Author + information
- Nicolas Girerd, MD, PhD,
- Faiez Zannad, MD, PhD,
- Patrick Rossignol, MD, PhD∗ (, )
- on behalf of INI-CRCT, Great Network, and the EF-HF Group
- ↵∗Address for correspondence:
Centre d’Investigations Cliniques-INSERM, CHU de Nancy, Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu, 4 rue du Morvan, 54500 Vandoeuvre Lès Nancy, France
We read with great interest the comment of Dr. de la Espriella-Juan and colleagues regarding our recently published state-of-the-art paper focused on the integrative assessment of congestion throughout the patient journey (1).
We completely agree that carbohydrate antigen (CA)-125 appears to be a promising tool for evaluating congestion in patients with heart failure. As emphasized by Dr. de la Espriella-Juan and colleagues, CA-125 production is not influenced by age or renal function, which actually circumvents some of the limitations of natriuretic peptides. The group led by Prof. Nunez and Bayes-Génis (2) provided an important contribution to the published reports showing that CA-125 alone has similar prognostic value to B-type natriuretic peptide (BNP) and improves risk stratification beyond the information provided by BNP following acute heart failure (AHF) (3). This group also recently reported the results of the CHANCE-HF (Carbohydrate Antigen-125-Guided Therapy in Heart Failure) trial that assessed the effects of CA-125–guided therapy (targeting a CA-125 <35 U/ml) in 380 patients with AHF (4). The CA-125 strategy was associated with a significant reduction in the occurrence of death or AHF admission (66 events vs. 84 events; p = 0.02).
Nonetheless, despite the aforementioned very promising evidence, we did not include CA-125 in our state-of-the-art article for the following reason: CA-125, as acknowledged in the CHANCE-HF trial, is both a congestion biomarker and an inflammation biomarker (in addition to being a cancer biomarker). Because inflammation is associated with poorer outcome following AHF (5), it is likely that CA-125 is associated with patient outcome both because of its congestion and inflammation quantification properties. In addition, the CHANCE-HF trial intended to lower CA-125 either by increasing the dose of diuretics, optimizing life-saving drugs (angiotensin converting enzyme inhibitors, beta-blockers, mineralocorticoids receptor antagonists), using intravenous iron, or enhancing the use of statins. Hence, the majority of the therapeutic options used to lower CA-125 were not specifically targeting decongestion. The complex/multiple pathophysiological processes underlying CA-125 production may (thus) limit its applicability in clinical practice, because physicians may not be able to ascertain whether its changes are the consequence of changes in congestion as opposed to changes in low-grade inflammation. By contrast, the short-term changes in estimated plasma volume based on hemoglobin and hematocrit, a biological biomarker that we chose to mention in the state-of-the-heart paper in addition to natriuretic peptides, appears to be more specific to changes in congestion (with the notable exception of patients with active bleeding).
We believe that most of the limitations that prevent us from including CA-125 could be halved if the IMPROVE-HF trial (Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) provides positive results. This trial aims to assess the clinical usefulness of CA-125 for tailoring the intensity of diuretic therapy in patients with cardiorenal syndrome type 1 (6). In contrast with the CHANCE-HF trial, this trial will formally provide evidence of the value of tailoring decongestion therapy on CA-125 (i.e., formally testing the value of the congestive aspect rather than the inflammatory aspect of CA-125). We hope that CA-125, following the results of this trial, will allow promoting the latter from a promising inflammatory/congestion biomarker accessible to a range of therapeutic interventions to an accepted congestion biomarker used to tailor decongestion therapy.
Please note: Dr. Girerd has received board fees from Novartis; and honoraria from Servier. Prof. Rossignol has received personal fees for consulting from Novartis, Relypsa, AstraZeneca, Grünenthal, Stealth, Peptides, Fresenius, Vifor Fresenius Medical Care Renal Pharma, Vifor, and CTMA; has received lecture fees from Bayer and CVRx; and is a cofounder of CardioRenal. Prof. Zannad has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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