Trends in Research on Hypertrophic Cardiomyopathy and Mitochondria From 2003 to 2023: A Bibliometric Analysis

ABSTRACT

Background

Mitochondria have emerged as a significant and promising area of research in hypertrophic cardiomyopathy (HCM). However, there is a notable scarcity of bibliometric studies in this field. Our aim is to conduct a bibliometric analysis of mitochondrial research in HCM, delineating research hotspots and trends to aid in understanding the focal points and evolving trajectories of both basic and clinical research.

Methods

Articles and reviews related to mitochondrial research in hypertrophic cardiomyopathy (HCM) from 2003 to 2023 were filtered from the Web of Science database. CiteSpace software was utilized to generate knowledge maps including keyword analysis, authorship networks, countries of origin, and journal distributions.

Results

A total of 285 relevant articles on HCM and mitochondria were included, with publication output steadily increasing over the years. These publications originated from 47 countries and regions, with the United States and China contributing the most publications. Primary research institutions included UDICE‐French Research Universities, Centro de Investigacion Biomedica en Red, and Institut National de la Sante et de la Recherche Medicale (Inserm). J BIOL CHEM and P NATL ACAD SCI USA emerged as prominent journals with substantial research output and authority. We identified 520 authors, with Rachid Boutoual and Scot C Leary having the highest publication outputs, while BJ Maron and D Ghezzi were cited most frequently. Through hotspot analysis, we identified frequently occurring keywords such as Hypertrophic cardiomyopathy, Oxidative stress, Heart failure, Lactic acidosis, Mutations, Disease, Dilated cardiomyopathy, Cardiomyopathy, Deficiency, and Cardiac hypertrophy. Mitochondrial diseases associated with HCM, including Leigh syndrome, Barth syndrome (BTHS), heart failure, arrhythmias, and cardiovascular diseases, represent current and evolving research areas.

Conclusion

Through bibliometric methods, we have elucidated the research hotspots and trends concerning hypertrophic cardiomyopathy (HCM) and mitochondria. The investigation of mitochondria, particularly in the context of cardiovascular medicine and HCM, demonstrates an unstoppable momentum. Research on mitochondria in HCM predominantly focuses on mechanisms, cardiovascular diseases, and therapeutic approaches, which will serve as pivotal areas for future exploration.

1. Introduction

The mitochondrion is a cellular organelle found in most eukaryotic cells, enclosed by two membranes. It serves as the structure responsible for energy production within the cell and is the primary site for aerobic respiration, often referred to as the “powerhouse.” Mitochondrial DNA plays a crucial role in the oxidative process of energy production, and thus, defects in mitochondrial DNA can impact nearly all organ systems [1]. All nucleated human cells contain mitochondria, each fulfilling various essential functions, including energy production, involvement in processes such as cell differentiation, cell signaling, and apoptosis, and possessing the ability to regulate cell growth and the cell cycle. Mitochondrial diseases result from mutations in genes encoding nuclear or mitochondrial DNA involved in oxidative phosphorylation (OXPHOS), leading to mitochondrial dysfunction [2]. Genetic or acquired alterations in mtDNA or nuclear DNA mitochondrial genes result in insufficient energy production, failing to meet the demands of various organs, particularly those with high energy requirements such as the heart, central nervous system, kidneys, and liver [3]. Due to the high‐energy demands of cardiac muscle, mitochondrial diseases can affect the heart, and cardiomyopathy is one of the most common cardiac manifestations of these diseases. The mitochondrial calcium transport channel plays a crucial role in regulating mitochondrial calcium homeostasis, which is essential for modulating energy supply, signal transduction, and apoptosis in cardiac muscle cells. These processes have a direct impact on cardiac electrical activity and contractile function. Mutational analysis of mitochondrial DNA revealed the presence of cardiomyopathy, as well as two novel heterozygous mutations: occurring at a highly conserved amino acid in the ND1 gene and at residue A54 located in the tRNA (Ile) gene These two variants may act synergistically to produce a cumulative negative effect on cardiac function, resulting in cardiomyopathy [4]. Because of the important role of mitochondria in myocardial energy metabolism, it has recently been proposed that variants in the mitochondrial DNA (mtDNA) genome may be a risk factor for the Noonan phenotype and hypertrophic cardiomyopathy (HCM), a common clinical feature of the Ras/MAPK pathway syndrome [5].

