Patient Sex Impacts Volume Phenotypes and Hemodynamics in Chronic Heart Failure: A Multicenter Analysis.

BACKGROUND: Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles in patients with chronic heart failure (HF). How patients' sex might impact this volume heterogeneity and its relationship to cardiac hemodynamics remains to be defined. METHODS: Retrospective analysis of clinical and quantitative BV, plasma volume (PV) and red blood cell (RBC) mass data was undertaken across 3 medical centers. BV was quantitated using nuclear medicine I-131-labeled plasma albumin indicator-dilution methodology with cardiac hemodynamics obtained within 24 hours. RESULTS: In an analysis of 149 males and 106 females, absolute BV was greater, on average, in males (6.9 ± 1.7 vs 5.0 ± 1.2 liters; P < 0.001); however, a wide range in BVs was demonstrated in both sexes (2.9-14.5 liters). Male sex was associated with higher prevalence of large (+ 25% of normal) BV and PV expansions (36% vs 15% and 51% vs 21%, respectively; both P < 0.001). In contrast, female sex was associated with higher prevalence of normal total BV (44% vs 27%; P = 0.005), PV (54% vs 27%; P < 0.001), hypovolemia (23% vs 11%; P = 0.005), and true anemia (42% vs 26%; P < 0.001). Cardiac hemodynamics differed by sex, but only modest associations were demonstrated between volume profiles and cardiac filling pressures. CONCLUSIONS: Findings support unique intravascular volume profiles reflecting sex-specific differences in the prevalence and distributions of total BV, PV and RBC mass profiles in patients with chronic HF. This underscores the importance of recognizing patients' sex as a significant factor influencing volume homeostasis, which needs to be taken into account to individualize volume-management strategies effectively.

Congestion/decongestion in heart failure: what does it mean, how do we assess it, and what are we missing?-is there utility in measuring volume?

Clinical congestion remains a major cause of hospitalization and re-hospitalizations in patients with chronic heart failure (HF). Despite the high prevalence of this issue and clinical concern in HF practice, there is limited understanding of the complex pathophysiology relating to the "congestion" of congestive HF. There is no unifying definition or clear consensus on what is meant or implied by the term "congestion." Further, the discordance in study findings relating congestion to physical signs and symptoms of HF, cardiac hemodynamics, or metrics of weight change or fluid loss with diuretic therapy has not added clarity. In this review, these factors will be discussed to add perspective to this issue and consider the factors driving "congestion." There remains a need to better understand the roles of fluid retention promoting intravascular and interstitial compartment expansions, blood volume redistribution from venous reservoirs, altered venous structure and capacity, elevated cardiac filling pressure hemodynamics, and heterogeneous intravascular volume profiles (plasma volume and red blood cell mass) with a goal to help demystify "congestion" in HF. Further, this includes highlighting the importance of recognizing that congestion is not the result of a single pathway but a complex of responses some of which produce symptoms while others do not; yet, we confine these varied responses to the single and somewhat vague term "congestion."

Serial blood volume measurements in patients with compensated chronic heart failure: How do volume profiles change over time?

Among patients with chronic heart failure (HF) intravascular volume profiles vary significantly despite similar clinical compensation. However, little is known regarding changes in blood volume (BV) profiles over time. The objective of this analysis was to identify the extent and character of changes in volume profiles over time. A prospective analysis was undertaken in patients who were hospitalized and treated for fluid overload. Quantitative BV analyses were obtained in a compensated state at hospital discharge (baseline) and follow-up at 1, 3, and 6 mo. Data were available on 10 patients who remained stable without rehospitalization or medication change over a 6-mo period. Baseline BV profiles were highly variable at hospital discharge with an average deviation of +28% above normal in 6 patients and normal BV in 4 patients. Over the follow-up period, the median change in BV was -201 mL [-3% (-6, +3%)] from baseline with profiles remaining in the same volume category in 9 out of 10 patients. Crossover from normal BV to mild contraction (-13% of normal) occurred in one patient. Red blood cell mass demonstrated the largest change over 6 mo [median -275 (-410, +175) mL] with a deviation from normal of -14 (-20, +8) % (reflecting mild anemia). These findings suggest that BV profiles in clinically compensated patients with HF do not change substantially over a 6-mo period regardless of baseline expanded or normal BV. This lack of change in volume profiles particularly from an expanded BV has implications for long-term volume management, clinical outcomes, and also our understanding of volume homeostasis in HF.NEW & NOTEWORTHY The novel findings of this study demonstrate that blood volume profiles while highly variable in clinically compensated patients with HF on stable medical therapy do not change substantially over a 6-mo period regardless of baseline expanded or normal blood volumes. This lack of change in volume profiles particularly from an expanded blood volume has implications for long-term volume management and also for how we understand the pathophysiology of volume homeostasis in chronic HF.

Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure.

BACKGROUND: The role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation. METHODS AND RESULTS: Patients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients' characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R2 = 0.009) and Valsalva (R2 = 0.003) and with right atrial (R2 = 0.049) and pulmonary capillary wedge (R2 = 0.047) pressure changes during leg raise. CONCLUSIONS: In patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.

Blood volume expansion, normovolemia, and clinical outcomes in chronic human heart failure: more is better.

Expansion in blood volume (BV) is a well-recognized response to arterial underfilling secondary to impaired cardiac output in heart failure (HF). However, the effectiveness of this response in terms of outcomes remains inadequately understood. Prospective analysis was undertaken in 110 patients with HF hospitalized and treated for fluid overload. BVs were measured in a compensated state at the hospital discharge using the indicator-dilution methodology. Data were analyzed for composite 1-year HF-related mortality/first rehospitalization. Despite uniform standard of care, marked heterogeneity in BVs was identified across the cohort. The cohort was stratified by BV expansion greater than or equal to +25% above normal (51% of cohort), mild-moderate expansion (22%), and normal BV (27%). Kaplan-Meier (K-M) survival estimates and regression analyses revealed BV expansion (greater than or equal to +25%) to be associated with better event-free survival relative to normal BV (P = 0.038). Increased red blood cell mass (RBCm; RBC polycythemia) was identified in 43% of the overall cohort and 70% in BV expansion greater than or equal to +25%. K-M analysis demonstrated polycythemia to be associated with better outcomes compared with normal RBCm (P < 0.002). Persistent BV expansion to include RBC polycythemia is common and, importantly, associated with better clinical outcomes compared with normal total BV or normal RBCm in patients with chronic HF. However, compensatory BV expansion is not a uniform physiological response to the insult of HF with marked variability in BV profiles despite uniform standard of care diuretic therapy. Therefore, recognizing the variability in volume regulation pathophysiology has implications not only for impact on clinical outcomes and risk stratification but also potential for informing individualized volume management strategies.NEW & NOTEWORTHY The novel findings of this study demonstrate that intravascular volume profiles among the patients with chronic heart failure (HF) vary substantially even with similar clinical compensation. Importantly, a profile of blood volume (BV) expansion (compared with a normal BV) is associated with lower HF mortality/morbidity. Furthermore, RBC polycythemia is common and independently associated with improved outcomes. These observations support BV expansion with RBC polycythemia as a compensatory mechanism in chronic HF.

Diuresis-Related Weight Loss Reflects Interstitial Compartment Decongestion with Minimal Impact on Intravascular Volume Expansion or Outcomes in Post-Acute Heart Failure: Metrics of Decongestion and Volume Status.

BACKGROUND: Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of interstitial and intravascular volume compartments to diuretic therapy and heterogeneity in volume profiles may confound the clinical interpretation of weight loss in patients with HF. METHODS AND RESULTS: Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in interstitial volume (-6.5 ± 4.4%) and PV (-7.5 ± 11%); however, absolute decreases in the PV (-254 mL, interquartile range -11 to -583 mL) were less than 10% of interstitial volume loss (-5040 mL, interquartile range -2800 to -7989 mL); greater interstitial fluid loss did not translate into better outcomes (log-rank P = .430). CONCLUSIONS: Diuresis-related decreases in weight reflect fluid loss from the interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular volume profiles potentially confounding weight loss as a prognostic metric in HF.

