Sex differences in cardiac autonomic regulation and in repolarisation electrocardiography

Invited Review

Abstract

The review summarises the present knowledge on the sex differences in cardiac autonomic regulations and in related aspects of electrocardiography with particular attention to myocardial repolarisation. Although some of the sex differences are far from fully established, multitude of observations show consistent differences between women and men. Despite more pronounced parasympathetic cardiac regulation, women have higher resting heart rate and lower baroreflex sensitivity. Of the electrocardiographic phenomena, women have longer QT interval duration, repolarisation sequence more synchronised with the inverse of the depolarisation sequence, and likely increased regional heterogeneity of myocardial repolarisation. Studies investigating the relationship of these sex disparities to hormonal differences led frequently to conflicting results. Although sex hormones seem to play a key role by influencing both autonomic tone and electrophysiological properties at the cellular level, neither the truly relevant hormones nor their detailed actions are known. Physiologic usefulness of the described sex differences is also unknown. The review suggests that new studies are needed to advance the understanding of the physiologic mechanisms responsible for these inequalities between women and men and provides key methodological suggestions that need to be followed in future research.

Keywords

Sympatho-vagal balance Heart rate Baroreflex sensitivity Myocardial repolarisation QT/RR relationship Sex hormones 

References

  1. 1.
    Abdel-Rahman AR, Merrill RH, Wooles WR (1994) Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans. J Appl Physiol 77:606–613PubMedGoogle Scholar
  2. 2.
    Acar B, Yi G, Hnatkova K, Malik M (1999) Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology. Med Biol Eng Comput 37:574–584PubMedCrossRefGoogle Scholar
  3. 3.
    Adams KF Jr, Sueta CA, Gheorghiade M, O'Connor CM, Schwartz TA, Koch GG, Uretsky B, Swedberg K, McKenna W, Soler-Soler J, Califf RM (1999) Gender differences in survival in advanced heart failure. Insights from the FIRST study. Circulation 99:1816–1821PubMedCrossRefGoogle Scholar
  4. 4.
    Agelink MW, Malessa R, Baumann B, Majewski T, Akila F, Zeit T, Ziegler D (2001) Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate. Clin Auton Res 11:99–108PubMedCrossRefGoogle Scholar
  5. 5.
    Ahnve S, Vallin H (1982) Influence of heart rate and inhibition of autonomic tone on the QT interval. Circulation 65:435–439PubMedCrossRefGoogle Scholar
  6. 6.
    Alboni P, Malacarne C, Pedroni P, Masoni A, Narula OS (1982) Electrophysiology of normal sinus node with and without autonomic blockade. Circulation 65:1236–1242PubMedCrossRefGoogle Scholar
  7. 7.
    Alpert MA, Terry BE, Cohen MV, Fan TM, Painter JA, Massey CV (2000) The electrocardiogram in morbid obesity. Am J Cardiol 85(908–910):A10Google Scholar
  8. 8.
    Alpert MA, Terry BE, Hamm CR, Fan TM, Cohen MV, Massey CV, Painter JA (2001) Effect of weight loss on the ECG of normotensive morbidly obese patients. Chest 119:507–510PubMedCrossRefGoogle Scholar
  9. 9.
    Antzelevitch C, Shimizu W, Yan GX, Sicouri S, Weissenburger J, Nesterenko VV, Burashnikov A, Di Diego J, Saffitz J, Thomas GP (1999) The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 10:1124–1152PubMedCrossRefGoogle Scholar
  10. 10.
    Badilini F, Maison-Blanche P, Childers R, Coumel P (1999) QT interval analysis on ambulatory electrocardiogram recordings: a selective beat averaging approach. Med Biol Eng Comput 37:71–79PubMedCrossRefGoogle Scholar
  11. 11.
    Bai CX, Kurokawa J, Tamagawa M, Nakaya H, Furukawa T (2005) Nontranscriptional regulation of cardiac repolarization currents by testosterone. Circulation 112:1701–1710PubMedCrossRefGoogle Scholar
  12. 12.
