Congestion explains many of the signs and symptoms of acute heart failure (AHF) and disease progression. However, accurate quantification of congestion is challenging in daily practice. Antigen ...carbohydrate 125 (CA125) or mucin 16 (MUC16), a large glycoprotein synthesized by mesothelial cells, has emerged as a reliable proxy of congestion and inflammation in patients with heart failure (HF). In AHF syndromes, CA125 is strongly associated with right‐sided HF parameters and a higher risk of adverse clinical events beyond standard prognostic factors, including natriuretic peptides. Furthermore, CA125 has the potential for both monitoring and guide HF treatment following a decompensated HF event. The wide availability of CA125 in most clinical laboratories, together with its standardized measurement and reduced cost, makes this marker attractive for routine use in decompensated HF. Further research is required to understand better its biological role and its promising utility as a tool to guide decongestive therapy in HF.
Scheme of the pathophysiology, clinical utility, and logistic advantages of antigen carbohydrate 125 (CA125) in heart failure (HF). In acute HF syndromes, plasma CA125: (i) is associated with proxies of clinical congestion, right‐sided HF, and inflammation; (ii) is positively associated with a higher risk of death and HF readmission; (iii) has emerged as a valuable tool for tailoring diuretic therapy; and (iv) is cheap, and widely available.
Aim
Emerging evidence suggests a beneficial effect of higher heart rates in some patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the impact of ...higher backup pacing rates in HFpEF patients with preexisting pacemaker systems that limit pacemaker‐mediated dyssynchrony across left ventricular (LV) volumes and LV ejection fraction (LVEF).
Methods and results
This is a post‐hoc analysis of the myPACE clinical trial that evaluated the effects of personalized accelerated pacing setting (myPACE) versus standard of care on changes in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), pacemaker‐detected activity levels, and atrial fibrillation (AF) burden in patients with HFpEF with preexisting pacemakers. Between‐treatment comparisons were performed using linear regression models adjusting for the baseline value of the exposure (ANCOVA design). This study included 93 patients with pre‐trial transthoracic echocardiograms available (usual care n = 49; myPACE n = 44). NT‐proBNP levels and MLHFQ scores improved in a higher magnitude in the myPACE group at lower indexed LV end‐diastolic volumes (iLVEDV) (NT‐proBNP–iLVEDV interaction p = 0.006; MLHFQ–iLVEDV interaction p = 0.068). In addition, personalized accelerated pacing led to improved changes in activity levels and NT‐proBNP, especially at higher LVEF (activity levels–LVEF interaction p = 0.009; NT‐proBNP–LVEF interaction p = 0.058). No evidence of heterogeneity was found across LV volumes or LVEF for pacemaker‐detected AF burden.
Conclusions
In the post‐hoc analysis of the myPACE trial, we observed that the benefits of a personalized accelerated backup pacing on MLHFQ score, NT‐proBNP, and pacemaker‐detected activity levels appear to be more pronounced in patients with smaller iLVEDV and higher LVEF.
Differential effect of personalized accelerated backup pacing rate settings across indexed left ventricular end‐diastolic volume. AF, atrial fibrillation; iLVEDV, indexed left ventricular end‐diastolic volume; LV, left ventricular; LVEF, left ventricular ejection fraction; MLHFQ, Minnesota Living with Heart Failure Questionnaire; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; PM, pacemaker.
We aimed to assess the association between CA125 and the long-term risk of total acute heart failure (AHF) admissions in patients with an index hospitalization with AHF and preserved ejection ...fraction (HFpEF). We prospectively included 2369 patients between 2008 and 2019 in three centers. CA125 and NT-proBNP were measured during early hospitalization and evaluated as continuous and categorized in quartiles (Q). Negative binomial regressions were used to assess the association with the risk of recurrent AHF admission. The mean age of the sample patients was 76.7 ± 9.5 years and 1443 (60.9%) were women. Median values of CA125 and NT-proBNP were 38.3 (19.0-90.0) U/mL, and 2924 (1590-5447) pg/mL, respectively. During a median follow-up of 2.2 (0.8-4.6) years, 1200 (50.6%) patients died, and 2084 AHF admissions occurred in 1029 (43.4%) patients. After a multivariate adjustment, CA125, but not NT-proBNP, was positively and non-linearly associated with the risk of cumulative AHF-readmission (p < 0.001). Compared to Q1, patients belonging to Q2, Q3, and Q4 showed a stepwise risk increase (IRR = 1.29, 95% CI 1.08-1.55, p = 0.006; IRR = 1.35, 95% CI 1.12-1.63, p = 0.002; and IRR = 1.62, 95% CI 01.34-1.96, p < 0.001, respectively). In conclusion, CA125 predicted the risk of long-term AHF-readmission burden in patients with HFpEF and a recent admission for AHF.
