Key Information
Abstract
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and frequently underdiagnosed cause of heart failure characterized by the pathological deposition of misfolded transthyretin (TTR) proteins in the cardiac tissue, leading to a poor prognosis and a significant reduction in quality of life. Despite its severity, therapeutic options remain limited, and knowledge gaps persist. This study aims to construct a knowledge map and identify research hotspots within the field of ATTR-CM.
Methods: Data were extracted from the Web of Science Core Collection (WoSCC), covering the period from January 1, 2000 to June 1, 2024. Bibliometric analyses were supplemented by qualitative assessments. VOSviewer, CiteSpace, and Bibliometrix were used to visualize academic community clusters, collaboration and citation networks to identify trends and hotspots in ATTR-CM research.
Results: A total of 1855 publications were analyzed. Contributions from multiple disciplines fueled a consistent upward trend in publications and citations. Europe and the United States dominated ATTR-CM research, with Mathew S. Maurer as the most prolific author, and the University of London as the leading research institution. The journals publishing these documents and references demonstrated credibility and broad disciplinary coverage. Reference analysis identified 10 main research fields. Keyword analysis unveiled five promising themes for research: early diagnosis and prognosis algorithm, specific medication development, management of comorbidities and complications, epidemiology and genotype-phenotype correlation, and molecular biology and mechanisms.
Conclusion: This study is the first comprehensive bibliometric analysis of the ATTR-CM field, supplemented by qualitative assessments. It systematically examines development trends, academic networks, and research themes, while identifying research hotspots and proposing future directions and approaches. These findings provide valuable insights to deepen the understanding of ATTR-CM and may foster advancements in scientific research and clinical applications.
Keywords: transthyretin amyloid cardiomyopathy, heart failure, tafamidis, molecular therapeutics, bibliometric analysis
Introduction
Heart failure is a major global public health concern and a leading cause of hospitalization and mortality 1external link, opens in a new tab. Transthyretin amyloid cardiomyopathy (ATTR-CM), also referred to as transthyretin cardiac amyloidosis (ATTR-CA), is a frequently under-recognized cause of heart failure associated with a poor prognosis, particularly among the elderly population 2external link, opens in a new tab. Previous studies demonstrated that approximately 13% of elderly patients with heart failure with preserved ejection fraction (HFpEF) were affected by ATTR-CM 3external link, opens in a new tab, and a substantial proportion of ATTR-CM patients also present with heart failure with reduced ejection fraction (HFrEF) and right heart failure 4external link, opens in a new tab. However, the median survival after diagnosis in inadequately treated ATTR-CM patients ranges from 31 to 69 months 5external link, opens in a new tab. The delayed or missed diagnosis of -CM is primarily attributed to its nonspecific clinical presentation, which closely resembles hypertensive heart disease or hypertrophic cardiomyopathy, insufficient clinician awareness, and the dependence on specialized diagnostic tools including endomyocardial biopsy.
Amyloidosis is a group of disorders characterized by the extracellular deposition of misfolded protein aggregates 6external link, opens in a new tab. ATTR-CM occurs when misfolded transthyretin (TTR) protein accumulates in the heart, leading to ventricular wall thickening and impaired cardiac function. ATTR-CM is the cardiac manifestation of transthyretin amyloidosis (ATTR amyloidosis), one of the most clinically significant forms of amyloidosis. Depending on the presence or absence of TTR gene mutations, ATTR is classified into two subtypes: variant ATTR amyloidosis (ATTRv amyloidosis) or wild-type ATTR amyloidosis (ATTRwt amyloidosis) 7external link, opens in a new tab. Beyond cardiac involvement, ATTR amyloidosis can involve multiple organ systems, such as the gastrointestinal and nervous systems, resulting in a wide spectrum of clinical manifestations 8external link, opens in a new tab. This underscores the need for multidisciplinary care and comprehensive research to optimize the management of patients with ATTR-CM. While liver transplantation and advancements in TTR-targeted therapies have improved outcomes for certain patients, therapeutic options for ATTR-CM remain scarce, and substantial gaps in the understanding of its pathophysiology and management persist 9external link, opens in a new tab, 10external link, opens in a new tab. Hence, ATTR-CM research is essential to improving patient prognosis and developing targeted therapies.
Bibliometrics provides a systematic approach to mapping the knowledge landscape and identifying research hotspots by analyzing large volumes of literature. Using this methodology, this study aims to analyze the current literature on ATTR-CM with the following objectives: (1) to identify seminal studies, key contributors, and academic community networks, (2) to uncover research trajectories and thematic developments in ATTR-CM, (3) to highlight underexplored areas, providing a foundation for further investigation and guiding future research directions to drive advancements in the field of ATTR-CM. Considering that citation-based metrics may not fully capture the full multidimensional value of a publication or research entity, bibliometric analyses were supplemented with qualitative assessments to ensure a more comprehensive evaluation.