Restrictive cardiomyopathy

ABCHF

Review Article

Filamin C and Cardiomyopathies: Linking Genetic Variants to Their Phenotypic Impact

Natália Olivetti et al. Márya Pagotti Bruno Moreira Santos Marjorie Mizuta … Bianca Linnenkamp Paula de Mendonça Senra Fernanda Andrade Mariana Lombardi Peres de Carvalho Luciana Sacilotto José Eduardo Krieger

Abstract

Filamin C (FLNC) plays a critical role in maintaining the structural integrity of muscle cells, particularly within the cardiac sarcomere. Pathogenic variants in the FLNC gene are increasingly recognized as significant contributors to a diverse range of cardiomyopathies, including dilated (DCM), hypertrophic (HCM), arrhythmogenic (ACM), and restrictive cardiomyopathy (RCM). This review explores the genotype-phenotype correlations in FLNC-related cardiomyopathies, emphasizing how the type and location of genetic variants influence the clinical presentation. Truncating variants are primarily associated with DCM and ACM, characterized by a high risk of arrhythmic events and severe outcomes, while missense variants often lead to HCM and RCM, with unique phenotypic features. The review also discusses the inheritance patterns, molecular mechanisms, and clinical phenotypes of FLNC-associated myopathies, highlighting the need for genetic testing in risk stratification and management. Future perspectives emphasize the importance of expanding research into the underlying mechanisms of FLNC variants and their interactions with other genetic and environmental factors. This integrated understanding is critical for improving the clinical management of patients with FLNC-related cardiomyopathies.

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ABC

Review Article

Cardiac Abnormalities in Hypereosinophilic Syndromes

Viviane Tiemi Hotta et al. Rafael Ruas Nastari Gardênia da Silva Lobo Oishi Alexandre Eiji Kayano … Juliana Alzira Gonzales Oliveira Ruiza Gonçalves Rocha Ana Olga Mocumbi Fernanda Salles Seguro José Eduardo Krieger Fábio Fernandes Vera Maria Cury Salemi

Abstract

Hypereosinophilia (HE) is defined as an eosinophil count exceeding 1500 cells/microL in peripheral blood in two tests, performed with an interval of at least one month and/or anatomopathological confirmation of HE, with eosinophils comprising more than 20% of all nucleated cells in the bone marrow. Hypereosinophilic syndrome (HES) indicates the presence of HE with organ involvement due to eosinophil action, which can be classified as primary (or neoplastic), secondary (or reactive), and idiopathic. Cardiac involvement occurs in up to 5% of cases in the acute phase and 20% of the chronic phase of the disease, ranging from oligosymptomatic cases to fulminant acute myocarditis or chronic restrictive cardiomyopathy (Loeffler endomyocarditis). However, the degree of cardiac dysfunction does not directly correlate with the degree of eosinophilia. The cardiac involvement of HES occurs in three phases: initial necrotic, thrombotic, and finally necrotic. It can manifest as heart failure, arrhythmias, and thromboembolic phenomena. The diagnosis of cardiopathy is based on multimodality imaging, with an emphasis on the importance of echocardiography (echo) as the primary examination. TTE with enhanced ultrasound agents can be used for better visualization, allowing greater accuracy in assessing ventricular apex, and myocardial deformation indices, such as longitudinal strain, may be reduced, especially in the ventricular apex (reverse apical sparing). Cardiac magnetic resonance imaging allows the characterization of subendocardial late gadolinium enhancement, and endomyocardial biopsy is considered the gold standard in diagnosing cardiopathy. Treatment is based on the etiology of HES.