ABSTRACT
Valvular heart disease (VHD) is highly prevalent among dialysis patients, affecting up to 30%–40% of the population. Aortic and mitral valves are the most frequently affected and commonly ...lead to valvular stenosis and regurgitation. Although it is well established that VHD is associated with a high morbimortality burden, the optimal management strategy remains unclear, and treatment options are limited due to the high risk of complications and mortality after surgical and transcatheter interventions. In this issue of Clinical Kidney Journal, Elewa et al. provide new evidence in this field by reporting the prevalence and associated outcomes of VHD in patients with kidney failure on renal replacement therapy.
Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the ...circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction.
This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of <60 mL/min/1.73 m2). DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and DE was evaluated by using multivariate linear regression analysis. The median cumulative DE at 24 and 72 hour was 747 mL (interquartile range 490–1167 mL) and 1844 mL (interquartile range 1142–2625 mL), respectively. The median sST2 and mean estimated glomerular filtrate rate were 72 ng/mL (interquartile range 47–117 ng/mL), and 34.0 ± 8.5 mL/min/1.73 m2, respectively. In a multivariable setting, higher sST2 were significant and nonlinearly related to lower DE both at 24 and 72 hours (P = .002 and P = .019, respectively).
In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.
Circulating levels of soluble ST2 are independently and negatively associated with a poor diuretic response, both at 24 and 72 hours. sST2, soluble, circulating form of interleukin-1 receptor-like 1; Na, renal tubular sodium reabsorption. Display omitted
•In this subanalysis of the DAPA-VO2 randomized clinical trial, dapagliflozin lead to a significant short-term increases in hemoglobin levels.•Short-term hemoglobin changes were associated with the ...magnitude of between-treatment differences (dapagliflozin vs placebo) in maximal functional capacity, quality of life and natriuretic peptides.•The magnitude of hemoglobin increase emerges as a simple and widely available parameter for monitoring SGLT2i responses.
We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels.
This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels.
At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012). Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively).
In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.
•Right heart dysfunction parameters are increasingly important in heart failure.•The combination of a reduced tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio and ...a significant tricuspid regurgitation is associated with a higher risk of recurrent cardiovascular and heart failure admissions.•This association in mainly observed in patients with left ventricular ejection fraction of 40% or greater, because no significant differences were observed in patients with heart failure with reduced ejection fraction.
Right heart dysfunction (RHD) parameters are increasingly important in heart failure (HF). This study aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF).
We included 3383 consecutive patients discharged for acute HF. Of them, in 1435 patients (42.4%), the pulmonary artery systolic pressure could not be measured accurately, leaving a final sample size of 1948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure of less than 0.36 and significant tricuspid regurgitation (n = 196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions. At a median follow-up of 2.2 years (interquartile range 0.63–4.71), 3782 readmissions were registered in 1296 patients (66.5%). Patients with advanced RHD showed higher readmission rates, but only if the LVEF was 40% or greater (P < .001). In multivariable analyses, this differential association persisted for cardiovascular and HF recurrent admissions (P value for interaction = .015 and P = .016; respectively). Advanced RHD was independently associated with the risk of recurrent cardiovascular and HF admissions if HF with an LVEF of 40% or greater (incidence rate ratio 1.64, 95% confidence interval 1.18–2.26, P = .003; and incidence rate ratio 1.73; 95% confidence interval 1.25–2.41, P = .001;respectively). In contrast, it was not associated with readmission risks if the LVEF was less than 40%.
After an admission for acute HF, advanced RHD was strongly associated with a higher risk of recurrent cardiovascular and HF admissions, but only in patients with an LVEF of 40% or greater.
Display omitted (A) Study flow chart. (B) Rates of CV and HF recurrent admissions per 100 person-years in patients with HF with LVEF of less than 40% or 40% or greater, according to advanced RHD parameters. (C) Risk of recurrent CV and HF-related admissions in the multivariable regression models associated with advanced RHD (TAPSE/PASP of <0.36 with significant TR). CI, confidence interval; CV, cardiovascular; HF, heart failure; LVEF, left ventricular ejection fraction; PASP, pulmonary arterial systolic pressure; RHD, right heart dysfunction; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.