Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria

P1077Late gadolinium enhancement with cardiac magnetic resonance imaging demonstrates left ventricular involvement is under-recognized in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Left Ventricular Involvement in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Assessed by Echocardiography Predicts Adverse Clinical Outcome

Medical conception of a disease begins with in vivo observation and develops with recognition of cognate findings on gross anatomy, histology, and cellular pathology. It was histopathology that established myocyte disarray as the cardinal feature of hypertrophic cardiomyopathy, present even in cases where left ventricular (LV) hypertrophy is subtle or absent. To this day, clinical-pathological association retains its historical value as the primary means of gaining insight into underlying disease processes. Enhancing its appeal is its accessibility to physicians, most of whom are familiar with histopathology from medical school and attuned to visual diagnosis. Article see p 632 With the advent of molecular genetics, however, the limitations of clinical-pathological association have become apparent and nowhere more so than in the inherited arrhythmia syndromes. In the long-QT and Brugada syndromes and catecholaminergic polymorphic ventricular tachycardia, a structurally normal heart belies the propensity to ventricular arrhythmia and sudden cardiac death (SCD). How this might be possible began to unravel with the isolation of mutations in genes encoding ion channels, transporters, and binding proteins. Genetic studies also have provided fresh insights into diseases with an obvious pathological substrate, such as hypertrophic cardiomyopathy, in which sarcomeric mutations predominate. Families with a high incidence of SCD and myocyte disarray but minimal LV hypertrophy were found to have mutations in troponin T,1 lending further support to the inclusion of this phenotype within the spectrum of hypertrophic cardiomyopathy. Redefining diseases according to their genetic etiology, while attractive, is less straightforward than immediately obvious. Defects in sarcomeric components, for example, have been implicated in both hypertrophic cardiomyopathy and dilated cardiomyopathy. In some heritable disorders, such as dilated cardiomyopathy, marked locus heterogeneity precludes delineation of a single genetic determinant. The ultimate solution to disease classification involves going 1 step further and identifying a unifying molecular mechanism, which may …

Background The prevalence and course of heart failure (HF) in arrhythmogenic cardiomyopathy (ACM) is unresolved, and previous studies have mostly focused on the right-dominant variant of the disease, less prone to HF. Conversely, ACM variants with left ventricular (LV) involvement are now increasingly recognized, often initially ‘mis-diagnosed’ as dilated cardiomyopathy. Aim of this study was therefore to describe the prevalence and clinical course of advance HF in the full clinical spectrum of ACM. Methods We retrospectively reviewed records of all ACM patients diagnosed before 2021 from 3 Italian Cardiomyopathy Referral Centres (Azienda Ospedaliero Universitaria Careggi; Policlinico Sant’Orsola; Azienda Ospedaliero Universitaria Sant’Andrea). LV involvement was diagnosed in the presence of subepicardial late gadolinium enhancement (LGE) in at least 3 contiguous segments in the same short-axis slice at cardiac magnetic resonance, independent of whether it fulfilled the 2010 Task Force criteria for right-dominant ACM (biventricular ACM) or not (left-dominant ACM); in this latter case, diagnosis was reached after careful exclusion of other differential diagnosis, and only when at least one of the following features was present: likely pathogenic/pathogenic genetic variant associated with ACM; familial history of ACM; electrocardiographic abnormalities suggestive of ACM with LV involvement. Advanced HF was defined as NYHA functional class III/IV and/or referral for heart transplantation. Median follow-up was 6 years. Results Forty-four out of 174 ACM patients (25%) developed advanced HF: 10 right-dominant ACM and 34 with LV involvement. Twenty ACM patients were initially diagnosed with dilated cardiomyopathy; as such, development of advanced HF in 17 cases preceded the diagnosis of ACM. Five patients were diagnosed with ACM after heart transplantation, by histological examination. In the other 22, median time from ACM diagnosis to advanced HF development was 4 years. As compared to those without, advanced HF patients were more likely to present LV involvement. During clinical course, 20 (46%) advanced HF patients received at least one appropriate ICD intervention, with 13 experiencing an electrical storm. Twenty-six (59%) patients required HF-related hospitalization, and 32 (72%) were referred for heart transplantation with 25 ultimately receiving it. ACM patients with advanced HF, compared to those without, experienced a higher rate of mortality (36% vs. 6%; OR 3.5 [95%CI: 1.4-8.7], p=0.01) and ventricular arrhythmic events (41% vs. 11%; OR 2.4 [95%CI: 1.1-5.0], p=0.02). Conclusions Advanced HF progression in ACM is not rare, and occurs more frequently in variants with LV involvement. Advanced HF is associated with increased mortality and arrhythmic risk.

Long-Term Follow-Up Data on Flecainide Use as an Antiarrhythmic in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multicenter Study.

Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Sleep-disordered breathing (SDB) is an important comorbidity in patients with cardiac arrhythmias. Previous studies confirmed associations between supraventricular and ventricular arrhythmias and SDB. In heart failure patients, SDB was also found independently associated with a shorter event-free survival to the occurrence of malignant ventricular arrhythmias requiring appropriate cardioverter-defibrillator therapy. In obstructive sleep apnea, repetitive hypoxemia, mechanical stress (wall tension), arousals from sleep, and activation of the sympathetic nervous system promote cardiac arrhythmias. Pathophysiological concepts for the link between Cheyne-Stokes respiration and malignant arrhythmias are not fully understood and require further research. In addition, large-scale, randomized, controlled trials are awaited to prove whether adequate treatment of SDB is associated with a risk reduction for the occurrence of arrhythmias, in general, and malignant ventricular arrhythmias, in particular, in these patients.