Hypertrophic cardiomyopathy (HCM) is a highly prevalent genetic heart condition characterized by impaired left ventricular (LV) diastolic function and asymmetric thickening of the left ventricle, often resulting in left ventricular outflow tract (LVOT) obstruction. It may be driven by mitochondrial dysfunction [6]. Recent studies have suggested that mutations in cardiac contractile proteins lead to HCM. Given that mitochondrial dysfunction has been described in cardiac diseases, we tested the hypothesis that mitochondrial dysfunction contributes to different phenotypes of HCM [7]. In addition to the G11778A mutation in the ND4 gene of mitochondrial DNA (mtDNA), which is one of the most common mutations in LHON patients, recent evidence suggests that the G12192A mutation in the IRNA (His) gene is a risk factor for cardiomyopathy. Furthermore, research indicates that the 5‐HT2B receptor in the heart is the first genetic evidence associated with compensatory hypertrophic cardiomyopathy and mitochondrial proliferation. Serotonin (5‐hydroxytryptamine; 5‐HT) plays a significant role in the occurrence of myocardial hypertrophy by activating 5‐HT receptors [8]. The ultrastructure of myocardial cells includes mitochondria, glycogen granules, degradation remnants, and myelin structures. Dysregulation of the autophagic mechanism in myocardial cells leads to cell death, loss, and heart failure [9].

Bibliometric analysis focuses on the systematic and characteristic examination of literature. It involves both qualitative and quantitative analysis of scientific literature and is widely used to understand knowledge structures and uncover hot topics and development trends [10, 11]. Bibliometric analysis methods allow for quantitative measurement of the profile distribution, relationships, and clustering within a research field. In addition to describing and predicting the future development of a specific research area, they enable comparison of contributions from different authors, institutions, countries, and journals. This analytical approach plays a crucial role in guideline development, understanding research hotspots, and assessing research trends [12]. Digestive disorders [13], tumors [14], rheumatic diseases [15], and neurological diseases [16] have been studied using this method.

However, there is scarce bibliometric analysis concerning mitochondrial aspects in hypertrophic cardiomyopathy. Therefore, this study employs bibliometric methods and utilizes CiteSpace software to summarize and consolidate the current status of mitochondrial research in the field of hypertrophic cardiomyopathy, depicting relevant scientific knowledge maps for analysis. The aim is to construct and identify the overall structure, research hotspots, and trends of mitochondrial involvement in hypertrophic cardiomyopathy, assisting and guiding future research directions.

2. Materials and Methods

2.1. Data Collection

A comprehensive literature search was conducted using the Science Citation Index Expanded and Social Sciences Citation Index of the Web of Science Core Collection to identify relevant studies pertaining to hypertrophic cardiomyopathy and its association with mitochondrial function. Search Techniques: The search utilized a combination of specific search terms and Boolean operators to maximize the retrieval of pertinent articles. The primary search terms were defined as follows: Hypertrophic Cardiomyopathy Terms: TS = (Cardiomyopathy, Hypertrophic) OR TS = (Cardiomyopathies, Hypertrophic) OR TS = (Hypertrophic Cardiomyopathies) OR TS = (Hypertrophic Cardiomyopathy) OR TS = (Cardiomyopathy, Hypertrophic Obstructive) OR TS = (Cardiomyopathies, Hypertrophic Obstructive) OR TS = (Hypertrophic Obstructive Cardiomyopathies) OR TS = (Hypertrophic Obstructive Cardiomyopathy) OR TS = (Obstructive Cardiomyopathies, Hypertrophic) OR TS = (ObstructiveCardiomyopathy, Hypertrophic). Mitochondrial Terms: TS = (Mitochondria) OR TS = (Mitochondrion) OR TS = (Mitochondrial Contraction) OR TS = (Contraction, Mitochondrial) OR TS = (Contractions, Mitochondrial) OR TS = (Mitochondrial Contractions). These terms were selected based on their relevance to both hypertrophic cardiomyopathy and mitochondrial biology, ensuring a comprehensive capture of literature at the intersection of these fields. Inclusion/Exclusion Criteria: Articles were included in the analysis based on the following criteria:Inclusion Criteria:Peer‐reviewed articles published between 2003 and 2023 that specifically discussed hypertrophic cardiomyopathy and mitochondrial function. Studies that provided empirical data, reviews, or meta‐analyses focusing on the pathophysiology, treatment, or genetic aspects of hypertrophic cardiomyopathy in relation to mitochondria. Exclusion Criteria: Articles not published in English. Studies that did not provide original research or significant insights into the mechanisms linking hypertrophic cardiomyopathy and mitochondrial activity. Publications primarily addressing unrelated cardiac conditions or those lacking sufficient focus on the specified topics. The application of these criteria resulted in a total of 308 publications. Data Processing Procedures: All retrieved data were exported as a text file and saved as “download_txt.” To ensure data integrity and consistency, the article retrieval and extraction processes were completed on October 16, 2023. Each publication was screened based on the inclusion/exclusion criteria, and relevant data were extracted systematically. The data extraction process involved coding the information according to predefined categories, including study type, sample size, key findings, and relevance to hypertrophic cardiomyopathy and mitochondrial function. This structured approach facilitated an organized synthesis of the literature, enabling a comprehensive analysis of current research trends and gaps. The specific research process is illustrated in Figure 1.

