The recent 10-year landscape of aortic dissection research: a bibliometric analysis.

BACKGROUND: We aimed to comprehensively analyze all the literature related to aortic dissection (AD) in the past decade using Web Scrapping technology from PubMed, revealing the research dynamics in this field.
METHODS: Data were retrieved and downloaded from PubMed with search strategy as "(aortic dissection [Title/Abstract]) AND (2010[EDAT]: 2020[EDAT])". Information on the PMID, journal name, title, number of citations, publication year, authors, affiliations, abstract, study type, and keywords of the research was recorded.
RESULTS: A total of 7,470 publications were identified. Most of the articles were published in J Thorac Cardiovasc Surg; Japan was the country with the largest publications number; the USA was far ahead of other countries regarding the highly cited studies; Yale University and Baylor College of Medicine took the first place for publishing most of the highly cited articles; the most frequently cited article is the 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases; most of the clinical trials were published on J Vasc Surg; John A. Elefteriades ranked first by cumulative publication numbers; Christoph A. Nienaber took the lead by both cumulative citations and impact factors; Dianna M. Milewicz was the only female researcher on all the three ranking lists; the most common keywords in aortic dissection were Treatment Outcome and Retrospective Studies.
CONCLUSIONS: This study provides interesting insights into the AD scientific landscape in recent 10 years and generates some objective evidence for comprehensive understanding and evaluation of this field. This investigation may ultimately inform managers, researchers and policymakers. 2021 Journal of Thoracic Disease. All rights reserved.

Introduction

Aortic dissection (AD), the well-known “ticking time bomb” in medicine, was estimated to be 4.4 per 100,000 person-year (1). In view of its urgency and high risk, researchers have always had a strong interest in this disorder, rendering it one of the hotspots in cardiovascular researches. A large number of literature about AD are published every year. It is no exaggeration to say that we are in an era of information explosion, which is of both opportunity and challenge. It’s very hard for any researcher in this filed to grasp the “full image” of AD research. Therefore, it is important to sort out and summarize the literature systematically, so that readers can obtain information more efficiently and in a broader view. Traditionally, Review has been the main approach of literature mining and curation, which requires a lot of manual reading and extraction, so it can only be used to summarize and evaluate specific parts of a specialty. To establish a more comprehensive summarization and evaluation, a more efficient and advanced way is necessitated-bibliometrics.

Bibliometrics refers to an interdisciplinary science of quantitative analysis of literature using mathematics and statistics. At present, there are few bibliometric reports in the field of AD. We aimed to comprehensively analyze all the literature related to AD on PubMed in the past decade using Web Scrapping technology, from different aspects of researchers, journals, institutions, and countries, etc., revealing the research dynamics in this field, and to a certain extent, helping other researchers foresee the research trends.

Methods

The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT-20180041), with informed consent waived. Statistical analysis and data visualization were performed using the R 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).

Data were retrieved and downloaded using RISmed and pubmed.mineR packages from PubMed, a website (http://www.ncbi.nlm.nih.gov/pubmed/) that provides free access to biomedical journal citations and abstracts. A total of 7,470 publications were identified using the following PubMed search strategy: “(aortic dissection [Title/Abstract]) AND (2010 [EDAT]: 2020 [EDAT])”. Of note, the closing date for the current study was July 31st, 2020. There were no other restrictions such as study types, abstract availability, language, etc. Information on the PMID, journal name (both full name and abbreviated), title, number of citations, publication year, authors, affiliations, abstract, study type, and keywords of the research was recorded. The full text was downloaded if necessary.

Statistical analysis

The following R packages were used for cleaning, analysis, and plotting: rio, stringr, plyr, ggplot2, circlize, ggmap, maps, and ggrepel. Descriptive analyses were conducted to calculate the frequencies of published articles on the level of journals, authors, countries, etc. Association between the journal IF and the number of citations was assessed using the Pearson Correlation test and a two-sided P value of less than 0.05 was considered significant. Further, Word cloud diagrams were generated to visualize the keywords frequencies. The authors’ cooperation network was represented by a chord graph. In addition, we used maps to present geographic information (such as countries and research centers). The top 100 highly cited articles in the past decade were independently screened and evaluated by two researchers (Rui Zhao and Donglin Zhuang). Any discrepancies between the two authors would be discussed in a core meeting to reach an agreement.

