Petra Nijst

Hyponatremia in acute decompensated heart failure: depletion versus dilution.

Hyponatremia frequently poses a therapeutic challenge in acute decompensated heart failure (ADHF). Treating physicians should differentiate between depletional versus dilutional hyponatremia. The former is caused by diuretic agents, which enhance sodium excretion, often with concomitant potassium/magnesium losses. This can be treated with isotonic saline, whereas potassium/magnesium administration may be helpful if plasma concentrations are low. In contrast, as impaired water excretion, rather than sodium deficiency, is the culprit in dilutional hyponatremia, isotonic saline administration may further depress the serum sodium concentration. Because free water excretion is achieved by continuous sodium reabsorption in distal nephron segments with low water permeability, diuretic agents that impair this mechanism (e.g., thiazide-type diuretic agents and mineralocorticoid receptor antagonists) should be avoided, and proximally acting agents (e.g., acetazolamide and loop diuretic agents) are preferred. Vasopressin antagonists, which promote low water permeability in the collecting ducts and, hence, free water excretion, remain under investigation for dilutional hyponatremia in ADHF.

Urinary Composition During Decongestive Treatment in Heart Failure With Reduced Ejection Fraction

Background—The urinary composition, including sodium (Na+) and chloride (Cl−) concentrations, might provide useful information in addition to urine output during decongestive treatment in heart failure. Methods and Results—Consecutive patients with heart failure (n=61), ejection fraction ⩽45%, worsening symptoms, and scheduled treatment with intravenous loop diuretics were included. Patients received protocol-driven therapy until complete decongestion, assessed clinically and by echocardiography. Three consecutive 24-hour urinary collections were performed. With 2 mg (1–4 mg), 1 mg (0–2 mg), and 1 mg (0–1 mg) bumetanide administered in bolus during consecutive 24-hour intervals, in addition to combinational diuretic therapy in ≈70% and both oral spironolactone and vasodilators in ≈90%, euvolemia was reached, often within 24 hours. Urine output was higher during the first when compared with the second or third 24-hour interval (2700 versus 1550 or 1375 mL, respectively; P<0.001), but this was no longer significant after correction for diuretic dose (P=0.263), indicating preserved diuretic efficiency during the study. In contrast, urinary Na+ and Cl− excretion both decreased significantly, even after correction for diuretic dose (P=0.040 and 0.004, respectively), leading to decreasing urinary concentrations with progressive decongestion. After reaching euvolemia, lower urinary Na+/Cr and Cl−/Cr ratios were both associated with urine output ⩽1500 mL (area under the curve, 0.830 and 0.826, respectively; P<0.001 for both), in contrast to plasma N-terminal pro–B-type natriuretic peptide levels that were not (area under the curve, 0.515; P=0.735) Conclusions—The urinary composition during progressive decongestion in heart failure with reduced ejection fraction is characterized by a drop in urinary Na+ and Cl− concentrations. The urinary Na+/Cr or Cl−/Cr ratio might provide insightful information to titrate diuretic therapy.

Renal sodium avidity in heart failure: from pathophysiology to treatment strategies

Increased neurohumoral stimulation resulting in excessive sodium avidity and extracellular volume overload are hallmark features of decompensated heart failure. Especially in case of concomitant renal dysfunction, the kidneys often fail to elicit effective natriuresis. While assessment of renal function is generally performed by measuring serum creatinine-a surrogate for glomerular filtration-, this only represents part of the nephrons function. Alterations in tubular sodium handling are at least equally important in the development of volume overload and congestion. Venous congestion and neurohumoral activation in advanced HF further promote renal sodium and water retention. Interestingly, early on, before clinical signs of heart failure are evident, intrinsic renal derangements already impair natriuresis. This clinical review discusses the importance of heart failure (HF) induced changes in different nephron segments. A better understanding of cardiorenal interactions which ultimately result in sodium avidity in HF might help to treat and prevent congestion in chronic and acute HF.

Current Approach to Decongestive Therapy in Acute Heart Failure

Congestion, defined by elevated cardiac filling pressures, is the major driver of hospitalization in acute decompensated heart failure. Careful clinical assessment should allow to determine whether volume overload or volume misdistribution is the predominating mechanism of congestion. Differentiation is imperative because therapy differs. If volume overloads prevails, loop diuretics are considered the mainstay therapy. However, early use of combinational therapy with diuretics acting more proximal or distal in the nephron could allow for a more profound natriuresis and diuresis. A stepped guided pharmacological treatment should focus on achieving complete decongestion, because persistent congestion is a major driver of readmission. If diuretic strategies remain unsuccessful, ultrafiltration should be considered. Ultrafiltration should be used with caution in the setting of worsening of renal function. When volume misdistribution and impaired venous capacitance predominate the picture of congestion, unloading—more than diuretics—with arteriolar and venous vasodilators might mitigate the clinical picture of congestion. This review offers a thorough overview and practical insight in the use of current and potential decongestive therapies.