    Bai X, Li J, Zhou L, Li X (2009) Influence of the menstrual cycle on nonlinear properties of heart rate variability in young women. Am J Physiol Heart Circ Physiol 297:H765–H774PubMedCrossRefGoogle Scholar
  13. 13.
    Batchvarov VN, Ghuran A, Smetana P, Hnatkova K, Harries M, Dilaveris P, Camm AJ, Malik M (2002) QT–RR relationship in healthy subjects exhibits substantial intersubject variability and high intrasubject stability. Am J Physiol Heart Circ Physiol 282:H2356–H2363PubMedGoogle Scholar
  14. 14.
    Bazett H (1920) An analysis of the time-relations of electrocardiograms. Heart 7:353–370Google Scholar
  15. 15.
    Benatar A, Carbonez K (2010) Behavior of the electrocardiographic T peak to end interval in childhood. Ann Noninvasive Electrocardiol 15:11–16PubMedCrossRefGoogle Scholar
  16. 16.
    Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA (1994) Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. J Am Med Assoc 271:840–844CrossRefGoogle Scholar
  17. 17.
    Bertinieri G, Di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G (1985) A new approach to analysis of the arterial baroreflex. J Hypertens 3:S79–S81Google Scholar
  18. 18.
    Beske SD, Alvarez GE, Ballard TP, Davy KP (2001) Gender difference in cardiovagal baroreflex gain in humans. J Appl Physiol 91:2088–2092PubMedGoogle Scholar
  19. 19.
    Bidoggia H, Maciel JP, Capalozza N, Mosca S, Blaksley EJ, Valverde E, Bertran G, Arini P, Biagetti MO, Quinteiro RA (2000) Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone. Am Heart J 140:678–683PubMedCrossRefGoogle Scholar
  20. 20.
    Bidoggia H, Maciel JP, Capalozza N, Mosca S, Blaksley EJ, Valverde E, Bertran G, Arini P, Biagetti MO, Quinteiro RA (2000) Sex-dependent electrocardiographic pattern of cardiac repolarization. Am Heart J 140:430–436PubMedCrossRefGoogle Scholar
  21. 21.
    Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Schneider WJ, Stein PK (1995) RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction. Circulation 91:1936–1943PubMedCrossRefGoogle Scholar
  22. 22.
    Bonarjee VV, Rosengren A, Snapinn SM, James MK, Dickstein K, OPTIMAAL study group (2006) Sex-based short- and long-term survival in patients following complicated myocardial infarction. Eur Heart J 27:2177–2183PubMedCrossRefGoogle Scholar
  23. 23.
    Britton A, Shipley M, Malik M, Hnatkova K, Hemingway H, Marmot M (2007) Changes in heart rate and heart rate variability over time in middle-aged men and women in the general population (from the Whitehall II Cohort Study). Am J Cardiol 100:524–527PubMedCrossRefGoogle Scholar
  24. 24.
    Brockbank CL, Chatterjee F, Bruce SA, Woledge RC (2000) Heart rate and its variability change after the menopause. Exp Physiol 85:327–330PubMedCrossRefGoogle Scholar
  25. 25.
    Browne KF, Zipes DP, Heger JJ, Prystowsky EN (1982) Influence of the autonomic nervous system on the Q–T interval in man. Am J Cardiol 50:1099–1103PubMedCrossRefGoogle Scholar
  26. 26.
    Burke JH, Ehlert FA, Kruse JT, Parker MA, Goldberger JJ, Kadish AH (1997) Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults. Am J Cardiol 79:178–181PubMedCrossRefGoogle Scholar
  27. 27.
    Burke JH, Goldberger JJ, Ehlert FA, Kruse JT, Parker MA, Kadish AH (1996) Gender differences in heart rate before and after autonomic blockade: evidence against an intrinsic gender effect. Am J Med 100:537–543PubMedCrossRefGoogle Scholar
  28. 28.
    Busjahn A, Voss A, Knoblauch H, Knoblauch M, Jeschke E, Wessel N, Bohlender J, McCarron J, Faulhaber H-D, Schuster H, Dietz R, Luft FC (1998) Angiotensin-converting enzyme and angiotensinogen gene polymorphisms and heart rate variability in twins. Am J Cardiol 81:755–760PubMedCrossRefGoogle Scholar
  29. 29.
