Julien Roussel1, François Labarthe2, Jerome Thireau1, Fabio Ferro3, Charlotte Farah1, Jerome Roy1, Masahisa Horiuchi4, Martine Tardieu2, Bruno Lefort2, Jean François Benoist5, Alain Lacampagne1, Sylvain Richard1, Jeremy Fauconnier1, Dominique Babuty6, Jean Yves Le Guennec1. 1. INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France. 2. Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France. 3. INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France; Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France. 4. Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. 5. Laboratoire de Biochimie Hormonologie, Hôpital R Debré, AP-HP, Paris, France. 6. Service de Cardiologie, CHRU de Tours, Université François Rabelais, Tours, France. Electronic address: d.babuty@chu-tours.fr.
Abstract
BACKGROUND: Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have been implicated in early T-wave repolarization. OBJECTIVE: The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency. METHODS: We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88. RESULTS: MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation. CONCLUSION: Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart.
BACKGROUND:Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have been implicated in early T-wave repolarization. OBJECTIVE: The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency. METHODS: We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88. RESULTS:MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation. CONCLUSION: Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart.
Authors: Najim Lahrouchi; Elisabeth M Lodder; Maria Mansouri; Rafik Tadros; Layla Zniber; Najlae Adadi; Sally-Ann B Clur; Karin Y van Spaendonck-Zwarts; Alex V Postma; Abdelaziz Sefiani; Ilham Ratbi; Connie R Bezzina Journal: Eur J Hum Genet Date: 2017-03-15 Impact factor: 4.246
Authors: Roberta Pereira; Oscar Campuzano; Georgia Sarquella-Brugada; Sergi Cesar; Anna Iglesias; Josep Brugada; Fernando E S Cruz Filho; Ramon Brugada Journal: Clin Res Cardiol Date: 2017-03-16 Impact factor: 5.460
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Back Sternick Eduardo; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong-Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti Mac Intyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Pablo Ochoa Juan; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: J Arrhythm Date: 2022-05-31
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Eduardo Back Sternick; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti MacIntyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Juan Pablo Ochoa; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: Europace Date: 2022-09-01 Impact factor: 5.486
Authors: Suzan J G Knottnerus; Jeannette C Bleeker; Rob C I Wüst; Sacha Ferdinandusse; Lodewijk IJlst; Frits A Wijburg; Ronald J A Wanders; Gepke Visser; Riekelt H Houtkooper Journal: Rev Endocr Metab Disord Date: 2018-03 Impact factor: 6.514