Atrial Flutter in PRKAG2 Syndrome: Clinical and Electrophysiological Characteristics

Abstract

Background: PRKAG2 syndrome is a rare autosomal dominant disease, a phenocopy of hypertrophic cardiomyopathy characterized by intracellular glycogen accumulation. Clinical manifestations include ventricular preexcitation, cardiac conduction disorder, ventricular hypertrophy, and atrial arrhythmias.

Objective: To compare the clinical and electrophysiological characteristics observed in patients with atrial flutter, with and without PRKAG2 syndrome.

Methods: An observational study comparing patients with atrial flutter: group A consisted of five patients with PRKAG2 syndrome from a family, and group B consisted of 25 patients without phenotype of PRKAG2 syndrome. The level of significance was 5%.

Results: All patients in group A had ventricular preexcitation and right branch block, and four had pacemakers (80%). Patients in group A were younger (39±5.4 vs 58.6±17.6 years, p=0.021), had greater interventricular septum (median=18 vs 10 mm; p<0.001) and posterior wall thickness (median=14 vs 10 mm; p=0.001). In group A, four patients were submitted to an electrophysiological study, showing a fasciculoventricular pathway, and atrial flutter ablation was performed in tree. All patients in group B were submitted to ablation of atrial flutter, with no evidence of accessory pathway. Group B had a higher prevalence of hypertension, diabetes mellitus, coronary artery disease and sleep apnea, with no statistically significant difference.

Conclusion: Patients with PRKAG2 syndrome presented atrial flutter at an earlier age and had fewer comorbidities when compared to patients with atrial flutter without mutation phenotype. The occurrence of atrial flutter in young individuals, especially in the presence of ventricular preexcitation and familial ventricular hypertrophy, should raise the suspicion of PRKAG2 syndrome.

Figura 1. Heredograma da família portadora da síndrome do PRKAG2, com identificação dos 5 pacientes com flutter atrial. MP: marca-passo; CDI: cardioversor desfibrilador implantável. Indivíduos com genotipagem para mutação do gene PRKAG2 identificados como portadores (+) ou não portadores (-). Uma paciente foi submetida a implante de CDI, devido a diagnóstico equivocado de miocardiopatia hipertrófica sarcomérica.

Figura 2. A) Eletrocardiograma inicial do paciente III:15, evidenciando ritmo atrial ectópico, e o aspecto de pré-excitação ventricular, com intervalo PR curto seguido por pseudo-onda delta, e complexo QRS com morfologia de BRD. B) Eletrocardiograma do paciente II:10 com padrão típico da síndrome de PRKAG2, sendo evidenciado flutter atrial com condução 2:1.

Figura 3. Traçado do estudo eletrofisiológico da paciente II:10. Eletrocardiograma de 5 derivações e intervalos básicos durante estimulação atrial, demonstrando HV = 33 ms. AV: átrio-ventricular; A: eletrograma atrial; H: eletrograma do His; V: eletrograma ventricular.

Figure 1. Heredogram of the family with PRKAG2 syndrome, with identification of the five patients with atrial flutter. PM: pacemaker; ICD: cardioverter implantable defibrillator. Individuals tested for a PRKAG2 mutation are identified as carriers (+) or non-carriers (-). A patient underwent ICD implantation due to a misdiagnosis of hypertrophic cardiomyopathy.

Figure 2. A) Initial electrocardiogram of patient III:15, evidencing ectopic atrial rhythm and the aspect of ventricular preexcitation, with short PR interval followed by pseudo-delta wave, and QRS complex with right bundle block morphology. B) Electrocardiogram of patient II:10 with the typical pattern of PRKAG2 syndrome, showing atrial flutter with 2:1 conduction.

Figure 3. Tracing of the electrophysiological study of patient II:10. 5-lead electrocardiogram and basic intervals during atrial stimulation, demonstrating HV = 33 ms. AV: atrium-ventricular; A: atrial electrogram; H: His electrogram; V: ventricular electrogram.