Figure 1.

Flowchart of terature selection.

2.2. Data Analysis

CiteSpace software is a citation visualization and analysis tool developed by Professor Chaomei Chen at Drexel University. This Java‐programmed tool employs data visualization techniques and scientometric methods to extract valuable information, including keyword co‐occurrence, keyword clustering, co‐citation of journals, co‐citation of documents, and co‐citation of authors. Through these data, CiteSpace generates maps that unveil the distribution, patterns, and structure of scientific knowledge. Additionally, the software provides timeline views that aid in comprehending the current status of research in a specific field and predicting research hotspots and trends [17].

3. Results

3.1. Trends in Publication Distribution

We excluded documents deemed invalid, such as meeting abstracts (7), editorial materials (5), proceeding papers (4), news items (3), and letters (4). A total of 285 publications (229 articles and 56 reviews) met the selection criteria. The quantity of papers published over time reflects the developmental trends in this research field, as illustrated in Figure 2. From 2003 to 2030, there is an overall upward trend in the number of publications related to mitochondrial research in HCM. During the period from 2003 to 2010, the number of articles published was relatively low, indicating that mitochondrial research in HCM was in its nascent stage. From 2011 to 2015, there is a noticeable overall increasing trend in the annual growth rate of paper publications. From 2017 to 2022, there is a significant increase in the number of papers related to cardiovascular medicine and extracellular vesicles, with a total output of 24 papers in 2022. This trend suggests that mitochondrial research in HCM has garnered increasing attention from researchers.

Figure 2.

Publication trends of mitochondrial research in HCM nearly 21 years.

3.2. Analysis of Countries and Institutions

A total of 285 articles were published by 336 institutions from 47 countries/regions. The highest number of publications originated from the United States (93, 30.19%) and China (42, 13.63%), followed by Germany and Italy, both with 29 publications (9.41%), the United Kingdom (26, 8.44%), and Canada (25, 8.11%), as shown in Table 1. Notably, the combined total of articles from the United States and China accounts for nearly half of the overall total. While several countries and institutions, such as Italy (0.36), Germany (0.23), France (0.15), the Spanish Biomedical Research Center for Red Biomedicine (0.15), and the Helmholtz Association (0.14), exhibit higher centrality, the causes of regional inequalities in research outcomes remain underexplored. Understanding these disparities may shed light on the dynamics of global research and identify areas for future international cooperation.

Table 1.

Distribution of publications from different countries and institutions.

No.	Country	Year	Centrality	Count (%)	Institution	Centrality	Count (%)
1	USA	2003	0.14	93 (32.63%)	UDICE‐French Research Universities	0.01	13 (4.56%)
2	Peoples R China	2010	0.00	42 (14.73%)	Centro de Investigacion Biomedica en Red	0.15	13 (4.56%)
3	Germany	2003	0.23	29 (10.17%)	Institut National de la Sante et de la Recherche Medicale (Inserm)	0.07	11 (3.85%)
4	Italy	2005	0.36	29 (10.17%)	CIBERER	0.01	10 (3.50%)
5	Japan	2003	0.04	26 (9.12%)	Assistance Publique Hopitaux Paris (APHP)	0.11	10 (3.50%)
6	England	2005	0.19	26 (9.12%)	Universite Paris Cite	0.00	9 (3.15%)
7	Canada	2003	0.01	25 (8.77%)	Hopital Universitaire Necker‐Enfants Malades ‐ APHP	0.04	8 (2.80%)
8	France	2003	0.15	19 (6.66%)	Hopital Universitaire Cochin ‐ APHP	0.04	8 (2.80%)
9	Netherlands	2006	0.18	19 (6.66%)	Harvard University	0.13	7 (2.45%)
10	Spain	2006	0.00	15 (5.26%)	Helmholtz Association	0.14	7 (2.45%)