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure.

BACKGROUND: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. METHODS AND RESULTS: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139). CONCLUSIONS: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

A giant right atrial myxoma-The growth rate and multi-modality imaging.

A young and healthy woman presented with progressive dyspnea on exertion. An echocardiogram showed a giant right atrial mass. Cardiac CT angiography provided the most accurate estimate for the tumor size, while 2-D echo, 2-D, and 3-D trans-esophageal echo underestimated the dimensions of the cardiac tumor when referenced by the surgical specimen. We also calculated the growth rate of the right atrial myxoma to be at least 1.2 mm per month based on a normal chest CT 54 months before her presentation. Surgical pathology confirmed typical features of cardiac myxoma in the right atrium.

Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

Impact of Obesity on Volume Status in Patients With Ambulatory Chronic Heart Failure.

BACKGROUND: Fluid overload is common in heart failure (HF) and obesity; however, the relationship between the extent of intravascular volume expansion and indices such as body mass index (BMI) in obese and non-obese patients with HF has not been defined to address the issue of a HF obesity phenotype. METHODS: Total blood volume (TBV) was measured clinically using a radiolabeled albumin indicator-dilution technique in patients with predominately class III ambulatory chronic HF (N=66). Obesity was defined by BMI ≥30 kg/m2. RESULTS: Markedly increased intravascular volume expansion (defined by TBV expansion >+25% above normal) was highly prevalent in the obese (53%) compared to non-obese patients with HF (29%, P = .04) driven by plasma volume expansion. TBV was correlated with excess body weight and BMI (both P < .01). Also, cardiac index was higher, systemic vascular resistance lower, and left ventricular filling pressures comparable in obese compared with non-obese patients. CONCLUSIONS: Quantitative assessment of intravascular volume demonstrates for the first time that severe (not mild or moderate) volume expansion is highly common in obese patients with ambulatory chronic HF. This supports an evolving concept of an obesity-specific HF phenotype. Further study is needed to understand the mechanisms controlling volume regulation and the potential compensatory or detrimental impact on outcomes in obesity and HF.

Homecare Safety Virtual Quality Improvement Collaboratives.

With Canada's aging population, innovations in technology and changes in patient preferences regarding where they receive care, there is a growing reliance on homecare services. Professionals in the homecare sector want to provide the best care possible for their clients, whereas homecare organizations look to foster a greater patient safety culture. The Canadian Patient Safety Institute and the Canadian Home Care Association conducted two learning collaboratives aimed at increasing quality improvement capability in homecare settings. Teams from across the country have increased their capacity and capability to engage patients and families, mitigate and prevent harm from homecare safety incidents such as falls and specifically address issues such as improving interprofessional collaboration, teamwork and communication.

Calculated Estimates of Plasma Volume in Patients With Chronic Heart Failure-Comparison With Measured Volumes.

BACKGROUND: Calculated estimates of plasma volume (PV) have been developed with the use of hemoglobin/hematocrit-body weight-based methods. The accuracy of such formula-derived values has not been thoroughly evaluated. The objective of this analysis was to compare the calculated estimate and a quantitative measure of PV in patients with chronic heart failure (HF). METHODS AND RESULTS: PV was measured with the use of a standardized computer-based indicator-dilution-labeled albumin technique in 110 patients with clinically stable chronic HF and correlated with paired Kaplan-Hakim (K-H) and Strauss formula estimates of PV. The K-H formula underestimated (3.4 ± 0.7 L) and the Strauss formula overestimated (5.3 ± 1.5 L) PV relative to the measured volume (4.3 ± 1.1 L). Calculated PV was only moderately correlated with measured PV by the K-H formula (r = 0.64; P < .001) and weakly by the Strauss formula (r = 0.285; P = .003). Strauss formula estimates of change (%) in PV were also poorly correlated with paired measured changes in PV (r = 0.162; P = .999; n = 40). CONCLUSIONS: Calculated estimates of PV demonstrate limited association with measured volumes. These findings indicate that although formula-based estimates of PV have been shown to have prognostic value, they are limited in their reliability for volume management in patients with chronic HF.

