Evolution and paradigms in ion channel and cardiac remodeling

Abstract

Objective:

This study aims to conduct a bibliometric analysis of the literature on the role of ion channels in cardiac remodeling.

Methods:

Articles on ion channels and cardiac remodeling from 1979 to 2024 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization utilized CiteSpace, VOSviewer, and the R package “bibliometrix.” The analysis examined publication trends, citation patterns, influential journals, countries, authors, institutions, and keywords.

Results:

This study analyzed 1148 articles (1979–2024) on ion channels and cardiac remodeling, involving 6931 authors from 3709 institutions. Annual publications peaked at 82 in 2019, with the U.S. leading. The most cited paper appeared in Circulation Research (2014). Circulation published the most studies (65), while Cardiovascular Research had the strongest links. Stanley Nattel was the top author, and the University of Montreal/Montreal Heart Institute ranked highest among institutions. Research hotspots included therapeutic strategies, potassium/calcium channel remodeling, and clinical implications. Key keywords were “expression,” “heart failure,” and “mechanisms,” with “dysfunction” exhibiting the strongest citation burst. Emerging focal points include fibrosis, oxidative stress, and microRNAs.

Conclusions:

Future bibliometric trends highlight targeting ion channels as a prominent research direction, warranting further mechanistic and clinical evidence synthesis for precision therapy development.

1. Introduction

Cardiac remodeling refers to a series of molecular, cellular, and interstitial alterations, primarily characterized by hypertrophy of cardiomyocytes, increased collagen deposition, cardiomyocyte reorganization, and fibrosis.^[1] Clinically, these changes manifest as alterations in the size, quality, geometry, and function of the heart following injury, potentially leading to ventricular dysfunction and malignant arrhythmias.^[2] This phenomenon is particularly prevalent among patients with hypertension, myocardial hypertrophy, and myocardial infarction, often resulting in adverse prognoses.^[3] According to projections by the World Health Organization, cardiovascular diseases are anticipated to account for 23.3 million deaths by 2030, rendering them a leading cause of mortality.^[1] Current therapeutic strategies for cardiac remodeling encompass drug therapy, implantable medical devices, lifestyle modification, and surgical intervention. Despite recent advancements in treatment modalities, cardiovascular diseases stemming from cardiac remodeling continue to impose a substantial burden on healthcare systems. Research indicates that biochemical changes, such as oxidative stress,^[4] autophagy,^[5] apoptosis,^[6] and endoplasmic reticulum stress,^[7] play significant roles in the development of cardiac remodeling. Furthermore, abnormal ion channels have been identified as crucial regulators of cardiac electrical activity and key contributors to the progression of cardiac remodeling.^[8,9]

Ion channels are a class of transmembrane proteins that enable ions to pass through the cell membrane.^[10] They are necessary for action potential generation and propagation, as well as for maintaining resting membrane potential.^[11] More recently, roles of ion channels in non-electrical processes such as cell proliferation and death have been recognized as pertinent for cardiac remodeling.^[12,13] Piezo1 can exacerbate cardiac remodeling in myocardial infarction patients via the mediation of neurogenic inflammatory responses.^[14] Almost all canonical transient receptor potential (TRPC) channels exert a significant impact on cardiac disease development via cardiac modeling.^[15] To date, there has been considerable interest in the complex interplay between ion channels and cardiac remodeling. Studies have spanned from the molecular pathways of ion channel dysfunction in heart disease to potential therapeutic targets for limiting or reversing pathologic cardiac remodeling.^[16–18] Although there is a rich literature on this topic, to our knowledge no single study has yet reported the magnitude and influence of research in this domain through comprehensive bibliometric analysis.

Bibliometrics is a significant approach to assess the impact and trends in scientific literature, bringing a quantitative perspective on research evolution,^[19] which can help researchers identify current areas of concern and guide future research trends.^[20] To fill this knowledge gap, this bibliometric analysis aims to yield valuable insights that can inform future advancements in ion channels and cardiac remodeling, attempting to identify research trends and potential hot spots in this field.