The close collaboration among countries and institutions has significantly advanced the field. Each node represents a country, with node size proportional to the number of published documents. Lines between nodes indicate collaborative connections, with thicker lines denoting closer collaboration. Figure 3 displays 47 nodes and 170 connections, resulting in a network density of 0.1573, while Figure 4 presents 336 nodes and 957 connections, with a network density of 0.017. Notably, collaboration has tightened among countries such as the United States, China, Germany, and Italy, particularly between the United States and other nations. Institutions like the Spanish Biomedical Research Center for Red Biomedicine, the French National Institute of Health and Medical Research (INSERM), and Assistance Publique Hôpitaux de Paris (APHP) are engaged in close cooperation, further highlighting the need to examine regional disparities in research outcomes.

Figure 3.

Distribution of publications from diferent countries.

Figure 4.

Distribution of publications from different institutions.

3.3. Analysis of Journals and Co‐Cited Journals

We identified 285 articles related to mitochondria in HCM published in 162 academic journals. The journals with the highest number of publications were the American Journal of Physiology Heart and Circulatory Physiology (12 articles, 4.43%), Mitochondrion (11 articles, 3.27%), Scientific Reports (9 articles, 3.15%), Journal of Molecular and Cellular Cardiology (8 articles, 2.80%), and Human Molecular Genetics (7 articles, 2.45%). Among the top 10 journals, Nucleic Acids Research had the highest impact factor (IF) at 14.90, followed by the American Journal of Human Genetics with an IF of 9.8. The total citation frequency often reflects the influence of a journal in a specific research field, and it is typically demonstrated through the total citation frequency. Among the 395 journals with total citations, 14 journals had more than 100 citations. As shown in Table 2, J Biol Chem (192) had the highest number of citations, followed by P Natl Acad Sci USA (176) and Circulation (155). Among the top 10 journals, Nature had the highest impact factor at 64.80, followed by Science with an IF of 56.90. Most of the journals with total citations are located in the Q1 area, as evident from Table 2. Additionally, by constructing a dual‐map overlay of journals, the citation relationships between journals are highlighted. The left side represents citing journal collections, while the right side represents cited journal collections. Colorful paths indicate the citation relationships between them. As shown in Figure 5, there is a major yellow citation path, indicating that research published in Molecular/Biology/Immunology journals is cited by research in Molecular/Biology/Genetics journals.

Table 2.

Top 10 journals and co‐cited journals related to HCM mitochondria.

No.	Journal	Count (%)	IF (2022)	Co‐cited journal	Citation	IF (2022)	JCR
1	American Journal of Physiology Heart and Circulatory Physiology	12 (4.21%)	4.8	J Biol Chem	192	4.8	Q2
2	Mitochondrion	11 (3.85%)	4.4	P Natl Acad Sci USA	176	11.1	Q1
3	Scientific Reports	9 (3.15%)	4.6	Circulation	155	37.8	Q1
4	Journal of Molecular and Cellular Cardiology	8 (2.80%)	5	Circ Res	139	20.1	Q1
5	Human Molecular Genetics	7 (2.45%)	3.5	Hum Mol Genet	129	3.5	Q2
6	Nucleic Acids Research	6 (2.10%)	14.9	Nature	125	64.8	Q1
7	American Journal of Human Genetics	5 (1.75%)	9.8	Science	125	56.9	Q1
8	Frontiers in Genetics	5 (1.75%)	3.7	Nat Genet	121	30.8	Q1
9	International Journal of Cardiology	5 (1.75%)	3.5	Am J Hum Genet	115	9.8	Q1
10	Plos One	5 (1.75%)	3.7	J Mol Cell Cardiol	114	5	Q2

Abbreviations: IF, impact factor; JCR, journal citation reports.

Figure 5.

The dual‐map overlay of journals on HCM mitochondrial research.

