Dr. Amit Goyal, along with episode chair Dr. Dinu Balanescu (Mayo Clinic, Rochester), and FIT leads Dr. Sonu Abraham (University of Kentucky) and Dr. Natasha Vedage (MGH), dive into the fascinating topic of channelopathies with Dr. Michael Ackerman, a genetic cardiologist and professor of medicine, pediatrics, and pharmacology at Mayo Clinic, Rochester, Minnesota. Using a case-based approach, they review the nuances of diagnosis and treatment of channelopathies, including Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and long QT syndrome. Dr. Sonu Abraham drafted show notes. Audio engineering for this episode was expertly handled by CardioNerds intern, Christiana Dangas.

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1. What are the diagnostic criteria for Brugada syndrome (BrS)?

Three repolarization patterns are associated with Brugada syndrome in the right precordial leads (V1-V2):

It is important to note that only a type 1 pattern is diagnostic for Brugada syndrome, whereas patients with type 2/3 patterns may benefit from further testing.

The Shanghai score acknowledges that relying solely on induced type 1 ECG changes has limitations. Therefore, one cannot equate the presence of a type 1 Brugada ECG pattern alone to the diagnosis of Brugada syndrome. The score suggests incorporating additional information—such as clinical history, family history, and/or genetic testing results—to achieve a definitive diagnosis.

2. What is the significance of genetic testing in Brugada syndrome?

There are 23 alleged Brugada syndrome susceptibility genes published with varying levels of evidence. However, only one gene mutation, the loss-of-function variants in the SCN5A gene encoding for the α-subunit of the NaV1.5 sodium channel, is considered to have sufficient evidence.

The overall yield of BrS genetic testing is 20%. The presence of PR prolongation (>200 ms) along with type I EKG pattern increases the yield to 40%. On the contrary, in the presence of a normal PR interval, the likelihood of SCN5A positivity drops to <10%.

3. How would you risk-stratify a patient with Brugada syndrome?

Serious arrhythmic events (SAE), including resuscitated cardiac arrest and sudden cardiac death, rarely represent the initial symptoms of Brugada syndrome. Thus, risk stratification is important.

Factors that increase risk include:

4. What are the treatment options for Brugada syndrome?

5. What are the four diagnostic tests to be done in a patient who presents with an episode of exertional syncope?

Exertional syncope is a high-risk presentation that demands a comprehensive evaluation! This includes:

Do not stop at an EKG and echo alone!

Think of catecholaminergic polymorphic ventricular tachycardia (CPVT) in a patient with exertional syncope and a normal EKG!

6. What are the features on the exercise treadmill test that increase the suspicion for CPVT?

Bidirectional VT is considered a hallmark of CPVT, with digoxin toxicity being the only real imitator. This finding is specific in the absence of digoxin but not sensitive.

During exercise testing in CPVT, as the patient’s heart rate rises with increasing workload, PVCs begin to appear, progressing to bigeminy, couplets, and, in some instances, bidirectional couplets. The ectopy typically vanishes within 30 seconds of the recovery phase. This pattern increases suspicion of CPVT and warrants a detailed family history and genetic testing.

7. What are the genetic underpinnings of CPVT?

Mutations in the ryanodine receptor (RyR2 gene) render calcium release channels leaky, leading to diastolic calcium overload. This ultimately triggers arrhythmias in CPVT.

8. What are therapeutic interventions for a patient with CPVT?

Medical therapy is the mainstay of treatment in CPVT. Drugs include non-selective beta-blockers like nadolol or propranolol. Standard of care currently includes a combination of nadolol plus flecainide. An ICD is indicated only in the case of an aborted cardiac arrest. ICD therapy is never prescribed as monotherapy in these patients.

9. How do we correctly measure the QTc?

The QT interval is measured from the beginning of the QRS complex to the end of the T wave. The end of the T wave is determined using the maximum slope intercept method, in which a tangent line is drawn through the maximum down slope of the T wave. The point at which this tangent line crosses the isoelectric line is the end of the T wave. The U wave is excluded.

10. What are the three primary mutations implicated in Long QT syndrome?