Effects of hemodialysis on blood volume, macro- and microvascular function.

BACKGROUND: Vascular dysfunction is considered to spur the progression of cardiovascular disease in hemodialysis (HD) patients. Whether the HD procedure itself contributes to vascular dysfunction remains incompletely investigated. The present study sought to comprehensively assess the effects of HD on arterial and venous function along with concomitant changes in blood volume (BV). METHODS AND RESULTS: We determined BV with high-precision, automated carbon monoxide-rebreathing, arterial stiffness using applanation tonometry and intrinsic microvascular function via retinal vessel analysis prior to and after conventional 4-hour HD in fasting-controlled conditions in 10 patients. All HD patients were non-smokers and non-obese (body mass index = 22.8 ±â€¯2.8 m·kg-2). Hypertension (70%), coronary artery disease (40%) and diabetes mellitus (20%) were the most prevalent comorbidities. Prior to HD, all patients presented with hypervolemia (+2208 ±â€¯1213 ml). HD decreased body weight (-1.72 ±â€¯1.25 kg, P = 0.002) and plasma volume (-689 ±â€¯566 ml, P = 0.004), while hematocrit (Hct) was concomitantly increased (+4.8 ±â€¯4.5%, P = 0.009). HD did not affect large elastic artery stiffness, as determined by carotid-femoral pulse wave velocity (P = 0.448) and carotid distensibility (P = 0.562). In contrast, flicker light-induced retinal venular dilation was reduced by three-fourths after HD (-2.4 ±â€¯1.7%, P = 0.039), in parallel to increased retinal venular diameter (+11.2 ±â€¯4.9 µm, P = 0.002). In regression analyses, a negative association was observed between HD-induced changes in Hct and retinal venular dilation (r ≥ -0.89, P ≤ 0.045). CONCLUSION: Conventional HD resulting in substantial plasma volume removal do not alter large artery elastic properties, whereas intrinsic microvascular venular dilator function is markedly impaired, an effect directly associated with the increase in hemoconcentration.

Retinal microvascular dysfunction in heart failure.

Aims: Retinal vessel analysis (RVA) represents a novel, non-invasive, and reliable method to study the microcirculation in the eye. The goal of this study was to assess the extent of retinal microvascular dysfunction in patients with chronic heart failure (CHF) compared to controls and established measures of vascular function. Methods and results: In this prospective, single-centre, observational study, 74 patients with compensated CHF (mean age 63.5 ± 11.2 years, 32% female, mean left-ventricular ejection fraction 37 ± 12.8%), 74 patients with cardiovascular risk factors (CVRF; 64.1 ± 12.7 years, 34% female), and 74 healthy controls (HC; 57.8 ± 14.2 years, 35% female) were included. The primary endpoint, flicker-induced dilatation of retinal arterioles (FIDart), was significantly reduced in patients with CHF compared to CVRF and HC (mean FIDart 0.9 ± 0.2 vs. 2.3 ± 0.3 and vs. 3.6 ± 0.3%, respectively, both P < 0.001 before and after propensity score-weighted analysis). Similar differences were seen for venular FID. FIDart was less impaired in patients with dilated compared to ischaemic cardiomyopathy. No significant differences were observed for arteriovenous ratio and flow-mediated dilatation. Impaired FIDven was associated with echocardiographically estimated systolic pulmonary artery pressure and left atrial volume index. Conclusion: Retinal microvascular dilatation in response to flicker light is impaired in CHF. RVA may represent a new and useful method to non-invasively monitor microvascular abnormalities in heart failure in an easy and standardized way without the use of radiation.

Clinical benefits and safety of renal denervation in severe arterial hypertension: A long-term follow-up study.

The clinical benefits of renal denervation are still under discussion, since randomized controlled clinical studies have provided inconsistent results. The present retrospective study examined the clinical effects of renal denervation with focus on office blood pressure, heart rate, and changes in renal function. Patients with treatment-resistant hypertension (blood pressure ≥ 140/90 mm Hg in spite of 3 antihypertensive drugs including a diuretic) underwent renal denervation at the University Hospital of Zurich, Switzerland and were followed up until 36 months. Renal denervation was performed using 3 different renal denervation systems. The primary outcome consisted of change in office blood pressure, heart rate, and plasma creatinine at 1, 6, 12, 24, and 36 months after renal denervation. 58 patients underwent renal denervation between August 2010 and December 2017. After exclusion, 50 patients were included in the analyses. At 36 months, the mean office systolic and diastolic blood pressure change was -26.4/-8.8 mm Hg (95% CI: -34.6 to -18.2/-13.5 to -4.2 mm Hg; P < .001 for both). Office heart rate showed no significant change during follow-up (P = .361). Plasma creatinine increased from 90.6 µmol/L (95% CI: 82.1 to 99.0 µmol/L) at baseline to 102.1 µmol/L (95% CI: 95.8 to 108.3 µmol/L) at 36 months (P = .007). No major adverse events occurred. Renal denervation is a safe and effective procedure for patients with treatment-resistant hypertension with a clinically significant antihypertensive effect. Further randomized trials are needed to determine the specific context within which renal denervation should be considered a therapeutic option in antihypertensive care.