3.4. Analysis of Authors and Co‐Cited Authors

A total of 520 authors have contributed to publications on mitochondrial research in HCM (see Table 3). The author with the highest number of publications is Boutoual Rachid from the United States (4 articles, 1.40%), followed by Leary Scot C (3, 1.05%), Armengod M‐Eugenia (3, 1.05%), Murohara Toyoaki (3, 1.05%), and Arbustini Eloisa (2, 0.70%), Okamoto Rie (2, 0.70%), and Bertini Enrico (2, 0.70%). It is worth noting that the authors exhibit relatively low centrality (≤ 0.01), indicating that their influence in the field of mitochondrial research in HCM needs further enhancement. Each circle represents an author, with the size of the circle indicating the number of articles published. Thicker lines represent a closer collaboration between authors, and different colors of the circles denote relatively closely cooperating groups, as shown in Figure 6. Authors who are cited together in one or more subsequent papers are referred to as co‐cited authors (as shown in Figure 7). Among the 673 co‐cited authors, only 8 authors have been cited more than 20 times, including Maron Bj (40 times), Ghezzi D (30 times), Wallace Dc (24 times), among others.

Table 3.

Top 10 authors and co‐cited authors related to HCM mitochondrial research.

No.	Author	Count (%)	Centrality	Co‐cited author	Citation	Centrality
1	Boutoual Rachid	4 (1.40%)	0.00	Maron BJ	40	0.15
2	Leary Scot C	3 (1.05%)	0.00	Ghezzi D	30	0.06
3	Armengod M ‐Eugenia	3 (1.05%)	0.00	Wallace DC	24	0.1
4	Murohara Toyoaki	3 (1.05%)	0.00	Dimauro S	23	0.02
5	Cheng Xian Wu	3 (1.05%)	0.00	Suzuki T	22	0.02
6	Carrozzo Rosalba	3 (1.05%)	0.00	Ashrafian H	22	0.22
7	Hirashiki Akihiro	3 (1.05%)	0.00	Marian AJ	21	0.12
8	Arbustini Eloisa	2 (0.70%)	0.00	Jaksch M	20	0.06
9	Okamoto Rie	2 (0.70%)	0.00	Papadopoulou LC	19	0.01
10	Powell Christopher A	2 (0.70%)	0.00	Taylor RW	19	0.02

Figure 6.

CiteSpace visualization of authors in HCM mitochondrial research.

Figure 7.

CiteSpace visualization of co‐cited authors in HCM mitochondrial research.

3.5. Analysis of Co‐Cited References

Co‐cited literature refers to the situation where multiple academic papers share common citations when citing other literature. This indicates that these papers have common value and influence in researching a specific field. Co‐cited literature can be considered as an indicator of the scholarly impact of academic publications. We have listed the top 10 most frequently co‐cited literature related to mitochondrial research in HCM. Among the 669 co‐cited literature, 10 papers have been cited more than 5 times, with the top three papers having been cited more than 9 times (see Table 4). The most frequently co‐cited paper is titled “MTO1 Mutations are Associated with HCM and Lactic Acidosis and Cause Respiratory Chain Deficiency in Humans and Yeast.” This suggests that MTO1 mutations are related to HCM, lactic acidosis, and other manifestations. It underscores the significance of recombinant yeast as a meaningful system for testing rare pathogenic risk factors and expresses an understanding of the impact on biochemical phenotypes [18].

Table 4.

Top 12 co‐cited references related to mitochondria in HCM.

No.	Reference	Citation	Year	Centrality
1	MTO1 Mutations are Associated with Hypertrophic Cardiomyopathy and Lactic Acidosis and Cause Respiratory Chain Deficiency in Humans and Yeast	10	2013	0.00
2	Mutations of the Mitochondrial‐tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis	9	2012	0.00
3	Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease	9	2018	0.01
4	Mutations in GTPBP3 Cause a Mitochondria! Translation Defect Associated with Hypertrophic Cardiomyopathy, Lactic Acidosis, and Encephalopathy	9	2014	0.00
5	A complete landscape of post‐transcriptional modifications in mammalian mitochondrial tRNAs	9	2014	0.01
6	Deficient methylation and formylation of mt‐tRNAMet wobble cytosine in a patient carrying mutations in NSUN3	7	2016	0.00
7	Mitochondria: Impaired mitochondrial translation in human disease	6	2014	0.00
8	Complete chemical structures of human mitochondrial tRNAs	6	2020	0.00
9	Mitochondrial dysfunction in pathophysiology of heart failure	6	2018	0.00
10	Enzymology of tRNA modification in the bacterial MnmEG pathway	6	2012	0.00