    Buxton AE, Hafley GE, Lehmann MH, Gold M, O'Toole M, Tang A, Coromilas J, Hook B, Stamato NJ, Lee KL (1999) Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables. Circulation 99:1843–1850PubMedCrossRefGoogle Scholar
  30. 30.
    Carlsson MB, Trägårdh E, Engblom H, Hedström E, Wagner G, Pahlm O, Arheden H (2006) Left ventricular mass by 12-lead electrocardiogram in healthy subjects: comparison to cardiac magnetic resonance imaging. J Electrocardiol 39:67–72PubMedCrossRefGoogle Scholar
  31. 31.
    Carnethon MR, Anthony MS, Cascio WE, Folsom AR, Rautaharju PM, Liao D, Evans GW, Heiss G (2003) Prospective association between hormone replacement therapy, heart rate, and heart rate variability. The Atherosclerosis Risk in Communities Study. J Clin Epidemiol 56:565–571PubMedCrossRefGoogle Scholar
  32. 32.
    Casadei B (2004) Physiological background of baroreflex. In: Malik M, Camm AJ (eds) Dynamic electrocardiography. Blackwell Futura, New York, pp 143–153Google Scholar
  33. 33.
    Chapleau MW, Li Z, Meyerelles SS, Ma X, Abboud FM (2001) Mechanisms determining sensitivity of baroreceptor afferents in health and disease. Ann N Y Acad Sci 940:1–19PubMedCrossRefGoogle Scholar
  34. 34.
    Charbit B, Christin-Maître S, Démolis JL, Soustre E, Young J, Funck-Brentano C (2009) Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol 103:887–890PubMedCrossRefGoogle Scholar
  35. 35.
    Chen G, Yang X, Alber S, Shusterman V, Salama G (2011) Regional genomic regulation of cardiac sodium–calcium exchanger by oestrogen. J Physiol 589:1061–1080PubMedCrossRefGoogle Scholar
  36. 36.
    Cheng J (2006) Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human. Fundam Clin Pharmacol 20:1–8PubMedCrossRefGoogle Scholar
  37. 37.
    Christ M, Seyffart K, Wehling M (1999) Attenuation of heart-rate variability in postmenopausal women on progestin-containing hormone replacement therapy. Lancet 353:1939–1940PubMedCrossRefGoogle Scholar
  38. 38.
    Colaco R, Reay P, Beckett C, Aitchison TC, Mcfarlane PW (2000) False positive ECG reports of anterior myocardial infarction in women. J Electrocardiol 33(Suppl):239–244PubMedCrossRefGoogle Scholar
  39. 39.
    Convertino VA (1998) Gender differences in autonomic functions associated with blood pressure regulation. Am J Physiol 275:R1909–R1920PubMedGoogle Scholar
  40. 40.
    Cooke WH, Ludwig DA, Hogg PS, Eckberg DL, Convertino VA (2002) Does the menstrual cycle influence the sensitivity of vagally mediated baroreflexes? Clin Sci (Lond) 102:639–644CrossRefGoogle Scholar
  41. 41.
    Coumel P, Fayn J, Maison-Blanche P, Rubel P (1994) Clinical relevance of assessing QT dynamicity in Holter recordings. J Electrocardiol 27(Suppl):62–66PubMedCrossRefGoogle Scholar
  42. 42.
    Dalageorgou C, Ge D, Jamshidi Y, Nolte I, Riese H, Savelieva I, Carter N, Spector T, Snieder H (2008) Heritability of QT interval: how much is explained by genes for resting heart rate? J Cardiovasc Electrophysiol 19:386–391PubMedCrossRefGoogle Scholar
  43. 43.
    Dart AM, Du XJ, Kingwell BA (2002) Gender, sex hormones and autonomic nervous control of the cardiovascular system. Cardiovasc Res 53:678–687PubMedCrossRefGoogle Scholar
  44. 44.
    Davies CL, Francis DP, Jurak P, Piepoli M, Coats AJS (1999) Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure. Clin Sci 97:515–522PubMedCrossRefGoogle Scholar
  45. 45.