2. Materials and methods

2.1. Search strategy

A comprehensive screen was performed using the Web of Science Core Collection (WoSCC) database. A search query was used to identify articles as: (((TS = (Ion Channel)) OR TS = (Membrane Channel)) OR TS = (Ionic Channel)) AND (((((((TS = (Cardiac Remodeling)) OR TS = (Heart Remodeling)) OR TS = (Cardiac Structural Change)) OR TS = (Ventricular Remodeling)) OR TS = (Ventricle Remodeling)) OR TS = (Atrial Remodeling)) OR TS = (Myocardial Remodeling)).^[21,22] The search strategy was directed towards a broad spectrum of studies concerning the interplay between ion channels and cardiac remodeling. The search strategy was designed to capture the overall research landscape of ion channels in cardiac remodeling rather than individual channel families. Therefore, broad ion-channel terms were used instead of exhaustively including specific channel names or subtypes. The search was updated on June 12, 2024, to ensure alignment and prevent critical divergences due to database updates. Publications were required to be in English, and the study considered only articles as document types, collecting all information in text format. Data collected for further bibliometric analysis included the publication and citation counts, countries/regions, institutions, authors, journals, and keywords. Notably, as the analysis used only publicly available literature metrics, with no human/animal involvement or personal data, ethical clearance was unnecessary per governing standards and journal policy.

2.2. Data analysis

Bibliometric analysis and visualization were conducted using 3 powerful and widely adopted software tools: R package “bibliometrix” (4.3.3), VOSviewer 1.6.20, and CiteSpace 6.3. R package “bibliometrix” enabled advanced statistical analysis and the computation of bibliometric indices, such as the h-index, g-index, and m-index, for prominent authors and/or source journals, as applicable.^[23] The h-index is defined as the largest number h such that an author has published h papers, each of which has been cited at least h times, thereby balancing research productivity and citation impact.^[24] To address the limitation that the h-index underutilizes highly cited papers, the g-index was introduced. It is the largest number g for which the top g articles, ranked in decreasing order of citations received, have collectively accumulated at least g²citations, thus assigning greater weight to highly cited works.^[25] Because the h-index scales with career length and thereby disadvantages early-career researchers, the m-index normalizes this effect by dividing the h-index by the number of years since the author’s first publication (m = h/ career length),^[24] enabling equitable comparison across researchers at different career stages. In this study, the h-index was directly retrieved from WoSCC. The g-index and m-index were computed using bibliometrix, with the field parameter set to “author” or “source” as appropriate, applied to the WoSCC-derived bibliographic data frame.

VOSviewer was used to visualize co-authorship networks of countries, institutions, and authors, journal co-citation and bibliographic coupling networks, and keyword co-occurrence networks.^[26] In these network maps, nodes represented the corresponding entities, while thicker connecting lines indicated stronger network relationships.^[27] Total link strength indicates the total strength of the co-authorship links of a given country/institution/author with others.^[28]

CiteSpace examined the burst of research trends regarding ion channels and cardiac remodeling over time.^[29] This analysis spanned from January 1994 to June 2024, utilizing keywords as node types and slicing the data annually. The start year was set to 1994 due to sparse publication and keyword data before 1994, which precluded reliable burst detection. A visual timeline was generated, highlighting the top 5 keywords in each slice through a combined pruning method. The resulting maps exhibited clusters of research topics, where the color gradient indicated the duration of research activity across time.^[30]

To assess journal influence, Journal Citation Reports (JCR) metrics were utilized, including the Impact Factor for 2024 and quartile ranking (Q1–Q4) for 2024. The Impact Factor measures the average number of citations per article published in the journal within a year, while quartile ranking divides journals into 4 impact groups, with Q1 representing the highest tier of journals.

3. Results

3.1. Publication trends and overall characteristics

The screen process was illustrated in Figure 1. Our bibliometric analysis identified a total of 1148 articles on ion channels and cardiac remodeling published between 1979 and 2024. These publications involved 6931 authors from 3709 institutions, appearing in 315 journals and citing 37,822 references. The annual publication output showed a general increasing trend over the 45-year period (Fig. 2). The heightened publication trend dates back to the mid-1990s, when publications rose from only 1 in 1994 to an impressive number of 19 by early 1999, marking the beginning of sustained interest in this research area. During the 2000s, their numbers grew steadily, reaching around 30–40 titles a year at the end of the decade. In 2019, the most articles were published (82 articles).

