Chronic thromboembolic pulmonary hypertension: insights from the 100 most cited papers: a bibliometric perspective

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) represented a significant cardiovascular challenge, characterized by precapillary pulmonary hypertension and imaging evidence of chronic thromboembolism (1). Defined by a mean pulmonary artery pressure (mPAP) greater than 20 mmHg at rest and a pulmonary capillary wedge pressure of 15 mmHg or less, according to the 2019 World Symposium on Pulmonary Hypertension (WSPH) criteria (2), CTEPH often emerges as a severe complication following pulmonary embolism (PE) (3). The pathophysiology of CTEPH involves the fibrotic transformation of pulmonary arterial thromboembolism, leading to vascular remodeling and chronic obstruction of major pulmonary arteries (4). With an incidence ranging from 0.9 to 9.1 cases per million annually and a cumulative incidence of 0.1% to 9.1% among survivors of acute PE, CTEPH represents a substantial healthcare burden (5). Despite its nonspecific clinical presentation, which complicates early diagnosis, advancements in diagnostic techniques like ventilation/perfusion scintigraphy and computed tomography pulmonary angiography have significantly improved detection (6). Treatment strategies for CTEPH have also evolved considerably; pulmonary endarterectomy (PEA) remains the gold standard for operable cases (7), while balloon pulmonary angioplasty (BPA) serves as an alternative for inoperable patients (8). Pharmacological interventions—including riociguat, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists—are crucial for management (9-11), with combination therapy showing promise in enhancing outcomes (12).

In recent years, bibliometric analysis has emerged as a valuable tool in evaluating research trends, collaboration networks, and the evolution of scientific knowledge within a field (13). Unlike systematic reviews and meta-analyses—which aim to synthesize and critically appraise data from original studies to answer specific clinical questions—bibliometric analysis quantitatively examines patterns in the scientific literature itself, such as publication counts, citation frequencies, influential authors or institutions, and thematic developments. While systematic reviews focus on the quality and findings of studies, and meta-analyses aggregate numerical data to derive pooled estimates, bibliometric analysis provides a macroscopic view of how a research field grows, matures, and shifts over time (14). By mapping intellectual structures and identifying influential contributions, bibliometric analysis complements traditional evidence synthesis approaches, offering a unique perspective on the dynamics and impact of research activity.

Given the rapid advancements and increasing complexity in CTEPH research and management, systematic analysis of the scientific literature is essential to identify trends and knowledge gaps. While comprehensive bibliometric studies have provided valuable macro-level overviews of the entire field’s activity and growth, encompassing thousands of publications over decades (15), focusing on publication volume and broad trends, a distinct gap remains in understanding the core intellectual pillars that have fundamentally shaped CTEPH research. To address this, our study deviates from broad-scope analyses by uniquely employing bibliometric methods to scrutinize the 100 most frequently cited articles on CTEPH. These seminal works represent the field’s intellectual bedrock, reflecting the most impactful discoveries, methodological advancements, and conceptual breakthroughs that have profoundly influenced clinical practice and subsequent research. We aim to systematically map the intellectual landscape and identify key research trends, critical focal points, and the driving forces within this highly influential subset of literature, thereby providing unique and in-depth insights for researchers, clinicians, and policymakers in this vital field. We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1746/rc).

Methods

Literature search and screening

On May 13, 2025, a comprehensive literature review was conducted utilizing the Web of Science Core Collection (WoSCC), a robust multidisciplinary database (16). The search strategy employed the following terms: (TS=(“chronic thromboembolic pulmonary hypertension”)) OR TS=(“chronic thromembolism pulmonary hypertension”), with a focus on publications spanning from 1973 to 2021 (17). Inclusion criteria were restricted to original research articles published exclusively in the English language, thereby excluding reviews, letters, and conference abstracts. The initial screening of the literature was performed by two independent researchers according to these criteria, with any discrepancies resolved through discussion or consultation with a third researcher. To ensure sufficient citation accumulation and to minimize potential bias from recently published articles, the time window was restricted to publications up to 2021, despite the literature search being conducted in 2025.

Data collection

Subsequent to the initial search, all retrieved publications were systematically organized in descending order based on citation frequency. From this extensive compilation, the 100 most frequently cited articles pertaining to CTEPH were selected for in-depth analysis. To ensure the integrity of the data and to eliminate duplicates or irrelevant entries, two independent reviewers conducted a thorough screening of these articles. The complete records and cited references of the selected 100 articles were then exported in plain text format, facilitating the extraction of detailed information, including authors, countries/regions, institutions, titles, publication years, citation counts, journals, and keywords.