Results

As shown in , most of the literature about AD were published in J Thorac Cardiovasc Surg (389, 5.2%), followed by Ann Thorac Surg (373, 4.9%), Eur J Cardiothorac Surg (308, 4.1%), J Vasc Surg (231, 3.1%), and Interact Cardiovasc Thorac Surg (210, 2.8%). shows the year-on-year changes in the number of publications of the three major cardiothoracic surgery journals (J Thorac Cardiovasc Surg, Ann Thorac Surg, and Eur J Cardiothorac Surg). The publication volume of the three journals was comparable before 2018. After that, the number of AD papers published in J Thorac Cardiovasc Surg increased significantly. To be noted, the publication data of 2020 was not complete, as the deadline for data retrieval was July 26, 2020. According to the dependent territory of the journal, most articles were published in United States (2,676, 35.8%), followed by United Kingdom (1,241, 16.6%), Netherlands (803, 10.7%), Japan (620, 8.3%), Germany (562, 7.5%), and China (438, 5.9%). We further analyzed the sources of articles in three major cardiothoracic surgery journals and a Chinese Journal (J Thorac Dis) as a comparison. Out of the 1,164 articles published in the aforementioned four journals, information on first affiliations was successfully extracted in 796 (68.4%). The top five source countries of J Thorac Cardiovasc Surg (n=244), belonging to USA, were Japan (52, 21.3%), China (35, 14.3%), Germany (33, 13.5%), Italy (18, 7.4%), and USA (18, 7.4%), respectively; The top five source countries of Ann Thorac Surg (n=248), belonging to USA, were Japan (55, 22.2%), Germany (31, 12.5%), China (31, 12.5%), USA (23, 9.3%), and Italy (19, 7.7%), respectively; The top five source countries of Eur J Cardiothorac Surg (n=215), belonging to Germany, were Germany (59, 27.4%), Japan (44, 20.5%), USA (23, 10.7%), China (22, 10.2%), and Switzerland (12, 5.6%), respectively. The top five source countries of J Thorac Dis (n=89), belonging to China, were China (53, 60.0%), USA (8, 9.0%), Japan (5, 5.6%), South Korea (5, 5.6%), and Germany (3, 3.4%), respectively. As demonstrated above, the three major cardiothoracic surgery journals were highly internationalized, with balanced sources. No obvious regional publication discrimination or tendency was found. As a relatively “young” journal, J Thorac Dis still needs time to grow.

Figure 1

Rose plot displaying the journal ranking by publication numbers of aortic dissection.

Figure 2

Publication data of the three major cardiovascular surgery journals. (A) Year-on-year changes in the number of publications of the three major cardiothoracic surgery journals (J Thorac Cardiovasc Surg, Ann Thorac Surg, and Eur J Cardiothorac Surg). (B) The proportion of publication types of the three major cardiothoracic surgery journals (J Thorac Cardiovasc Surg, Ann Thorac Surg, and Eur J Cardiothorac Surg).

In terms of publication types of those 7,470 articles, Journal Article accounted for the majority (4,181, 55.9%), followed by Case Reports (2,250, 30.1%), Comparative Study (365, 4.8%), Editorial (197, 2.6%), Letter (187, 2.5%), etc. We further analyzed the article types of the three major cardiothoracic surgery journals (). As expected, Journal Article was the most common type, especially for Eur J Cardiothorac Surg. J Thorac Cardiovasc Surg published more Editorials while Ann Thorac Surg published more Case Reports compared to others. This information may be helpful to guide researchers to choose the appropriate journal according to the article type. It is worth noting that from the 7,470 articles, only 10 clinical trials (0.5%) were found based on the article type marked by PubMed. The basic information of these 10 clinical trials was shown in . Most of the clinical trials were published on J Vasc Surg (4, 40%), followed by Ann Thorac Surg (2, 20%). The USA contributed 5 (50%) clinical trials, followed by the United Kingdom (2, 20%), Canada (2, 20%) and Germany (1, 10%). Most clinical trials focused on endovascular treatment of type B dissection (6, 60%), and hybrid operation for type A dissection (2,20%). The total number of citations of these 10 clinical trials was 88, and the endovascular treatment of type B dissection accounted for up to 78 (88.6%) citations.