3.6. Analysis of Keywords and Keywords Burst

By analyzing keywords, we can gain insights into the research hotspots of a specific field. High‐frequency keywords are shown in Table 5. Keywords such as “oxidative stress” and “mutations” appear more than 20 times, suggesting that there may be significant potential in mitochondrial research in HCM. Using CiteSpace software to cluster keywords, it can provide directions for future research. The dots and labels form an irregular element, with different colors representing different clusters. Figure 8 displays clusters in red, yellow, orange, and blue, representing different research directions. The red cluster's keyword is “cytochrome c oxidase,” the yellow cluster's keyword is “ATP synthase,” the orange cluster's keyword is “heart failure,” and the blue cluster's keyword is “mitochondrial dysfunction.” The keyword bursts vividly illustrate the trends and hotspots in mitochondrial research in HCM, allowing for better predictions of future research directions. Figure 9 describes the top 25 keyword bursts, along with their start and end years and burst strength. The blue line represents the timeline from 2003 to 2023, while the red line indicates keyword bursts during this period.

Table 5.

Top 20 keywords related to mitochondria in HCM.

No.	Keywords	Count	Centrality	No.	Keywords	Count	Centrality
1	Hypertrophic cardiomyopathy	132	0.36	11	Cytochrome c oxidase	21	0.08
2	Oxidative stress	38	0.16	12	Expression	19	0.1
3	Heart failure	35	0.31	13	Gene	18	0.08
4	Lactic acidosis	29	0.08	14	Dysfunction	15	0.06
5	Mutations	28	0.13	15	Heart	14	0.04
6	Disease	27	0.1	16	Skeletal muscle	14	0.04
7	Dilated cardiomyopathy	26	0.19	17	Biogenesis	13	0.05
8	Cardiomyopathy	26	0.21	18	Leigh syndrome	12	0.06
9	Deficiency	24	0.13	19	Apoptosis	10	0.05
10	Cardiac hypertrophy	21	0.09	20	Energy metabolism	9	0.04

Figure 8.

Visualization of HCM mitochondrial keyword cluster.

Figure 9.

Top 25 keywords with the strongest citations related to mitochondria in HCM visualized by Citespace.

3.7. Analysis of Timeline

The timeline view is designed to explore research trajectories based on the interactions and mutation relationships between keywords in a specific field. Figure 10 is a mitochondrial timeline view in HCM drawn using CiteSpace software. It provides an intuitive comparison over time, depicting the periodic hotspots and development process of mitochondrial research in HCM. From 2003 to 2015, mitochondrial research in HCM did not receive sufficient attention, and during this period, the research primarily focused on keywords such as “cytochrome c oxidase,” “ATP synthase,” “heart failure,” “therapy,” “gene,” “oxidative stress,” “dilated cardiomyopathy,” “calcineurin,” and “adenine nucleotide translocator.” From 2015 to 2020, research on mitochondria in HCM began to increase, and the research mechanisms accelerated. The main keywords during this period included “adult zebrafish,” “arrhythmias,” “artery endothelial cells,” “stress,” “aerobic exercise,” “respiratory chain,” “mitochondrial,” “pathogenesis,” and “atrioventricular.” In recent years, scholars have begun to explore the potential and value of extracellular vesicles (exosomes) in clinical research, with key terms such as “altered mechanisms,” “animal models,” “mitochondrial dysfunction,” “heart,” “mutation,” and “adrenergic receptor stimulation.”

Figure 10.

Visualization map of the mitochondria‐related timeline viewer in HCM.

4. Discussion

Through the selection of the knowledge map generated by CiteSpace software, research on the hotspots and development trends of hypertrophic cardiomyopathy and mitochondria in the past 20 years has been conducted, leading to the following conclusions:

The overall trend in the number of publications shows a fluctuating increase, with an evident growth rate starting from 2011, indicating a deeper research focus on hypertrophic cardiomyopathy and mitochondria. In terms of countries, the top 10 ranked nations include six European countries, two North American countries, and two Asian countries. From the research, it is evident that the United States holds a central position in the study of hypertrophic cardiomyopathy, followed by China with the highest number of publications. In terms of centrality, Italy has the highest centrality at 0.36, indicating its high research quality and significant influence. From the perspective of research institutions, UDICE‐French Research Universities, Centro de Investigacion Biomedica en Red, and Institut National de la Sante et de la Recherche Medicale (Inserm) are ranked in the top five. These research institutions, which have significant influence in this field, have extensive collaborative relationships. The ranking of publication volume does not align with centrality ranking. The Network Biomedical Research Center ranks second in publication volume but first in centrality, while the Helmholtz Association ranks tenth in publication volume but second in centrality. This indicates that their research papers have significant impact and high quality. Therefore, further collaboration and in‐depth research are crucial for guiding researchers to publish high‐quality papers in the field of hypertrophic cardiomyopathy and mitochondria.

