A Study to Evaluate the Disease Development and Impact of Intravascular Volume Expansion Profiles in Relation to Neuroendocrine and Renal Function in Post-Acute Heart Failure


About this study

The purpose of this study is to assess intravascular volume heterogeneity in relation to neuroendocrine profiles in patients admitted to hospital with decompensated acute on chronic systolic heart failure with serial assessments post-discharge



Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age greater than 18 years or older.

Exclusion Criteria:

  • Age < 18 years.
  • Having received any investigational drug or device within 30 days prior to entry into the study.
  • Clinically unstable patients (e.g. systolic blood pressure < 90 mmHg, ongoing requirement for vasopressors or mechanical circulatory support, or mechanical ventilation).
  • Hospitalization within three months prior to study for hemodialysis or an ongoing requirement for hemodialysis or ultrafiltration.
  • Prior organ transplantation or being on a waiting list for organ transplantation.
  • Presence of cardiac conditions such as clinically significant cardiac valve stenosis, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or primary arterial pulmonary hypertension (Group 1 PAH).
  • History of blood pressure > 190/115 mmHg or unexplained syncope within the past 3 months.
  • Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months.
  • Clinically significant intrinsic renal disease (eGFR <15 ml/min/1.72m2), renal artery stenosis, or history of fibromuscular dysplasia of the renal arteries.
  • Baseline hemoglobin < 8.5 g/dl, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that is five times or more the upper limit of normal or bilirubin three times or more the upper limit of normal.
  • History of alcohol abuse within the past 6 months.
  • Women who are pregnant, or breast-feeding.


Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Wayne Miller, M.D., Ph.D.

Open for enrollment

Contact information:

Diana Albers B.S.