Intravascular Volume Profiles in Patients With Class I and II Systolic Heart Failure: Heterogeneity and Volume Overload Are Common Even in Mild Heart Failure.

BACKGROUND: Although volume overload is a commonly described clinical feature of advanced heart failure (HF), less is known regarding volume profiles of patients with less severe class I and II HF. METHODS: Intravascular volume was quantitated by radiolabeled-albumin indicator-dilution technique in clinic outpatients. RESULTS: Forty-six patients (age 61 ± 13years, left ventricular ejection fraction 30 ± 8%) were prospectively evaluated with 28 undergoing repeat evaluations at 1 year. There was no difference in averaged total blood volume (TBV) at baseline between class I (N = 26) and II (N = 20) patients (5.6 ± 1.6vs 6.0 ± 1.3 L, P = .368) and at 1-year of follow-up. However, there was marked heterogeneity in plasma volume (-13% to +69% of normal) and red cell mass (RBCM -31% to +50%) profiles with TBV expansion identified in 46% of the cohort, whereas only 48% had a normal TBV. RBCM deficit (true anemia) was common (39%), but a low hemoglobin concentration was accurate in identifying anemia in only 11% of the cohort. RBCM excess (polycythemia) also was identified in 20% of the cohort. CONCLUSIONS: Marked heterogeneity in plasma volume and RBCM volume profiles is present even in mild HF, and identifying volume overload, which was common in early HF, has the potential to help guide therapy in the reduction of HF progression. Intravascular volume as a modifiable risk factor in early HF warrants further study.

Detailed Analysis of Criteria and Particle Emissions from a Very Large Crude Carrier Using a Novel ECA Fuel.

Ocean going vessels (OGVs) operating within emission control areas (ECA) are required to use fuels with ≤0.1 wt % sulfur. Up to now only distillate fuels could meet the sulfur limits. Recently refiners created a novel low-sulfur heavy-fuel oil (LSHFO) meeting the sulfur limits so questions were posed whether nitric oxide (NOx) and particulate matter (PM) emissions were the same for the two fuels. This project characterized criteria pollutants and undertook a detailed analysis of PM emissions from a very large crude oil carrier (VLCC) using a distillate ECA fuel (MGO) and novel LSHFO. Results showed emission factors of NOx were ∼5% higher with MGO than LSHFO. PM2.5 emission factors were ∼3 times higher with LSHFO than MGO, while both were below values reported by Lloyds, U.S. EPA and CARB. A detailed analysis of PM revealed it was >90% organic carbon (OC) for both fuels. Elemental carbon (EC) and soot measured with an AVL microsoot sensor (MSS) reflected black carbon. PM size distributions showed unimodal peaks for both MGO (20-30 nm) and LSHFO (30-50 nm). Particle number (PN) emissions were 28% and 17% higher with the PPS-M compared to the SMPS for LSHFO and MGO, respectively.

Prognostic Value of Serial Measurements of Soluble Suppression of Tumorigenicity 2 and Galectin-3 in Ambulatory Patients With Chronic Heart Failure.