Bibliometric analysis and visualization of results

For data analysis and visualization, we used a combination of tools: R 4.3.3, CiteSpace 6.3.R1, and VOSviewer 1.6.20. We began with a basic statistical analysis of the dataset using Bibliometrix, which provided a comprehensive bibliometric overview, including annual scientific production, top authors, institutions, and countries, along with document coupling (18). The “biblioshiny” package was employed to extract various features related to CTEPH research literature from 1973 to 2021, including main information, most relevant authors, authors’ production over time, and most globally cited documents. Next, we used CiteSpace to identify and visualize emerging trends and critical turning points in the CTEPH research field (19). We set the time slicing to one year from 1973 to 2021 and selected the top 5% per slice for generating the network. CiteSpace also enabled keyword clustering, dual map overlay analysis of journals, identification of the strongest cited bursts, and the construction of co-cited reference timeline maps of publications. VOSviewer was additionally used to create and visualize bibliometric networks, including co-authorship, co-occurrence, and bibliographic coupling networks (20). For keyword analysis, we set the minimum number of occurrences of a term to 5, and for co-authorship analysis, the minimum number of documents per author was also set to 5. In our visualization networks, the size of a node represents the frequency or strength of an item, while its color indicates different clusters or time periods. The thickness of the lines between nodes reflects the strength of connections. We utilized several bibliometric indices in our analysis, including the H-index, G-index, and M-index, to measure researcher productivity and impact (21,22). For journal evaluation, we referred to the Journal Citation Reports (JCR 2023) quartile rankings and impact factor (IF 2023) (23,24).

Results

Overview of publication status and growth trend analysis

Based on the literature screening flow chart (Figure 1). The analysis of the 100 most highly cited studies, spanning the years 1973 to 2021 (Figure 2A), revealed that 2012 and 2016 were the most productive years within this dataset, with each year yielding 9 publications. Among these leading articles, 36% exhibited international co-authorship, with an average document age of 16.2 years at the time of data collection (Figure 2B). Table S1 delineates the top ten most-cited articles. The article with the highest citation count was a Practice Guideline authored by JAFF MR and his team, published in the journal Circulation in 2011. This work garnered an impressive total of 1,635 citations, thereby establishing it as the most influential publication within this cohort. In contrast, the article with the fewest citations achieved 112 citations. The overall average citation count per article was 284.6, with nine articles surpassing 500 citations, and every article within the list attaining a minimum of 100 citations.

Figure 1 Flowchart of data screening process.

Figure 2 Overview of CTEPH research: (A) annual growth of publications on CTEPH; (B) comprehensive overview of the bibliometric analysis. CTEPH, chronic thromboembolic pulmonary hypertension.

Country distribution and collaboration analysis

The top 100 publications analyzed originated from 56 countries or regions. Germany and the USA were the most productive countries, each contributing 31 articles, followed by France with 28 articles and the United Kingdom (UK) with 23 articles. In terms of citation impact, Germany ranked first with 10,749 total citations (TCs), followed by the USA [10,480] and France [9,055]. The collaboration network analysis highlighted Germany’s leading position with a total link strength of 121, followed by France [110] and the UK [108] (Figure 3, Table S2).

Figure 3 Global distribution and international collaboration in CTEPH: visualization map of country-level networks. CTEPH, chronic thromboembolic pulmonary hypertension.

University and institutional contributions

At the institutional level, a total of 10 top institutions were shown in the graph, representing significant contributors to the field (Figure 4A). Assistance Publique Hopitaux Paris (APHP) emerged as the leading institution, with a total of 30 publications. This was closely followed by the University of California San Diego and the University of California System, each with 28 articles. The Medical University of Vienna also demonstrated a strong research presence, contributing 27 publications.

Figure 4 Institutional contributions and collaborations in CTEPH. (A) Top 10 institutions by article count and rank. The circle size shows the article count, with darker shades indicating higher ranks. (B) Visualization map depicting the collaboration among different institutions. CTEPH, chronic thromboembolic pulmonary hypertension.

Among the 70 institutions involved in international collaborations with a minimum of 2 articles, Hannover Medical School has the highest total link strength [99], followed by University of Pavia [92] and Medical University Vienna [76] (Figure 4B).

