV status on prognosis of HF. Methods and Results: We calculated PV status as the following: Actual PV=(1-hematocrit)х[a+(bхbody weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV=cхbody weight (c=39 in males and c=40 in females), and PV status=[(actual PV-ideal PV)/ideal PV]х100(%). We analyzed 1115 patients with HF who admitted to our hospital. These patients were divided into 3 groups based on the PV status: 1 st (PV status&lt;41.9%, n=371), 2 nd (41.9%≤PV status&lt;49.1%, n=372) and 3 rd tertiles (49.1%≤PV status, n=372). In the multiple regression analysis to determine PV status, among considerable clinical variables, B-type natriuretic peptide (BNP), sodium and estimated glomerular filtration rate (eGFR) were predictors of PV status (BNP: ß=0.280, P&lt;0.001; sodium: ß=-0.197, P&lt;0.001; and eGFR: ß=-0.214, P&lt;0.001). In the average follow-up of 1007 days, 287 deaths (149 cardiac deaths and 138 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1 st to 2 nd and 3 rd groups (13.5%, 21.2% and 42.5%, P&lt;0.001). In the Cox proportional hazard analysis, after adjusting for potential confounding factors including age, NYHA class, ejection fraction, BNP, sodium, eGFR, co-morbidities and medications, PV status was an independent predictor of all-cause mortality in HF patients (hazard ratio 1.420, 95% confidence interval 1.227-1.625, P&lt;0.001). Conclusion: PV status, a marker of intravascular compartment and congestion, can identify high mortality in HF patients.

Calculated plasma volume status and prognosis in chronic heart failure.

Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.

Abstract 18594: Plasma Volume Status Calculated Instantaneously from Weight and Hematocrit Relates to Objectively Measured Plasma Volumes and Powerfully Predicts Death and First Morbid Events in Chronic Heart Failure

Background: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and hematocrit are intimately related to PV, we derived an index of relative PV status (PVS) using validated equations based on these simple indices. We tested the validity and prognostic utility of our index in a logical sequence of analyses. Methods: First, we correlated current PV measured using 125 Iodine-human serum albumin to calculated values ([1-hematocrit] x [a + (b x weight)]). Second, we subtracted calculated current PV from ideal PV (c x weight) to derive PVS ([(current-ideal)/ideal] x 100%) in CHF patients (pts). Third, we assessed the prognostic implications of PVS in 5002 pts in the Val-HeFT trial (age 62±11y, LVEF 27±7%, 37% NYHA≥3) and validated this in an accrued ‘real world’ sample of 246 CHF pts (age 67±13y, LVEF 28±8%). Results: Calculated and measured PV correlated at baseline in normal subjects (n=119, r=0.68) with a bias of 78mL, and at baseline (n=22, r=0.44) and over time (r=0.60) in hospitalized CHF pts. In the Val-HeFT cohort, PVS was -10±11% (median [±IQR]) and related to volume biomarkers such as NT-BNP, urea, eGFR, albumin, and sodium (all P&lt;0.01). Over 2 years, 977 (20%) pts died. PVS was associated with death (Fig A ) and first morbid events in a ‘J-shaped’ fashion with the highest and lowest risks seen with a PVS&gt; - 4% and between -12% to -14%, respectively. Stratification into quartiles confirmed this with a PVS&gt; - 4% (versus ≤ - 4%) prognostic (unadjusted HR 1.65, 95% CI 1.44-1.88, χ 2 54, P&lt;0.001, Fig B ) even after adjustment for 22 variables including NT-BNP. These results were mirrored in the validation cohort. Conclusions: PVS calculated from simple clinical indices reliably reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. Titrating CHF therapy to keep PVS below - 4% and ideally between -12% to -14% might increment survival.

104 Prognostic utility of calculated plasma volume status in chronic heart failure

Background Plasma volume (PV) expansion is a hallmark feature of worsening heart failure that is notoriously underestimated by clinical examination. While radioisotope assays optimally quantify PV status, numerous haemodialysis-based equations also exist for its estimation. The prognostic utility of such formulas in chronic heart failure (CHF) is unknown. Methods We analysed the relation between estimated PV status and mortality in 246 outpatients with CHF (mean (±SD) age 67±13 years, NYHA class 2±1, LVEF 28±8%). PV status was calculated (Hakim RM, et al) by subtracting the patients actual PV ((1-haematocrit) × (a + (b × weight)); a and b are gender-specific constants) from their ideal PV ((c × weight); c=gender-specific constant). Results Median (±IQR) PV status was—261±550 ml with 78% and 21% of patients having PV contraction and expansion, respectively. Patients with PV excess had significantly higher creatinine and lower albumin levels. Over a median follow-up of 13±16 months, 36 (15%) patients died. PV status predicted mortality (HR 1.001, 95% CI 1.001 to 1.002, p=0.001) in a graded fashion (Abstract 104 figure 1A) and did so independently of NYHA class, LVEF, weight, haematocrit and creatinine. A PV status ≤−178 ml optimally predicted survival (ROC AUC 0.68, p=0.0007) and conferred a 75% reduced hazard for death (HR 0.16, 95% CI 0.07 to 0.37, p Conclusions Calculating plasma volume status in CHF patients appears prognostically useful and suggests that dehydration is better tolerated than volume excess in these individuals and that targeting therapy to achieve a plasma volume status ≤178 ml might increment survival.