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Cardiac Amyloidosis and Heart Failure: Clinical Pathophysiology, Diagnosis, and Therapeutic Strategies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: 15 November 2026 | Viewed by 2732

Special Issue Editors

Dr. Ilaria Dentamaro

E-Mail Website
Guest Editor
Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy
Interests: cardiac amyloidosis; cardiomiopathy; cardiac magnetic resonance (CMR); advanced echocardiography; heart failure; hypertrophic cardiomyopathy; bicuspid aortic valve; multimodality imaging
Special Issues, Collections and Topics in MDPI journals
Dr. Laura Fusini

E-Mail Website
Guest Editor
Cardiovascular Imaging Department, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy
Interests: cardiac imaging; mitral valve; prolapse; mitral regurgitation; aortic stentosis; valve prosthesis; left and right ventricular function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiac amyloidosis, once considered a rare and underdiagnosed cause of heart failure, is now recognized as an increasingly prevalent condition, particularly among elderly patients and those with heart failure with preserved ejection fraction. Advances in imaging, biomarkers, and non-invasive diagnostic techniques have significantly improved early recognition, while the therapeutic landscape has evolved rapidly with the introduction of disease-modifying agents. This Special Issue will provide a comprehensive overview of the clinical pathophysiological mechanisms linking amyloid deposition to cardiac dysfunction, highlight the latest developments in diagnostic tools—including cardiac imaging and novel biomarkers—and explore emerging and established therapeutic strategies. By bringing together original research, state-of-the-art reviews, and expert opinions, this Special Issue will enhance our understanding of the complex interplay between cardiac amyloidosis and heart failure.

We hope that this Special Issue will serve as a valuable resource for clinicians, researchers, and all professionals engaged in the care and study of patients with cardiac amyloidosis.

Dr. Ilaria Dentamaro
Dr. Laura Fusini
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiology
  • cardiac heart failure
  • cardiac amyloidosis
  • cardiac imaging
  • cardiomyopathy

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Published Papers (4 papers)

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Research

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11 pages, 892 KB  
Article
Prediagnostic Electrocardiographic Abnormalities in Transthyretin Amyloid Cardiomyopathy: A Longitudinal Observational Study
by Ashwin Venkateshvaran, Helin Mert Karaoglu and Björn Pilebro
J. Clin. Med. 2026, 15(6), 2201; https://doi.org/10.3390/jcm15062201 - 13 Mar 2026
Viewed by 390
Abstract
Background: Early diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) remains challenging. Although ECG and morphological abnormalities at diagnosis are well-described, their temporal evolution has not been systematically evaluated. This study characterized the prevalence and longitudinal progression of electrical and structural cardiac abnormalities preceding ATTR-CM [...] Read more.
Background: Early diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) remains challenging. Although ECG and morphological abnormalities at diagnosis are well-described, their temporal evolution has not been systematically evaluated. This study characterized the prevalence and longitudinal progression of electrical and structural cardiac abnormalities preceding ATTR-CM diagnosis. Methods: We retrospectively analyzed patients with confirmed ATTR-CM evaluated at a specialist amyloidosis center between 2006 and 2023. Diagnosis was established by grade 2–3 myocardial uptake on 99mTc-DPD scintigraphy. Standard 12-lead ECGs and transthoracic echocardiograms were reviewed at diagnosis and at baseline, 3–5 years earlier. Results: Sixty-three patients (79% men; mean age 77 ± 8 years) were studied, including 33 (52%) with hereditary ATTR (ATTRv) and 30 (48%) with wild-type ATTR (ATTRwt). Overall, 95% had a NAC score ≤ 2, consistent with less advanced disease at diagnosis. During the prediagnostic phase, 79% of patients exhibited pathological ECGs. Non-specific ST–T abnormalities (40%), prolonged QTc (38%), left-axis deviation (35%), first-degree AV block (33%) and anterior infarction pattern (33%) were each observed in at least one-third of patients. From baseline to diagnosis, significant prolongation was observed in the PR interval (+26 ms), QRS duration (+11 ms), and QTc interval (+22 ms) (p < 0.001 for all), and a leftward shift observed in the electrical axis (−12.03°, p = 0.011). Low voltage was uncommon at both time points. Although interventricular septal thickness increased significantly (+3.42 mm; p < 0.001), left ventricular ejection fraction and dimensions were relatively stable. Conclusions: In this proof-of-concept study, electrical remodeling precedes functional changes and outperforms low voltages to raise clinical suspicion of ATTR-CM. Full article
(This article belongs to the Special Issue Cardiac Amyloidosis and Heart Failure: Clinical Pathophysiology, Diagnosis, and Therapeutic Strategies)
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12 pages, 811 KB  
Article
Cardiovascular Prognosis in Stable Patients with Cardiac Amyloidosis: A Novel and Simple Risk Score
by Ilaria Dentamaro, Pietro Guida, Yassin Belahnech, Marco Maria Dicorato, Paolo Basile, Maria Cristina Carella, Francesco Mangini, Eduardo Urgesi, Sergio Dentamaro, Cinzia Forleo, Massimo Grimaldi, Marco Matteo Ciccone, Jose F. Rodriguez-Palomares and Andrea Igoren Guaricci
J. Clin. Med. 2026, 15(5), 2045; https://doi.org/10.3390/jcm15052045 - 7 Mar 2026
Viewed by 822
Abstract
Background: Cardiac amyloidosis (CA) is frequently diagnosed in clinically stable patients, yet the risk of subsequent heart failure (HF) hospitalization remains difficult to predict using readily available tools. Early identification of high-risk outpatients is crucial to optimize follow-up and therapeutic strategies. Purpose: To [...] Read more.
Background: Cardiac amyloidosis (CA) is frequently diagnosed in clinically stable patients, yet the risk of subsequent heart failure (HF) hospitalization remains difficult to predict using readily available tools. Early identification of high-risk outpatients is crucial to optimize follow-up and therapeutic strategies. Purpose: To develop a simple, non-invasive risk score to predict HF hospitalization in stable patients with cardiac amyloidosis using standard electrocardiographic and echocardiographic parameters. Methods: We prospectively enrolled 100 consecutive patients with confirmed cardiac amyloidosis from three tertiary centers. Baseline evaluation included clinical assessment, electrocardiography, and transthoracic echocardiography. The primary endpoint was HF hospitalization during follow-up; secondary endpoints were HF-related and all-cause mortality. Cox regression analysis was used to identify independent predictors of HF hospitalization and to derive a point-based risk (CAMY-HF) score. Results: During a median follow-up of 36 months, 55% of patients required HF hospitalization and 47% died. Low QRS voltage, interventricular septal thickness ≥14 mm, and left ventricular ejection fraction ≤40% independently predicted HF hospitalization and were incorporated into the CAMY-HF score (range, 0–4). HF hospitalization occurred in 0% of low-risk, 47.9% of intermediate-risk, and 80.6% of high-risk patients at 3 years. Higher CAMY-HF scores were also associated with increased HF-related and all-cause mortality. Conclusions: The CAMY-HF score is a simple, widely applicable tool for early risk stratification in clinically stable patients with cardiac amyloidosis. By relying on routine ECG and echocardiographic parameters, it may help identify outpatients at high risk of HF hospitalization and guide follow-up intensity and management strategies. Full article
(This article belongs to the Special Issue Cardiac Amyloidosis and Heart Failure: Clinical Pathophysiology, Diagnosis, and Therapeutic Strategies)
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Review

