Monday, April 17, 2023

Catecholaminergic polymorphic ventricular tachycardia

Sammy Berko, a teenage boy from Missouri City, Texas, went to a rock climbing gym where he suffered cardiac arrest and died. Two hours later he was alive.

"He climbed to the top of the wall, rang the bell, as we were told, and then his body went limp, and it looked like he was either playing around or passed out. They weren't quite sure and when they realized he was unresponsive, they lowered him slowly," Jennifer Berko, Sammy's mother, told Houston's Fox 26.

Paramedics and doctors proceeded to administer CPR for two hours before informing Jennifer that, "He's, gone." She and her husband, Craig, sat with their son for a few minutes to say their goodbyes.

"I started talking to him, just telling him how much I love him and sorry that we didn't know how to save him. Suddenly, as I started praying, my husband said, 'Oh my gosh, he's moving,'" said Jennifer to the local news station.

The couple shouted for the medical team who raced back in and began administering aid.

Due to how long Sammy went without oxygen there was fear he suffered a major brain injury. However, aside from some physical injury, he has so far only experienced short term memory loss. "I don't remember anything about the day it happened. The last thing I remember is the night before we had to sign waivers online (for the rock climbing gym), and then I woke up, not even in the pediatric ICU," Sammy told Fox 26. "I woke up in the transitional ICU and that's the first thing I remember. Then I remember my dad telling me, this is what happened and you better remember this time, because he said it so many times."

Despite how lucky Sammy was, that does not mean the road to recovery has been easy. Sammy has been working to recover strength in his legs after a month in the hospital and is undergoing physical therapy for the ischemic spine injury.

"I was very struck by his story. It's very gripping and very unusual. That only young man you know, who had this Catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a super rare genetic disorder that affects his heart," Dr. Stacey Hall, Medical Director of the Pediatric Rehabilitation Program at TIRR Memorial Hermann told Fox 26. "We do see kids all the time here who have had CPR, but with very prolonged CPR, we typically see very severe global anoxic brain injury, so to me, he is a literal miracle."

The Berkos are currently preparing their home to accommodate Sammy's wheelchair.

"I knew it would be a weird, crazy experience learning to walk again and working on strength without using my legs to be able to balance me. It has just been an amazing experience here actually, like I've noticed that I'm better every day! I'm doing something new every single day," Sammy told the local station.

This tragedy also shed some light on a past tragedy as, three years prior, the Berkos lost their son Frankie to what they now know is the same genetic mutation that almost killed Sammy. He and his mother underwent testing and are currently taking medication to help prevent any future issues.

Przybylski R, Abrams DJ. Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor. Curr Opin Cardiol. 2023 Mar 28. doi: 10.1097/HCO.0000000000001051. Epub ahead of print. PMID: 37016946.


Purpose of review: Gain-of-function variants in the gene encoding the cardiac ryanodine receptor (RYR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). The exercise stress test (EST) has long been fundamental in diagnosis and management, but recent work has further explored its role. A new entity termed calcium release deficiency syndrome (CRDS) has been associated with loss-of-function RYR2 variants and a different arrhythmic phenotype.

Recent findings: Standard EST is not perfectly reproducible with regards to provocation of arrhythmia in CPVT. A newly described burst EST protocol may be more sensitive in this regard. Nadolol is the most effective beta blocker in CPVT, though arrhythmic events remain frequent and dual therapy with flecainide and/or left cardiac sympathetic denervation may add protection. A recent report renews debate regarding the use of implantable defibrillator therapy in CPVT. CRDS is characterized by later age of presentation, normal/near normal EST, and ventricular arrhythmia induced by a novel ventricular stimulation protocol.
Summary: Burst EST may aid in the diagnosis and management of CPVT. Nadolol is the preferred beta blocker in CPVT, and consideration should be given to early dual therapy. CRDS should be suspected in patients with arrhythmic events, rare RYR2 variants, and a phenotype inconsistent with CPVT.

PĂ©rez PR, Hylind RJ, Roston TM, Bezzerides VJ, Abrams DJ. Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia. Heart Lung Circ. 2023 Apr 7:S1443-9506(23)00110-5. doi: 10.1016/j.hlc.2023.01.018. Epub ahead of print. PMID: 37032191.


Over the last three decades, the genetic basis of various inherited arrhythmia syndromes has been elucidated, providing key insights into cardiomyocyte biology and various regulatory pathways associated with cellular excitation, contraction, and repolarisation. As varying techniques to manipulate genetic sequence, gene expression, and different cellular pathways have become increasingly defined and understood, the potential to apply various gene-based therapies to inherited arrhythmia has been explored. The promise of gene therapy has generated significant interest in the medical and lay press, providing hope for sufferers of seemingly incurable disorders to imagine a future without repeated medical intervention, and, in the case of various cardiac disorders, without the risk of sudden death. In this review, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT), discussing the clinical manifestations, genetic basis, and molecular biology, together with current avenues of research related to gene therapy.

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