Sudden Death in a Young Man with Catecholaminergic Polymorphic Ventricular Tachycardia and Paroxysmal Atrial Fibrillation

Pizzale, Stephen; Gollob, Michael H.; Gow, Robert M.; Birnie, David H.

doi:10.1111/j.1540-8167.2008.01211.x

Cited by 95 publications

(69 citation statements)

References 12 publications

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“…According to this double-hit concept, the AF substrate could be a genetic mutation (for instance, in RyR2) or atrial remodeling (electrical or structural). Three recent studies have demonstrated evidence for AF under certain circumstances in patients with genetic defects in the Ryr2 gene (37)(38)(39), albeit genetic forms of RyR2-mediated AF are not very common. In addition, enhanced CaMKII phosphorylation of RyR2 was confirmed in atrial biopsies from mice with atrial enlargement and spontaneous AF development, goats with lone AF, and patients with chronic AF.…”

Section: Figurementioning

confidence: 99%

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

Chelu¹,

Sarma²,

Sood³

et al. 2009

J. Clin. Invest.

219

245

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Atrial fibrillation (AF), the most common human cardiac arrhythmia, is associated with abnormal intracellular Ca 2+ handling. Diastolic Ca 2+ release from the sarcoplasmic reticulum via "leaky" ryanodine receptors (RyR2s) is hypothesized to contribute to arrhythmogenesis in AF, but the molecular mechanisms are incompletely understood. Here, we have shown that mice with a genetic gain-of-function defect in Ryr2 (which we termed Ryr2 R176Q/+ mice) did not exhibit spontaneous AF but that rapid atrial pacing unmasked an increased vulnerability to AF in these mice compared with wild-type mice.

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Section: Figurementioning

confidence: 99%

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

Chelu¹,

Sarma²,

Sood³

et al. 2009

J. Clin. Invest.

219

245

View full text Add to dashboard Cite

show abstract

“…Indeed, ICDs have not prevented sudden death in several patients, often because of exhausted therapies after arrhythmic storms or inappropriate discharges triggered by supraventricular tachycardias. 10,11 Recently, preliminary data have suggested the potential value of combination drug therapy involving β-blockers and flecainide, but definitive evidence is still lacking. 12,13 In 2008, we demonstrated that left cardiac sympathetic denervation (LCSD) was quite effective in 3 patients with CPVT who continued to experience ventricular fibrillation and aborted cardiac arrest (ACA) despite full-dose β-blockers.…”

Section: Editorial See P 2169 Clinical Perspective On P 2193mentioning

confidence: 99%

“…Median age at LCSD was 15 years (IQR, 11-17 years), with no difference between symptomatic and asymptomatic patients. The approaches were mostly thoracoscopic (45, 71%) and supraclavicular (13, 21%), and LCSD was complete (from T1-T4) ≥1 end-of-treatment condition 5 (9) Age at first symptom, median (IQR), y 8.5 (6)(7)(8)(9)(10)(11) Age at diagnosis, median (IQR), y 9 (7-14)…”

Section: Lcsd Surgerymentioning

confidence: 99%

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia

et al. 2015

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Background-Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. β-Βlockers are the mainstay of therapy; when they fail, implantable cardioverter-defibrillators (ICDs) are used but often cause multiple shocks. Preliminary results with flecainide appear encouraging.We proposed left cardiac sympathetic denervation (LCSD) as useful additional therapy, but evidence remains anecdotal. Methods and Results-We report 63 patients with CPVT who underwent LCSD as secondary (n=54) or primary (n=9) prevention. The median post-LCSD follow-up was 37 months. The 9 asymptomatic patients remained free of major cardiac events. Of the 54 patients with prior major cardiac events either on (n=38) or off (n=16) optimal medical therapy, 13 (24%) had at least 1 recurrence: 0 patients had an aborted cardiac arrest, 2 patients had syncope only, 10 patients had ≥1 appropriate ICD discharges, and 1 patient died suddenly. The 1-and 2-year cumulative event-free survival rates were 87% and 81%. The percentage of patients with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (P<0.001) after LCSD, and among 29 patients with a presurgical ICD, the rate of shocks dropped by 93% from 3.6 to 0.6 shocks per person per year (P<0.001). Patients with an incomplete LCSD (n=7) were more likely to experience major cardiac events after LCSD (71% versus 17%; P<0.01) than those with a complete LCSD. Conclusions-LCSD is an effective antifibrillatory intervention for patients with CPVT. Whenever syncope occurs despite optimal medical therapy, LCSD could be considered the next step rather than an ICD and could complement ICDs in patients with recurrent shocks.

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“…In situations with excessive intracellular Ca 2ϩ load, this electrogenic exchange generates a depolarization recognized as a DAD (183,295,434,503). Intracellular Ca 2ϩ overload can be subsequent to Ca 2ϩ leak from mutant ryanodine receptors (RyR) in the sarcoplasmic reticulum, which can result in catecholaminergic polymorphic ventricular tachycardia and concomitant fibrillation (347). Hyperphosphorylation of RyR as a consequence of increased sympathetic drive can also provoke phase 4 Ca 2ϩ overload and DADs (106).…”

Section: A Triggers Of Arrhythmiasmentioning

confidence: 99%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

202

197

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About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K+ channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The underlying posttranscriptional and posttranslational remodeling of the individual K+ channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry arrhythmia.

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Sudden Death in a Young Man with Catecholaminergic Polymorphic Ventricular Tachycardia and Paroxysmal Atrial Fibrillation

Cited by 95 publications

References 12 publications

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

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