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ABC

Case Report

FLNC Associated Restrictive Cardiomyopathy and Hypertrabeculation, a Rare Association

Ana M. Aristizabal et al. Carlos Alberto Guzmán-Serrano María Isabel Lizcano Walter Mosquera … Juliana Lores Harry Pachajoa Cesar Cely

Abstract

A six-year-old girl with restrictive cardiomyopathy and hypertrabeculation, due to the early onset of her disease, whole exome sequencing was conducted, revealing the presence of a novel heterozygous missense variant in the FLNC gene. The same gene variant was also identified in her father, who, at an adult age, displayed normal imaging results and was symptom-free. This variant has not been reported in population databases or current medical literature and is classified as likely pathogenic.

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ABCHF

Viewpoint

Restrictive Cardiomyopathies: What’s New on the War Front?

Luiz Claudio Danzmann et al. Liciani de Mello Feliciano Elisa Kalil Paula Loredo Siminovich Marianna de Moura Nora

A rare – or not so rare – condition?

Restrictive cardiomyopathies, caused by primary pathologies of the heart muscle, are considered rare diseases, corresponding to about 5% of all cardiomyopathies. The most frequent form of restrictive cardiomyopathy is cardiac amyloidosis (CA), which can be considered a benchmark since, with the availability of diagnostic technologies, its detection has been made much more frequent, associated with the fact that there are effective treatment possibilities.

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ABCHF

Editorial

Amyloidosis: Rare or Underdiagnosed Disease?

Mariano Napoli Llobera et al. Atilio Costa Vitali

Transthyretin amyloidosis

Transthyretin amyloidosis (ATTR) is caused by the deposition of transthyretin (TTR), a protein synthesized by the liver, which has a stable tetrameric structure and whose function is the transport of thyroid hormones and retinol. TTR can dissociate into monomers and oligomers and then be deposited as amyloid fibrils, in a natural (wtATTR or “wild type”, previously known as senile systemic amyloidosis) or genetic manner (hATTR or “hereditary”).

The number of patients diagnosed with ATTR has increased over the years, and it has come to be considered that it may be more prevalent than AL.

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ABCHF

Case Report

Familial Transthyretin Cardiac Amyloidosis with Homozygous Val122Ile Mutation Mimicking Hypertrophic Cardiomyopathy

Caio Rebouças Fonseca Cafezeiro et al. Aristoteles Comte de Alencar Neto Bruno Vaz Kerges Bueno João Henrique Rissato … André Luiz Dabarian Viviane Tiemi Hotta Fábio Fernandes

Abstract

Systemic amyloidosis is a group of diseases caused by the deposition of an amyloid protein that forms fibrils and deposits in tissues. With respect to age and phenotype, patients with the Val122Ile transthyretin (TTR) mutation are similar to those with wild-type cardiac amyloidosis, causing a late-onset restrictive cardiomyopathy with minimal neuropathy, whose median age of onset is 69 years. Homozygous mutation is rare. We report the case of a male patient who had recent-onset heart failure and phenotype of hypertrophic cardiomyopathy. Technetium scintigraphy showed cardiac uptake and absence of circulating immunoglobulins, suggesting TTR cardiac amyloidosis. Genetic analysis confirmed cardiac amyloidosis caused by the homozygous Val122Ile mutant TTR protein.

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ABCHF

Case Report

Sustained Ventricular Tachycardia as an Isolated Presentation of Transthyretin Amyloidosis Cardiomyopathy – Val50Met

Edileide de Barros Correia et al. Larissa Ventura Ribeiro Bruscky Kelin Chen Priscila Cestari Quagliato … Yoná Afonso Francisco Líria Maria Lima da Silva Ana Cristina de Souza Murta

Introduction

Amyloidosis is characterized by extracellular deposition of insoluble proteins (amyloid deposition) in multiple organs and progressive organ dysfunction. It is classified by the type of protein that is deposited, including transthyretin amyloidosis (ATTR), which can occur due to a genetic variant and aging. Approximately 120 genetic variants have been recognized to cause ATTR; one of the most common is Val50Met. The phenotypic presentation of ATTR due to the Val50Met mutation is mostly neurological, known as familial amyloidotic polyneuropathy (FAP), but cardiac involvement is being increasingly recognized. Sporadic cases with strictly cardiac manifestation, causing ventricular wall hypertrophy, dysfunction diastolic, and conduction disturbances have already been described in the literature.

