Increased QT variability in young asymptomatic patients with β-thalassemia major
Damiano Magrì
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorSusanna Sciomer
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorFrancesco Fedele
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorPellegrina Pugliese
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorAnna Losardo
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorGiancarlo Ferrazza
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorEleonora Pasquazzi
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorErika Schifano
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorMarzia Magnanti
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorSabrina Matera
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorVincenzo Marigliano
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorGianfranco Piccirillo
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorDamiano Magrì
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorSusanna Sciomer
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorFrancesco Fedele
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
Search for more papers by this authorPellegrina Pugliese
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorAnna Losardo
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorGiancarlo Ferrazza
U.O.C. of ImmunoEmatologia e Medicina Trasfusionale
Search for more papers by this authorEleonora Pasquazzi
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorErika Schifano
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorMarzia Magnanti
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorSabrina Matera
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorVincenzo Marigliano
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorGianfranco Piccirillo
Dipartimento di Scienze dell’Invecchiamento, Policlinico Umberto I, Università“La Sapienza”, Rome, Italy
Search for more papers by this authorAbstract
Background: Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with β-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons.
Methods: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QTv), QTv normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values.
Results: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QTv, QTVN and QTVI values were significantly higher in patients than those in controls (QTv, P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data.
Conclusions: Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM.
References
- 1 Borna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complication in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89: 1187–93.
- 2 Zurlo MG, De Stefano P, Borgna-Pignatti C, et al. Survival and causes of death in thalassemia major. Lancet 1989; 2: 27–30.
- 3 Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci 2005; 1054: 445–50.
- 4 Taher A, Sheikh-Taha M, Koussa S, Inati A, Neeman R, Mourad F. Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients. Eur J Hematol 2001; 67: 30–4.
- 5 Borna-Pignatti C, Cappellini MD, De Stefano P, et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 2006; 107: 3733–7.
- 6 Pennell DJ, Berdoukas V, Karagiorga M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006; 107: 3738–44.
- 7 Atiga WL, Calkins H, Lawrence JH, Tomaselli GF, Smith JM, Berger RD. Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death. J Cardiovasc Electrophysiol 1998; 9: 899–908.
- 8 Piccirillo G, Magrì D, Matera S, et al. QT variability strongly predicts sudden cardiac death in asymptomatic subjects with mild or moderate left ventricular dysfunction: a prospective study. Eur Heart J 2007; 28(11): 1344–50.
- 9 Haigney MC, Zareba W, Gentlesk PJ, et al. QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. J Am Coll Cardiol 2004; 44: 1481–7.
- 10 Ulger Z, Aydinok Y, Levent E, Gurses D, Ozyurek AR. Evaluation of QT dispersion in β-thalassemia major patients. Am J Hematol 2006; 81: 901–6.
- 11 Zabel M, Klingenheden T, Franz MR, Honloser SH. Assessment of QT dispersion for predication of mortality or arrhythmic event after myocardial infarction: result of prospective, long-term follow up study. Circulation 1998; 97: 2543–50.
- 12 Brendorp B, Elming H, Jun L, et al. QT dispersion has no prognostic information for patients with advanced congestive heart failure and reduced left ventricular systolic function. Circulation 2001; 103: 831–5.
- 13 Piccirillo G, Santagada E, Viola E, et al. Autonomic modulation of heart rate and blood pressure in hypertensive subjects with symptoms of anxiety. Clin Sci 1998; 95: 43–52.
- 14 Piccirillo G, Viola E, Bucca C, et al. QT interval dispersion and autonomic modulation in subjects with anxiety. J Clin Lab Med 1999; 133: 461–8.
- 15 Piccirillo G, Germanò G, Vitarelli A, et al. Autonomic cardiovascular control and diastolic dysfunction in hypertensive subjects. Int J Cardiol 2006; 110: 160–6.
- 16 Sahan DJ, De Maria A, Kisslo J, et al. Recommendations regarding quantitation in M-mode echocardiography: result of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–80.
- 17 De Simone G, Daniels SR, Devereux RB, et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and the impact of overweight. J Am Coll Cardiol 1992; 20: 1251–60.
- 18 Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2 star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001; 22: 2171–9.
- 19 Westwood M, Anderson LJ, Firmin D, et al. A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload. J Magn Reson Imaging 2003; 18: 33–9.
- 20 El-Omar M, Kardos A, Casadei B. Mechanism of respiratory sinus arrhythmia in patients with mild heart failure. Am J Physiol Heart Circ Physiol 2001; 280: H215–31.
- 21 Berger RD, Kasper EK, Baughman KL, Marban E, Calkins H, Tomaselli GF. Beat-to-beat QT interval variability. Novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy. Circulation 1997; 96: 1557–65.
- 22 Bazett HC. An analysis of the time relations of electrocardiograms. Heart 1920; 7: 353–70.
- 23
Bland JM,
Altman DG.
Statistical methods for assessing agreement between two methods of clinical measurements.
Lancet
1986; 8: 307–10.
10.1016/S0140-6736(86)90837-8 Google Scholar
- 24 Piccirillo G, Quaglione R, Nocco M, et al. Effects of long-term β-blocker therapy on QT variability index in subjects with chronic heart failure. Am J Cardiol 2002; 90: 1113–7.
- 25 Piccirillo G, Magnanti M, Matera S, et al. Age and QT variability index during free breathing, controlled breathing and tilt in patient with chronic heart failure and healthy control subjects. Transl Res 2006; 148: 72–8.
- 26 Piccirillo G, Germanò G, Quaglione R, et al. QT-interval variability and autonomic control in hypertensive subjects with left ventricular hypertrophy. Clin Sci 2002; 102: 363–71.
- 27 Piccirillo G, Cacciafesta M, Lionetti M, et al. The influence of age, the autonomic nervous system and anxiety on QT interval variability. Clin Sci 2001; 101: 429–38.
- 28 Tomaselli GF, Zipes DP. What causes sudden death in heart failure? Circ Res 2004; 95: 754–63.
- 29 Buja LM, Roberts WC. Iron in the heart: etiology and clinical significance. Am J Med 1971; 51: 209–21.
- 30 Laurita KR, Chuck ET, Yang T, et al. Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. J Lab Clin Med 2003; 142: 83–9.
- 31 Kuryshev YA, Brittenham GM, Fujioka H, et al. Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implication for the arrhythmogenesis of human siderotic heart disease. Circulation 1999; 100: 675–83.
- 32 Schwartz KA, Li Z, Schwartz DE, Cooper TG, Braselton WE. Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction. J Appl Physiol 2002; 93: 746–51.
- 33 Piccirillo G, Quaglione R, Fimognari F, et al. Influence of L-arginine and vitamin C on the autonomic nervous system in chronic heart failure secondary to ischemic cardiomyopathy. Am J Cardiol 2004; 93: 650–4.
- 34 Romero Mestre JC, Hernandez A, Agramonte O, Hernandez P. Cardiovascular autonomic dysfunction in sickle cell anemia: a possible risk factor for sudden death? Clin Auton Res 1997; 7: 121–5.
- 35 Livrea MA, Tesoriere L, Pintaudi AM, et al. Oxidative stress and antioxidant status in thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood 1996; 88: 3608–14.
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