The 2023 European Task Force Criteria for Diagnosis of Arrhythmogenic Cardiomyopathy: Historical Background and Review of Main Changes.

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disease featured by non-ischemic myocardial scarring linked to ventricular electrical instability. As there is no single gold-standard test, diagnosing ACM remains challenging and a combination of specific criteria is needed. The diagnostic criteria were first defined and widespread in 1994 and then revised in 2010, approaching and focusing primarily on right ventricular involvement without considering any kind of left ventricular variant or phenotype. Years later, in 2020, with the purpose of overcoming previous limitations, the Padua Criteria were introduced by an international expert report. The main novel elements were the introduction of specific criteria for left ventricular variants as well as the use of cardiac magnetic resonance for tissue characterization and scar detection. The last modifications and refinement of these criteria were published at the end of 2023 as the European Task Force criteria, by a "head-quarter" of ACM international experts, proving the emerging relevance of this condition besides its difficult diagnosis. In this review, emphasizing the progress in understanding the aetiology of the cardiomyopathy, an analysis of the new criteria is presented. The introduction of the term "scarring/arrhythmogenic cardiomyopathy" sets an important milestone in this field, underlying how non-ischemic myocardial scarring-typical of ACM-and arrhythmic susceptibility could be the main pillars of numerous different phenotypic variants regardless of etiology.

The "Padua classification" of cardiomyopathies: Combining pathobiological basis and morpho-functional remodeling.

Over the last 20 years, the scientific progresses in molecular biology and genetics in combination with the increasing use in the clinical setting of contrast-enhanced cardiac magnetic resonance (CMR) for morpho-functional imaging and structural myocardial tissue characterization have provided important new insights into our understanding of the distinctive aspects of cardiomyopathy, regarding both the genetic and biologic background and the clinical phenotypic features. This has led to the need of an appropriate revision and upgrading of current nosographic framework and pathobiological categorization of heart muscle disorders. This article proposes a new definition and classification of cardiomyopathies that rely on the combination of the distinctive pathobiological basis (genetics, molecular biology and pathology) and the clinical phenotypic pattern (morpho-functional and structural features), leading to the proposal of three different disease categories, each of either genetic or non-genetic etiology and characterized by a combined designation based on both "anatomic" and "functional" features, i.e., hypertrophic/restrictive (H/RC), dilated/hypokinetic (D/HC) and scarring/arrhythmogenic cardiomyopathy (S/AC). The clinical application of the newly proposed classification approach in the real-world practice appears crucial to design a targeted clinical management and evaluation of outcomes of affected patients. Although current treatment of cardiomyopathies is largely palliative and based on drugs, catheter ablation, device or surgical interventions aimed to prevent and manage heart failure and malignant arrhythmias, better knowledge of basic mechanisms involved in the onset and progression of pathobiologically different heart muscle diseases may allow to the development of disease-specific curative therapy.

[Diagnosis of arrhythmogenic cardiomyopathy: 20 years of progress and innovation]. / La diagnosi della cardiomiopatia aritmogena: vent'anni di progressi ed innovazioni.

Arrhythmogenic cardiomyopathy (CMA) is a cardiac disease characterized by non-ischemic ventricular scarring and electrical instability. The diagnosis of CMA still remains challenging today and requires the use of a set of criteria, since no single diagnostic test represents the gold standard. The first diagnostic criteria were defined and disseminated in 1994 and then revised in 2010, focusing mainly on right ventricular involvement. In 2019, an international panel of experts identified the limitations of the previous diagnostic criteria. The 2020 Padua criteria included a specific pathway for the diagnosis of left ventricular variants and emphasized the need for the use of cardiac magnetic resonance imaging in the characterization of myocardial scarring. These criteria were further refined and published in 2023 as European Task Force (TF) criteria, thus gaining international recognition.Exploring the history of CMA and its diagnosis, in this review we analyze the changes and progress in the 20 years that have occurred from the first version of the criteria in 1994 to the latest in European TF of 2023, highlighting the evolution of our knowledge of the pathobiology and morpho-functional characteristics of the disease. One of the most relevant updates is undoubtedly the introduction of the concept of "scarring/arrhythmogenic cardiomyopathy", a definition that enhances the main features of the pathology and emphasizes the multiplicity of phenotypes and clinical presentations independent of etiology.