Journal analysis

The European Respiratory Journal published the most articles [18], followed by Chest [12] and Circulation [10] (Table S3). The European Respiratory Journal also had the highest H-index [18] and a substantial IF (16.6) among the listed journals, and it ranked first in total publications (TPs), highlighting its central role in disseminating CTEPH research. Chest followed with an H-index of 12 and an IF of 9.5, ranking second in both TPs [12] and TCs [302]. Circulation stood out for its exceptionally high impact factor (35.5) and ranked first in TCs [319], despite a moderate H-index [10] and fewer publications [10]. Among the 38 journals identified in the co-occurrence network (Figure 5A), the three key journals with the highest total link strength were European Respiratory Journal [194], Circulation [184], and Chest [81]. The journal coupling network (Figure 5B) reveals that the European Respiratory Journal had the highest total link strength [2,443], followed by Circulation [2,270] and Chest [1,139].

Figure 5 Network analyses of journals in CTEPH: (A) the co-occurrence networks of journals; (B) the coupling networks of journals. CTEPH, chronic thromboembolic pulmonary hypertension.

Author contribution analysis

The updated analysis of highly productive authors highlights Simonneau Gerald as the most prolific and influential contributor in the field, with the highest H-index (12), TPs [12], and TCs [4,904] (Table S4). Hoeper Marius M. follows closely, with an H-index of 11, 11 publications, and 4,220 citations, underscoring his significant impact. Delcroix Marion is also among the leading authors, with an H-index of 9, 9 publications, and 3,398 citations. Notably, Jansa Pavel, with 8 publications and 3,782 citations, demonstrates a particularly high citation-to-publication ratio. The G-index values reflect these patterns, further confirming the prominence of these authors in highly cited research. The majority of top authors began making significant contributions between 2006 and 2008, indicating a period of intensified scholarly activity in CTEPH research. The collaboration network (Figure 6) shows that among the 110 authors involved in international collaborations with a minimum of 2 articles, Simonneau Gerald has the highest total link of strength [79], followed by Mayer Eckhard [71] and Jansa Pavel [61].

Figure 6 Author collaboration network in CTEPH. CTEPH, chronic thromboembolic pulmonary hypertension.

Keywords co-occurrence and burst analysis

The keyword co-occurrence network (Figure 7A) visually demonstrates the major research themes and interconnections within the CTEPH field. Central and high-frequency keywords include “arterial hypertension”, “thromboendarterectomy”, “endarterectomy”, “embolism”, and “management”, each forming prominent nodes within the network. These keywords are deeply interconnected with others such as “outcomes”, “diagnosis”, “guidelines”, “risk factors”, and “angiography”, reflecting the multidisciplinary and evolving nature of CTEPH research. The clustering structure highlights several thematic groupings: Surgical and Interventional Management: Centered around terms like “endarterectomy” and “thromboendarterectomy”, indicating a sustained focus on operative therapies. Clinical Assessment and Diagnosis: Encompassing keywords such as “arterial hypertension”, “embolism”, “diagnosis”, and “computed tomography”, underscoring advances in diagnostic evaluation and imaging modalities. Patient Outcomes and Guidelines: Including “management”, “outcomes”, “guidelines”, and “follow-up”, reflecting the increasing attention to evidence-based practice and long-term patient care.

Figure 7 Keyword analysis in CTEPH: (A) keyword co-occurrence network; (B) citation burst analysis of keywords. CTEPH, chronic thromboembolic pulmonary hypertension.

The citation burst analysis (Figure 7B) provides a temporal perspective on shifting research priorities by highlighting the keywords with the strongest increases in citations over specific intervals. Early research (1990s–early 2000s): focused on foundational concepts such as “hypertension”, “pulmonary arteries”, “angiography”, and “stenosis or obstruction”, as well as early surgical interventions like “pulmonary thromboendarterectomy”. Mid-2000s to 2016: marked by a rise in clinical research and therapeutic innovation, with citation bursts for “bosentan therapy”, “endarterectomy”, “follow-up”, and “survival”, reflecting an expanding interest in pharmaceutical management and long-term patient outcomes. Recent years (2016–2021): show a growing emphasis on large-scale registries and precision diagnostics, with strong citation bursts for “international prospective registry”, “management”, “diagnosis”, and “computed tomography”. This indicates a shift toward data-driven approaches, early detection, and individualized patient care.

Discussion

General information

This updated bibliometric analysis reveals evolving global patterns in CTEPH research output and impact. Germany and the USA stand out as the most productive countries, each contributing 31 articles among the top 100 most cited publications, followed by France and the United Kingdom. Notably, the country-level analysis demonstrates that Germany leads in TC [10,749], underscoring its longstanding influence and robust research infrastructure. In terms of research dissemination, the European Respiratory Journal has emerged as the leading platform for CTEPH publications, distinguished by its highest H-index (18), substantial publication volume, and a strong IF (16.6). Chest and Circulation are also key journals in the field, with Circulation attaining significant influence and citation impact (IF: 35.5), despite a lower number of CTEPH-specific articles. The authorship analysis identifies a new core group of influential researchers, with Simonneau Gerald, Hoeper Marius M., and Delcroix Marion leading in both productivity and citation metrics. The author collaboration network reveals distinct research clusters, suggesting the emergence of specialized focus areas within the broader CTEPH community, which has likely accelerated scientific advancement through the cultivation of expertise and sustained cross-institutional partnerships.