Table 1

Clinical trials in recent 10 years regarding aortic dissection

PMID	Titles	Journal	Year	Impact factor	First author	First affiliation
20807993	External aortic root support for Marfan syndrome: early clinical results in the first 20 recipients with a bespoke implant	J R Soc Med	2010	5.238	John Pepper	Royal Brompton Hospital
22169668	Prospective multicenter clinical trial (STABLE) on the endovascular treatment of complicated type B aortic dissection using a composite device design	J Vasc Surg	2011	3.405	Joseph V. Lombardi	Cooper University Hospital
23800455	Fenestrated and branched endovascular aorticrepair for chronic type B aortic dissection with thoracoabdominal aneurysms	J Vasc Surg	2013	3.405	Atsushi Kitagawa	Cleveland Clinic Foundation
24560244	Aortic remodeling after endovascular treatment of complicated type B aortic dissection with the use of a composite device design	J Vasc Surg	2014	3.405	Joseph V. Lombardi	Cooper University Hospital
24952999	Mid-term outcomes and aortic remodelling after thoracic endovascular repair for acute, subacute, and chronic aortic dissection: the VIRTUE Registry	Eur J Vasc Endovasc Surg	2014	5.328	R Heijmen	St. George’s Hospital
25669649	Do not leave the heart arrested. Non-cardioplegic continuous myocardial perfusion during complex aortic arch repair improves cardiac outcome	Eur J Cardiothorac Surg	2015	3.486	Andreas Martens	Hannover Medical School
26209487	Outcomes of Thoracic Endovascular Aortic Repair in Acute Type B Aortic Dissection: Results From the Valiant United States Investigational Device Exemption Study	Ann Thorac Surg	2015	3.639	Joseph E. Bavaria	University of Pennsylvania
26211376	Multicenter clinical trial of the conformable stent graft for the treatment of acute, complicated type B dissection	J Vasc Surg	2015	3.405	Richard P. Cambria	Massachusetts General Hospital
30501947	Dissected Aorta Repair Through Stent Implantation trial: Canadian results	J Thorac Cardiovasc Surg	2018	4.451	Sabin J. Bozso	University of Alberta
31254509	Single-Stage Management of Dynamic Malperfusion Using a Novel Arch Remodeling Hybrid Graft	Ann Thorac Surg	2019	3.639	Sabin J. Bozso	University of Alberta

To demonstrate the most influential and active researchers in this field, we first counted the publication numbers by individual researchers (first and senior author) in the past decade (). John A. Elefteriades ranked first, followed by Christoph A. Nienaber and Lizhong Sun. Of note, two female researchers also entered the top 30 list regarding publication numbers: Ourania Preventza and Dianna M. Milewicz. Specifically, the top 10 female researchers by publication numbers were Ourania Preventza, Dianna M. Milewicz, Jolien W Rooshesselink, Rossella Fattori, Rachel E. Clough, Elizabeth L. Norton, Akiko Tanaka, Jennifer S. Lawton, Julie De Backer, and Sherene Shalhub. Next, we ranked the researchers according to the cumulative number of citations (), with Raimund Erbel being the first, Ivan Kravchenko the second, and Christoph A. Nienaber the third. The most frequently cited article in the AD field is the 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases, a product of the collective effort by a group of extraordinary aortic experts (2). So, we made another ranking by excluding this Guideline to eliminate the potential biased effect on the individual ranking of citations. In the updated ranking, Christoph A. Nienaber stood in the first place, followed by Dianna M. Milewicz and John A. Elefteriades. Although not 100% perfect, the impact factor is still an important measure of the journal level and the difficulty of publication, so we also ranked the researchers according to their cumulative impact factors (). Christoph A. Nienaber took the first place, followed by Kim A. Eagle, and John A. Elefteriades. A total of 13 researchers were on all the three lists (top 30) by publication numbers, cumulative citations, and cumulative impact factors: John A. Elefteriades, Christoph A. Nienaber, Lizhong Sun, Yutaka Okita, Zaiping Jing, Joseph S. Coselli, Bartosz Rylski, Martin Czerny, Santi Trimarchi, Kim A. Eagle, Scott A. Lemaire, Dianna M. Milewicz, and G. Chad Hughes. Of note, John A. Elefteriades and Christoph A. Nienaber were the only two researchers entering all the three lists (top 3) by either publication numbers, cumulative citations, or cumulative impact factors. What’s more, we also made a chord graph to show the authors’ collaboration network (). If the number of collaborative articles between the two authors was greater than 15, they would appear on this network. The more cooperations between two authors, the thicker the connection.