BACKGROUND: B-Type natriuretic peptides (BNP) and cardiac troponin T (cTnT) predict cardiovascular events in heart failure (HF) patients, but additional refinement in risk stratification may be possible by targeting pathways leading to fibrosis. We aimed to assess the value of serial measurements of soluble suppression of tumorigenicity 2 (sST2) and galectin-3 to identify risk for adverse pathophysiologic processes. METHODS: New York Heart Association (NYHA) functional class III-IV HF patients (n = 180; LVEF ≤40%) were prospectively evaluated with biomarkers collected every 3 months over 2 years and analyzed regarding a primary end point of death/cardiac transplantation and a secondary end point of HF-related hospitalization or death/transplantation. RESULTS: Time-dependent univariate analyses demonstrated that elevations of sST2 (≥49.3 ng/mL male, ≥33.5 ng/mL female) and galectin-3 (≥22.1 ng/mL) were predictive of the primary and secondary end points. In multivariate models adjusted for BNP, cTnT, and clinical variables, sST2 but not galectin-3 remained an independent predictor (hazard ratio 3.22, 95% confidence interval 1.76-5.89; P < .001). With serial measurements, only sST2 demonstrated incremental value in reclassifying patients to higher risk. CONCLUSIONS: Serial monitoring of sST2 (indicating myocardial fibrosis and remodeling) and cTnT (reflecting myocardial injury) identifies highest-risk HF outpatients and may be valuable to guide patient tailored therapy during follow-up evaluations. Serial galectin-3 monitoring in ambulatory HF patients may not be of benefit.

Community adaptations to an impending food desert in rural Appalachia, USA.

INTRODUCTION: The United States Department of Agriculture (USDA) describes a food desert as an urban neighborhood or rural town without ready access to fresh, healthy, and affordable food. An estimated 2.3 million rural Americans live in food deserts. One goal of the USDA is to eliminate food deserts. However, at a time when some food deserts are being eliminated, hundreds of grocery stores are closing, causing other food deserts to arise. The literature is scarce on how a community adapts to an impending food desert. Alderson, West Virginia, USA (population 1184) rallied to face an impending food desert when the only grocery store in town closed in December 2014. This study investigated how this small rural community adapted to its oncoming food desert. METHODS: A community member survey was administered to 155 Alderson families (49%) to determine how the new food desert affected family food acquisition and storage behaviors. A restaurant survey was given to the town's four restaurants to determine how the food desert affected their businesses. Sales data for a new food hub (Green Grocer) was obtained to see if this new initiative offset the negative effects of the food desert. ANOVA and t-tests were used to compare group numerical data. Two group response rates were compared by testing the equality of two proportions. Categorical data were analyzed with the χ2 or frequency distribution analysis. Group averages are reported as mean ± standard error of the mean. Significance for all analyses was set at p<0.05. RESULTS: Even though 86% of the population shopped at the new Green Grocer, 77% did most of their shopping at a store at least 17.7 km (11 miles) from home. The number of long-distance monthly shopping trips made after the food desert (3.3±0.4) did not change significantly (p=0.16) from the number before the food desert (2.8±0.3). Price comparisons among the Green Grocer and three distant supermarkets showed a 30% savings by traveling to distant supermarkets. Frequency of monthly restaurant visits did not change after the emergence of the food desert (2.98±0.54 vs 3.05±0.51, p=0.85). However, restaurant patrons requested to buy fresh produce and dairy from the restaurants to use for their own home cooking. Food pantry use increased by 43%, with community members requesting more fresh produce, meat, and dairy. The food desert triggered a 21% increase in home gardening and an 11% increase in home food preservation. CONCLUSIONS: Opening a Green Grocer offset only some of the effects of the food desert, because community members use it as a convenience store to purchase fresh produce and dairy products that families may lack before their next long-distance trip to a supermarket. Alderson's low-income residents now rely more heavily on food pantry assistance, while a small number of other residents have started gardening and food preservation. The first factor governing food acquisition behavior in rural Appalachia is food pricing, with the proximity of food access coming in second. How to overcome these two major barriers to food security in the midst of current economics and marketing remains to be answered.

Blood volume phenotypes and patient sex in resistant hypertension.