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

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.

Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients.

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume (BV) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HFpEF patients. Central venous pressure (CVP) assessed via the internal jugular vein (IJV) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25-30°) head-up tilt (HUT) in 18 stable HFpEF patients (71.2 ± 7.3 years), 14 elderly (EC), and 10 young (YC) healthy controls. Parallel endocrine measurements comprised main BV-regulating hormones: pro-atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin (EPO). At supine rest, the IJV aspect ratio was higher (>30%) in HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) (P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (-52%), with similar hemodynamic effects in all groups (P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO, which was increased in YC (+10%) but remained unaltered in HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age-dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition.

Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a continuum?

AIMS: Dynamic retinal vessel analysis is a novel, non-invasive method to assess microvascular function. The primary aim of this study was to investigate whether retinal microcirculation is impaired in patients with stable coronary artery disease (CAD) compared to patients with heart failure due to CAD (ischaemic heart failure, IHF). METHODS AND RESULTS: A total of 150 adults were enrolled to prospectively assess micro- and macrovasculature. The pre-defined primary outcome was flicker-induced arterial dilatation (FIDa) in patients with CAD [n = 40; median age 63 years, interquartile range (IQR) 53-70] and IHF (n = 40; median age 63 years, IQR 59-71) compared to healthy controls (HC, n = 70; median age 57 years, IQR 41-69). Secondary outcomes included arterial stiffness, flow-mediated dilatation, biomarkers, and ergospirometry parameters. Patients with CAD demonstrated impairment in FIDa that was even more pronounced in patients with IHF (CAD: 1.93 ± 0.28% vs. IHF: 0.41 ± 0.28%, P < 0.001; FIDa in HC: 3.69 ± 0.21%, both P < 0.001) adjusting for age, sex, concomitant medication, and co-morbidities. While pulse wave velocity was increased and flow-mediated dilatation reduced in CAD and IHF patients (both P < 0.001 compared to HC), neither differed between CAD and IHF patients. N-terminal pro-B-type natriuretic peptide (r = -0.49, P < 0.001,) and high-sensitivity troponin T (r = -0.28, P = 0.003) correlated with FIDa. Intriguingly, mean metabolic equivalents (5.3 ± 2.3 kcal/kg/h, n = 39) showed a positive correlation with FIDa (r = 0.58, P < 0.001). CONCLUSION: This study demonstrates a decline of retinal arterial function in CAD patients that is significantly more pronounced in the presence of reduced left ventricular ejection fraction, suggesting a continuum of microvascular damage.

Retinal microvascular dysfunction in hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is one of the most important contributors to atherosclerosis. Whether hypercholesterolemia also affects the retinal microcirculation is unclear. OBJECTIVE: The goal of our study was to assess the association of cholesterol levels with retinal microvascular function using dynamic and static retinal vessel analysis (RVA) in a primary prevention setting. METHODS: This cross-sectional, observational study prospectively recruited 67 patients with hypercholesterolemia without known cardiovascular disease (mean age 64.4 ± 10.4 years; 45% female) and 78 healthy controls (mean age 61.8 ± 11.2 years; 45% female). The primary end point of the study was flicker-induced dilatation of retinal arterioles (FIDart) with secondary exploratory outcomes including venular FID (FIDven), arteriovenous ratio, flow-mediated dilatation and arterial stiffness as measured with augmentation index and pulse wave velocity. Multiple regression analysis was performed to study the association of cholesterol levels with retinal microvascular function. RESULTS: FIDart was significantly impaired in patients with hypercholesterolemia compared with healthy controls (mean FIDart 2.1 ± 1.8 vs 3.1 ± 1.8%, P = .001). This association remained when analysis was restricted to dyslipidemic patients without coexisting hypertension or lipid-lowering therapy. No significant differences remained for FIDven, flow-mediated dilatation, arteriovenous ratio, or arterial stiffness between the groups. Low-density lipoprotein, but not high-density lipoprotein, cholesterol was a significant negative predictor of FIDart in multiple regression analysis. CONCLUSION: Hypercholesterolemia is associated with significant retinal microvascular dysfunction as evidenced by a reduction in flicker-induced dilatation of retinal arterioles. Dynamic RVA may be a promising method for the study of retinal microvascular dysfunction in populations at elevated cardiovascular risk.