Heart failure with improved ejection fraction in pediatric cardiomyopathy

We are writing to comment on the article titled “Analysis of Clinical Features of heart failure in Children with Cardiomyopathy and improved ejection fraction” written by Yang et al.’s (1). We praise the authors for their inestimable contribution to this field. Cardiomyopathies occur rarely in young patients, with an annual rate of 1.1 to 1.2 per 100,000 children. Dilated cardiomyopathy (DCM) which is characterized by the reduction in systolic function and dilation of the ventricles is the most prevalent cardiomyopathy amongst the pediatrics (2). This paper, which focuses on heart failure with recovered ejection fraction (HFrecEF), in pediatric cardiomyopathy, offers a crucial perspective on the understanding of heart failure (HF). Although this study provides a substantial contribution, some aspects call for it to be further explored.

In the article the authors have mentioned in the inclusion criteria that they selected those patients who satisfied the diagnostic criteria for cardiomyopathy; however, they have not specified which form of cardiomyopathy was the pivot of the study because children who had a diagnosis of arrhythmogenic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy were excluded by them. As there are several types of cardiomyopathies, the type of patients that were included should be emphasized for better outcomes (2).

The authors have discussed B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) in this study, but high-sensitivity troponin-T (hs-TnT), which is a very crucial biomarker, for analyzing left ventricular function (LVF) is not part of the discussion. Cardiac troponins, especially hs-TnT, are very important for understanding myocardial injury and have shown immense prognostic value in both acute and chronic HF settings (3). In one adult HF patient with persistent heart failure with reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) does not improve, and serum troponin levels grow over time, but in other individuals with HFrecEF, LVEF improves late and troponin levels remain constant (4). Incorporating these biomarkers into detail can enhance the clinical relevance of these findings and offer additional guidance for clinicians who deal with pediatric HF. This is because individuals with HFrecEF have a better prognosis than those with HFrEF and heart failure with preserved ejection fraction (HFpEF) (5). This will contribute to the understanding of late left ventricular remodeling mechanisms (4).

In this article, a comparison of both the groups showed that the HFrecEF group had a lower suppression of tumorigenicity 2 (ST2) expression; smaller left atrial diameter; lower platelet-to-lymphocyte (PLT:LYM) ratios; and lower creatinine levels compared to the HFrEF group; it doesn’t discuss other variables influencing the severity of “heart failure” in patients with “reduced ejection fraction”. The recent article explains the impact of gut microbes on the severity of HF. Alteration in the composition of gut microbe might influence the development of HF signifying a possible role of gut health in diagnosing and managing HF. “Microbial culture” methods have detected high levels of pathogenic bacteria such as (Campylobacter salmonella, Shigella, species of Yersinia, and species of yeasts such as Candida) in patients with chronic HF with reduced ejection fraction. These elevated levels tend to increase the severity of cardiac failure (6).

Logistic evaluations show several factors predicting betterment in HF patients, including 95% confidence interval, viral infection, treatment with intravenous immunoglobulin (IVIG), and low ST2 expression showed significantly increased chances of LVEF recovery. The results provide valuable insights into the forecasters of LVEF recovery in children with cardiac failure. The authors highly appreciate the efforts of the author for emphasizing these factors however; the study neglects other factors influencing “LVEF recovery” which include lower functional class, treatment with renin-angiotensin-aldosterone system inhibitors and beta-blockers, absence of defibrillator use, and non-ischemic etiology (7).

Moreover, the results show notable improvement in children who were given IVIGs as a treatment for bacterial or viral infection. Following the onset of myocarditis or atrial fibrillation (AF), neutrophils infiltrate the injured tissue, increasing the inflammatory response. Neutrophil extracellular traps (NETs) play an important role in the development of cardiovascular diseases. Elevated NET markers, such as citrullinated histone 3 and myeloperoxidase (MPO)-DNA complexes, have been linked to defective heart function. NETs formation (NETosis) leads to atherosclerosis, promoting thrombosis in complex plaques with “intraplaque hemorrhages”. NETosis, NETs along with prothrombotic markers, can predict adverse clinical events in AF which is not discussed in the article (8). Because two patients died and four received heart transplants during the study, these factors may be a potential cause of fatality in patients belonging to the HFrEF group.

Also, the study employs a binary classification of splitting patients into two groups namely HFrEF and HFrecEF based simply on the changes in LVEF. This likely oversimplifies a much more complex recovery mechanism of the heart. To take into account the heterogeneity in recovery trajectories for different patients, they should be divided into more nuanced categories namely HF improved ejection fraction, HFpEF, Borderline HFpEF, HFrecEF, and HF mid-range EF (9). This will provide a better classification of patients whose LVEFs resided between 40% and 50% following 1 year of treatment.

The efforts that the authors have put into this study are highly commendable and worthwhile but considering the above-mentioned factors would make the study more impactful.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-413/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

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