In the research on hypertrophic cardiomyopathy and mitochondria, Boutoual Rachid and Leary Scot C are the most prolific authors. Among them, Maron BJ and Ghezzi D are the most cited authors internationally. The American Journal of Physiology Heart and Circulatory Physiology, Mitochondrion, Scientific Reports, and Journal of Molecular and Cellular Cardiology are the journals with the most publications related to hypertrophic cardiomyopathy and mitochondria research. The Journal of Biological Chemistry and Proceedings of the National Academy of Sciences are the journals with the highest citation rates. The most cited paper is by Enrico Baruffini et al., published in 2013, which confirmed the association of MTO1 mutations with mitochondrial diseases. The features include hypertrophic cardiomyopathy, lactic acidosis, and mitochondrial respiratory chain (MRC) deficiency, with a wide range of lesions that can frequently affect the brain. Additionally, the study indicates that appropriate recombinant yeast models can validate the pathogenic effects of variants found in human patients [19].

From the perspective of keywords and keyword clustering, the top 10 keywords include Hypertrophic cardiomyopathy, Oxidative stress, Heart failure, Lactic acidosis, Mutations, Disease, Dilated cardiomyopathy, Cardiomyopathy, Deficiency, and Cardiac hypertrophy. These terms represent the most frequently cited terminologies in research related to hypertrophic cardiomyopathy over the past 20 years. The keyword clustering includes Cytochrome c oxidase, Heart failure, ATP synthase, Adenine nucleotide translocator (ANT), Therapy, Cardiovascular diseases, Chagasic cardiomyopathy, Rat, Danon disease, and Mitochondrial dysfunction. Research mainly focuses on mechanisms, cardiovascular diseases, and treatment aspects. The diagnosis of advanced heart failure in HCM patients requires a comprehensive range of diagnostic tests including echocardiography, cardiac MRI, right heart catheterization, and CPET. Left ventricular assist devices (LVADs) may benefit a very small number of HCM patients who experience regression of left ventricular hypertrophy and develop left ventricular dilation, but heart transplantation remains the best cardiac replacement therapy for HCM patients [20]. Through multi‐omics studies, we have discovered that HCM exhibits significant metabolic features, characterized by a decrease in high‐energy phosphate metabolites [ATP, ADP, and phosphocreatine (PCr)], as well as a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Alongside these metabolic disruptions, we observe increased oxidative damage, leading to severe mitochondrial structural and functional defects. Upregulation of mitochondrial quality control failure exacerbates these defects, thereby increasing energy impairment [21]. HCM is caused by mutations in sarcomeric proteins, and oxidative stress may exacerbate these mutations. Reactive oxygen species (ROS) stimulate the activation of signaling kinases and transcription factors, thereby altering the function of crucial cellular proteins and signaling pathways in the heart, promoting cardiac hypertrophy remodeling. Animal experiments have shown that mitochondrial ROS release increases in HCM hearts, leading to impaired oxidative phosphorylation (OXPHOS) capacity with both non‐fatty acid and fatty acid substrates [22].

The emergence of keywords reflects the development trends of the forefront of research in a specific field at a particular time. The earliest peak in keyword emergence occurred in 2003 with “Saccharomyces cerevisiae,” “Cytochrome c oxidase,” and “Leigh syndrome,“ indicating that during this period, the research hotspot in this field was focused on mechanistic studies. Under normal physiological conditions, yeast cells can maintain redox homeostasis. Cells have evolved various enzymatic (such as catalase, thioredoxin, and superoxide dismutase) and nonenzymatic (such as ascorbate and glutathione) antioxidant defense mechanisms to mitigate the damaging effects of excessive ROS and maintain redox homeostasis [23]. Recent research hotspots include “Mitochondrial dysfunction,” “mutation,“ and “heart,” indicating that mitochondrial damage in HCM is associated with myocardial cell structural damage and is related to the septal hypertrophy in genotype‐negative patients. The impairment of NADH‐linked respiration, associated with reduced nicotinamide adenine dinucleotide (NAD+) levels, is a primary mitochondrial respiratory defect. This can be enhanced through treatments aimed at increasing mitochondrial NAD+ levels and Elamipretide therapy. Mitochondrial‐targeted therapy may prevent or ameliorate cardiomyopathy [6]. Animal experiments have provided new insights into the pathophysiology of HCM and have demonstrated that restoring mitochondrial redox status is beneficial for HCM treatment [22].