Figure 1.

Literature search and screening flowchart.

Figure 2.

Analysis of Annual Research Output.

3.2. Analysis of national publication counts

The United States (355) had the most publications, accounting for 30.9% of the included publications, followed by China (178) and Germany (113), suggesting the leading role of the United States in ion channel and cardiac remodeling. Moreover, the United States has the most multiple-country publications, indicating a substantial amount of international cooperation. China, Germany, and Canada also show high levels of international collaboration. Based on multiple country publication (MCP) ratios, Belgium and Denmark had the highest MCP ratio at 0.667 (Fig. 3A and Table S1, Supplemental Digital Content 1). In addition, a collaborative network was constructed containing the 57 countries undergoing international collaboration (Fig. 3B). These countries were mainly divided into 8 clusters represented by different colors. The green cluster, including China, the United States, and Japan, was the biggest. The United States had the highest total link strength (293), followed by Germany (161) and the United Kingdom (161).

Figure 3.

Analysis of Countries. (A) Distribution of publications by country, including single-country publications and multiple-country publications. (B) Country co-authorship network.

3.3. Analysis of journal’s publication quantity and impact

The 1148 articles were published in 315 journals. The top 20 journals, accounting for 562 publications (48.95%) of the total publication volume, were ranked by h-index (Table S2, Supplemental Digital Content 2). Such lines of research were predominantly published in a core group of journals, providing important dissemination platforms. The single journal with the largest number of studies published (n = 65; 5.7%; IF = 37.8, 2024) was Circulation, followed by Cardiovascular Research (n = 60; 5.2%; IF = 10.8, 2024), and Journal of Molecular and Cellular Cardiology (n = 57; 5.0%; IF = 20.1, 2024).

Journal co-citation analysis, reflecting how often the publications from 2 different journals are associated in the bibliographies of scholarly articles,^[31] showed that the 3 key journals with the highest total link strength were Circulation (440), Cardiovascular Research (362), and Circulation Research (268) (Fig. 4A). Besides, bibliographic coupling analysis was performed, capturing the degree to which the research published in 2 different journals relies on the same body of prior work,^[32] and the 3 key journals with the highest total link strength were Cardiovascular Research (10,635), Circulation (10,386), and Journal of Molecular and Cellular Cardiology (7662) (Fig. 4B). These journals were mainly divided into 2 clusters represented by different colors. The red cluster contained journals on biological chemistry, such as Journal of Molecular and Cellular Cardiology, Frontiers in Physiology, and Biophysical Journal. The green cluster included Circulation and Cardiovascular Research, highlighting cardiovascular diseases.

Figure 4.

Visualization analysis of influential journals. (A) Journal co-citation network. (B) Journal bibliographic coupling network. Journals with at least 6 links were included for network visualization.

3.4. Analysis of authors

A total of 6931 authors were involved in the domain of ion channels in cardiac remodeling. We ranked authors based on the h-index to identify high-impact researchers. According to the data in Table S3, Supplemental Digital Content 3, the leading author was Stanley Nattel (h-index = 23, 24 articles), followed by Dobromir Dobrev (h-index = 18, 22 articles). The numbers reflect their research output as well as their sustained participation in the field over time. We generated a collaborative network based on authors with more than or equal to 7 articles (Fig. 5A). Dobromir Dobrev stood out with the highest total link strength (13,284), followed by Stanley Nattel (11,804)), and Niels Voigt (6957).

Figure 5.

Analysis of authors and institutions. (A) Co-authorship network of active authors. (B) Top 10 institutions by article count and rank. (C) Institutional co-authorship network.

3.5. Analysis of institution publications

139 publications originated from the University de Montreal as a major contributor, followed by 129 publications attributed to the University System of Ohio and 87 publications attributed to the University of California System (Fig. 5B). Besides, 193 institutions with 4 or more publications were identified, and a visualized network concerning the cooperation was made. The results find strong links between the University of Montreal and the Montreal Heart Institute (link strength: 142), reflecting geographical proximity and established research partnerships. Other strong collaborations were observed between the Montreal Heart Institute and McGill University (link strength: 129), and between the University of Manchester and the University of Duisburg-Essen (link strength: 75), indicating the presence of productive research networks both within and across national boundaries (Fig. 5C).