Contemporary diagnostic approach to arrhythmogenic cardiomyopathy: the three-step work-up.

Arrhythmogenic Cardiomyopathy (ACM) is a cardiac disorder characterized by non-ischemic myocardial scarring, which may lead to ventricular electrical instability and systolic dysfunction. Diagnosing ACM is challenging as there is no single gold-standard test and a combination of criteria is required. The first diagnostic criteria were established in 1994 and revised in 2010, focusing primarily on right ventricular involvement. However, in 2019, an international expert report identified limitations of previous diagnostic scoring and developed the 2020 Padua criteria with also included criteria for diagnosis of left ventricular variants and introduced CMR tissue characterization findings for detection of left ventricular myocardial scar. These criteria were further refined and published in 2023 as the European Task Force criteria, gaining international recognition. This review provides an overview of the 20 years of progresses on the disease diagnostic from the original 1994 criteria to the most recent 2023 European criteria, highlighting the evolution into our understanding of the pathobiology and morpho-functional features of the disease.

The role of echocardiography in sports cardiology: An expert opinion statement of the Italian Society of Sports Cardiology (SIC sport).

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to long-term, intense training, previously known as the athlete's heart, and to rule out the presence of conditions at risk of sudden cardiac death, including cardiomyopathies, coronary artery anomalies, congenital, aortic and heart valve diseases. Moreover, TTE is useful for distinguishing physiological cardiac adaptations during intense exercise from pathological behavior due to an underlying CVD. In this expert opinion statement endorsed by the Italian Society of Sports Cardiology, we discussed common clinical scenarios where a TTE is required and conditions falling in the grey zone between the athlete's heart and underlying cardiomyopathies or other CVD. In addition, we propose a minimum dataset that should be included in the report for the most common indications of TTE in sports cardiology clinical practice.

A Comprehensive Analysis of Non-Desmosomal Rare Genetic Variants in Arrhythmogenic Cardiomyopathy: Integrating in Padua Cohort Literature-Derived Data.

Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease associations have yet to be determined for the increasing number of genes included in clinical panels. Genetic variants evaluation was undertaken for the most relevant non-desmosomal disease genes. We retrospectively studied 320 unrelated Italian ACM patients, including 243 cases with predominant right-ventricular (ARVC) and 77 cases with predominant left-ventricular (ALVC) involvement, who did not carry pathogenic/likely pathogenic (P/LP) variants in desmosome-coding genes. The aim was to assess rare genetic variants in transmembrane protein 43 (TMEM43), desmin (DES), phospholamban (PLN), filamin c (FLNC), cadherin 2 (CDH2), and tight junction protein 1 (TJP1), based on current adjudication guidelines and reappraisal on reported literature data. Thirty-five rare genetic variants, including 23 (64%) P/LP, were identified in 39 patients (16/243 ARVC; 23/77 ALVC): 22 FLNC, 9 DES, 2 TMEM43, and 2 CDH2. No P/LP variants were found in PLN and TJP1 genes. Gene-based burden analysis, including P/LP variants reported in literature, showed significant enrichment for TMEM43 (3.79-fold), DES (10.31-fold), PLN (117.8-fold) and FLNC (107-fold). A non-desmosomal rare genetic variant is found in a minority of ARVC patients but in about one third of ALVC patients; as such, clinical decision-making should be driven by genes with robust evidence. More than two thirds of non-desmosomal P/LP variants occur in FLNC.

Prevalence and determinants of low QRS voltages and QRS fragmentation in children and adolescents undergoing sports pre-participation screening.