Recent multicenter studies using high-tech cardiac imaging and novel translational technologies have shown that cardiac fibrofatty replacement, characteristic of arrhythmogenic cardiomyopathy (ACM), is observed in both ventricles; left ventricular (LV) involvement may be minimal, on par with the right ventricle (RV), or dominant. In 2019, the Heart Rhythm Society (HRS) proposed a new approach to the assessment of arrhythmic and genetic diseases with the inclusion of new phenotypes — left-dominant ACM and biventricular ACM. In 2020, to improve the diagnosis of left ventricular phenotypes, European experts revised ACM criteria (based on the 2010 ITF criteria), which are called the Padua criteria. The presented article highlights the clinical and genetic aspects of the new concept and the difficulties in ACM diagnosis, the practical experience of using new diagnostic algorithm. To help practitioners, step-by-step differential diagnosis and risk stratification of right and left ventricular phenotypes are presented using clinical examples (leftdominant ACM with a pathogenic variant in the LMNA gene; right-dominant ACM associated with a desmoplakin gene mutation, with predominant RV and moderate LV involvement; and an isolated RV ACM associated with a mutation in the plakophilin 2 gene).

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria (“the Padua criteria”) were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.

case presentation: A 48-year-old woman presents with exertional dyspnea and recurrent syncope. One year earlier, a permanent pacemaker was placed after she complained of fatigue and was found to have high-grade atrioventricular block. Now, she has echocardiographic evidence of moderate to severe left ventricular (LV) systolic dysfunction with regional wall-motion abnormalities. Nuclear imaging is notable for heterogeneous myocardial uptake of technetium Tc99m sestamibi, and coronary angiography reveals widely patent epicardial vessels. Multiple episodes of nonsustained ventricular tachycardia (VT) are documented on continuous ECG monitoring. What are the diagnostic considerations for this patient, and what further evaluations are indicated? This patient presents with dilated cardiomyopathy (DCM) with electric instability (DCM+E), which we define as conduction disease and arrhythmia out of proportion to the severity of LV systolic dysfunction. Diverse causes can result in DCM+E and fall into general categories of inflammatory, infectious, hereditary, and infiltrative processes. Cardiac presentation associated with these conditions is distinct from more common causes of DCM such as ischemic heart disease, viral myocarditis, valvular dysfunction, pregnancy, or substance abuse. Clinical features that are suggestive of DCM+E include supraventricular arrhythmias or conduction disease that precedes cardiomyopathy, multiple VT morphologies, and features suggestive of ischemic heart disease (Q waves, regional wall-motion abnormalities, perfusion defects, ventricular aneurysm) in the absence of epicardial stenoses. In this Clinician Update, we focus on the diagnostic approach to patients with DCM+E. Emphasis is placed on diagnoses that are relatively common or for which the clinical management would be impacted significantly by recognition of the underlying cause. Ischemic heart disease may present with conduction disease and a high burden of arrhythmia, especially in the setting of acute myocardial ischemia/infarction. The exclusion of obstructive coronary artery disease is strongly recommended in patients with DCM+E because atherosclerosis is so prevalent, evidence-based treatment is readily available, and the …

Sudden killer

Objective To investigate the characteristics of clinical and cardiovascular magnetic resonance imaging(CMR) of arrhythmogenic cardiomyopathy with left ventricular(ALVC) involvement. Methods Ten cases of arrhythmogenic cardiomyopathy with left ventricular involvement and sixteen randomly chosen cases of arrhythmogenic cardiomyopathy with right ventricular (ARVC) involvement were enrolled in this study. Clinical symptoms, cardiac electrophysiological changes as well as the cardiac morpharage, ventricular functions and delayed enhancement of myocardium assessed by CMR were compared between the two groups. The size of heart chambers, global ventricular functions and the fat/fibrosis infiltration were evaluated by turbo fast spin echo, ture FISP cine and delayed enhancement. These were statistically analyzed by independent samples t test, respectively. Results There was no significant difference in age and gender between two groups. All the patients in two groups presented non-specific clinical manifestations with no significant differences (P>0.05) except for short of breath(P=0.034). The end-diastolic diameter of left ventricular, left ventricular end-diastolic volume index, left and right ejection fraction in ALVC and ARVC group were (64.2±7.7), (49.2±5.9) mm (t=5.551 , P<0.001), (113.9±24.0), (69.2± 30.0) ml/m2 (t=3.962, P<0.001), (38.5±3.1)%, (56.0±8.4)%(t= -6.733,P<0.001), (42.0±5.5) %, (18.0±7.3)% (t=8.817, P<0.001) respectively. An medium of 11 and 14 segments of fat or fat/fibrosis were found in intramural wall of the LV myocardiumin patients with ALVC,while only 0 segment(all P<0.001)was found in patients with ARVC. Conclusions The clinical manifestations of arrhythmogenic cardiomyopathy with left ventricular involvement was similar to ARVC, however, with regarding to cardiac morphological, functional and myocardial lesions, these two diseases have different characteristics in CMR features.one-stop-shop MRI examination has high value in the diagnosis of arrhythmogenic cardiomyopathy with Left ventricular involvement. Key words: Ventricular dysfunction, left; Arrhythmogenic right ventricular dysplasia; Magnetic resonance imaging

Clinical predictors of left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy According to Revised 2010 Task Force Criteria With Inclusion of Non-Desmosomal Phospholamban Mutation Carriers