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Cardiac sympathetic innervation in a patient with catecholaminergic polymorphic ventricular tachycardia Matthias Paul, MD,* Peter Kies, MD,† Michael Schäfers, MD,†‡ Eric Schulze-Bahr, MD§ From the *Division of Cardiology, Department of Cardiovascular Medicine, and †Department of Nuclear Medicine, University Hospital Münster, Münster, Germany, ‡European Institute for Molecular Imaging, University of Münster, Münster, Germany, and §Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
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Myocardial perfusion [
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Sympathetic innervation
Sympathetic innervation
[ C]-hydroxyephedrine-PET
[ C]-hydroxyephedrine-PET
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Figure 1
We report the case of a woman who presented with recurrent syncope in childhood and was treated for epilepsy at the age of 12. She was finally diagnosed as suffering from catecholaminergic polymorphic ventricular tachycardia (CPVT1) at the age of about 36 when exercise testing demonstrated polymorphic ventricular tachycardia (VT; including periods of bidirectional VT), and genetic testing KEYWORDS Catecholaminergic polymorphic ventricular tachycardia; [11C]Hydroxyephedrine positron emission tomography; Sympathetic innervation ABBREVIATIONS CPVT ¼ catecholaminergic polymorphic ventricular tachycardia; [11C]-HED ¼ [11C]-hydroxyephedrine; LV ¼ left ventricular/ventricle; PET ¼ positron emission tomography; SPECT ¼ single photon emission computed tomography; VT ¼ ventricular tachycardia (Heart Rhythm 2013;0:1–2) The first 2 authors contributed equally to this work. Address reprint requests and correspondence: Dr Eric Schulze-Bahr, Institut für Genetik von Herzerkrankungen, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1 (Gebäude D3), D-48149 Münster, Germany. Funded by German Research Foundation (DFG) SFB656. E-mail address: [email protected].
1547-5271/$-see front matter B 2013 Heart Rhythm Society. All rights reserved.
revealed a mutation at amino acid position 3872 in the gene, encoding the cardiac ryanodine receptor 2 gene (RyR2; CPVT-12; c.11616 C4G, Ile3872Met). Given the exercise-induced symptoms, we postulated an underlying sympathetic dysfunction and investigated the left ventricular (LV) presynaptic norepinephrine release and reuptake using positron emission tomography (PET; tracer: 11 C-labeled norepinephrine analog [11C]-hydroxyephedrine, 11 [ C]-HED). Briefly, [11C]-HED (350 MBq) was infused intravenously over a period of 1 minute and a dynamic emission scan of 65-minute duration was recorded (ECAT921; Siemens/CTI). HED-PET revealed a reduced tracer activity in the lateral wall of the LV, indicating a presynaptic sympathetic innervation defect. In order to exclude abnormal myocardial perfusion as a potential cause of impaired sympathetic innervation, [99mTc]-tetrofosmin SPECT was performed and showed normal uptake (Figure 1, left and middle columns). The patient was treated with nebivolol (5 mg/d) and verapamil (360 mg/d). No further syncope occurred. However, http://dx.doi.org/10.1016/j.hrthm.2013.10.037
2 the continuously documented symptomatic nonsustained VT eventually led to the implantation of an automatic implantable cardioverter-defibrillator for the secondary prevention of sudden arrhythmic death 3 years later in 2006. Until 2009, no sustained VT was recorded or treated by the device. Multiple symptomatic ventricular runs and nonsustained VT required a change in medication from verapamil to flecainide (200 mg/d), which improved the clinical course. Under this combination therapy, we performed a second [11C]-HED-PET scan by using the same technique (ie, tracer, PET scanner, and protocol). Now a homogeneous tracer distribution in the LV was noted (Figure 1, right column). To our knowledge, this is the first demonstration of a regional, sympathetic innervation defect in a patient with CPVT. Interestingly, a follow-up PET investigation showed
Heart Rhythm, Vol 0, No 0, Month 2013 a normalized and homogeneous innervation. Whether this may be attributed to the long-standing β-blocker therapy or has been affected by the recently initiated flecainide therapy remains to be elucidated. Our finding may give rise to further larger-scale investigations in patients with CPVT using [11C]-HED-PET to clarify the involvement of sympathetic (dys-)function in the pathophysiology of the disease and its potential implications for risk stratification.
References 1. Venetucci L, Denegri M, Napolitano C, Priori SG. Inherited calcium channelopathies in the pathophysiology of arrhythmias. Nat Rev Cardiol 2012;9: 561–575. 2. Priori SG, Chen SR. Inherited dysfunction of sarcoplasmic reticulum Ca2þ handling and arrhythmogenesis. Circ Res 2011;108:871–883.
