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Cardiac retention of [¹¹C]HED in genotyped long QT patients: a potential amplifier role for severity of the disease

¹Centre d'Exploration et de Recherche Médicales par Émission de Positons, 69003 Lyon; ²Centre de Recherche et d'Applications en Traitement de l'Image et du Signal, Unité Mixed de Recherche-Centre National de Recherche Scientifique 5515, 69394 Lyon; ³Hôpital Cardiovasculaire et Pneumologique et Université Claude Bernard, 6934 Cedex 03 Lyon; ⁴Unité 533, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Formation et Recherche de Medecine, Hôpital Laënnec, Nantes 44035; and ⁵Unité 523, INSERM, Institut de Myologie, Groupe Hospitalier Pitié-Salpétrière, Paris 75013, France

Submitted 27 March 2003 ; accepted in final form 22 May 2003

Although mutations in cardiac sodium and potassium channel genes are associated with congenital long QT syndrome (LQTS), a "modifier" role of the sympathetic nervous system was proposed to explain the distinct severity of the disease. We evaluated cardiac sympathetic innervation using [¹¹C]hydroxyephedrine ([¹¹C]HED) and positron emission tomography (PET) in genotyped LQTS patients. H₂¹⁵O and [¹¹C]HED PET studies were performed in 11 patients (5 symptomatic) and 8 controls. Perfusion and [¹¹C]HED images were depicted as 36-sector polar maps. Sectorial values of perfusion (H₂O_%), absolute (HED_Ret) and relative retention (HED_%Ret) of [¹¹C]HED, and the ratio of HED_%Ret to H₂O_% (HED_%Ret/H₂O_%) were calculated. Normal databases were obtained from controls. Sectorial values below 2SD database values were defined as "outside sectors." Controls and patients showed similar sectorial perfusion. Sectorial HED_Ret did not differ between groups, but means of HED_%Ret were lower in three sectors for patients (P < 0.05). Three sectors from 3 controls had HED_%Ret below 2SD, whereas 36 sectors in 9 patients were outside sectors (P < 0.01). In patients, average HED_%Ret/H₂O_% was lower in 9 sectors (P < 0.05 vs. controls); 2 outside sectors were found in controls, but 43 outside sectors were found in patients (P < 0.01), 77% of them in the 5 symptomatic patients. Heterogeneous [¹¹C]HED retention was localized in the septal, anterior, and lateral walls. Most LQTS patients showed a localized and decreased pattern of [¹¹C]HED retention. The larger number of heterogeneous sectors in symptomatic patients suggests that sympathetic function could play an amplifier role for severity of the disease.

long QT syndrome; genetics; positron emission tomography; sympathetic nervous system; [¹¹C]hydroxyephedrine

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