The relationship of blood volume (BV) to systemic blood pressure (BP) is not well defined in resistant hypertension (RH). The goal of this study was to examine the extent to which systemic BP stratified by patient sex would impact BV phenotypes. A retrospective analysis of clinical and quantitative BV data was undertaken in a cohort of ambulatory patients with a history of controlled and uncontrolled RH. We analyzed 253 unique BVs with 54% of patients above goal BP of <150 mmHg. BV phenotypes were highly variable but no correlation of systolic BP to absolute BV or percentage deviation from normal volume was identified in either sex. Males demonstrated overall larger absolute BVs with higher prevalence of large plasma volume (PV) expansion; females were overall more hypovolemic by total BV but with a higher frequency of normal PV than males. Females trended towards more RBC mass deficit (true anemia) (49% vs. 38%. P  = 0.084) while more males demonstrated RBC mass excess (erythrocythemia) (21% vs. 11%, P  = 0.029). Importantly, a significant portion (52%) of patients with true anemia identified by BVA would go undetected by hemoglobin measurement alone. BV phenotypes are highly diverse in patients with RH. However, absolute BV or variability in BV phenotypes even when stratified by patient sex did not demonstrate an association with systemic BP. BV phenotyping provides a key to optimizing clinical management by identifying RBC mass profiles particularly distinguishing true anemia, dilutional anemia, and erythrocythemia and the contribution of PV expansion. Findings support the clinical utility of BV phenotyping in RH.

Comparison of Blood Volume Profiles in Heart Failure With Preserved and Reduced Ejection Fractions: Sex Makes a Difference.

BACKGROUND: Blood volume (BV) profiles vary markedly in patients with heart failure (HF), but how HF phenotypes and patient sex impact volume profiles remain to be explored. The aim of the study was to differentiate BV, plasma volume, and red blood cell mass profiles by phenotypes of preserved and reduced left ventricular ejection fractions and assess the impact of patient sex on profile heterogeneity. METHODS: Retrospective analysis of clinical and BV data was undertaken in patients with chronic New York Heart Association II-III heart failure. BV was quantitated using the nuclear medicine indicator-dilution methodology. RESULTS: A total of 530 BV analyses (360 HF with reduced ejection fraction and 170 HF with preserved ejection fraction) were identified in 395 unique patients. Absolute BV was greater in HF with reduced ejection fraction (6.7±1.8 versus 5.9±1.6 liters: P<0.001); however, large variability in frequency distribution of volume profiles was observed in both phenotypes (-22% deficit to +109% excess relative to normal volumes). HF with reduced ejection fraction was characterized by a higher prevalence of BV expansion ≥+25% of normal (39% versus 26%; P=0.003), and HF with preserved ejection fraction was characterized a by more frequent normal BV (42% versus 24%; P<0.001). Male sex in both phenotypes was associated with a larger absolute BV (7.0±1.6 versus 5.1±1.3 liters; P<0.001) and higher frequency of large BV and plasma volume expansions above normal (both P<0.001), while females in both phenotypes demonstrated a higher prevalence of normal BV and plasma volume (both P<0.001). CONCLUSIONS: Findings support significant differences in BV, plasma volume, and red blood cell mass profile distributions between heart failure phenotypes, driven in large part by sex-specific factors. This underscores the importance of identifying and distinguishing individual patient volume profiles to help guide volume management strategies.

MANP in Hypertension With Metabolic Syndrome: Proof-of-Concept Study of Natriuretic Peptide-Based Therapy for Cardiometabolic Disease.

Hypertension and metabolic syndrome frequently coexist to increase the risk for adverse cardiometabolic outcomes. To date, no drug has been proven to be effective in treating hypertension with metabolic syndrome. M-atrial natriuretic peptide is a novel atrial natriuretic peptide analog that activates the particulate guanylyl cyclase A receptor. This study conducted a double-blind, placebo-controlled trial in 22 patients and demonstrated that a single subcutaneous injection of M-atrial natriuretic peptide was safe, well-tolerated, and exerted pleiotropic properties including blood pressure-lowering, lipolytic, and insulin resistance-improving effects. (MANP in Hypertension and Metabolic Syndrome [MANP-HTN-MS]; NCT03781739).