Cardiac sympathetic innervation in a patient with catecholaminergic polymorphic ventricular tachycardia Matthias Paul, MD,* Peter Kies, MD,† Michael Schäfers, MD,†‡ Eric Schulze-Bahr, MD§ From the *Division of Cardiology, Department of Cardiovascular Medicine, and †Department of Nuclear Medicine, University Hospital Münster, Münster, Germany, ‡European Institute for Molecular Imaging, University of Münster, Münster, Germany, and §Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
Short axis
Sep
Ant
Ant
Ant Lat
Lat Sep
Sep
Inf
Inf
Inf
Sep
Sep Long axis
Sep
Lat Lat
Myocardial perfusion [
Lat
Tc]-tetrofosmin-SPECT
2003
Lat
Sympathetic innervation
Sympathetic innervation
[ C]-hydroxyephedrine-PET
[ C]-hydroxyephedrine-PET
2003
Figure 1
We report the case of a woman who presented with recurrent syncope in childhood and was treated for epilepsy at the age of 12. She was finally diagnosed as suffering from catecholaminergic polymorphic ventricular tachycardia (CPVT1) at the age of about 36 when exercise testing demonstrated polymorphic ventricular tachycardia (VT; including periods of bidirectional VT), and genetic testing KEYWORDS Catecholaminergic polymorphic ventricular tachycardia; [11C]Hydroxyephedrine positron emission tomography; Sympathetic innervation ABBREVIATIONS CPVT ¼ catecholaminergic polymorphic ventricular tachycardia; [11C]-HED ¼ [11C]-hydroxyephedrine; LV ¼ left ventricular/ventricle; PET ¼ positron emission tomography; SPECT ¼ single photon emission computed tomography; VT ¼ ventricular tachycardia (Heart Rhythm 2013;0:1–2) The first 2 authors contributed equally to this work. Address reprint requests and correspondence: Dr Eric Schulze-Bahr, Institut für Genetik von Herzerkrankungen, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1 (Gebäude D3), D-48149 Münster, Germany. Funded by German Research Foundation (DFG) SFB656. E-mail address: [email protected].
1547-5271/$-see front matter B 2013 Heart Rhythm Society. All rights reserved.
revealed a mutation at amino acid position 3872 in the gene, encoding the cardiac ryanodine receptor 2 gene (RyR2; CPVT-12; c.11616 C4G, Ile3872Met). Given the exercise-induced symptoms, we postulated an underlying sympathetic dysfunction and investigated the left ventricular (LV) presynaptic norepinephrine release and reuptake using positron emission tomography (PET; tracer: 11 C-labeled norepinephrine analog [11C]-hydroxyephedrine, 11 [ C]-HED). Briefly, [11C]-HED (350 MBq) was infused intravenously over a period of 1 minute and a dynamic emission scan of 65-minute duration was recorded (ECAT921; Siemens/CTI). HED-PET revealed a reduced tracer activity in the lateral wall of the LV, indicating a presynaptic sympathetic innervation defect. In order to exclude abnormal myocardial perfusion as a potential cause of impaired sympathetic innervation, [99mTc]-tetrofosmin SPECT was performed and showed normal uptake (Figure 1, left and middle columns). The patient was treated with nebivolol (5 mg/d) and verapamil (360 mg/d). No further syncope occurred. However, http://dx.doi.org/10.1016/j.hrthm.2013.10.037
2 the continuously documented symptomatic nonsustained VT eventually led to the implantation of an automatic implantable cardioverter-defibrillator for the secondary prevention of sudden arrhythmic death 3 years later in 2006. Until 2009, no sustained VT was recorded or treated by the device. Multiple symptomatic ventricular runs and nonsustained VT required a change in medication from verapamil to flecainide (200 mg/d), which improved the clinical course. Under this combination therapy, we performed a second [11C]-HED-PET scan by using the same technique (ie, tracer, PET scanner, and protocol). Now a homogeneous tracer distribution in the LV was noted (Figure 1, right column). To our knowledge, this is the first demonstration of a regional, sympathetic innervation defect in a patient with CPVT. Interestingly, a follow-up PET investigation showed
Heart Rhythm, Vol 0, No 0, Month 2013 a normalized and homogeneous innervation. Whether this may be attributed to the long-standing β-blocker therapy or has been affected by the recently initiated flecainide therapy remains to be elucidated. Our finding may give rise to further larger-scale investigations in patients with CPVT using [11C]-HED-PET to clarify the involvement of sympathetic (dys-)function in the pathophysiology of the disease and its potential implications for risk stratification.
References 1. Venetucci L, Denegri M, Napolitano C, Priori SG. Inherited calcium channelopathies in the pathophysiology of arrhythmias. Nat Rev Cardiol 2012;9: 561–575. 2. Priori SG, Chen SR. Inherited dysfunction of sarcoplasmic reticulum Ca2þ handling and arrhythmogenesis. Circ Res 2011;108:871–883.