    Davos CH, Davies LC, Piepoli M (2002) The effect of baroreceptor activity on cardiovascular regulation. Hell J Cardiol 43:145–155Google Scholar
  46. 46.
    de Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel JH, Grobbee DE (1999) Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study. Eur Heart J 20:278–284PubMedCrossRefGoogle Scholar
  47. 47.
    De Leo V, la Marca A, Agricola E, Morgante G, Mondillo S, Setacci C (2000) Resting ECG is modified after oophorectomy and regresses with estrogen replacement therapy in premenopausal women. Maturitas 36:43–47PubMedCrossRefGoogle Scholar
  48. 48.
    deBoer RW, Karemaker JM, Strackee J (1987) Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. Am J Physiol 253:H680–H689PubMedGoogle Scholar
  49. 49.
    Dekker JM, Schouten EG, Klootwijk P, Pool J, Kromhout D (1994) Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen study. Circulation 90:779–785PubMedCrossRefGoogle Scholar
  50. 50.
    Del Rio G, Verlardo A, Zizzo G, Marrama P, Della Casa L (1993) Sex differences in catecholamine response to clonidine. Int J Obes Relat Metab Disord 17:465–469PubMedGoogle Scholar
  51. 51.
    Devereux RB, Lutas EM, Casale PN, Kligfield P, Eisenberg RR, Hammond IW, Miller DH, Reis G, Alderman MH, Laragh JH (1984) Standardization of M-mode echocardiographic left ventricular anatomic measurements. J Am Coll Cardiol 4:1222–1230PubMedCrossRefGoogle Scholar
  52. 52.
    Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL (1996) Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 94:1471–1474PubMedCrossRefGoogle Scholar
  53. 53.
    Du XJ, Riemersma RA, Dart AM (1995) Cardiovascular protection by oestrogen is partly mediated through modulation of autonomic nervous function. Cardiovasc Res 30:161–165PubMedGoogle Scholar
  54. 54.
    Dutoit AP, Hart EC, Charkoudian N, Wallin BG, Curry TB, Joyner MJ (2010) Cardiac baroreflex sensitivity is not correlated to sympathetic baroreflex sensitivity within healthy, young humans. Hypertension 56:1118–1123PubMedCrossRefGoogle Scholar
  55. 55.
    Eberle T, Hessling G, Ulmer HE, Brockmeier K (1998) Prediction of normal QT intervals in children. J Electrocardiol 31(Suppl):121–125PubMedCrossRefGoogle Scholar
  56. 56.
    Ebert SN, Liu XK, Woosley R (1998) Female gender as a risk factor for drug-induced cardiac arrhythmias. Evaluation of clinical and experimental evidence. J Womens Health 7:547–557PubMedCrossRefGoogle Scholar
  57. 57.
    Eisenstein I, Edelstein J, Sarma R, Sanmarco M, Selvester RH (1982) The electrocardiogram in obesity. J Electrocardiol 15:115–118PubMedCrossRefGoogle Scholar
  58. 58.
    Ernsting J, Parry D (1957) Some observations on the effects of stimulating the stretch receptors in the carotid artery of man. J Physiol Lond 137:P45–P46Google Scholar
  59. 59.
    Evans JM, Ziegler MG, Patwardhan AR, Ott JB, Kim CS, Leonelli FM, Knapp CF (2001) Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes. J Appl Physiol 91:2611–2618PubMedGoogle Scholar
  60. 60.
    Extramiana F, Maison-Blanche P, Badilini F, Pinoteau J, Deseo T, Coumel P (1999) Circadian modulation of QT rate dependence in healthy volunteers: gender and age differences. J Electrocardiol 32:33–43PubMedCrossRefGoogle Scholar
  61. 61.
    Fagard R, Pardaens K, Staessen JA (1999) Influence of demographic, anthropometric and lifestyle characteristics on heart rate and its variability in the population. J Hypertens 17:1589–1599PubMedCrossRefGoogle Scholar
  62. 62.
    Farag NH, Nelesen RA, Parry BL, Loredo JS, Dimsdale JE, Mills PJ (2002) Autonomic and cardiovascular function in postmenopausal women: the effects of estrogen versus combination therapy. Am J Obstet Gynecol 186:954–961PubMedCrossRefGoogle Scholar
  63. 63.
    Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG (1995) Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 155:469–473PubMedCrossRefGoogle Scholar
  64. 64.
    Fernandes EO, Moraes RS, Ferlin EL, Wender MC, Ribeiro JP (2005) Hormone replacement therapy does not affect the 24-hour heart rate variability in postmenopausal women: results of a randomized, placebo-controlled trial with two regimens. Pacing Clin Electrophysiol 28(Suppl 1):S172–S177PubMedCrossRefGoogle Scholar
  65. 65.
    Föll D, Jung B, Schilli E, Staehle F, Geibel A, Hennig J, Bode C, Markl M (2010) Magnetic resonance tissue phase mapping of myocardial motion: new insight in age and gender. Circ Cardiovasc Imaging 3:54–64PubMedCrossRefGoogle Scholar
  66. 66.
    Fridericia LS (1920) Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 53:469–486CrossRefGoogle Scholar
  67. 67.
    Friedman HS (2007) Determinants of the total cosine of the spatial angle between the QRS complex and the T wave (TCRT): implications for distinguishing primary from secondary T-wave abnormalities. J Electrocardiol 40:12–17PubMedCrossRefGoogle Scholar
  68. 68.
    Funck-Brentano C, Jaillon P (1993) Rate-corrected QT interval: techniques and limitations. Am J Cardiol 72:17B–22BPubMedCrossRefGoogle Scholar
  69. 69.
    Gaitskell K, Perera R, Soilleux EJ (2011) Derivation of new reference tables for human heart weights in light of increasing body mass index. J Clin Pathol 64:358–362PubMedCrossRefGoogle Scholar
  70. 70.
    Gautschy B, Weidmann P, Gnadinger MP (1986) Autonomic function tests as related to age and gender in normal man. Klin Wochenschr 64:499–505PubMedCrossRefGoogle Scholar
  71. 71.
    Gerritsen J, TenVoorde BJ, Dekker JM, Kostense PJ, Bouter LM, Heethaar RM (2000) Baroreflex sensitivity in the elderly: influence of age, breathing and spectral methods. Clin Sci (Lond) 99:371–381CrossRefGoogle Scholar
  72. 72.
    Gleim GW, Stachenfeld NS, Coplan NL, Nicholas JA (1991) Gender differences in the systolic blood pressure response to exercise. Am Heart J 121:524–530PubMedCrossRefGoogle Scholar
  73. 73.
    Greenland P, Daviglus ML, Dyer AR, Liu K, Huang CF, Goldberger JJ, Stamler J (1999) Resting heart rate is a risk factor for cardiovascular and noncardiovascular mortality: the Chicago Heart Association Detection Project in Industry. Am J Epidemiol 149:853–862PubMedCrossRefGoogle Scholar
  74. 74.
    Greenland P, Reicher-Reiss H, Goldbourt U, Behar S (1991) In-hospital and 1-year mortality in 1,524 women after myocardial infarction. Comparison with 4,315 men. Circulation 83:484–491PubMedCrossRefGoogle Scholar
  75. 75.
    Gustafson AB, Kalkhoff RK (1982) Influence of sex and obesity on plasma catecholamine response to isometric exercise. J Clin Endocrinol Metab 55:703–708PubMedCrossRefGoogle Scholar
  76. 76.
    Haarmark C, Kyvik KO, Vedel-Larsen E, Budtz-Jørgensen E, Kanters JK (2011) Heritability of T peakT end interval and T-wave amplitude: a twin study. Circ Cardiovasc Genet 4:516–522PubMedCrossRefGoogle Scholar
  77. 77.
    Hanson B, Tuna N, Bouchard T, Heston L, Eckert E, Lykken D, Segal N, Rich S (1989) Genetic factors in the electrocardiogram and heart rate of twins reared apart and together. Am J Cardiol 63:606–609PubMedCrossRefGoogle Scholar
  78. 78.
    Hara M, Danilo P Jr, Rosen MR (1998) Effects of gonadal steroids on ventricular repolarization and on the response to E4031. J Pharmacol Exp Ther 285:1068–1072PubMedGoogle Scholar
  79. 79.
    Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach J, Joyner MJ (2011) Sex and ageing differences in resting arterial pressure regulation: the role of the β-adrenergic receptors. J Physiol 589:5285–5297PubMedCrossRefGoogle Scholar
  80. 80.
    Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach JH, Joyner MJ (2009) Sex differences in sympathetic neural–hemodynamic balance: implications for human blood pressure regulation. Hypertension 53:571–576PubMedCrossRefGoogle Scholar
  81. 81.
    Hart EC, Joyner MJ, Wallin BG, Charkoudian N (2012) Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors. J Physiol 590:2069–2079PubMedCrossRefGoogle Scholar
  82. 82.
    Hayashi K, Miyachi M, Seno N, Takahashi K, Yamazaki K, Sugawara J, Yokoi T, Onodera S, Mesaki N (2006) Fluctuations in carotid arterial distensibility during the menstrual cycle do not influence cardiovagal baroreflex sensitivity. Acta Physiol (Oxford) 186:103–110CrossRefGoogle Scholar
  83. 83.
    Hering H (1923) Der Karotisdruckversuch. Muench Med Wochschr 70:1287–1290Google Scholar
  84. 84.
    Hirshoren N, Tzoran I, Makrienko I, Edoute Y, Plawner MM, Itskovitz-Eldor J, Jacob G (2002) Menstrual cycle effects on the neurohumoral and autonomic nervous systems regulating the cardiovascular system. J Clin Endocrinol Metab 87:1569–1575PubMedCrossRefGoogle Scholar
  85. 85.
    Hnatkova K, Gang Y, Batchvarov VN, Malik M (2006) Precision of QT interval measurement by advanced electrocardiographic equipment. Pacing Clin Electrophysiol 29:1277–1284PubMedCrossRefGoogle Scholar
  86. 86.
    Hnatkova K, Smetana P, Toman O, Bauer A, Schmidt G, Malik M (2009) Systematic comparisons of electrocardiographic morphology increase the precision of QT interval measurement. Pacing Clin Electrophysiol 32:119–130PubMedCrossRefGoogle Scholar
  87. 87.
    Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D (1993) Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 88:107–115PubMedCrossRefGoogle Scholar
  88. 88.
    Hogarth AJ, Mackintosh AF, Mary DA (2007) Gender-related differences in the sympathetic vasoconstrictor drive of normal subjects. Clin Sci (Lond) 112:353–361CrossRefGoogle Scholar
  89. 89.
    Huikuri HV, Pikkujämsä SM, Airaksinen KE, Ikäheimo MJ, Rantala AO, Kauma H, Lilja M, Kesäniemi YA (1996) Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. Circulation 94:122–125PubMedCrossRefGoogle Scholar
  90. 90.
    Hulot JS, Démolis JL, Rivière R, Strabach S, Christin-Maitre S, Funck-Brentano C (2003) Influence of endogenous oestrogens on QT interval duration. Eur Heart J 24:1663–1667PubMedCrossRefGoogle Scholar
  91. 91.
    Hunt BE, Taylor JA, Hamner JW, Gagnon M, Lipsitz LA (2001) Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women. Circulation 103:2909–2914PubMedCrossRefGoogle Scholar
  92. 92.
    Huxley VH (2007) Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently. Adv Physiol Educ 31:17–22PubMedCrossRefGoogle Scholar
  93. 93.
    Iliff A, Lee VA (1952) Pulse rate, respiratory rate, and body temperature of children between two months and eighteen years of age. Child Dev 23:237–245PubMedCrossRefGoogle Scholar
  94. 94.
    James AF, Arberry LA, Hancox JC (2004) Gender-related differences in ventricular myocyte repolarization in the guinea pig. Basic Res Cardiol 99:183–192PubMedCrossRefGoogle Scholar
  95. 95.
    Jones PP, Snitker S, Skinner JS, Ravussin E (1996) Gender differences in muscle sympathetic nerve activity: effect of body fat distribution. Am J Physiol 270:E363–E366PubMedGoogle Scholar
  96. 96.