Figure 3

Top researchers of the aortic dissection research. (A) Researchers ranking by the number of publications. (B) Researchers ranking by the number of cumulative citations. (C) Researchers ranking by the number of cumulative impact factors. (D) Chord graph showing the researchers’ collaboration network.

We extracted the first affiliations from the 7,470 articles and mapped them geographically (). The darker the color, the greater the number of publications. Japan stands in the first place regarding publication volume, followed by China, USA, Germany, and Italy. Since the number of citations can comprehensively reflect the influence and spread of an article, we listed the top 10 articles with the highest citation rates in the past decade () and provided the top 100 articles with the highest citation rates in the Table S1. We further marked the institutions where the top 100 most cited articles were from on the map according to the city coordinates (). The larger the red circle, the more articles with a high citation rate were published in a specific area. It shows that almost all the highly cited papers were from the USA and Europe. The USA was far ahead of other countries regarding the highly cited studies, especially the East. Institutions with 3 or more highly cited articles included Yale University, Baylor College of Medicine, Erasmus University Medical Center, Fondazione RiMED, Mayo Clinic, University of Pennsylvania, University of Rostock, and University of Texas.

Figure 4

Geographical demonstration of the aortic dissection research. (A) World map showing the countries ranking by the number of publications. (B) World map showing the geographical distribution of the highly cited publications (top 100).

Table 2

Top 10 articles ranked by impact factor during 2010-2020 regarding aortic dissection

PMID	Titles	Journal	Year	Impact factor	First author	Citations
20872991	Images in clinical medicine. Aortic dissection during diagnostic aortography	N Engl J Med	2010	74.699	Samad Ghaffari	1
25229939	Images in clinical medicine. Aortic dissection	N Engl J Med	2014	74.699	Amritpal Singh Nat	0
25405392	Atenolol versus losartan in children and young adults with Marfan’s syndrome	N Engl J Med	2014	74.699	Ronald V. Lacro	108
25662791	Management of acute aortic dissection	Lancet	2015	60.392	Christoph A. Nienaber	61
21917581	Incidence of aortic complications in patients with bicuspid aortic valves	JAMA	2011	45.54	Hector I. Michelena	122
27533160	Acute Aortic Dissection and Intramural Hematoma: A Systematic Review	JAMA	2016	45.54	Firas F. Mussa	34
30535217	Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial	JAMA	2018	45.54	Tetsuo Shoji	10
27440162	Aortic dissection	Nat Rev Dis Primers	2016	40.689	Christoph A. Nienaber	19
27440218	Aortic dissection	Nat Rev Dis Primers	2016	40.689	−	0
27560366	Aortic dissection	Nat Rev Dis Primers	2016	40.689	Christoph A. Nienaber	2

We further analyzed the correlation between impact factors and citation times, and found that there was a positive correlation between them (Pearson index: 0.31, 95% CI: 0.28–0.33, P<0.001). We listed the top 10 articles with the highest impact factor in and the top 100 as Table S2.

