We read with interest the article1 and scientific letter2 published by Domingo et al in Revista Española de Cardiología, and would like to congratulate the authors for their work demonstrating the pathogenicity of the RyR2R420Q mutation as the cause of catecholaminergic polymorphic ventricular tachycardia (CPVT), as well as the description of individuals with the RyR2 C2277R mutation. These are 2 important contributions to our knowledge about this disease.
However, we would like to mention a series of considerations concerning the diagnosis of CPVT, the criteria used, the details of the diagnostic protocol used by the authors and, singularly, the extraordinary diagnostic yield of the exercise stress test (performed on a treadmill according to the Bruce protocol).
The exercise stress test is considered to be the most important and most widely recommended diagnostic test for CPVT,3 but it is not reproducible and the results can be negative4 in individuals with the disease. In the context of family screening, the recommendation of international experts representing Europe, the United States, and the Asia-Pacific region is that the observation of ventricular premature beats is sufficient for the test to be considered positive.5
The fact is that diagnostic sensitivity is highly problematic in this disease. Up to 30% of the patients in published series who experienced sudden cardiac death had been asymptomatic until that time, and events have been reported in individuals with a negative baseline exercise stress test.6 Moreover, the sensitivity of the exercise stress test is too low (13%-56% in carriers of RyR2 mutations).7
The diagnostic criteria are not completely defined. Initial requirements were the documentation of polymorphic or bidirectional ventricular tachycardias or ventricular fibrillation during exercise stress testing or following catecholamine infusion.8 Recently, there have been reports of the use of diagnostic thresholds such as more than 10 premature ventricular contractions/minute,7 bigeminy,6 or couplets as the “minimum” ventricular arrhythmia, whose presence is indicative of a diagnosis of CPVT. In addition, although catecholamine infusion is not a totally reliable test, it continues to be used to enhance sensitivity in the diagnosis of this disease, especially when dealing with an index case. However, recent studies have reported the limited usefulness of catecholamine infusion because of its very low sensitivity (28%)7,9 and specificity9 for the diagnosis of CPVT. In one study, it was positive in 56 patients with a negative exercise stress test.7
The reality is that the available tests are insufficiently sensitive, and their negative predictive value is much lower than desired. However, the articles referred to in this letter reports results in terms of sensitivity (89%) and negative predictive value (93%) that do not agree with those reported to date, and convey the message that a negative exercise stress test rules out CPVT. These data probably require an in-depth study of a larger number of members of the family in question and, of course, cannot be extrapolated to other populations with other mutations in what, in our opinion, constitutes a selection bias.
In accordance with the recommendation of the scientific societies,5 a negative exercise stress test does not rule out CPVT. The disease can be confirmed by the presence of specific ventricular arrhythmias during exercise but, in the context of family screening, just 1 premature ventricular contraction is enough to render the results of the test abnormal, and probably justifies the introduction of preventive treatment with beta-blocker therapy. Moreover, the use of catecholamine infusion should be restricted to selected cases, and should not be included in the protocol to be applied on a general basis.