In this article, we report a case of ATTR due to the Val50Met mutation, with the phenotypic expression of cardiac involvement, with sustained ventricular tachycardia as an isolated presentation.

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ABCHF

Viewpoint

What is the Importance of Clinical Clues, and How can we Avoid Mistakes in Following Them?

Salvador Rassi et al. Daniela do Carmo Rassi Aguinaldo Figueiredo Freitas Junior

Approximately half of patients with heart failure (HF) have preserved ejection fraction (EF), and approximately half of these patients have increased left ventricular (LV) wall thickness . This increase in LV wall thickness is usually attributed to left ventricular hypertrophy induced by arterial hypertension (AH). However, cardiac amyloid fibril infiltration also increases ventricular wall thickness, and it can lead to a clinical syndrome of HF with preserved EF (HFpEF).

Light chain amyloidosis (AL) cardiomyopathy occurs in patients with AL or primary amyloidosis, which is a hematologic disease with specific hematologic treatment. Both hereditary transthyretin (hATTR) and wild-type (ATTRwt) amyloidosis can cause transthyretin amyloid cardiomyopathy (ATTR-CM).

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ABCIC

Case Report

Cardiac Amyloidosis: Infiltrative Cardiomyopathy with Restrictive Hemodynamic Behavior – Case Report

José Leonardo Gomes Rocha Júnior et al. Ivan Lucas Rocha Liberato Larissa Ferreira Lopes Letícia Maria Queiroz Rocha Christiane Bezerra Rocha Liberato

Abstract

Amyloidosis is a rare heterogeneous group of disorders that occur with the extracellular deposition of fibrillar protein aggregates in the tissues and organs. Here we report the case of a 76-year-old with a 2-month history of progressive dyspnea on minimal effort. In the investigation, a global cardiac increase was observed, and echocardiography showed infiltrative restrictive heart disease and a pericardial effusion. Cardiac magnetic resonance imaging findings were highly suggestive of cardiac amyloidosis. Thus, as reported here, cardiac involvement primarily manifests as restrictive cardiomyopathy, a chronic heart failure with a difficult-to-diagnose etiology in patients over 50 years of age and a very poor prognosis. Thus, although it remains a diagnostic challenge for clinicians, cardiac amyloidosis must always be considered in the absence of another cause of such findings.

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ABC

Research Letter

Emerging Topics in Heart Failure: New Paradigms in Cardiac Amyloidosis

Marcus Vinicius Simões et al. Silvia Marinho Martins Alves Fabio Fernandes Otávio Rizzi Coelho Filho Sandrigo Mangini

Abstract

Recent evidence suggests cardiac amyloidosis (CA) is a mostly underdiagnosed condition, particularly in the transthyretin-mediated form, and is a frequent cause of heart failure with preserved ejection fraction (HFpEF) in the elderly. New paradigms about CA also involve the development of disease-modifying specific therapies. This article summarizes these new concepts.

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ABC

Case Report

Atrioventricular block pathology in cardiomyopathy by desmin deposition

Luiz Alberto Benvenuti et al. Vera Dermarchi Aiello Breno Alencar Araripe Falcão Silvia Gelás Lage

Generally, restrictive cardiomyopathy due to desmin deposition is characterized by restriction to ventricular diastolic filling and different degrees of atrioventricular block (AVB). In this report, we describe the pathological changes of the cardiac conduction system related to AVB. The sinus node, the compact node, and the penetrating bundle (bundle of His) had no abnormalities, however, there was extensive fibrosis of the terminal portions of the branching bundle and the beginning of the left and right bundles at the top of the ventricular septum. The pathogenesis of this fibrous replacement is probably the same that leads to extensive fibrosis of the working ventricular myocardium, and remains to be elucidated.

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