3.6. Citation analysis

This analysis identified multiple important papers in the field, illustrating the historic importance of studies implicating ion channels with cardiac remodeling. The top 50 cited references in the field of ion channels and cardiac remodeling were listed in Table S4, Supplemental Digital Content 4. Among them, the top 3 articles based on citations were “The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms” by Andrade et al in Circulation Research,^[33] “Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation,” by Yue et al in Circulation Research^[34] and “Atrial fibrillation: Arrhythmia pathophysiology and implications for management” by Iwasaki et al in Circulation,^[35] covering the full spectrum from what we know with respect to basic science and clinical applications, highlighting some of the benefits that exist for development in this field.

3.7. Keyword analysis

In total, 189 keywords with a minimum of 10 occurrences were identified for co-occurrence network analysis in Figure 6A, where node size represented keyword frequency and colors corresponded to thematic clusters. The most frequently occurring terms were “expression” (214 occurrences), “heart failure” (165 occurrences), and “mechanisms” (146 occurrences). These keywords can be grouped into 5 categories. The red cluster centered around the therapeutic strategy for cardiac remodeling via ion channels, including “protects,” “inhibition,” and “overexperssion.” The green cluster emphasized the role of K⁺ in cardiac remodeling, with terms like “K⁺ current,” “K⁺ channel,” and “Potassium channel.” The blue highlighted the role of Ca2⁺ in cardiac remodeling via regulation of gene expression, featuring keywords such as “Calcium,” “expression,” and “gene.” The yellow focused on the animal model with keywords, such as “dog,” “model” and “canine.” The purple emphasized the clinical characterizations and implications in cardiac remodeling via alternations of ion channels, with keywords like “hypertrophy,” “arrhythmias,” and “atrial-fibrillation.”

Figure 6.

Analysis of Keywords. (A) Keyword co-occurrence network. (B) Time-overlay visualization map of co-occurrence keywords. (C) Top 20 keywords with the strongest citation bursts.

The time-overlay visualization map was established in Figure 6B. Around 2008 (purple), keywords such as “outward current,” “cardiac arrhythmia,” “refractoriness,” and “contractile dysfunction” emerged, but they did not exhibit high co-occurrence intensity. Around 2012 (green), the keyword with the high co-occurrence intensity was “heart failure” (strength = 772), accompanied by “expression” (strength = 926) and “mechanism” (strength = 671) during the same period. Around 2016 (yellow), notable keywords included “fibrosis,” “protects,” and “reduced synchrony.”

3.8. Analysis of burst keywords

As shown in Figure 6C, the top 20 keywords with the strongest citation bursts were listed, reflecting the evolution of research focus over time. “Dysfunction” showed the strongest citation burst, indicating a shift in focus from normal physiology to pathological changes in ion channel function and cardiac remodeling. “Fibrosis” emerged as a significant burst term from 2015 onwards, reflecting growing recognition of the importance of structural remodeling in arrhythmogenesis and heart failure progression. “Oxidative stress” showed a strong burst starting in 2018, highlighting a recent emphasis on understanding the role of cellular stress responses in cardiac pathology. The burst in “microRNA” research from 2016 indicates growing interest in epigenetic regulation of ion channels and its role in cardiac remodeling.