More information


  • This study sought to evaluate the impact of sodium restriction on heart failure (HF) outcomes. Read More on PubMed
  • This study aimed to characterize volume profiles and their differences in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ventricular systolic function. Read More on PubMed
  • Peripheral venous hemoglobin (Hb) measurements are considered to accurately reflect circulating red blood cell mass (RBCM). In volume overload decompensated chronic heart failure (DCHF), reliance on Hb values may be misleading. Using quantitative radiolabel blood volume analysis (BVA), we evaluated the relation of RBCM to volume overload and reliability of Hb measurements to reflect RBC status in patients hospitalized for DCHF. Of 32 patients evaluated (LVEF <50 %), 19 met WHO Hb criteria for anemia. By BVA, however, only 4/19 had true anemia (low Hb and low RBCM) while 15/19 demonstrated plasma volume expansion dilution-related "anemia" (6 low Hb/normal RBCM, 9 low Hb/excess RBCM). The remaining 13/32 had normal range Hb (12 with excess RBCM). Overall, 66 % of cohort demonstrated RBCM excess. RBC profiles are highly variable in DCHF, and peripheral Hb values are often misleading in identifying RBC status. These findings have implications for volume management. Read More on PubMed
  • The purpose of this study was to assess the relationship between biomarkers of renin-angiotensin-aldosterone system (RAAS) activation and decongestion strategies, worsening renal function, and clinical outcomes. Read More on PubMed
  • We sought to investigate the role of aldosterone as a mediator of disease and its relationship with the counter-regulatory natriuretic peptide (NP) system. We measured plasma aldosterone (n=1674; aged≥45 years old) in a random sample of the general population from Olmsted County, MN. In a multivariate logistic regression model, aldosterone analyzed as a continuous variable was associated with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96; P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32-1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The associations with hypertension, central obesity, metabolic syndrome, triglycerides, and concentric left ventricular hypertrophy remained significant after further adjustment for body mass index, NPs, and renal function. Furthermore, aldosterone in the highest tertile correlated with lower NP levels and increased mortality. Importantly, most of these associations remained significant even after excluding subjects with aldosterone levels above the normal range. In conclusion, we report that aldosterone is associated with hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric left ventricular hypertrophy, and lower NPs in the general community. Our data suggest that aldosterone, even within the normal range, may be a biomarker of cardiorenal and metabolic disease. Further studies are warranted to evaluate a therapeutic and preventive strategy to delay the onset and progression of disease, using mineralocorticoid antagonists or chronic NP administration in high-risk subjects identified by plasma aldosterone. Read More on PubMed
  • This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. Read More on PubMed
  • To investigate the relationship between signs and symptoms of congestion, renal impairment and outcome in chronic heart failure (CHF) patients. Read More on PubMed
  • Symptoms of intravascular volume overload and increased cardiac filling pressures in the systemic and pulmonary venous circulations are among the most common complaints in patients with chronic heart failure (CHF). The clinical utility of physical examination for estimation of intravascular volume status in patients with CHF is limited due to poor specificity and sensitivity of most signs of congestion. Direct measurement of blood volume with radioisotope techniques is FDA-approved and has been shown to be closely associated with invasive measurements of cardiac filling pressures in patients with CHF. Unrecognized volume overload is common in CHF patients and is associated with adverse clinical outcomes. Additional work is needed to determine the clinical utility of serial blood volume measurements in the management of patients with CHF. Read More on PubMed
  • Our facility's current blood volume measurement protocol has involved separate measurement of plasma and red cell volumes. The purpose of this study is to determine whether measurement with a recently FDA-approved, one-compartment semiautomated system provides similar accuracy. Read More on PubMed
  • Patients with acute heart failure syndromes (AHFS) typically present with signs and symptoms of systemic and pulmonary congestion at admission. However, elevated left ventricular (LV) filling pressures (hemodynamic congestion) may be present days or weeks before systemic and pulmonary congestion develop, resulting in hospital admission. This "hemodynamic congestion," with or without clinical congestion, may have deleterious effects including subendocardial ischemia, alterations in LV geometry resulting in secondary mitral insufficiency, and impaired cardiac venous drainage from coronary veins resulting in diastolic dysfunction. It is possible that these hemodynamic abnormalities in addition to neurohormonal activation may contribute to LV remodeling and heart failure progression. Approximately 50% of patients admitted for AHFS are discharged with persistent symptoms and/or minimal or no weight loss in spite of the fact that the main reason for admission was clinical congestion. Accordingly, the assessment and management of pulmonary and systemic congestion in these patients require reevaluation. Read More on PubMed
  • Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. Read More on PubMed
  • Patients with chronic congestive heart failure have a sequential and incessant activation of those neurohormonal systems, which control body fluids, cardiac output and systemic blood pressure. Neurohormonal activation is initially selective and regional. Generalized activation is a late event in the natural history of congestive heart failure. Although the ultimate stimulus responsible for the activation of these neurohormonal systems is unknown, a decreased cardiac output and diminished effective blood volume have been proposed as the responsible mechanisms. However, extensive clinical and experimental research suggest that cardiac remodeling and loading of low-pressure cardiac receptors with sympathetic afferents could be the triggering events followed by unloading of high-pressure carotid receptors by decreased cardiac output and diminished effective blood volume. Read More on PubMed
  • Clinically unrecognized intravascular volume overload may contribute to worsening symptoms and disease progression in patients with chronic heart failure (CHF). The present study was undertaken to prospectively compare measured blood volume status (determined by radiolabeled albumin technique) with clinical and hemodynamic characteristics and patient outcomes in 43 nonedematous ambulatory patients with CHF. Blood volume analysis demonstrated that 2 subjects (5%) were hypovolemic (mean deviation from normal values -20 +/- 6%), 13 subjects (30%) were normovolemic (mean deviation from normal values -1 +/- 1%), and 28 subjects (65%) were hypervolemic (mean deviation from normal values +30 +/- 3%). Physical findings of congestion were infrequent and not associated with blood volume status. Increased blood volume was associated with increased pulmonary capillary wedge pressure (p = 0.01) and greatly increased risk of death or urgent cardiac transplantation during a median follow-up of 719 days (1-year event rate 39% vs 0%, p <0.01 by log-rank test). Systolic blood pressure was significantly lower in hypervolemic patients than in those with normovolemia or hypovolemia (107 +/- 2 vs 119 +/- 2 mm Hg, p = 0.008), and hypotension was independently associated with increased risk of hypervolemia in multivariate analysis (odds ratio 2.64 for a 10-mm Hg decrease in systolic blood pressure, 95% confidence interval 1.13 to 6.19, p = 0.025). These findings demonstrate that clinically unrecognized hypervolemia is frequently present in nonedematous patients with CHF and is associated with increased cardiac filling pressures and worse patient outcomes. Read More on PubMed
  • Comparison of results of red cell mass (RCM) measurement by 51Cr and 125I methods in 119 patients showed virtual equivalence. Both methods have an acceptable coefficient of variation (CV) that is < 5%. The 125I method is simpler and much less expensive. Unrealistically narrow "normal ranges" for RCM are likely to lead to misdiagnosis of polycythemia vera. Upper normal limits of 39 mL/kg (males) and 32 mL/kg (females) are consistent with originally published data in normal persons; use of these limits as criteria would reduce the risk of misdiagnosis. No cases of "stress erythrocytosis" or Gaisbock Syndrome were encountered among the 119 cases reviewed. Read More on PubMed
  • In studies in experimental animals and in edematous patients, the nonosmotic release of vasopressin has been found to be consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system is known to modulate the nonosmotic release of vasopressin and activation of the renin-angiotensin-aldosterone system. These findings led to our proposal that body fluid volume regulation involves dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular fluid volume nor total blood volume are determinants of renal sodium and water excretion. With a decrease in effective arterial blood volume (EABV) initiated by either decreased cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The renal vasoconstriction, which accompanies either decreased cardiac output or peripheral arterial vasodilation, causes a decreased distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing normal escape from the sodium-retaining effect of aldosterone. The elevated glomerular filtration rate and filtered sodium load seen in pregnant women allow increased distal sodium and water delivery despite a decrease in EABV, thus limiting edema formation during gestation. Read More on PubMed
  • This study provides data on plasma hormone levels in patients with severe clinical congestive cardiac failure who had never received therapy and in whom the presence of an accumulation of excess water and sodium had been established. Eight patients were studied; two had ischemic cardiac disease, and six had dilated cardiomyopathy. Mean hemodynamic measurements at rest were as follows: cardiac index, 1.8 l/min/m2; pulmonary wedge pressure, 30 mm Hg; right atrial pressure, 15 mm Hg. Total body water content was 16% above control, extracellular liquid was 33% above control, plasma volume was 34% above control, total exchangeable sodium was 37% above control, renal plasma flow was 29% of control, and glomerular filtration rate was 65% of control. Plasma norepinephrine was consistently increased (on average 6.3 times control), whereas adrenaline was unaffected. Although plasma renin activity and aldosterone varied widely, they were on average above normal (renin 9.5 times control, aldosterone 6.4 times control). Plasma atrial natriuretic peptide (14.3 times control) and growth hormone (11.5 times control) were consistently increased. Cortisol was also increased on average (1.7 times control). Vasopressin was increased only in one patient. Read More on PubMed