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27 pages, 3686 KB  
Review
New Insights in the Diagnosis and Treatment of Atrial Fibrillation in Patients with Hypertrophic Obstructive Cardiomyopathy
by Cristina-Mihaela Angelescu, Toma Andrei Iosifescu, Cristina Ioana Căldăraru, Andrei Daniel Dermengiu, Oana Raluca Ioniţă, Horaţiu Moldovan and Lucian Florin Dorobanţu
J. Clin. Med. 2026, 15(8), 3014; https://doi.org/10.3390/jcm15083014 - 15 Apr 2026
Viewed by 245
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common genetic disease in the general population, with a variable phenotypic expression and symptomatology. Atrial fibrillation (AF) is the most common arrhythmia identified among patients diagnosed with HCM. Treatment of both AF and HCM has continuously evolved [...] Read more.
Hypertrophic cardiomyopathy (HCM) is the most common genetic disease in the general population, with a variable phenotypic expression and symptomatology. Atrial fibrillation (AF) is the most common arrhythmia identified among patients diagnosed with HCM. Treatment of both AF and HCM has continuously evolved over time, leading to a significant improvement in the prognosis and life expectancy of symptomatic patients. Numerous studies have demonstrated that the risk of developing this arrhythmia correlates with atrial morphological, functional and electrical remodeling, a process known as atrial myopathy. Once a first episode of AF is diagnosed, permanent anticoagulation is required among patients diagnosed with HCM, regardless of the CHA2 DS2-VA score. Additionally, atrial cardiomyopathy is associated with an increased thromboembolic risk, independent of AF presence, in patients with stable sinus rhythm, in the context of atrial mechanical and endothelial dysfunction. This article aims to evaluate the current scientific evidence and treatment approaches in patients diagnosed with HCM. Full article
(This article belongs to the Special Issue Cardiac Amyloidosis and Heart Failure: Clinical Pathophysiology, Diagnosis, and Therapeutic Strategies)
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Other

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12 pages, 3803 KB  
Case Report
Severe Acute Decompensated Heart Failure in a Patient with Cardiac Sarcoidosis
by Mateusz Lucki, Ewa Straburzyńska-Migaj, Szczepan Cofta and Maciej Lesiak
J. Clin. Med. 2025, 14(23), 8462; https://doi.org/10.3390/jcm14238462 - 28 Nov 2025
Viewed by 638
Abstract
Introduction: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening manifestation of systemic sarcoidosis, often leading to arrhythmias, conduction abnormalities, or heart failure. Diagnosis is challenging due to nonspecific symptoms and the need for advanced imaging or biopsy. Case Presentation: We describe a [...] Read more.
Introduction: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening manifestation of systemic sarcoidosis, often leading to arrhythmias, conduction abnormalities, or heart failure. Diagnosis is challenging due to nonspecific symptoms and the need for advanced imaging or biopsy. Case Presentation: We describe a 49-year-old man admitted with severe decompensated heart failure (NYHA IV). He had a history of complete heart block treated with pacemaker implantation and subsequent CRT-D upgrade. On admission, echocardiography revealed biventricular dysfunction with severe mitral and tricuspid regurgitation. Cardiac MRI demonstrated extensive non-ischemic late gadolinium enhancement. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA) and intravenous antibiotics were initiated. Despite diuretics and inotropes, his condition deteriorated. Corticosteroid therapy was started due to high suspicion of sarcoidosis. Endomyocardial biopsy confirmed CS. The patient developed neuropsychiatric complications and, despite urgent listing for heart transplantation, died during hospitalization. Conclusions: This case highlights the diagnostic and therapeutic challenges of CS, the limitations of corticosteroid therapy in advanced disease, and the importance of early recognition with advanced imaging modalities. Full article
(This article belongs to the Special Issue Cardiac Amyloidosis and Heart Failure: Clinical Pathophysiology, Diagnosis, and Therapeutic Strategies)
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