4. Discussion

4.1. General information

The bibliometric screen identified 1148 articles over 45 years, with publication trends evolving through 3 phases: initiation (1979–1994) with sparse output and nascent understanding; rapid growth (1995–2014) marked by accelerating interest; and maturation (2015–2024) showing sustained expansion. The peak in 2019 (82 articles) coincided with mechanistic breakthroughs such as Piezo1’s role in remodeling,^[36] reflecting a transition from foundational ion-channel physiology toward molecular pathology. The concentration of publications in basic-science journals (e.g., Circulation, Cardiovascular Research) indicates that current inquiry remains predominantly mechanistic, though citation classics (Andrade et al,^[33] Yue et al,^[34] Iwasaki et al^[35]) bridge electrophysiology with clinical atrial fibrillation management. Geographically, leadership by the United States, China, and Germany, coupled with high MCP ratios in smaller nations (Belgium, Denmark), shows that international collaboration amplifies impact. However, the low overall co-authorship rate (~1/5) in major producers suggests untapped potential. Institutional and author centrality (e.g., Nattel, Dobrev) aligns with established North American and European electrophysiology hubs, reinforcing how historic basic-science funding models continue to shape the field’s intellectual structure.^[37,38]

4.2. Keyword analysis and research trends

From the keyword analysis and thematic evolution map, we identified the research hotspots. These clusters included therapeutic strategy, potassium ion, calcium transport, animal models, and clinical characterization and implications.

4.3. Red cluster: Therapeutic strategy

Ion channels are widely distributed in the human body and represent attractive targets for drug development. In the treatment of cardiovascular diseases, ion channel inhibitor drugs are used to block specific channels and transport proteins to redistribute ions and restore the normal function of the heart.^[39] K201 can inhibit the Na⁺ current in a voltage- and frequency-dependent manner, as well as Ca2⁺ current and inward-rectifier K⁺ current,^[40] exhibiting protective effects against myocardial ischemia and catecholamine-induced myocardial injury.^[41] Ca²⁺ channel blockers bind to voltage-dependent Ca²⁺ channels in the cell membrane, inhibiting the influx of Ca²⁺ ions into the cell. Increasingly, both basic and clinical trials have confirmed the efficacy of these drugs when used alone or in combination with other medications, for example, the combination therapy of benazepril (Cibacen) and amlodipine. However, further research is still needed in this field.^[42]

4.4. Green cluster: Potassium channel remodeling

K⁺ channels represent the most functionally diverse cardiac ion channel type. Cardiac K⁺ channels vary in their permeability properties, membrane potential dependence, and their opening or closing activation and inactivation kinetics.^[43] Marked changes in the densities and/or properties of myocardial K⁺ currents, typically referred to as K + channel remodeling, are observed in association with both cardiac and systemic diseases, including cardiac hypertrophy, heart failure, atrial fibrillation, diabetes, and in the ischemic myocardium.^[44] Electrical remodeling in the failing heart reflects, at least in part, reductions in the densities of repolarizing K⁺ currents, including I_to,f,^[45] I_Kr, and I_Ks,^[46] resulting in action potential prolongation, early after depolarizations, and increased dispersion, all of which are arrhythmogenic. Besides, experimental cardiac hypertrophy supported that action potential duration (APD) prolongation upon hypertrophy is attributable to alterations in K⁺ channels, such as increased K⁺ current, decreased delayed rectifier K⁺ current.^[47]

4.5. Blue cluster: Calcium transport

Calcium transport through the sarcoplasmic reticulum is one of the underlying causes of cardiac remodeling.^[48] Membrane and intracellular systems (L-type calcium channels, ryanodine receptor, calsequestrin) regulate the supply of calcium to contractile proteins during contraction. Also, stimulation of calmodulin kinase and phosphorylation of phospholamban activates enzymes (SERCA-2a) that mediate calcium uptake by the sarcoplasmic reticulum and enhances cardiac relaxation.^[49] Evidence suggests that alterations in the calcium transport system occur in ventricular remodeling and dysfunction, including decreased L-type calcium channels, ryanodine receptors, calsequestrin, and calmodulin kinase activity. Hence, cardiac remodeling leads to reduced calcium release during systole and increased release during diastole. Therefore, alterations in proteins involved in calcium transportation may contribute to cardiac dysfunction in remodeled hearts.^[50,51] Recent clinical studies link calcium-handling abnormalities to adverse clinical outcomes: RyR1 glycation in circulating lymphocytes was associated with CRT response in heart failure,^[52] while altered calcium handling precedes arrhythmia recurrence after thoracoscopic ablation for persistent atrial fibrillation.^[53]

