Dr. Champion makes some interesting observations about the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) related to the fact that stress imaging features are not included in the current task force criteria for diagnosis. As Dr. Champion states, the diagnosis of ARVC/D can be challenging, because at rest the right ventricular (RV) structure and function of endurance athletes as assessed by echocardiography may look similar to that of affected ARVC/D probands. Endurance exercise has been shown to increase the risk for adverse events in patients with ARVC/D, suggesting that the stress imposed upon the right ventricle during vigorous exercise can accelerate or exacerbate the disease. Thus, Dr. Champion encourages clinicians to pay close attention to RV function during stress imaging in patients suspected of having ARVC/D. His hypothesis is that the response of the right ventricle during stress echocardiography can assist in the diagnosis of ARVC/D and in screening first-degree relatives. He concludes that the RV response to exercise should be included in future revisions of task force diagnostic criteria.

However, there are few data regarding how the right ventricle in patients with ARVC/D responds acutely to exercise. Studying this can be challenging, because the responses of these affected individuals may vary as a function of their resting RV shape, RV function, and symptom status. A few small studies of exercise testing in asymptomatic carriers of gene mutations associated with ARVC/D and patients meeting criteria for ARVC/D have yielded conflicting results with respect to the utility of the evaluation of the electrocardiogram during exercise but did not incorporate echocardiography. For the diagnosis of ARVC/D, only one study used stress echocardiography to evaluate speckle-tracking strain imaging at rest and at peak stress. In this study, the impaired RV strain exhibited in patients with ARVC/D at rest did not significantly change with peak exercise, while it did improve both in healthy subjects with normal longitudinal strain at rest and in endurance athletes who had impaired RV strain at rest. Although these data are intriguing, it is important to note that these patients with ARVC/D were overt cases who met the task force criteria for ARVC/D at rest even without the stress imaging response. Thus, to date there are no studies examining the additive value of stress echocardiography (with or without the use of RV strain imaging) to diagnose ARVC/D prospectively or to risk-stratify patients with suspected ARVC/D or asymptomatic gene carriers.

Dr. Champion also comments on the use of echocardiographic strain measurements in ARVC/D probands, indicating that some of the studies have demonstrated that indices of RV deformation at rest can differentiate patients with ARVC/D from healthy control subjects. Several small studies have demonstrated abnormal resting RV strain parameters in patients with ARVC/D compared with healthy control subjects. These studies included patients with impaired RV function by other metrics, again rendering concordant data unsurprising. The role of strain imaging in risk stratification of asymptomatic gene carriers, those with borderline diagnoses, or identification of those at higher risk for arrhythmias also remains an area of interest. Increasingly, ARVC/D is being recognized as a myopathy that can involve the right, left, or both ventricles. A multilayer strain analysis of left ventricular function in 27 asymptomatic gene carriers revealed reductions in global and regional left ventricular longitudinal strain of the epicardium compared with healthy control subjects. With respect to risk stratification, Alizade et al. reported that RV free wall global longitudinal strain and strain rate were significantly lower in 17 patients with ARVC/D with histories of ventricular arrhythmias compared with 17 asymptomatic patients diagnosed by genetics or cardiac magnetic resonance imaging. Both groups were free of right heart failure and did not differ by conventional echocardiographic parameters. At least two small studies have found a greater degree of mechanical dispersion of both the right and left ventricles in patients with ARVC/D complicated by arrhythmias, compared with asymptomatic patients, suggesting mechanical dispersion as a means of identifying patients with ARVC/D at higher risk for arrhythmia. Asymptomatic patients with ARVC/D also exhibited more mechanical dispersion compared with healthy individuals. Thus, the potential application of strain imaging in the rest and stress echocardiographic evaluation of patients with ARVC/D, those with borderline diagnoses, and asymptomatic gene carriers, for both diagnostic purposes and risk stratification, is intriguing.

The applications of strain imaging and stress echocardiography in ARVC/D are still in the relatively early stages, and there are many unanswered questions. Among the questions are what is the best parameter to use as a marker of RV structure and function during stress testing. This parameter needs to be easy to measure at the increased heart rates achieved with stress and should enhance the diagnostic accuracy above that of resting parameters. It is a challenge to study any parameter of RV structure and function by echocardiography, because one must ensure that the RV free wall is visualized within the imaging sector throughout the cardiac cycle. A confounding factor for patients with ARVC/D is that their RV free walls are often very thin. Another challenge is that because ARVC/D is a rare disease, most studies are composed of small numbers, and thus there is a question of generalizability of the results. The North American Multidisciplinary Study of Arrhythmogenic Cardiomyopathy/Dysplasia and its North American ARVC Registry has investigated this disease with a larger, well-characterized population. For stress echocardiography and/or RV strain to have added diagnostic value, as mentioned above, it will be critical to study them at all stages of the disease, including asymptomatic carriers of genetic mutations.

Dr. Champion has presented a compelling argument that certain echocardiographic features may improve the diagnosis of ARVC/D. Regardless of whether these are stress echocardiographic parameters or resting strain parameters, more studies are required to delineate the numeric values that will differentiate patients with ARVC/D from normal or those with other RV pathologies. We hope this discussion can initiate more investigation. Interestingly, resting strain echocardiography was just beginning to be applied to patients with ARVC/D at the time of the last revision of the task force criteria. Hopefully, by the time of the next task force revision, there will be sufficient data to determine if it deserves inclusion. Of particular interest is whether stress echocardiography, with or without the addition of strain imaging, may aid in the diagnostic evaluation and risk stratification of patients with borderline diagnoses or asymptomatic gene carriers, especially as genetic testing becomes more widespread in clinical practice. Thus, although the present data are not sufficiently robust to support incorporation of stress echocardiography into current guideline recommendations, they may lay the groundwork for further study.