Catecholaminergic polymorphic ventricular tachycardia complicated by dilated cardiomyopathy: a case report

Abstract Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe genetic arrhythmogenic disorder characterized by adrenergically induced ventricular tachycardia manifesting as stress-induced syncope and sudden cardiac death. While CPVT is not associated with dilated cardiomyopathy (DCM) in most cases, the combination of both disease entities poses a major diagnostic and therapeutic challenge. Case summary We present the case of a young woman with CPVT. The clinical course since childhood was characterized by repetitive episodes of exercise-induced ventricular arrhythmias and a brady-tachy syndrome due to rapid paroxysmal atrial fibrillation and sinus bradycardia. Medical treatment included propranolol and flecainide until echocardiography showed a dilated left ventricle with severely depressed ejection fraction when the patient was 32 years old. Cardiac magnetic resonance imaging revealed non-specific late gadolinium enhancement. Myocardial inflammation, however, was excluded by subsequent endomyocardial biopsy. Genetic analysis confirmed a mutation in the cardiac ryanodine receptor but no pathogenetic variant associated with DCM. Guideline-directed medical therapy for HFrEF was limited due to symptomatic hypotension. Over the next months, the patient developed progressive heart failure symptoms that were finally managed by heart transplantation. Discussion Management in patients with CPVT and DCM is challenging, as Class I antiarrhythmic drugs are not recommended in structural heart disease and prophylactic internal cardioverter-defibrillator implantation without adjuvant antiarrhythmic therapy can be detrimental. Regular echocardiographic screening for DCM is recommendable in patients with CPVT. A multidisciplinary team of heart failure specialists, electrophysiologists, geneticists, and imaging specialists is needed to collaborate in the delivery of clinical care.

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Tetrodotoxin‐Sensitive Neuronal‐Type Na + Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation

Journal of the American Heart Association ◽

10.1161/jaha.119.015119 ◽

2020 ◽

Vol 9 (11) ◽

Author(s):

Mark A. Munger ◽

Yusuf Olğar ◽

Megan L. Koleske ◽

Heather L. Struckman ◽

Jessica Mandrioli ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ventricular Tachycardia ◽

Medical Center ◽

Close Association ◽

Academic Medical Center ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Atrial Arrhythmias ◽

Neuronal Type

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca 2+ ‐dependent nature of both of these pathologies, AF often responds to Na + channel blockers. We investigated how targeting interdependent Na + /Ca 2+ dysregulation might prevent focal activity and control AF. Methods and Results We studied AF in 2 models of Ca 2+ ‐dependent disorders, a murine model of catecholaminergic polymorphic ventricular tachycardia and a canine model of chronic tachypacing‐induced heart failure. Imaging studies revealed close association of neuronal‐type Na + channels (nNa v ) with ryanodine receptors and Na + /Ca 2+ exchanger. Catecholamine stimulation induced cellular and in vivo atrial arrhythmias in wild‐type mice only during pharmacological augmentation of nNa v activity. In contrast, catecholamine stimulation alone was sufficient to elicit atrial arrhythmias in catecholaminergic polymorphic ventricular tachycardia mice and failing canine atria. Importantly, these were abolished by acute nNa v inhibition (tetrodotoxin or riluzole) implicating Na + /Ca 2+ dysregulation in AF. These findings were then tested in 2 nonrandomized retrospective cohorts: an amyotrophic lateral sclerosis clinic and an academic medical center. Riluzole‐treated patients adjusted for baseline characteristics evidenced significantly lower incidence of arrhythmias including new‐onset AF, supporting the preclinical results. Conclusions These data suggest that nNa V s mediate Na + ‐Ca 2+ crosstalk within nanodomains containing Ca 2+ release machinery and, thereby, contribute to AF triggers. Disruption of this mechanism by nNa v inhibition can effectively prevent AF arising from diverse causes.

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The Role of Flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia

Arrhythmia & Electrophysiology Review ◽

10.15420/aer.2016.3.3 ◽

2016 ◽

Vol 5 (1) ◽

pp. 45 ◽

Cited By ~ 10

Author(s):

Krystien VV Lieve ◽

◽

Arthur A Wilde ◽

Christian van der Werf ◽

◽

...

Keyword(s):

Heart Disease ◽

Ventricular Tachycardia ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Structural Heart Disease ◽

Current Data ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Β Blockers

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope and sudden cardiac death due to polymorphic VT or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease. The cornerstone of medical therapy for CPVT is β -blockers. However, recently flecainide has been added to the therapeutic arsenal for CPVT. In this review we summarise current data on the efficacy and role of flecainide in the treatment of CPVT.

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Catecholaminergic polymorphic ventricular tachycardia with structural heart disease is caused by a mutation in calsequestrin 2 that leads to increased spark-mediated calcium leak in cardiomyocytes

Journal of Electrocardiology ◽

10.1016/j.jelectrocard.2007.03.157 ◽

2007 ◽

Vol 40 (4) ◽

pp. S14

Author(s):

Aygun Dindar ◽

Oya Uyguner ◽

ES Sahin ◽

D Terentyev ◽

Kemal Nisli ◽

...

Keyword(s):

Heart Disease ◽

Ventricular Tachycardia ◽

Structural Heart Disease ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia

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A Clinical Case of Catecholaminergic Polymorphic Ventricular Tachycardia: The Clinical Suspicious and the Need of Genetics

Cardiology ◽

10.1159/000475461 ◽

2017 ◽

Vol 138 (2) ◽

pp. 69-72 ◽

Cited By ~ 1

Author(s):

Annamaria Del Franco ◽

Francesca Gualandi ◽

Michele Malagù ◽

Alessandra Ferlini ◽

Dang Xiao ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Clinical Case ◽

Current Knowledge ◽

Correct Diagnosis ◽

Structural Heart Disease ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Strenuous Exercise ◽

History Of ◽

Cardiac Channelopathy

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a very rare genetic cardiac channelopathy, which has not been sufficiently studied yet. The first clinical manifestation has been described during the first decade of life, linked to strenuous exercise or acute emotion. The absence of structural heart disease and a family history of possible arrhythmogenic disorder generally guide the diagnosis towards a potential channelopathy. The opportunity to perform an extensive genetic analysis allows physicians to make the correct diagnosis and to optimize clinical management. The identification of more CPVT cases could affirm what we already know and primarily implement the current knowledge.

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Atropine-induced sinus tachycardia protects against exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia

EP Europace ◽

10.1093/europace/euaa029 ◽

2020 ◽

Vol 22 (4) ◽

pp. 643-648

Author(s):

Prince J Kannankeril ◽

M Benjamin Shoemaker ◽

Kathryn A Gayle ◽

Darlene Fountain ◽

Dan M Roden ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Exercise Test ◽

Ventricular Arrhythmias ◽

Sinus Bradycardia ◽

Recovery Period ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Ventricular Ectopy ◽

Ectopic Beats ◽

Exercise Induced

Abstract Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients. Methods and results We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22–57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52–64) to 98 b.p.m. (84–119), P = 0.02. Peak HRs (149 b.p.m., range 136–181 vs. 149 b.p.m., range 127–182, P = 0.46) and exercise duration (612 s, range 544–733 vs. 584 s, range 543–742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6–192) to 0 (0–29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects. Conclusion Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT.

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