Table 3

Top 10 most cited articles during 2010-2020 regarding aortic dissection

PMID	Titles	Journal	Year	Impact Factor	First Author	Citations
25173340	2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult	Eur Heart J	2014	22.673	Raimund Erbel	463
20579534	Bicuspid aortic valve disease	J Am Coll Cardiol	2010	20.589	Samuel C. Siu	151
21917581	Incidence of aortic complications in patients with bicuspid aortic valves	JAMA	2011	45.54	Hector I. Michelena	122
23922146	Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial	Circ Cardiovasc Interv	2013	5.493	Christoph A. Nienaber	110
20185035	Thoracic aortic aneurysm clinically pertinent controversies and uncertainties	J Am Coll Cardiol	2010	20.589	John A. Elefteriades	108
21055718	Mutations in myosin light chain kinase cause familial aortic dissections	Am J Hum Genet	2010	10.502	Li Wang	108
25405392	Atenolol versus losartan in children and young adults with Marfan’s syndrome	N Engl J Med	2014	74.699	Ronald V. Lacro	108
26205591	Presentation, Diagnosis, and Outcomes of Acute Aortic Dissection: 17-Year Trends From the International Registry of Acute Aortic Dissection	J Am Coll Cardiol	2015	20.589	Linda A. Pape	100
23771987	Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type	Circ Cardiovasc Imaging	2013	5.691	Malenka M. Bissell	95
23599348	Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study	Circulation	2013	23.603	Dominic P. J. Howard	90

Next, we extracted the keywords and removed those words that were obviously highly frequent such as “aortic dissection”, “aortic aneurysm”, etc., and then calculated the frequency of the keywords. As shown in , word frequency was presented in the form of a word cloud. The higher the word frequency is, the larger the area it occupies in the word cloud. During 2010 and 2014, the top 10 keywords were Treatment Outcome, Retrospective Studies, Risk Factors, Blood Vessel Prosthesis Implantation, Tomography (X-ray computed), Endovascular Procedures, Stents, Aortography, Hospital Mortality, and Postoperative Complications. During 2015 and 2020, the top ten keywords were Retrospective Studies, Treatment Outcome, Risk Factors, Blood Vessel Prosthesis Implantation, Endovascular Procedures, Postoperative Complications, Stents, Blood Vessel Prosthesis, Computed Tomography Angiography, and Follow-Up Studies. To a certain extent, keyword frequency can reflect the research direction and hot spots in this field. We found that the research direction of AD had little change in the past decade. Most of the researches were about Treatment Outcome, Risk Factors, Blood Vessel Prosthesis Implantation, and the main research method was Retrospective Studies.

Figure 5

Word cloud of the key words. (A) Word cloud displaying the keyword frequencies between 2010–2014. (B) Word cloud displaying the keyword frequencies between 2015–2020.

Comment

This study provides interesting insights into AD scientific landscape in recent 10 years by identifying many “firsts” or “mosts” as follows: most of the articles were published in J Thorac Cardiovasc Surg; Japan was the country with the largest publications number; the USA was far ahead of other countries regarding the highly cited studies; Yale University and Baylor College of Medicine took the first prize for publishing most of the highly cited articles; Journal Article was the most common article type; the most frequently cited article was the 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases (2); most of the clinical trials were published on J Vasc Surg; John A. Elefteriades ranked first by cumulative publication numbers; Christoph A. Nienaber took the lead by both cumulative citations and impact factors; Dianna M. Milewicz was the only female researcher on all the three ranking lists; The most common keywords in aortic dissection were Treatment Outcome and Retrospective Studies, etc.