Plasma Volume Is Normal but Heterogeneously Distributed, and True Anemia Is Highly Prevalent in Patients With Stable Heart Failure

BACKGROUND Intravascular volume overload and depletion as well as anemia are associated with increased hospital admissions and mortality in patients with heart failure. This study aimed to accurately measure plasma volume and red cell mass (RCM) in stable patients with chronic heart failure with reduced ejection fraction (HFrEF) and gain more insight into plasma volume regulation and anemia in stable conditions of HFrEF. METHODS AND RESULTS Plasma volume and RCM measurement based on 99Tc-labeled red blood cells, venous blood sample,s and clinical parameters were obtained in 24 stable HFrEF patients under optimal medical therapy. Measured plasma volume values were compared with predicted values based on body surface area. Plasma volume was on average normal (99.98% of predicted) but heterogeneously distributed (variations of 81%-133%). Neurohumoral activation and medication use were not associated with plasma volume status. Furthermore, anemia based on actual measurement of RCM was present in up to 75% of subjects, but rarely hemodilutional. CONCLUSIONS In stable chronic HFrEF patients under optimal medical therapy, plasma volume is overall normal but heterogeneously distributed. Anticipated factors such as neurohumoral activation and heart failure medication were not associated with plasma volume. Furthermore, anemia is more common than as assessed by hemoglobin.

Pulmonary vascular response to exercise in symptomatic heart failure with reduced ejection fraction and pulmonary hypertension

To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH).

Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy

BACKGROUND Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. METHODS AND RESULTS Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). CONCLUSIONS After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation.

Endothelial Glycocalyx as Biomarker for Cardiovascular Diseases: Mechanistic and Clinical Implications

IntroductionThe endothelial surface layer is covered with abundant proteoglycans, of which syndecans and glycosaminoglycans are major constituents.Recent FindingsAmong the endothelial glycocalyx (eGC) constituents, syndecan-1 (sdc1) is a main component, and an elevated serum level of sdc1 may indicate the degradation of eGC. In patients with ischemic heart disease or heart failure, elevation of serum sdc1 has been associated with worsening cardiac and renal function; however, the causal relationship between degradation of eGC and clinical outcomes is unclear.SummaryHerein, we review the previous literature on eGC in cardiovascular and noncardiovascular diseases and their clinical implications.

Prognostic Value of Glomerular Filtration Changes Versus Natriuretic Response in Decompensated Heart Failure With Reduced Ejection

BACKGROUND Glomerular filtration rate (GFR) and natriuretic response to diuretics represent important treatment targets in acute decompensated heart failure (ADHF). METHODS AND RESULTS Consecutive ADHF patients (n = 50) with ejection fraction ≤ 45% and clinical signs of volume overload received protocol-driven decongestive therapy. Serum creatinine (Cr), cystatin C (CysC), and β-trace protein (βTP) were measured on admission and three subsequent days of treatment. Worsening renal function (WRF) was defined as a ≥ 0.3 increase in absolute biomarker levels or ≥ 20% decrease in estimated GFR. Consecutive 24-hour urinary collections were simultaneously performed to measure Cr clearance and natriuresis. Serum Cr, CysC, and βTP were strongly correlated at admission (ρ = 0.788-0.909) and during decongestive treatment (ρ = 0.884-888). Moreover, derived GFR estimates correlated well with Cr clearance (ρ = 0.820-0.908). Nevertheless, WRF incidence differed markedly according to Cr- (26%-30%), CysC- (46%-54%), or βTP-based definitions (31%-48%). WRF by any definition was not associated with all-cause mortality or ADHF readmission, in contrast to stronger natriuresis per loop diuretic dose [hazard ratio 0.20 (95% confidence interval 0.06-0.64); P = .007]. CONCLUSIONS Serial measurements of CysC/βTP, compared with serum Cr, more frequently indicate WRF during decongestive treatment in ADHF. However, adverse clinical outcome in such patients might be better predicted by the natriuretic response to diuretic therapy.

Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction.

Abstract Background: Little information is available about the prevalence and impact on exercise capacity and outcome of iron deficiency in heart failure with mid-range (HFmrEF) and preserved (HFpEF) ejection fraction in comparison to heart failure with reduced ejection-fraction (HFrEF). Furthermore, no data is available about the progression of ID in patients without baseline anaemia. Methods: We evaluated baseline iron and haemoglobin-status in a single-centre, prospective heart failure database. Baseline functional status, VO2max, echocardiography and clinical-outcome (all-cause mortality and heart failure admissions) were evaluated. ID, anaemia, HFrEF, HFmrEF and HFpEF were defined according to established criteria. Results: A total of 1197 patients (71% male) were evaluated (HFrEF, n = 897; HFmrEF, n = 229; HFpEF, n = 72). The overall prevalence of ID was 53% (50% in HFrEF; 61% in HFmrEF; 64% in HFpEF) and 36% for anaemia. ID was associated with a lower VO2max in patients with HFrEF, HFmrEF and HFpEF (p < .001 in all). Iron status more closely related to a poor VO2max than anaemia status (p < .001). Furthermore, poor clinical-outcome was more strongly associated with iron status than anaemia status. Exposing eight patients without anaemia to iron deficiency for 39 months resulted in one patient developing new-onset anaemia (defined as progression of ID). Patients with progression of ID exhibited a significant higher risk of heart failure hospitalisation and all-cause mortality (HR = 1.4; CI = 1.01–1.94; p = .046) than patients without progression. Conclusions: Iron deficiency is common in patients with HFrEF, HFmrEF and HFpEF, and negatively affects VO2max and clinical-outcome. Progression of iron deficiency parallels an increased risk for worsening of heart failure.