  • The cardiovascular physical examination is used commonly as a basis for diagnosis and therapy in chronic heart failure, although the relationship between physical signs, increased ventricular filling pressure, and decreased cardiac output has not been established for this population. We prospectively compared physical signs with hemodynamic measurements in 50 patients with known chronic heart failure (ejection fraction, .18 +/- .06). Rales, edema, and elevated mean jugular venous pressure were absent in 18 of 43 patients with pulmonary capillary wedge pressures greater than or equal to 22 mm Hg, for which the combination of these signs had 58% sensitivity and 100% specificity. Proportional pulse pressure correlated well with cardiac index (r = .82), and when less than 25% pulse pressure had 91% sensitivity and 83% specificity for a cardiac index less than 2.2 L/min/m2. In chronic heart failure, reliance on physical signs for elevated ventricular filling pressure might result in inadequate therapy. Conversely, the adequacy of cardiac output is assessed reliably by pulse pressure. Our results facilitate decisions regarding treatment in chronic heart failure. Read More on PubMed
  • As the characteristics of sodium and water balance in heart failure remain undefined, we evaluated the hemodynamic, metabolic, and hormonal effects of balanced sodium intake in 10 patients with chronic congestive heart failure. We discontinued diuretics to avoid their confounding influence, and all patients received 1 wk of 10 meq and 100 meq balanced sodium intake and controlled free water. Comparing sodium intake of 10 with 100 meq, the following observations were made. There was weight gain (2.0 kg) and increased sodium excretion (11 +/- 3 to 63 +/- 15 meq/24 h), unaccompanied by increase of blood volume. Both renin-angiotensin system and sympathetic nervous system activity were greater during the 10 meq diet, and suppressed with the 100 meq sodium diet. For both diets, plasma renin and urinary aldosterone excretion were correlated with urinary sodium excretion (r = -0.768, r = -0.726, respectively; P less than 0.005). Systemic hemodynamics were minimally changed with increased sodium intake. However, reversal of vasoconstriction by captopril during the 10 meq diet, and its ineffectiveness during the 100 meq diet, indicated a renin-dependent mechanism in the former, and a renin-independent mechanism in the latter diet. There were two subgroups of response to the 100 meq diet: one group (n = 5) achieved neutral balance, while the second (n = 5) avidly retained sodium and water. Renin-angiotensin system activity was significantly higher in the latter group, and the mechanism for differences in sodium excretion for the subgroups could not be identified by blood volume or hemodynamic parameters. Orthostatic hypotension during tilt was greater during the 10 meq sodium diet, and in all cases, related to ineffective hemodynamic and hormonal compensatory responses. Read More on PubMed
  • The incidence of congestive heart failure is increasing in the United States. This common syndrome is characterized not only by impaired ventricular function but also by an increase in some endogenous vasoconstrictor substances, including norepinephrine, angiotensin II, and arginine vasopressin. Although activation of the systems that release these substances is presumed to be compensatory (to maintain perfusion pressure during inadequate flow), the sympathetic nervous system, renin-angiotensin-aldosterone system, and arginine vasopressin may contribute to the pathogenesis of the syndrome. The excessive vasoconstriction present in heart failure likely produces a further burden on the failing myocardium. New strategies in therapy are being developed to counteract the activation of vasoconstrictor forces in congestive heart failure. Data indicate that selective blockade of the renin-angiotensin system is useful. Preliminary data suggest that inhibition of the sympathetic nervous system may be helpful, and inhibition of vasopressin in animals with heart failure is being studied. New and more selective therapy for heart failure may come from these studies. Read More on PubMed
  • Predictions of blood volume (BV) assume the existence of a constant ratio between BV and body weight or surface area (SA). We examined the validity of this assumption by calculating BV from plasma volume and body hematocrit in 160 normal volunteers whose weights ranged from -38.7 to 210.8% of desirable weight (assessed by a modification of the Metropolitan Life Insurance Company Desirable Weight tables). BV is not a constant fraction of body weight or SA in this population. Its prediction from such constant ratios results in a large error of estimate which is systematically biased with respect to height and weight. BV prediction from the observed regressions of the parameter on weight and SA reduces the error substantially but remains biased with respect to height. BV prediction from the subject's degree of deviation from desirable weight affords a smaller error of estimate which is apparently free from systematic bias. Read More on PubMed

Mayo Clinic Footer