For the analysis of the biological and clinical consequences of hypertrophic cardiomyopathy and mitochondria, it is possible to look at the Mitochondrial Dysfunction: Impaired mitochondrial function in HCM can lead to decreased ATP production, resulting in energy deficits for cardiac contractility and relaxation [24]. Oxidative Stress: Elevated reactive oxygen species (ROS) contribute to cellular damage, further exacerbating cardiac hypertrophy and fibrosis [22]. Metabolic Remodeling: HCM often shifts energy substrate utilization from fatty acids to glucose, which is less efficient and contributes to metabolic disturbances [25]. Clinical Consequences:Heart Failure: Patients with HCM may progress to heart failure due to the sustained energy deficits and myocardial fibrosis [26]. Arrhythmias: Structural and electrical remodeling increases the risk of arrhythmias, which can lead to sudden cardiac death [27]. Exercise Intolerance: Impaired cardiac function and energy supply limits exercise capacity in HCM patients, significantly affecting their quality of life [28]. As for research Models:Mitochondria‐related research models, including genetically modified mice and patient‐derived iPSC cardiomyocytes, have provided insights into the mechanisms of HCM. These models help elucidate mitochondrial dynamics, calcium handling, and apoptotic pathways, contributing to our understanding of HCM pathophysiology.

This indicates that research on hypertrophic cardiomyopathy and mitochondria primarily focuses on mechanisms, treatments, and cardiovascular diseases. This study provides important insights into deepening our understanding of the relationship between hypertrophic cardiomyopathy and mitochondria, and offers crucial clues for exploring new therapeutic approaches, guiding future clinical practice.

5. Advantage and Limitations

Literature analysis necessitates a thorough examination of documents and visualization analysis through professional software, with both CiteSpace and systematic retrieval being indispensable. This study marks the inaugural bibliometric analysis of the research field concerning mitochondria and HCM, elucidating the most influential authors, countries, institutions, journals, as well as research hotspots and frontiers in this domain. However, the study does entail certain limitations. Initially, the articles included were sourced exclusively from WoSCC, without considering other databases. While WoSCC is presently the most authoritative and comprehensive international database, widely employed in bibliometric analyses, it is acknowledged that the articles incorporated in this study might not cover all potential sources. Secondly, some recent high‐quality articles may exhibit relatively low citation rates, potentially diminishing their perceived impact. Consequently, constructing a knowledge map based on CiteSpace and integrating it with specific literature serves as a more accurate and efficient method for literature analysis, laying a robust foundation for identifying future research hotspots and trends in the study of mitochondria in HCM.

6. Conclusion

The mitochondria hold significant research value and promising applications in hypertrophic cardiomyopathy, potentially providing better explanations for the causal relationship between mitochondria and cardiomyopathy. Utilizing CiteSpace software for visual analysis objectively depicts the true developmental trends and directions of research on hypertrophic cardiomyopathy and mitochondria. Additionally, there has been a notable increase in the number of articles published in international core journals, indicating a significant enhancement in their impact.

Author Contributions

Lulu Yang: writing–original draft, visualization, methodology, software, data curation. Heng Zhang: methodology, software, formal analysis. Zhiyang Zhu: conceptualization, validation, formal analysis, data curation, resources. Jianming Wang: conceptualization, writing–review and editing, data curation. Xiaojuan Liu: methodology, visualization, software. Lijie Lu: writing–review and editing, software, data curation, writing–original draft. Jinliang Huang: Investigation, project administration, methodology. Zhengchuan Zhu: resources, supervision, writing–review and editing, funding acquisition, visualization, validation, investigation.

Ethics Statement

This paper is a systematic review, a reanalysis of published papers, and does not involve additional human trials and therefore does not require ethics committee approval or consent.

Conflicts of Interest

The authors declare no conflicts of interest.

Transparency Statment

The lead author Miaoran Wang, Zhengchuan Zhu affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Data Availability Statement

This article, along with its supplementary material, encompasses the original contributions of the study. For additional inquiries, please contact the corresponding author directly.