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Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

ABSTRACT: A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hbmass ) were determined with high-precision, automated carbon monoxide (CO) rebreathing in 20 stable HFpEF patients (71.5 ± 7.3 years, left ventricular ejection fraction = 55.7 ± 4.0%) and 15 healthy age- and sex-matched control individuals. Additional measurements comprised key circulating BV-regulating hormones such as pro-atrial natriuretic peptide (proANP), copeptin, aldosterone and erythropoietin (EPO), as well as central hemodynamics and arterial stiffness via carotid-femoral pulse wave velocity (PWV). Carotid-femoral PWV was increased (+20%) in HFpEF patients versus control individuals. With respect to hematological variables, plasma volume (PV) did not differ between groups, whereas BV was decreased (-14%) in HFpEF patients. In consonance with the hypovolemic status, Hbmass was reduced (-27%) in HFpEF patients, despite they presented more than a twofold elevation of circulating EPO (+119%). Plasma concentrations of BV-regulating hormones, including proANP (+106%), copeptin (+99%), and aldosterone (+62%), were substantially augmented in HFpEF patients. HFpEF patients may present with hypovolemia and markedly reduced Hbmass , underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis. These findings provide a novel perspective on the pathophysiological basis of the HFpEF condition.

SUBMITTER: Montero D

PROVIDER: S-EPMC6854115 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

Montero David D Haider Thomas T Barthelmes Jens J Goetze Jens P JP Cantatore Silviya S Sudano Isabella I Ruschitzka Frank F Flammer Andreas J AJ

Physiological reports 20191101 21

A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hb<sub>mass</sub> ) were determined with high-precision, automated carbo ...[more]

PMID: 31724335

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Project description:BackgroundMicrovascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated.ObjectivesThis study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na+ excess.MethodsPatients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na+, and K+) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation).ResultsSkin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na+ excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001).ConclusionsPeripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.

Project description:AIMS:The study aimed at investigating the use of guideline-recommended diagnostic tools and medication in patients with heart failure (HF) in specialty care in Southwest Finland. We also compared the characteristics of the diagnosed and undiagnosed patients as well as laboratory tests, procedures, and treatments in everyday clinical practice. METHODS AND RESULTS:Patients diagnosed with HF, cardiomyopathy, or hypertension-induced heart disease (n = 20 878, primary cohort) or not diagnosed with HF but having a record of elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) (>125 ng/L, n = 24 321, secondary cohort) were included in the study from the specialty care patient register of the Hospital District of Southwest Finland during the years 2005-2017. Among patients with an International Classification of Diseases, Tenth Revision (ICD-10) code for HF, only 50% had ejection fraction (EF) data to be found by data mining from the electronic health records. Of these patients, 39% (n = 4042) had EF ? 40% [HF with reduced EF (HFrEF)] and 61% (n = 6347) had EF > 40%. Elevated NT-proBNP together with EF > 40% narrowed down the number to 4590 patients, a population defined as HF with preserved EF (HFpEF) patients. HFpEF patients were further stratified into HF with mildly reduced EF (HFmrEF; EF 41-50%, n = 1468) and EF > 50% patients (n = 3122) to compare clinical characteristics. NT-proBNP was higher within the HFrEF patients vs. HFpEF {4580 [inter-quartile range (IQR): 2065-9765] vs. 2900 [2065-9765] ng/L, P < 0.001}. Baseline co-morbidities differed between HFpEF and HFrEF groups. Further, HFpEF patients had more procedures and lab tests taken prior to diagnosis than had HFrEF patients. HFmrEF patients were found to resemble more HFrEF than EF > 50% patients. In 70% (n = 17 156) of patients in the secondary cohort, the NT-proBNP concentrations were >300 ng/L, median was 1090 (IQR 551-2558) ng/L and EF 58.4 ± 12.1% (n with EF available = 6845). Reduced EF was present in 6.8% of patients lacking HF diagnosis. CONCLUSIONS:Half of the patients with ICD-10 code for HF did not have EF data available after a visit at specialty care. In particular, the diagnosis of HFpEF seems challenging, reflected as an increase in procedures and laboratory test preceding diagnosis compared with those in HFrEF patients. Also, a large proportion of patients did not have HF diagnosis, yet they presented elevated NT-proBNP concentrations and clinical characteristics resembling those of HFpEF patients.

Project description:AimsThis study aimed to assess short-term outcomes among emergency department (ED) patients with acute heart failure (AHF) by preserved (≥50%) vs. reduced (<50%) ejection fraction (EF).Methods and resultsWe conducted a retrospective, multicentre study of adult ED patients with AHF from 2017 to 2018 in an integrated healthcare system with 21 hospitals. Among patients with known EF, our primary outcome was 30 day all-cause mortality, comparing patients with heart failure with preserved EF (HFpEF) and heart failure with reduced EF (HFrEF), adjusted for known risk factors. We ran separate multivariate regression models to compare 30 day mortality between HFpEF and HFrEF patients stratified by ED disposition (admit, observe, and discharge). Our secondary outcomes were adjusted 30 day all-cause return hospital admission and rates of non-fatal serious adverse events, including new intra-aorta balloon pump, endotracheal intubation, renal failure requiring dialysis, myocardial infarction, or coronary revascularization. We conducted a sensitivity analysis among patients with EF ≤ 40% and compared our primary and secondary outcomes among patients with EF ≤ 40% with those with EF ≥ 50%. Among the 26 050 total ED encounters for AHF, 15 275 (58.6%) had known EF and 62.4% had HFpEF. The mean age was 76, 49.6% were women, and 60.5% were white. We found that 62.4% of patients were admitted, 18.3% were observed, and 19.3% were discharged from the ED. The 30 day all-cause mortality rate was lowest among discharged patients (3.9%), intermediate among observed patients (5.9%), and highest among admitted patients (13.9%). Overall, the adjusted 30 day mortality rate was significantly higher among HFpEF patients compared with HFrEF patients (10.2% vs. 8.4%, P = 0.0004). HFpEF patients had higher mortality regardless of ED disposition, although the difference was only significant among admitted patients. The adjusted 30 day return hospital admission rates were not significantly different between HFpEF and HFrEF patients (17.9% vs. 17.8%, P = 0.89). The adjusted 30 day non-fatal serious adverse event rates were significantly higher among HFrEF patients compared with HFpEF patients (13.7% vs. 11.1%, P < 0.0001), driven by myocardial infarction and coronary revascularization. We found that 3692 patients had EF ≤ 40%. Patients with EF ≥ 50% had significantly higher adjusted 30 day mortality rates compared with those with EF ≤ 40% (10.2% vs. 8.4%, P < 0.05).ConclusionIn a contemporary population, almost three quarters of ED patients with AHF and known EF have HFpEF. These patients have higher 30 day adjusted mortality compared with those with HFrEF. Further studies might evaluate the underlying factors associated with this difference and target interventions to improve outcomes.

Project description:BackgroundLifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.MethodsParticipant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.ResultsWe included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.ConclusionsLifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.

Dataset Information

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

Publications

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

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