Editorial

Endomyocardial biopsy in arrhythmogenic right ventricular cardiomyopathy☆

Arrhythmogenic cardiomyopathy (ACM) is a disease of the myocardium in which arrhythmia plays a prominent and early role in the absence of causal abnormal loading conditions, ischemia or congenital heart disease. This process can primarily involve the right ventricle as in classical right ventricular cardiomyopathy (ARVC), the left ventricle referred to as left ventricular-dominant arrhythmogenic cardiomyopathy (LD-ACM), or both ventricles (biventricular ACM).

To review the genetic and molecular basis for ACM as well as the various phenotypes, diagnostic criteria, and management from an electrophysiologic standpoint.

ARVC is a disease of the desmosome mediated largely by variants in the PKP2 gene with characteristic early electrocardiographic changes and ventricular arrhythmias originating from the right ventricle. LD-ACM is predominantly caused by mutations in the DSP gene which encodes the desmosomal protein desmoplakin, but may also be mediated by variants in genes encoding non-desmosomal proteins.

Diagnostic criteria exist for both ARVC and LD-ACM and include electrocardographic, cardiac imaging, genetic, and personal and familial historical criteria. Management of these conditions from the perspective of the electrophysiologist centers on accurate diagnosis, risk stratification, and the prevention and treatment of life-threatening ventricular arrhythmias and may include treatment with antiarrhythmic medications, catheter-ablation and implantable cardioverter-defibrillator placement. Familial screening is an important part of the management of patients with ACM and consists of clinical and genetic testing, the latter of which should be undertaken in consultation with a team with expertise in cardiovascular genetics.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder of cardiac desmosomes associated with ventricular arrhythmias and sudden cardiac death. The clinical diagnosis is problematic and relies on a complex criteria composed of clinical and non-clinical parameters. In 2010, the original 1994 Task Force Criteria (TFC) was revised with particular attention given to the imaging parameters.

Five retrospective studies compared the diagnostic concordance between the 1994 and 2010 TFC. Three studies used cardiac magnetic resonance (CMR) and compared major and minor CMR criteria and three studies compared definite ARVC cases; one study assessed both.

Three studies with 1435 patients compared the 1994 imaging and the 2010 CMR criteria. Using the 1994 criteria, 123 (8.6%) and 419 (29.2%) patients satisfied major and minor criteria compared to only 52 (3.6%) and 28 (1.9%) using the 2010 criteria; 57.7% and 94.3% reduction in major and minor criteria (p value, 0.0001 and 0.0001). Three studies with 611 patients assessed for definite ARVC. Using the 1994 and 2010 criteria, 207 (33.9%) and 243 (39.8%) patients satisfied the parameters respectively. This resulted in a statistically significant 17.4% (p value, 0.0379) increase in ARVC cases driven largely by two sub-groups.

The 2010 revised TFC have resulted in a significant reduction in the number of patients that satisfy CMR criteria particularly those that satisfied minor imaging abnormalities using the 1994 criteria. In addition, in certain groups the revised criteria have significantly increased the number of patients diagnosed with definite ARVC.

Arrhythmogenic right ventricular cardiomyopathy is a life-threatening morbid entity, which drew the attention of the scientific community being a significant cause of premature death. In the modern era, it has been first reported in the late 1960s and 1970s as a cause of right ventricular hemodynamic impairment and electrocardiographic abnormalities (epsilon wave). Soon after, autopsy studies demonstrated that young people, especially athletes, may die suddenly and instantaneously because abrupt lethal cardiac arrhythmias, namely ventricular fibrillation, precipitated by exercise. A heredofamilial background was then demonstrated, opening the door to the genetic discoveries of mutations of genes encoding mostly for desmosomal proteins, so that it is now also termed “desmosomal disease.” Major advances have been achieved in terms of diagnostic criteria and imaging tools to detect the pathognomonic features of the disease, that is, the fibrofatty replacement of the ventricular myocardium due to progressive cell death leading often to wall thinning and aneurysms. Genotype–phenotype correlations clearly showed that the disease should not be considered anymore a cardiomyopathy of the right ventricle, but a biventricular disease (arrhythmogenic cardiomyopathy). The present chapter will deal with some aspects of the disease: history, terminology, biological background, pathology, and morphological criteria for diagnosis, endomyocardial biopsy, and recapitulation of the disease in transgenic mice.

The inflammatory involvement of vital organs may represent a dangerous and life-threatening situation: in particular, the inflammation of the myocardial tissue of the heart may lead to severe consequences since the clinical history of the disease may be completely asymptomatic, any clinical sign may be lacking, thus preventing correct diagnosis and treatment. This may occur even in the case of myocarditis and may lead to unexpected death whose cause can be assessable only by means of a thorough histopathological examination. The article reports the case of 61-year old female who developed a flu-like syndrome with very few symptoms, followed by sudden death in three weeks. The autopsy and following histopathological investigations identified the cause of death in a post-viral lymphocytic myocarditis, probably related to the previous infectious disease, and alternative causes (as arrhythmic ventricular dysplasia, vasculitis, sarcoidosis and giant cell myocarditis) were excluded. The exclusive location in the right ventricle was a peculiar finding. The case highlights the importance of the myocardium of the right ventricle, a tissue which is often less considered even in histopathological surveys. The exclusive location of myocarditis in the right ventricle is a rare event but in this case fully responsible for death.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic cardiomyopathy that most commonly affects young adults. The most commonly observed reason of death in patients suffering from ARVC/D is sudden cardiac death (SCD). On the other hand, idiopathic right ventricular outflow tract tachycardia (RVOT VT) usually has a benign course. Both of the entities may have ventricular tachycardia (VT) with left bundle branch block (LBBB) pattern and inferior axis. We tried to propose new discriminating electrocardiographic indices for differentiation of foretold entities.

This was a retrospective study. We reviewed records of patients admitted between 2003 and 2012 with the diagnosis of either ARVC/D or RVOT VT that presented with VT (LBBB morphology).

A total of fifty nine patients (30 RVOT VT and 29 ARVC/D) were enrolled. In ARVC/D group, men were dominant while the reverse was true of RVOT VT. Palpitation was more common in the RVOT VT group (90% vs. 66.7%), but aborted SCD and sustained VT were more common in ARVC/D group. The new ECG criteria proposed by us mean QRS duration in V1–V3, QRS difference in right and left precordial leads, S wave upstroke duration, JT interval dispersion, QRS and JT interval of right to left precordial leads were all significantly longer in ARVC/D when compared to RVOT VT patients (p < 0.001).

The proposed ECG criteria can be used for non-invasive diagnosis of ARVC/D and incorporation in the future updates of ARVC/D task force criteria.