According to the literature we searched, most AD researches are of a low hierarchy of evidence, with few clinical trials. As can be seen from the word cloud, most of the studies are retrospective, focusing on treatment outcome and risk factors. There are many problems to be solved in AD management, such as total arch replacement versus half arch replacement, unilateral perfusion versus bilateral perfusion, optimal circulatory arrest temperature, etc. Only high-quality data and research can provide convincing answers and promote the standardization of AD management. Admittedly, AD is a highly urgent and variable disorder, which makes it very difficult to carry out clinical trials. In recent ten years, there are only two Guidelines (2,3) for aortic disease, and both of them were put forward at least 6 years ago. Compared to other areas of cardiology or cardiac surgery, the Guideline update for the aortic disease is relatively slow, which might be partially due to the lack of high-level evidence that can influence clinical practice.

Notably, the International Registry of Acute Aortic Dissection (IRAD), the world's largest and most famous database of aortic dissection including 55 active sites in 12 countries, has set a benchmark and paradigm for the study of AD. Among the top 100 highly cited studies, IRAD contributed up to 11 articles! Prompted by IRAD, some other registered multi-center studies have also been launched such as the German Registry for Acute Aortic Dissection type A (GERAADA), Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD), Gore Global Registry for Endovascular Aortic Treatment (GREAT), and International Aortic Arch Surgery Study Group (IAASG), etc. GERAADA also contributed 3 articles in the top 100 highly cited studies. These registered multi-center studies will certainly continue to greatly influence the way we treat aortic dissection worldwide. There is a large number of publications from Asia, especially China and Japan, but few highly cited works were generated. In the future, these high-volume regions may consider how to translate their large sample size to high-impact research, with IRAD as a good model.

In addition, the researches of AD mainly focus on the treatment, especially endovascular treatment. The management of AD involves many aspects. In addition to treatment, we also need to investigate more on the epidemiology, prevention, diagnosis, and perioperative management. Among these retrieved studies, clinical research accounts for the vast majority, while basic researches are relatively rare (the top 10 frequent keywords are basically all clinical research related, and basic research only accounts for 33/105 (31.4%) of the highly cited papers). It remains unclear of the pathogenesis of aortic dissection, and no effective molecule- or pathway-targeted interventions were established. More investment in basic research is needed in the future.

Strikingly, we found that only a small proportion of aortic researchers were women. Although we cannot directly provide data on the proportion of male and female researchers in this study, out of the top 30 researchers by publication numbers, only two (2/32, 6.2%) are women (Ourania Preventza and Dianna M Milewicz). It was reported that (4) in the United States and Europe, women comprise at least 50% of medical graduates. Despite gender balance among medical trainees, only one-third of practicing physicians, and <20% of cardiology trainees are women. The gender gap is supposed to be even wider in aortic disease considering the higher work intensity. The gender gap in AD has potential adverse impacts on collegial support, mentoring, research and even patients outcomes, etc. Improving gender equality within cardiology has been identified as a powerful means to improve cardiovascular disease outcomes in women—“Small Numbers, Big Impact” (5). For example, our study shows that Dianna M. Milewicz as the only female in all the three ranking list (publication numbers, citations, impact factors), has been one of the mainstays in decoding the genetic predisposition to vascular diseases. As Burgess et al. have proposed, we must encourage a dialogue to identify barriers and provide potential solutions to empower more women to join this highly rewarding specialty (4).

Limitations

Our study should be interpreted in the context of several limitations. First, the cited rate is one of the most important tools in bibliometrics. However, it’s very hard for the newly published studies to have high citations regardless of its significance because of the limited exposure. So, bibliometrics should be a dynamic analysis tool and subject to regular updates. Second, to confirm the ratio of male and female researchers, we have tried many programs and websites that were claimed to be able to automatically identify gender by name, but the accuracy was very poor. Hopefully, there will be more accurate and efficient methods to match the name and gender in the future. Third, due to the diversity of institutions naming, we had no way to accurately rank all the institutions. Instead, we sorted institutions by the list of the top 100 most cited studies manually and mapped them. The results were consistent with our knowledge of the leading institutions in this field.

Conclusions

In this study, we performed a bibliometric analysis of AD in the recent ten years and many “firsts” or “mosts” have been identified, providing some objective evidence for comprehensive understanding and evaluation of this field, which might ultimately inform managers, researchers and policymakers.

The article’s supplementary files as