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.
Background
Intravenous ferric carboxymaltose (
FCM
) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after
FCM
administration in patients with heart failure and iron deficiency using cardiac magnetic resonance.
Methods and Results
Fifty‐three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous
FCM
or placebo in a multicenter, double‐blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least‐square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65–78) years, with N‐terminal pro‐B‐type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010–2828), 63 ng/mL (22–114), and 15.7% (11.0–19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the
FCM
arm (36.6 [34.6–38.7] versus 40 [38–42.1],
P
=0.025; 1061 [1051–1072] versus 1085 [1074–1095],
P
=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1–38.5] versus 41.1 [38.9–43.4],
P
=0.003), but not for T1 mapping (1075 [1065–1085] versus 1079 [1069–1089],
P
=0.577).
Conclusions
In patients with heart failure and iron deficiency,
FCM
administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion.
Clinical Trial Registration
URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
03398681.
Background: Plasma amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 levels are positively associated with a higher risk of adverse clinical outcomes in acute heart failure. As a proxy of congestion, antigen carbohydrate 125 has also been proposed as a right-sided heart failure marker. Thus, we aimed to determine in this population the main factors – including echocardiographic right-sided heart failure parameters – associated with antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide. Methods and results: We prospectively included 2949 patients admitted with acute heart failure. Amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were used as dependent variables in a multivariable linear regression analysis. The mean age of the sample was 73.9±11.1 years; 48.9% were female, 35.8% showed ischaemic aetiology, and 51.6% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were 4840 (2111–9204) pg/ml and 58 (26–129) U/ml, respectively. In a multivariable setting, and ranked in order of importance (R2), estimated glomerular filtration rate (43.7%), left ventricle ejection fraction (15.1%), age (12.4%) and high-sensitivity troponin T (10.9%) emerged as the most important factors associated with amino-terminal pro-B-type natriuretic peptide. The five main factors associated with antigen carbohydrate 125 were, in order of importance: the presence of pleural effusion (36.8%), tricuspid regurgitation severity (25.1%), age (11.9%), amino-terminal pro-B-type natriuretic peptide (6.5%) and peripheral oedema (4.3%). Conclusion: In patients with acute heart failure the main factors associated with amino-terminal pro-B-type natriuretic peptide were renal dysfunction, left ventricle ejection fraction and age. For antigen carbohydrate 125, clinical parameters of congestion and the severity of tricuspid regurgitation were the most important predictors. These results endorse the value of antigen carbohydrate 125 as a useful marker of right-sided heart failure.
BackgroundCarbohydrate antigen-125 (CA125) is an ovarian cancer marker, but recent work has examined its role in risk stratification in heart failure. A recent meta-analysis examined its prognostic value in heart failure generally. However, there has been no systematic evaluation of its role specifically in acute heart failure (AHF).MethodsPubMed and EMBASE databases were searched until 11 May 2018 for studies that evaluated the prognostic value of CA125 in AHF.ResultsA total of 129 and 179 entries were retrieved from PubMed and EMBASE. Sixteen studies (15 cohort studies, 1 randomised trial) including 8401 subjects with AHF (mean age 71 years old, 52% male, mean follow-up 13 months, range of patients 525.1±598.2) were included. High CA125 levels were associated with a 68% increase in all-cause mortality (8 studies, HRs: 1.68, 95% CI 1.36 to 2.07; p<0.0001; I2: 74%) and 77% increase in heart failure-related readmissions (5 studies, HRs: 1.77, 95% CI 1.22 to 2.59; p<0.01; I2: 73%). CA125 levels were higher in patients with fluid overload symptoms and signs compared with those without them, with a mean difference of 54.8 U/mL (5 studies, SE: 13.2 U/mL; p<0.0001; I2: 78%).ConclusionOur meta-analysis found that high CA125 levels are associated with AHF symptoms, heart failure-related hospital readmissions and all-cause mortality. Therefore, CA125 emerges as a useful risk stratification tool for identifying high-risk patients with more severe fluid overload, as well as for monitoring following an AHF episode.
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