Research hotspots and thematic evolution in CTEPH: insights from keyword analysis

The co-occurrence and burst analyses of keywords reveal that CTEPH research has undergone a clear thematic evolution over the past decades, transitioning from a focus on foundational disease mechanisms and surgical interventions to comprehensive, multidisciplinary management and advanced diagnostics.

Early focus: disease characterization and surgical management

In the early period (1990s to early 2000s), research hotspots were dominated by keywords such as “hypertension”, “pulmonary arteries”, “angiography”, and “stenosis or obstruction”, reflecting efforts to define CTEPH, understand its pathophysiology, and develop early diagnostic standards (3,4). Surgical treatment, particularly PEA, was established as the cornerstone of management, as highlighted by the prominence and early citation bursts of “thromboendarterectomy” and “endarterectomy” (25). The pivotal role of surgery is reinforced by major clinical analyses such as Jamieson et al.’s report of 1,500 cases, which set benchmarks for operative outcomes and safety (25).

Expansion to multimodal therapy and clinical outcomes

As the field matured, the research focus broadened to include pharmacological interventions and comprehensive disease management. Citation bursts for keywords such as “bosentan therapy”, “combination therapy”, and “follow-up” indicate growing interest in adjunct and alternative therapies for inoperable or residual CTEPH, exemplified by trials like BENEFiT and CHEST-1 (9,12,26). Attention to long-term outcomes, patient survival, and quality of life also became more prominent, as seen in the increasing frequency of terms such as “survival”, “outcomes”, and “management” (25). This shift toward holistic patient care is further evidenced by longitudinal studies and the growing adoption of multidisciplinary follow-up strategies (7,27).

Diagnostic advances and precision medicine

Recent years (2016–2021) have seen a marked shift toward advanced diagnostic techniques and precision medicine. Keywords with strong recent citation bursts—including “diagnosis”, “computed tomography”, and “international prospective registry”—underscore the adoption of high-resolution imaging, registry-based research, and early detection strategies (6,8). These developments have improved the sensitivity and specificity of CTEPH diagnosis and facilitated earlier intervention, as supported by evolving clinical guidelines (6).

Guidelines and clinical trials

The cluster encompassing “guidelines”, “arterial-hypertension”, and “clinical trials” reflects the maturation of CTEPH research into an evidence-based discipline. The emergence of “guidelines” as a major keyword parallels the publication of international consensus statements and major updates from societies such as the ESC/ERS (6), which have standardized diagnostic pathways and therapeutic indications. This cluster also highlights the role of large-scale clinical trials—such as CHEST-1 and BENEFiT—in shaping treatment standards, particularly for inoperable patients and those requiring medical therapy (9,12,26). The strong citation bursts for “guidelines” and “arterial-hypertension” align with the period during which CTEPH was increasingly recognized as a distinct form of pulmonary hypertension, requiring tailored management.

Pathogenesis and laboratory research

The “pathogenesis and laboratory research” cluster, including keywords like “angiography”, “endothelial growth-factor”, and “c-reactive protein”, represents a sustained research effort to elucidate the mechanisms driving CTEPH. Progress in this area is evidenced by studies investigating incomplete thrombus resolution, vascular remodeling, and the molecular signatures underlying disease progression (28). For instance, the identification of gene expression patterns by Stearman et al. (29) highlights the growing relevance of molecular and translational research. Such insights not only inform diagnostic and prognostic biomarker development but also support the rational design of novel therapies targeting vascular inflammation and remodeling.

Anticoagulation and risk factors

Distinct within the network is the cluster on “anticoagulation and risk factors”, with keywords like “risk-factors”, “deep-vein thrombosis”, and “oral anticoagulant therapy”. This reflects the clinical imperative to identify patients at risk for CTEPH following acute PE (5). The literature emphasizes persistent gaps in understanding the full spectrum of risk, including genetic, inflammatory, and thrombotic contributors (5,28). Citation bursts for “risk-factors” and “brain natriuretic peptide” mirror a growing emphasis on early detection and secondary prevention, supported by studies that have clarified the role of biomarkers in risk stratification and prognosis.

