Author Contributions:
Muhammad Hamza Shah – Conceptualization, Writing – original draft,
Writing – review and editing
Eleni Flari - Writing – original draft, Writing – review and editing
Brandon S H Low - Writing – original draft, Writing – review and
editing
Subham Roy - Writing – original draft, Writing – review and editing
Arjun Ahluwalia - Writing – original draft, Writing – review and
editing
Aditya Gaur - Writing – original draft, Writing – review and editing
John Hanna - Writing – original draft, Writing – review and editing
Ashna Arif - Writing – original draft, Writing – review and editing
Amer Harky - Writing – original draft, Writing – review and editing,
Supervision
Acknowledgements: Muhammad Hamza Shah 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 planned have been
explained.
Data Availability Statement: Data availability is not
applicable to this article as no new data were created or analysed in
this study.
Abstract: Carcinoid Heart Disease (CaHD) is a severe
complication arising in patients with carcinoid syndrome, primarily
impacting the heart’s right side through valvular dysfunctions such as
tricuspid regurgitation and pulmonary stenosis. The pathology is closely
linked to serotonin-induced fibrosis, challenging both diagnosis and
treatment. Advances in echocardiography and cardiac MRI have
significantly improved the early detection and assessment of CaHD, while
management strategies have evolved to include both medical treatments,
like somatostatin analogues and novel pharmacotherapies, and surgical
interventions, notably valve replacement surgeries. Despite progress,
debates persist around the optimal timing for surgery and the choice
between bioprosthetic and mechanical valves, given the distinct risks
and benefits of each. This review synthesises the current understanding
of CaHD, emphasising diagnostic advancements and the spectrum of
treatment options, and advocates for ongoing research to refine
therapeutic approaches..
Keywords: Carcinoid Heart Disease, Neuroendocrine Tumours,
Pathophysiology, Diagnosis, Management, Serotonin, Multidisciplinary
Care, Cardiac Imaging, Valve Replacement
Abbreviations: CaHD: Carcinoid Heart Disease, MRI: Magnetic
Resonance Imaging, NET: Neuroendocrine Tumour, TVR: Tricuspid Valve
Replacement, PVR: Pulmonary Valve Replacement, 5-HT: 5-Hydroxytryptamine
(Serotonin), 5-HIAA: 5-Hydroxyindoleacetic Acid, NT-proBNP: N-terminal
pro b-type Natriuretic Peptide, TTE: Transthoracic Echocardiography,
TOE: Transesophageal Echocardiography, CT: Computed Tomography, ECG:
Electrocardiogram, CXR: Chest X-Ray, NYHA: New York Heart Association,
PRRT: Peptide Receptor Radionuclide Therapy, RHF: Right Heart Failure,
Introduction:
Carcinoid Heart Disease (CaHD) represents a challenging cardiac
pathology, predominantly observed in patients with carcinoid syndrome.
This syndrome primarily arises from neuroendocrine tumours that are most
often located in the gastrointestinal tract or bronchopulmonary
system.1 Notably, up to 50% of patients with
carcinoid tumours develop symptoms of the carcinoid syndrome, leading to
CaHD, which significantly influences morbidity and
mortality.2 Historically, untreated CaHD has been
associated with a 3-year survival rate as low as 31%, markedly lower
than the 68% in patients without cardiac involvement. However, the
landscape of CaHD prognosis has considerably improved due to
advancements in cardiac imaging, antitumor treatments, and surgical
interventions.1 A retrospective study highlighted that
median survival rates have increased from 1.5 years in the 1980s to 4.4
years in the late 1990s, largely attributed to the rise in cardiac
surgery rates among these patients.3
CaHD is characterised by its distinctive involvement of the right side
of the heart, particularly affecting the tricuspid and pulmonary valves.
The result is a spectrum of valvular dysfunctions, predominantly leading
to conditions such as tricuspid regurgitation, pulmonary stenosis, and
ultimately right-sided heart failure.3 The
pathophysiological processes underlying CaHD implicates various
molecular pathways and cellular mechanisms. Most resources cite
vasoactive substances, particularly serotonin, in stimulating fibroblast
growth and fibrogenesis, contributing to the characteristic cardiac
valvular fibrosis observed in CaHD.1,3,4 Despite the
progress in understanding the disease, many aspects of its
pathophysiology remain elusive, prompting ongoing research to uncover
the intricate mechanisms and potential therapeutic targets.
Similarly, the diagnostic journey of CaHD has been revolutionised over
the years, transitioning from a primarily echocardiography-based
approach to a more comprehensive, multimodal strategy. Advanced imaging
modalities, including cardiac magnetic resonance and speckle-tracking
echocardiography, have enriched the diagnostic arsenal, allowing for
more nuanced visualisation and assessment of the cardiac structures
involved in CaHD.5 These advancements have not only
improved diagnostic precision but have also facilitated the early
detection of CaHD, potentially altering the clinical course of the
disease. Furthermore, the management of CaHD is inherently complex,
demanding a comprehensive, multidisciplinary approach that encompasses
medical and surgical strategies. Medical management focuses on
controlling the systemic malignancy and managing the release of
vasoactive substances, primarily through the use of somatostatin
analogues. In cases where valvular disease progresses, surgical
approaches, such as valve replacement surgeries, become paramount. These
procedures have shown promise in alleviating cardiac symptoms and
enhancing patient survival.6 However, they are
accompanied by their own set of challenges, including the careful
selection of suitable candidates and the meticulous management of
perioperative risks.
In this comprehensive review, we aim to synthesise our current
understanding of CaHD, summarising its pathophysiology, the nuances of
its diagnostic modalities, and the spectrum of its management
strategies, while also exploring the frontier of emerging therapies and
diagnostic tools that hold the promise of improving CaHD care.
Methodology:
This review evaluates the current understanding and management
strategies of Carcinoid Heart Disease. The inclusion criteria for this
review were limited to full-text articles written in English, covering
the period from 2000 to 2023. This timeframe was selected to provide a
comprehensive overview of the evolution of treatment protocols and
diagnostic advancements in the field, capturing both longstanding
practices and recent innovations.
Multiple databases were utilised for a thorough literature search,
including PubMed, EMBASE, Google Scholar, the Cochrane Library, and
Scopus. Key terms specifically related to Carcinoid Heart Disease were
employed in the searches, such as “Carcinoid Heart Disease,”
“Serotonin Heart Valve Disease,” “Neuroendocrine Tumours Cardiac
Complications,” “Carcinoid Tumours Heart,” and “Right Heart Valve
Dysfunction Carcinoid.” To broaden the search strategy, additional
sources were identified through a manual examination of references
listed in recent reviews focusing on CaHD and related cardiovascular
complications. Strict exclusion criteria were applied, which involved
omitting standalone abstracts, case reports, posters, and any
unpublished or non-peer-reviewed material. This approach was aimed at
maintaining the integrity of the review by ensuring the inclusion of
only high-quality and scientifically robust evidence.
The scope of the review was not restricted to a specific number of
studies, intending to encompass a comprehensive array of knowledge on
Carcinoid Heart Disease. It included diverse study designs such as
descriptive studies, animal-model studies, cohort studies, and
observational studies. This inclusive approach ensured a wide-ranging
understanding of Carcinoid Heart Disease, covering research conducted in
both pre-clinical and clinical settings. A summary of the methodology
used is provided in Table 1, illustrating the depth and breadth of the
literature search and selection process.