4.6. Yellow cluster: Animal model

Preclinical large animal models of cardiac remodeling are crucial to both understanding pathological remodeling and translating fundamental discoveries into novel therapeutics. The canine is the most frequently used large animal species for cardiac remodeling studies because of comparable cardiac anatomy to humans.^[54] Previous studies have shown that alterations in the density of Ca²⁺ current, Na⁺ current, and K⁺ current are important in a dog model of sustained AF that shows many electrophysiological features similar to those described in patients with AF, providing a potential molecular mechanism for the electrical remodeling and the persistence of AF.^[55] Moreover, Wang et al. used dogs with sustained AF and demonstrated that Irbesartan, an angiotensin II receptor blocker, significantly increased Na⁺ current densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF.^[56]

4.7. Purple cluster: Clinical characterization and implications

Clinical characterization of cardiac remodeling mainly points out morphological changes, such as mass (hypertrophy and atrophy), geometry (heart wall thickness and shape), and fibrosis.^[2] It is well established that cardiac remodeling is associated with malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation, contributing to poor prognosis.^[2] The key mechanism involves ion channel changes, including inactivation of sodium channels, changes in calcium and potassium channels, and alterations in the sodium/calcium exchanger function.^[57,58] Thus, these results support the clinical relevance of ion-channel modulation in cardiac remodeling. Extending this notion, recent evidence identifies RyR1 glycation in CRT recipients and altered SERCA-related calcium handling in persistent AF patients undergoing thoracoscopic ablation with clinical outcomes,^[52,53] further emphasizing the clinical relevance of ionic remodeling in cardiac remodeling.

The temporal overlay of keyword co-occurrence delineates a clear migration of the field’s intellectual center. In the late 2000s, the dominant purple cluster formed the research epicenter, reflecting an early focus on clinical electrophysiological manifestations and ionic alterations in atrial fibrillation and hypertrophy. By ∼ 2012, the green (potassium) and blue (calcium) clusters rose to prominence, marking a transitional phase in which molecular interrogation of K⁺ and Ca²⁺ pathways superseded purely phenotypic description. From ∼ 2016 onward, the yellow (animal model) and red (therapeutic strategy) clusters gained centrality, signaling a migration toward preclinical structural remodeling in large-animal models and interventional ion-channel modulation. Thus, the field evolved from a purple-cluster-centered clinical-electrophysiological axis toward an integrative paradigm combining green/blue molecular decoding with yellow preclinical validation and red strategic targeting.

Keyword burst detection delineates emerging thematic shifts. Between 2010 and 2020, the advent of the term “fibrosis” in 2015 is largely explained by an enhanced understanding that structural remodeling due to cardiac fibroblast (CFs) activity plays a major role driving arrhythmogenesis and progression of heart failure.^[59] During injury, functional CFs differentiate into myofibroblasts (myoFbs) that are typical cells secreting contractile proteins. In response to disease stimuli, myoFbs exhibit proliferative and invasive properties and initiate the reparative wound healing response. MyoFbs also remodel the interstitium by secreting ECM-degrading metalloproteinases (MMPs) and increasing collagen turnover. However, myoFbs show a persistent proliferation feature, which augments pro-inflammatory responses and causes collagen net formation.^[60] Moreover, prescribed therapeutic agents for cardiovascular disease (CVD) treatment, such as Angiotensin II (Ang II) inhibitors, have alleviated fibrosis by inhibiting the activation and proliferation of myoFb.^[60]

The prominent burst of “oxidative stress” starting in 2018 reflects its recognition as an aetiologic agent within prevailing cellular pathology.^[61] Reactive oxygen species (ROS) can inhibit contractile activity via modification of proteins central to excitation-contraction coupling. Meanwhile, ROS can also activate several signaling pathways involved in hypertrophy and enhance the proliferation of cardiac fibroblasts and activation of matrix metalloproteinases, causing the remodeling of the extracellular matrix. These cascades are important for the progression of pathological cardiac remodeling.^[62] Besides, it is crucial for inducing fibrosis that oxidative stress and transforming growth factor (TGF)-β interact. A positive feedback loop is created when TGF-β increases the creation of ROS, which causes oxidative stress, and when oxidative stress activates latent TGF-β, increasing myofibroblast differentiation and fibrogenesis.^[63]

