Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: ST-segment Elevation as an AF Endophenotype

Summary: The purpose of this study is to look for a similarity in people's genes that may help understand which people could benefit from certain drugs for the treatment of atrial fibrillation (AF).

Detailed description: Current drug therapies to suppress AF are incompletely and unpredictably effective and carry significant (albeit generally small) risks of serious adverse effects, including drug-induced long QT syndrome (diLQTS), other forms of proarrhythmia, increased mortality through uncertain mechanisms, and extracardiac toxicity. Identification of clinical and genetic subtypes of AF will permit stratification of therapeutic approaches and thereby facilitate the practice of personalized medicine. Furthermore, limited success of drug therapy and increase in drug toxicity in AF is probably because the arrhythmia represents a final common pathway of multiple initiating mechanisms, including some that are genetically-defined.
  Identifying specific intermediate phenotypes ("endophenotypes") associated with defined clinical courses in AF represents a potential method to systematically subtype patients by underlying mechanism and represents a much-needed clinical advance. Clinical endophenotypes that have been studied include atrial fibrillatory rate, prolonged signal-averaged P-wave duration, and biomarker profiles. The endophenotype we will study here is right precordial ST segment elevation, seen not only in Brugada syndrome (BrS) (where it is unmasked by sodium channel blocking drugs) but also commonly in early-onset ('lone') AF and in patients with AF-associated rare variants in genes encoding the cardiac sodium channel α- or β-subunits. Taken together these data suggest the hypothesis to be tested in this study, that variants in multiple genes can culminate in a similar AF-prone substrate by reducing sodium current that can be identified by screening for baseline or manifest right precordial ST segment elevation endophenotype after sodium channel block with intravenous procainamide.

Eligibility: Inclusion Criteria:
  -  18 years of age or older
  -  Undergoing AF ablation at Vanderbilt or MGH
  Exclusion Criteria:
  -  Patients taking membrane active anti-arrhythmic drugs with sodium channel blocking properties (amiodarone, dronedarone, flecainide, propafenone) at the time of the ablation
  -  Patients with a history of Brugada syndrome or type 1 Brugada ECG pattern on the baseline ECG
  -  Patients with a history of drug-induced torsades de pointes
  -  Patients with a known history of hypersensitivity to procainamide, procaine or related drugs
  -  Patients with a history of systemic lupus erythematosus and myasthenia gravis
  -  Patients with a history of second degree AV block (Mobitz type II) or third degree AV block
  -  Women of child-bearing potential unless post-menopausal, surgically sterile, or have a negative pregnancy test day on the day of procedure
  -  Patients with dual chamber pacemakers or implantable defibrillators requiring ventricular pacing (uninterpretable ECG)
  -  Patients unable to give informed consent

Relevance to patient case: not relevant