Trajectories of renal biomarkers and new-onset heart failure in the general population:Findings from the PREVEND study

AIMS: Renal dysfunction is one of the most critical risk factors for developing heart failure (HF). However, the association between repeated measures of renal function and incident HF remains unclear. Therefore, this study investigated the longitudinal trajectories of urinary albumin excretion (UAE) and serum creatinine and their association with new-onset HF and all-cause mortality.METHODS AND RESULTS: Using group-based trajectory analysis, we estimated trajectories of UAE and serum creatinine in 6881 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study and their association with new-onset HF and all-cause death during the 11-years of follow-up. Most participants had stable low UAE or serum creatinine. Participants with persistently higher UAE or serum creatinine were older, more often men, and more often had comorbidities, such as diabetes, a previous myocardial infarction or dyslipidaemia. Participants with persistently high UAE had a higher risk of new-onset HF or all-cause mortality, whereas stable serum creatinine trajectories showed a linear association for new-onset HF and no association with all-cause mortality.CONCLUSION: Our population-based study identified different but often stable longitudinal patterns of UAE and serum creatinine. Patients with persistently worse renal function, such as higher UAE or serum creatinine, were at a higher risk of HF or mortality.</p

The value of spot urinary creatinine as a marker of muscle wasting in patients with new-onset or worsening heart failure

Background: Muscle wasting and unintentional weight loss (cachexia) have been associated with worse outcomes in heart failure (HF), but timely identification of these adverse phenomena is difficult. Spot urinary creatinine may be an easily accessible marker to assess muscle loss and cachexia. This study investigated the association of urinary creatinine with body composition changes and outcomes in patients with new‐onset or worsening HF (WHF). Methods: In BIOSTAT‐CHF, baseline spot urinary creatinine measurements were available in 2315 patients with new‐onset or WHF in an international cohort (index cohort) and a validation cohort of 1431 similar patients from Scotland. Results: Median spot urinary creatinine concentrations were 5.2 [2.7–9.6] mmol/L in the index cohort. Median age was 69 ± 12 years and 73% were men. Lower spot urinary creatinine was associated with older age, lower height and weight, worse renal function, more severe HF, and a higher risk of &gt;5% weight loss from baseline to 9 months (odds ratio = 1.23, 95% CI = 1.09–1.39 per log decrease; P = 0.001). Spot urinary creatinine was associated with Evans criteria of cachexia (OR = 1.26 per log decrease, 95% CI = 1.04–1.49; P = 0.016) and clustered with markers of heart failure severity in hierarchical cluster analyses. Lower urinary creatinine was associated with poorer exercise capacity and quality of life (both P &lt; 0.001) and predicted a higher rate for all‐cause mortality [hazard ratio (HR) = 1.27, 95% CI = 1.17–1.38 per log decrease; P &lt; 0.001] and the combined endpoints HF hospitalization or all‐cause mortality (HR = 1.23, 95% CI = 1.15–1.31 per log decrease; P &lt; 0.001). Significance was lost after addition of the BIOSTAT risk model. Analyses of the validation cohort yielded similar findings. Conclusions: Lower spot urinary creatinine is associated with smaller body dimensions, renal dysfunction, and more severe HF in patients with new‐onset/WHF. Additionally, lower spot urinary creatinine is associated with an increased risk of weight loss and a poorer exercise capacity/quality of life. Urinary creatinine could therefore be a novel, easily obtainable marker to assess (risk of) muscle wasting in HF patients

Trajectories of Changes in Renal Function in Patients with Acute Heart Failure

Aims: Changes in renal function have been associated with differential outcome in patients with acute heart failure (HF). However, individual trajectories of changes in renal function are unknown and it is unclear whether these relate to different clinical characteristics and clinical outcome. Our aim was to investigate the prognostic importance of individual trajectories of changes in renal function in acute HF. Methods and Results: This was a retrospective, observational analysis from the double-blind, randomized, placebo controlled PROTECT trial in acute HF patients. We identified and internally validated 8 different renal trajectories among 1897 patients by visual inspection of inhospital serum creatinine changes. The primary outcome measure was all-cause mortality at 180 days. Mean age was 70±12 years, 70% were male, and mean baseline eGFR was 49.0 mL/min/1.73m2. A total of eight different trajectories were established. The most prevalent trajectories were an inhospital bump (19.0%), a sustained increase (17.6%), and a dip (14.5%) in serum creatinine. Overall, clinical characteristics of patients within different trajectories were remarkably similar. Crude 180-day mortality rates ranged from 12.0% in the trajectory with no significant changes to 18.3% in trajectory of sustained increase without significant differences. Overall, after multivariable adjustment, there was no trajectory of changes in renal function that was associated with significantly better or worse outcomes. Conclusions: Trajectories of changes in renal function in acute HF differ considerably on patient level. Despite these differences, clinical characteristics and outcome were similar, therefore questioning the prognostic importance of changes in renal function in acute HF