Patient outcomes and prognosis

The cluster on “patient outcomes and prognosis”, with terms such as “management”, “prognosis”, and “term-follow-up”, reflects the increased attention to long-term survival and quality of life in CTEPH patients. This shift is consistent with recent clinical research prioritizing holistic outcomes, as seen in longitudinal studies of treatment effectiveness and patient-reported measures (27). The strong citation burst for “management” in recent years corresponds to literature advocating for multidisciplinary care models and systematic follow-up (7,27), which are now recognized as essential for optimizing both survival and functional status.

Hemodynamics and exercise

Finally, the “hemodynamics and exercise” cluster, including “exercise”, “hypertension”, and “survival”, captures the importance of functional assessment and right heart hemodynamics in both diagnosis and prognosis. Serial evaluation of exercise capacity and hemodynamic parameters not only guides therapeutic decisions but also serves as key outcome measures in both clinical practice and research (7). The literature supports the use of exercise testing and right heart catheterization as integral components in the ongoing assessment of disease progression and response to therapy (6,8).

The temporal analysis of keyword bursts further contextualizes the thematic evolution of CTEPH research. Early bursts in “hypertension” and “angiography” reflect the foundational era of disease characterization, while subsequent surges in “endarterectomy”, “bosentan therapy”, and “follow-up” correspond to major advances in both surgical and medical therapy (9,25,26). More recent bursts for “management”, “diagnosis”, and “computed tomography” highlight the current focus on comprehensive, patient-centered care and the ongoing refinement of diagnostic strategies. This progression mirrors the larger trends in cardiovascular medicine, where integration of molecular, imaging, and clinical data is driving personalized and precision-based approaches (28,29).

Recent years have seen the publication of several bibliometric studies on CTEPH, reflecting a growing interest in quantitatively mapping the research landscape of this condition. For example, Lu et al. provided an analysis focused primarily on publication trends and international collaboration patterns (30), while Mo et al. emphasized co-authorship networks and the geographic distribution of research (31). Compared to traditional methods such as systematic reviews or meta-analyses—which synthesize clinical outcomes or aggregate data to answer predefined clinical questions—bibliometric analysis offers a complementary, macroscopic perspective on the evolution and structure of scientific knowledge within a field. While prior CTEPH bibliometric studies have mainly described broad publication patterns and collaboration, our study distinguishes itself by specifically targeting the 100 most frequently cited articles. This approach enables a focused examination of the most influential contributions and intellectual milestones that have shaped both clinical practice and future research directions. By integrating advanced bibliometric tools such as VOSviewer, CiteSpace, and Bibliometrix, our analysis not only confirms previous macro-level observations but also uncovers nuanced thematic clusters, research hotspots, and emerging frontiers not apparent in prior, broader analyses. Thus, our study provides a unique, high-resolution view of how seminal works have driven the evolution of CTEPH research, offering actionable insights for researchers, clinicians, and policymakers interested in the future direction of the field.

Strengths and limitations

The evolving research trends underscored in the keyword burst analysis reflect the dynamic nature of CTEPH research. This field has transitioned from an initial concentration on surgical techniques to a more holistic approach that integrates various treatment modalities, large-scale collaborative studies, and an increased emphasis on patient-centered outcomes and molecular mechanisms. This study introduced several significant strengths, particularly as it represented the first comprehensive bibliometric analysis of CTEPH research, providing an extensive overview of the field’s progression over the past two decades. Moreover, the application of multiple bibliometric tools (VOSviewer, CiteSpace, and Bibliometrix) enabled a robust and multifaceted examination of research trends, collaborations, and emerging topics. Nevertheless, certain limitations warrant consideration. Firstly, the analysis was limited to publications indexed in the WoSCC, potentially omitting relevant articles from other databases or non-indexed sources. Additionally, the exclusion of non-English publications might lead to an underrepresentation of research contributions from non-English-speaking countries, thereby potentially distorting the global perspective of CTEPH research presented in this study.

Conclusions

This study offered the first comprehensive bibliometric analysis of notable regional disparities in research output, identifying Germany, the USA, France and UK as the principal contributors. Notably, the focus of research hotspots has shifted from surgical interventions to advanced diagnostic techniques and emerging therapies, such as BPA and targeted medical treatments. Recent trends indicated an increasing emphasis on patient-centered outcomes and molecular mechanisms. Future research endeavors are expected to prioritize the optimization of early detection methods, refinement of treatment selection criteria, and exploration of genetic factors associated with the development of CTEPH. Furthermore, fostering international collaborations, particularly between developed and developing nations, will be essential for advancing the field and enhancing patient care.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1746/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1746/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1746/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.

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