The concomitant rise in “microRNA” (miRNA) research suggests increased epigenetic regulation of ion channels and its implication in cardiac remodeling.^[64] The role of miRNAs in the modulation of cardiac fibrosis following myocardial infarction has been assessed by independent groups. For instance, miR-144–3p enhances proliferation, migration aptitude, and collagen synthesis of cardiac fibroblasts by interfering with the expression of phosphatase and tensin homolog (PTEN), implying that the miR-144–3p/PTEN axis can be a candidate for therapeutic strategies for cardiac fibrosis following myocardial infarction.^[65] miR-200b is another miRNA that affects cardiac remodeling following abdominal aortic coarctation. DNA methyltransferase 3A (DNMT3A)-mediated control of miR-200b expression affects autophagy of cardiac fibroblasts during cardiac remodeling.^[66] Meanwhile, it is reported that cardiomyocyte-derived miR-328 can mediate cardiac fibrogenesis through a paracrine manner.^[67]

4.8. Implications for future research

The evolving research landscape emphasizes the need for collaborative, multidisciplinary efforts that integrate expertise from electrophysiology and molecular biology with clinical cardiology. Future initiatives should incorporate cutting-edge technologies such as single-cell sequencing, advanced imaging, and computational modeling^[68] to bridge mechanistic insight with clinically relevant translation. In a clinical setting, such understanding will ultimately lead to new opportunities for diagnosis and targeted therapies in cardiology.^[69,70]

4.9. Strengths and limitations

The strengths of this study are evident in several key areas. It is comprehensive in 2 respects: historically, as it spans 45 years, and thematically, as it focuses on the overall development of the field. Additionally, the study introduces multiple analyses of publication and citation counts, collaborations, and the extraction of research themes, providing a thorough overview of the research environment. Furthermore, the use of advanced bibliometric tools like VOSviewer and CiteSpace facilitates sophisticated network analyses and visualizations of research trends. However, the study also has significant limitations. The reliance on the Web of Science database, known for its high-quality data, may have caused the exclusion of some publications that were not indexed there. Additionally, the study only included English-language publications, which could have contributed to selection bias against research from non-English-speaking countries. Another drawback is the issue of citation delay; more recent publications are less likely to be represented in citation-based analyses due to the time it takes for newly published articles to gain citations. Finally, the search relied on generic terms (“ion channel,” “membrane channel,” “ionic channel”) and may have missed subtype-specific literature, leaving potential retrieval bias as a limitation. Future bibliometric studies focusing on specific ion channels or channel families should adopt more targeted and comprehensive search strategies incorporating relevant subtype-specific terms.

5. Conclusions

In conclusion, this bibliometric analysis provides a comprehensive overview of research trends related to ion channels and cardiac remodeling over the past 45 years. This area of study is gaining recognition among researchers worldwide with a gradual increase in publication counts. Research emphasis has been predominantly focused on Ca²⁺ and K⁺ related pathways, which emerged as the most salient thematic clusters. Importantly, the literature trajectory identifies targeting ion channels as a recurrent proposed direction for future investigation, underscoring the need for dedicated evidence synthesis to evaluate its therapeutic potential for cardiac remodeling.

Author contributions

Conceptualization: Xue Deng, Ziran Jia.

Methodology: Xue Deng, Pujue Huang.

Software: Xue Deng, Ziran Jia, Jiao Tang.

Writing – original draft: Xue Deng, Ziran Jia, Ting Luo, Zhen Se, Pujue Huang, Jiao Tang, Yang Zhai, Tao Wang.

Writing – review & editing: Xue Deng, Ziran Jia, Ting Luo, Zhen Se, Pujue Huang, Jiao Tang, Yang Zhai, Tao Wang.

Data curation: Ting Luo, Zhen Se, Yang Zhai.

Formal analysis: Ting Luo, Zhen Se.

Validation: Pujue Huang, Jiao Tang.

Visualization: Yang Zhai.

Funding acquisition: Tao Wang.

Investigation: Tao Wang.

Project administration: Tao Wang.

Supervision: Tao Wang.