Urinary marker profiles in heart failure with reduced versus preserved ejection fraction

Background: Recent data suggest different causes of renal dysfunction between heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We therefore studied a wide range of urinary markers reflecting different nephron segments in heart failure patients. Methods: In 2070, in chronic heart failure patients, we measured several established and upcoming urinary markers reflecting different nephron segments. Results: Mean age was 70 ± 12 years, 74% was male and 81% (n = 1677) had HFrEF. Mean estimated glomerular filtration rate (eGFR) was lower in patients with HFpEF (56 ± 23 versus 63 ± 23 ml/min/1.73 m2, P = 0.001). Patients with HFpEF had significantly higher values of NGAL (58.1 [24.0-124.8] versus 28.1 [14.6-66.9] μg/gCr, P  60 ml/min/1.73m2. Conclusions: HFpEF patients showed more evidence of tubular damage and/or dysfunction compared with HFrEF patients, in particular when glomerular function was preserved

Clinical implications of low estimated protein intake in patients with heart failure

Background: A higher protein intake has been associated with a higher muscle mass and lower mortality rates in the general population, but data about protein intake and survival in patients with heart failure (HF) are lacking. Methods: We studied the prevalence, predictors, and clinical outcome of estimated protein intake in 2516 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) index cohort. Protein intake was calculated in spot urine samples using a validated formula [13.9 + 0.907 * body mass index (BMI) (kg/m2) + 0.0305 * urinary urea nitrogen level (mg/dL)]. Association with mortality was assessed using multivariable Cox regression models. All findings were validated in an independent cohort. Results: We included 2282 HF patients (mean age 68 ± 12 years and 27% female). Lower estimated protein intake in HF patients was associated with a lower BMI, but with more signs of congestion. Mortality rate in the lowest quartile was 32%, compared with 18% in the highest quartile (P < 0.001). In a multivariable model, lower estimated protein intake was associated with a higher risk of death compared with the highest quartile [hazard ratio (HR) 1.50; 95% confidence interval (CI) 1.03–2.18, P = 0.036 for the lowest quartile and HR 1.46; 95% CI 1.00–2.18, P = 0.049 for the second quartile]. Conclusions: An estimated lower protein intake was associated with a lower BMI, but signs of congestion were more prevalent. A lower estimated protein intake was independently associated with a higher mortality risk.publishedVersio

Selenium and outcome in heart failure

Aims: Severe deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown. Methods and results: BIOSTAT‐CHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of all‐cause mortality and hospitalization for heart failure; secondary endpoint was all‐cause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was &lt;70 μg/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6‐min walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06–1.42] and all‐cause mortality (HR 1.52; 95% CI 1.26–1.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels. Conclusions: Selenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium

Diabetes Mellitus and Right Ventricular Dysfunction in Heart Failure With Preserved Ejection Fraction

Diabetes mellitus is associated with left-sided myocardial remodeling in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of diabetes mellitus on right ventricular (RV) function in HFpEF. We therefore studied the relation between diabetes mellitus and RV dysfunction in HFpEF. We have examined patients with HFpEF who underwent simultaneous right-sided cardiac catheterization and echocardiography. RV systolic function was assessed using multiple established echocardiographic parameters, and systolic dysfunction was present if parameters were outside the normal range. RV diastolic function was assessed using the peak diastolic tissue velocity of the lateral tricuspid annulus (RV e') and was present if = 7.0 mmol/L, a positive glucose intolerance test result, or a glycated hemoglobin level of >= 6.5%. A total of 91 patients were studied (mean age 74 +/- 9 years, 69% women). A total of 37% had RV systolic dysfunction and 23% RV diastolic dysfunction. Thirty-seven percent of the patients had type 2 diabetes mellitus. These patients had higher pulmonary artery pressure (34 mm Hg vs 29 mm Hg, p = 0.004), more RV systolic dysfunction (57% vs 29%, p = 0.009), more RV diastolic dysfunction (46% vs 12%, p = 0.001), and lower RV e' (8.7 cm/s vs 11.5 cm/s, p = 0.006). The presence of diabetes mellitus was independently associated with RV systolic dysfunction (odds ratio 2.84, 95% confidence interval 1.09 to 7.40, p = 0.03) and with RV diastolic dysfunction (odds ratio 4.33, 95% confidence interval 1.25 to 15.07, p = 0.02), after adjustment for age, gender, and pulmonary pressures. In conclusion, diabetes mellitus is strongly associated with RV systolic and diastolic dysfunctions in patients with HFpEF, independent of RV afterload. (C) 2017 Elsevier Inc. All rights reserved

Hemodynamic Characteristics of Mechanically Ventilated COVID-19 Patients: A Cohort Analysis

Background. Solid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients. Methods. A retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system. Results. The mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p<0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p<0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Qs/Qt) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p<0.001), but static lung compliance remained unchanged. Conclusions. In general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange