Author + information
- Sherif F. Nagueh, MD∗ ()
- ↵∗Address for correspondence:
Dr. Sherif F. Nagueh, Methodist Debakey Heart and Vascular Centre, 6550 Fannin Street, SM-677, Houston, Texas, 77030.
- arrhythmogenic cardiomyopathy
- arrhythmogenic right ventricular cardiomyopathy
- strain echocardiography
- ventricular arrhythmia
Arrhythmogenic cardiomyopathy (AC) is an important cause of sudden cardiac death (SCD) in young individuals, particularly male athletes (1). This disease is caused by defects in cardiac desmosomes. It has an autosomal-dominant inheritance in many patients and clinical manifestations are most frequently restricted to the heart without the cutaneous manifestations seen in Naxos disease and Carvajal syndrome (1,2). Pathologically, it is characterized by fibrofatty infiltration of not only right ventricular (RV) but also left ventricular (LV) myocardium. Accordingly, it is more accurate to use the terminology AC as opposed to arrhythmogenic RV cardiomyopathy. Echocardiography and cardiac magnetic resonance imaging (CMR) play an important role in establishing the diagnosis, along with clinical, electrocardiographic/electrophysiologic, and histopathologic findings (1,2). Presentation covers the wide spectrum of asymptomatic apparently healthy gene carriers to SCD or advanced heart failure. Risk stratification for SCD is an important target of disease management. Patients with previous cardiac arrest due to malignant ventricular arrhythmias or with advanced heart failure have the highest risk for SCD and warrant implantable cardioverter-defibrillator (ICD) implantation. However, it can be challenging to consider such therapy in other patients’ groups. In this issue of iJACC, Lie et al. (3) report on the role of additional imaging criteria in patients with a lower risk for SCD.
The investigators followed 117 AC probands and their family members for an average of 4 years after echocardiographic imaging. There were 18 patients who developed life-threatening ventricular arrhythmias as ascertained from electrocardiography, Holter monitoring, ICD recordings, and ICD shock therapy (ICD implanted previously for primary prevention). Expectedly, the majority of events (14 of 18) were in the probands. Some patients had chest pain or palpitations and 12 of the 18 patients with events had syncope that, if unexplained, usually conveys a higher risk of SCD. Based on the text, it is reasonable to assume that there were no signs or symptoms of heart failure. However, Table 2 indicates there were some patients with RV and LV dysfunction as surmised from the CMR findings with respect to the LV ejection fraction (EF) (patients with ventricular arrhythmia 51 ± 8%), and the RV EF (patients with ventricular arrhythmia 37 ± 8%). In addition, almost one-half the patients with ventricular arrhythmias had RV aneurysms and two-thirds exhibited segmental RV dysfunction. In this single-center cohort, the authors also identified a higher prevalence of abnormal RV function manifested by tricuspid annular plane systolic excursion, RV strain, and larger RV diastolic dimensions. Similarly, LV global longitudinal strain was more impaired in patients with arrhythmic events.
Because of the patchy nature of the ventricular involvement, the magnitude and the timing of segmental mechanical contraction is not homogeneous, which can be detected by imaging. There are several approaches to look at mechanical dyssynchrony or mechanical dispersion, including the standard deviation of the time to peak strain, which was used in this study (3). Interestingly, both RV and LV time indices of mechanical dispersion in this study were longer in patients with ventricular arrhythmia. High-intensity exercise, T-wave inversion, and LV mechanical dispersion were retained in the risk prediction model with variables having the highest Harell’s C statistic.
The authors are congratulated on this interesting study that opens the door to the evaluation of additional imaging parameters for risk stratification of SCD in this patient population. Aside from the issue of risk stratification, there are several important observations noted, including the adverse effects of exercise on outcome and the prolific evidence of LV involvement in patients with AC. Exercise can potentially promote the development of the disease, accelerate its progression, and induce arrhythmias (1). With respect to LV involvement, the differences between patients with and without ventricular arrhythmias in LV volumes, EF, global longitudinal strain, mechanical dispersion, and presence of delayed hyperenhancement are key findings that draw attention to the need for careful evaluation of not only RV structure and function, but also LV structure and function in patients with AC. Although abnormal RV strain in the subtricuspid region likely represents an early phenotypic expression of the disease (4), it is unknown how the evolution of RV and LV structural abnormalities is eventually related to arrhythmic events, particularly specific arrhythmias that are considered major criteria for diagnosis (ventricular tachycardia with superior axis and left bundle branch block morphology). Notwithstanding these considerations, it is tempting to attribute LV/RV mechanical dispersion to the presence of LV/RV histopathological changes, which could be the foci for reentrant ventricular tachycardia circuits.
An important question after reading this interesting article is whether indices of subtle LV and RV dysfunction should be incorporated in risk prediction models for SCD. The authors have done pioneering work in drawing attention to the importance of mechanical dispersion analysis in potentially identifying patients at high risk of SCD in the post-myocardial infarction setting (5,6). They have now extended this concept to patients with AC. Although encouraging, the small number of events precludes definitive recommendations to include LV mechanical dispersion for risk stratification of SCD. Nevertheless, this study is a good starting point to pose several questions for a multicenter effort aimed at developing a robust model for risk stratification of SCD, including the incremental value of LV mechanical dispersion, RV mechanical dispersion, and abnormal segmental/global function based on LV strain measurements in the setting of normal LV and RV EF and apparently normal segmental function, as well as CMR findings in both ventricles pertaining to replacement fibrosis (presence and distribution) and increased extracellular volume given the presence of increased fibrosis in AC.
Moving to other issues pertaining to AC, there are questions that imaging can help with respect to understanding the pathogenesis of arrhythmias in this disease as well as its treatment. For example, increased adrenergic activity could be a trigger for arrhythmia and disease progression, and beta-blockers are recommended for patients with a definite diagnosis. However, we do not know what effects, if any, beta-blockers have on RV and LV structure and function, including indices of mechanical dispersion. Catheter-based ablation of ventricular tachycardia is yet another treatment option for these patients, albeit restricted to specific groups. It is usually considered for patients with incessant ventricular tachycardia that is not responsive to antiarrhythmic medications. Because the re-entry circuits are often located in the epicardium, an epicardial approach for ventricular tachycardia ablation can be very effective in these scenarios. One can envision multilayered strain, as well as CMR for delayed hyper-enhancement, to shed insight into the location of the reentry circuit and hence the most suitable approach for ablation. Further, because the disease is progressive, regular imaging at suitable intervals (could be yearly or sooner should there be a change in clinical status) with echocardiography and CMR can draw attention to the extension of pathological changes to other LV and RV regions from which ventricular tachycardia may originate later on. The study by Lie et al (3) shows the time has come for imaging strategies to focus not just on diagnosis, but also on risk stratification and informing treatment decisions.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Nagueh has reported no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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