[State of the art and projects of the Italian Fabry Disease Cardiovascular Registry].

Anderson-Fabry disease is a panethnic, rare disease caused by α-galactosidase A deficiency, with subsequent systemic intracellular accumulation of glycosphingolipids. Confined as a nephrological disease for many decades, the widespread use of multimodality imaging techniques over the last 20 years (like cardiac magnetic resonance) has allowed to highlight the frequent and heterogeneous cardiovascular involvement, with important impact on therapeutic strategies and prognosis. However, many grey zones and knowledge gaps remain, both in diagnostic and management approaches.

Left Ventricular Ring-like Pattern: The Arrhythmic Tale of a Scarred Heart.

Cardiac magnetic resonance (CMR) imaging provides significant advantages in the non-invasive diagnosis of cardiac diseases. An emerging phenotype is increasingly being described in CMR reports, the LGE "ring-like" pattern, which resembles a circumferential/semi-circumferential LV scar. Different conditions exhibit this fibrosis distribution, the majority of them being genetically determined and mostly involving cardiomyopathy-causative genes (desmosomal but also other non-desmosomal related genes).

Evolution of Cardiac Damage Staged With Echocardiography in Fabry Disease.

Background: Fabry disease can be classified in 4 stages based on the extent of cardiac damage assessed with echocardiography. This staging is strongly associated with prognosis, with a doubled risk increase of cardiovascular events for each stage progression. The aims of the present study were to investigate the evolution of cardiac damage using this staging system during midterm follow-up and to identify predictors of stage worsening.

Electrocardiogram evolution in Anderson-Fabry disease patients during follow-up in relation to specific treatment and cardiac disease progression.

Aims: Electrocardiogram (ECG) analysis plays a central role in Anderson-Fabry disease (AFD) diagnosis and management. This study aimed to assess ECG evolution during follow-up in relation to specific treatment and disease progression.

Methods: Retrospective study of a multicentric cohort of AFD patients with ≥2 ECG and echocardiographic data.

Cocaine-Induced Sudden Cardiac Death Unravelling a SCN5A-Related Disease.

Cocaine consumption is a significant global problem, with an estimated 20 million users worldwide. Sudden cardiac death is frequently reported in this population, particularly among individuals <40 years of age. The role of underlying inherited heart disorders in these cases remains largely unexplored.

Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis.

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach.

Arrhythmic risk stratification in patients with left ventricular ring-like scar.

Aims: Left ventricular (LV) ring-like scar on cardiac magnetic resonance (CMR) has been linked to malignant arrhythmias in patients with non-ischaemic cardiomyopathy. This study aimed to perform a comprehensive evaluation of this phenotype and to identify risk factors for life-threatening arrhythmic events (LAEs), a composite of sudden cardiac death (SCD), aborted SCD, and sustained ventricular tachycardia.

Methods And Results: One hundred and fifteen patients [median age 39 (interquartile range, IQR, 28-52), 42% females] were identified at 6 referral centres.

Fabry disease in W162C mutation: a case report of two patients and a review of literature.

Background: Fabry disease is a multisystemic disorder characterized by deposition of globotriaosylceramide (Gb3) and its deacylated form in multiple organs, sometimes localized in specific systems such as the nervous or cardiovascular system. As disease-modifying therapies are now available, early diagnosis is paramount to improving life quality and clinical outcomes. Despite the widespread use of non-invasive techniques for assessing organ damage, such as cardiac magnetic resonance imaging (MRI) for patients with cardiac disease, organ biopsy remains the gold standard to assess organ involvement.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes.

Background: A minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes.

Methods: Data of all HCM patients from 7 Italian referral centres were retrospectively evaluated.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

Aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment.

Methods And Results: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure.

Background And Aims: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants.

Screening approaches to cardiac amyloidosis in different clinical settings: Current practice and future perspectives.

Cardiac amyloidosis is a serious and progressive infiltrative disease caused by the deposition of amyloid fibrils in the heart. In the last years, a significant increase in the diagnosis rate has been observed owing to a greater awareness of its broad clinical presentation. Cardiac amyloidosis is frequently associated to specific clinical and instrumental features, so called "red flags", and it appears to occur more commonly in particular clinical settings such as multidistrict orthopedic conditions, aortic valve stenosis, heart failure with preserved or mildly reduced ejection fraction, arrhythmias, plasma cell disorders.

Diagnostic delay in arrhythmogenic cardiomyopathy.

Aims: Diagnosis of arrhythmogenic cardiomyopathy (ACM) may be challenging, as it comprises diverse phenotypes (right dominant, biventricular, and left dominant), and each may overlap with other clinical entities. The issue of differential diagnosis with conditions mimicking ACM has been previously highlighted; however, a systematic analysis of ACM diagnostic delay, and of its clinical implications, is lacking.

Methods And Results: Data of all ACM patients from three Italian Cardiomyopathy Referral Centres were reviewed to assess the time from first medical contact to definitive ACM diagnosis; a significant diagnostic delay was defined as a time to ACM diagnosis ≥2 years.

Myocardial infarction with non-obstructive coronary arteries in hypertrophic cardiomyopathy vs Fabry disease.

Background: Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.

Methods: In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD.

Clinical presentations leading to arrhythmogenic left ventricular cardiomyopathy.

Objectives: To describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations.

Methods: Patients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation familial history of AC red flags for ALVC (ie, negative T waves in V4-6/aVL, low voltages in limb leads, right bundle branch block like ventricular tachycardia) or (2) pathology examination of explanted hearts or autoptic cases suffering sudden cardiac death (SCD).

[Mitral valve prolapse and mitral annulus disjunction: be aware of a potential arrhythmogenic substrate].

Mitral valve prolapse is a relatively common disease with a good overall prognosis. However, in specific clinical and instrumental contexts, patients at high risk of ventricular arrhythmias and sudden cardiac death can be identified. Female sex, history of palpitations or syncope, bi-leaflet myxomatous valve, ECG repolarization abnormalities in the inferior leads, complex ventricular arrhythmias, left ventricular fibrosis detected by cardiac magnetic resonance correlate with a higher risk clinical profile.

Pediatric Restrictive Cardiomyopathies.

Restrictive cardiomyopathy (RCM) is the least frequent phenotype among pediatric heart muscle diseases, representing only 2.5-3% of all cardiomyopathies diagnosed during childhood. Pediatric RCM has a poor prognosis, high incidence of pulmonary hypertension (PH), thromboembolic events, and sudden death, is less amenable to medical or surgical treatment with high mortality rates.

Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson-Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT.

Standard ECG for differential diagnosis between Anderson-Fabry disease and hypertrophic cardiomyopathy.

Objectives: To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM).

Methods: In this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed.

A Pathogenic Galactosidase A Mutation Coexisting With an MYBPC3 Mutation in a Female Patient With Hypertrophic Cardiomyopathy.

The coexistence of GLA (Pro259Ser, c.775C>T) and MYBPC3 (c.1351+2T>C) mutations was found in a female patient with hypertrophic cardiomyopathy.