AIMS: Low QRS voltages (LQRSV) in limb leads and QRS fragmentation (FQRS) are possible electrocardiographic signs of myocardial fibrosis and cardiomyopathy, but they are not listed in current criteria for interpreting athlete's electrocardiogram (ECG). We investigated the prevalence and determinants of LQRSV and FQRS in a cohort of young apparently healthy athletes undergoing pre-participation screening (PPS). METHODS AND RESULTS: We analysed a consecutive series of 2140 ECG obtained during PPS of young athletes (mean age 12.5 ± 2.6 years, 7-18-year-old, 49% males). The peak-to-peak QRS voltage was measured in all limb leads, and LQRSV were defined when maximum value was <0.5 mV. Fragmented QRS morphologies were grouped into five patterns. Lead aVR was not considered. Maximum peak-to-peak QRS voltage in limb leads was 1.4 ± 0.4 mV, similar between younger and older athletes, but significantly lower in females than males (1.35 ± 0.38 mV vs. 1.45 ± 0.42 mV; P < 0.001). There was a weak correlation between maximal QRS voltages and body mass index (BMI), but not with type of sport or training load. Only five (0.2%) individuals showed LQRSV. At least one fragmented QRS complex was identified in 831 (39%) individuals but excluding the rSr' pattern in V1-V2, only 10 (0.5%) showed FQRS in ≥2 contiguous leads. They were older than those without FQRS, but did not differ in terms of gender, BMI, type of sport, or training load. CONCLUSION: Low QRS voltages in limb leads and FQRS in ≥2 contiguous leads excluding V1-V2 are rare in young apparently healthy athletes and are not related to the type and intensity of sport activity. Therefore, they may require additional testing to rule out an underlying disease particularly when other abnormalities are present.

Low QRS voltages (LQRSV) in limb leads and QRS fragmentation (FQRS) are possible electrocardiographic signs of myocardial fibrosis and cardiomyopathy. In our study, we analysed the occurrence and characteristics of FQRS and LQRSV in young athletes undergoing pre-participation screening.We found a low prevalence of these abnormalities, with only 0.2% showing LQRSV and 0.5% displaying FQRS.These abnormalities were not associated with factors such as gender, age, type of sport, or training load.

LATERAL EPICONDYLE SLIDING OSTEOTOMY IN KNEE ARTHROPLASTIES WITH VALGUS DEFORMITY.

OBJECTIVE: To evaluate the efficacy and safety of sliding osteotomy of the lateral epicondyle in correcting rigid valgus deformity in knee arthroplasty. METHODS: A retrospective study of patients undergoing total knee arthroplasty with lateral epicondyle sliding osteotomy between 2006 and 2018. The main outcome was the incidence of complications and adverse events. Secondary outcomes were Visual Analog Scale for Pain, varus stress test, and varus knee thrust during gait. RESULTS: 19 knees (19 participants) were included in the study. The mean follow-up was 4.2 years. There were no cases of infection or reoperation due to instability. Two participants (10.5%) had mild or moderate knee pain (VAS pain = 4.6 ± 1.9). Two arthroplasties (10.5%) had mild varus stress. No participant presented varus thrust. CONCLUSION: Sliding osteotomy of the lateral epicondyle allows fast and safe ligament balance of knee valgus deformities. Level of Evidence I, Case series.

Avaliar a eficácia e a segurança da osteotomia de deslizamento do epicôndilo lateral na correção da deformidade em valgo rígida na artroplastia de joelho. Métodos: Estudo retrospectivo de pacientes submetidos à artroplastia total do joelho com osteotomia de deslizamento do epicôndilo lateral entre 2006 e 2018. O principal desfecho foi a incidência de complicações e eventos adversos. Os desfechos secundários foram escala visual analógica para dor, teste de estresse em varo e flambagem em varo do joelho durante a marcha. Resultados: Foram incluídos no estudo 19 joelhos (19 participantes). O seguimento médio foi de 4,2 anos. Não houve nenhum caso de infecção ou reoperação devido à instabilidade. Dois participantes (10,5%) apresentaram algum tipo de dor leve ou moderada no joelho (EVA = 4,6 ± 1,9). Duas artroplastias (10,5%) apresentaram estresse em varo leve. Nenhum participante apresentou flambagem em varo. Conclusão: A osteotomia de deslizamento do epicôndilo lateral possibilitou o balanço ligamentar das deformidades em valgo do joelho de forma rápida e segura. Nível de Evidência IV, Série de Casos.

First report from the European registry for anomalous aortic origin of coronary artery (EURO-AAOCA).

OBJECTIVES: Anomalous aortic origin of a coronary artery (AAOCA) is a group of rare congenital heart defects with various clinical presentations. The lifetime-risk of an individual living with AAOCA is unknown, and data from multicentre registries are urgently needed to adapt current recommendations and guide optimal patient management. The European AAOCA Registry (EURO-AAOCA) aims to assess differences with regard to AAOCA management between centres. METHODS: EURO-AAOCA is a prospective, multicentre registry including 13 European centres. Herein, we evaluated differences in clinical presentations and management, treatment decisions and surgical outcomes across centres from January 2019 to June 2023. RESULTS: A total of 262 AAOCA patients were included, with a median age of 33 years (12-53) with a bimodal distribution. One hundred thirty-nine (53.1%) were symptomatic, whereas chest pain (n = 74, 53.2%) was the most common complaint, followed by syncope (n = 21, 15.1%). Seven (5%) patients presented with a myocardial infarction, 2 (1.4%) with aborted sudden cardiac death. Right-AAOCA was most frequent (150, 57.5%), followed by left-AAOCA in 51 (19.5%), and circumflex AAOCA in 20 (7.7%). There were significant differences regarding diagnostics between age groups and across centres. Seventy-four (28.2%) patients underwent surgery with no operative deaths; minor postoperative complications occurred in 10 (3.8%) cases. CONCLUSIONS: Currently, no uniform agreement exists among European centres with regard to diagnostic protocols and clinical management for AAOCA variants. Although surgery is a safe procedure in AAOCA, future longitudinal outcome data will hopefully shed light on how to best decide towards optimal selection of patients undergoing revascularization versus conservative treatment.

Promoting pain coping skills in haemophilia: A remote intervention integrating exercise and pain education.

BACKGROUND: Chronic joint pain is a significant and widespread symptom in people with haemophilia (PWH). Despite medical advancements, effective pain management remains challenging. AIM: This study presents an innovative approach that integrates remote physical exercises, pain neuroscience education, and coping strategies to address chronic pain in PWH. METHODS: The remote intervention consisted of sixteen 5-min videos encompassing physical exercises for chronic pain management and pain education strategies. These videos formed an 8-week remote intervention program. Clinical and physical assessments were conducted before and after the intervention. RESULTS: A total of thirty-one PWHs, with a median age of 34 years (ranging from 16 to 59 years), completed the remote intervention. The study revealed significant improvements in pain intensity, disability, and physical performance among PWH with chronic pain. Enhanced functional capacity was evident in the Timed Up and Go and Single Leg Stance tests, accompanied by improved scores on the Functional Independence Score in Haemophilia (FISH). Although lacking a control group, our findings are consistent with other successful exercise and pain education programs. CONCLUSIONS: This innovative intervention holds promise for managing chronic pain in PWH, underscoring patient empowerment, education, and collaboration. Notably, our study stands out by uniquely combining pain education and coping strategies, bolstering evidence for effective pain management.

Interpolated junctional extrasystoles mimicking complex polymorphic ventricular arrhythmias in a healthy young athlete: a case report.

Background: In young competitive athletes, ventricular arrhythmias could be a reason for concern as they may represent the sign of a serious underlying cardiac condition. On the other hand, atrial or conduction system premature beats are usually benign. However, when the properties of the His-Purkinje system lead to conduction aberrancies, there is a risk of misinterpreting benign arrhythmias as potentially at risk ventricular ectopic beats. Case summary: We described the case of a healthy young athlete with asymptomatic interpolated junctional ectopic beats interpreted as polymorphic ventricular tachycardia during pre-participation screening. Discussion: Strange and rare electrocardiogram pictures may be observed during sport pre-participation screening. The small atrioventricular (AV) junction is made up of many specialized fibres with different conduction properties. Junctional arrhythmias can have a normal anterograde conduction or can be conducted with aberrancy. Rarely, they can be interpolated and cause PR prolongation or bundle branch block by increasing the refractory period of the AV node and/or the conduction system. When aberrancy occurs, they can be mistaken for 'atypical' ventricular arrhythmias. Prognosis of these events remains uncertain.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.