    Jonsson MK, Vos MA, Duker G, Demolombe S, van Veen TA (2010) Gender disparity in cardiac electrophysiology: implications for cardiac safety pharmacology. Pharmacol Ther 127:9–18PubMedCrossRefGoogle Scholar
  97. 97.
    Jose AD, Collison D (1970) The normal range and determinants of the intrinsic heart rate in man. Cardiovasc Res 4:160–167PubMedCrossRefGoogle Scholar
  98. 98.
    Kadish AH, Greenland P, Limacher MC, Frishman WH, Daugherty SA, Schwartz JB (2004) Estrogen and progestin use and the QT interval in postmenopausal women. Ann Noninvasive Electrocardiol 9:366–374PubMedCrossRefGoogle Scholar
  99. 99.
    Kannankeril PJ, Roden DM (2007) Drug-induced long QT and torsade de pointes: recent advances. Curr Opin Cardiol 22:39–43PubMedCrossRefGoogle Scholar
  100. 100.
    Kannel WB, Sorlie P, McNamara PM (1979) Prognosis after initial myocardial infarction: the Framingham Study. Am J Cardiol 44:53–59PubMedCrossRefGoogle Scholar
  101. 101.
    Kannel WB, Wilson PW, D'Agostino RB, Cobb J (1998) Sudden coronary death in women. Am Heart J 136:205–212PubMedCrossRefGoogle Scholar
  102. 102.
    Kardos A, Watterich G, de Menezes R, Csanády M, Casadei B, Rudas L (2001) Determinants of spontaneous baroreflex sensitivity in a healthy working population. Hypertension 37:911–916PubMedCrossRefGoogle Scholar
  103. 103.
    Kaufman ES (2011) Arrhythmic risk in congenital long QT syndrome. J Electrocardiol 44:645–649PubMedCrossRefGoogle Scholar
  104. 104.
    Kautzner J (2004) Noninvasive provocations of baroreflex sensitivity. In: Malik M, Camm AJ (eds) Dynamic electrocardiography. Blackwell Futura, New York, pp 162–169CrossRefGoogle Scholar
  105. 105.
    Kawasaki R, Machado C, Reinoehl J, Fromm B, Baga JJ, Steinman RT, Lehmann MH (1995) Increased propensity of women to develop torsades de pointes during complete heart block. J Cardiovasc Electrophysiol 6:1032–1038PubMedCrossRefGoogle Scholar
  106. 106.
    Kenttä T, Karsikas M, Kiviniemi A, Tulppo M, Seppänen T, Huikuri HV (2010) Dynamics and rate-dependence of the spatial angle between ventricular depolarization and repolarization wave fronts during exercise ECG. Ann Noninvasive Electrocardiol 15:264–275PubMedCrossRefGoogle Scholar
  107. 107.
    Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD (1988) Age-related changes in normal human hearts during the first 10 decades of life: part II (Maturity). A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 63:137–146PubMedCrossRefGoogle Scholar
  108. 108.
    Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262PubMedCrossRefGoogle Scholar
  109. 109.
    Kligfield P, Gettes LS, Bailey JJ, Childers R, Deal BJ, Hancock EW, van Herpen G, Kors JA, Macfarlane P, Mirvis DM, Pahlm O, Rautaharju P, Wagner GS, Josephson M, Mason JW, Okin P, Surawicz B, Wellens H, American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology, American College of Cardiology Foundation, Heart Rhythm Society (2007) Recommendations for the standardization and interpretation of the electrocardiogram: part I: the electrocardiogram and its technology a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 49:1109–1127PubMedCrossRefGoogle Scholar
  110. 110.
    Kligfield P, Lax KG, Okin PM (1996) QT interval–heart rate relation during exercise in normal men and women: definition by linear regression analysis. J Am Coll Cardiol 28:1547–1555PubMedCrossRefGoogle Scholar
  111. 111.
    Krasemann T, Strompen C, Blumenberg J, Gehrmann J, Burkhardtsmaier G, Vogt J (2009) Changes of the corrected QT interval in healthy boys and girls over day and night. Eur Heart J 30:202–208PubMedCrossRefGoogle Scholar
  112. 112.
    Kuch B, Hense HW, Sinnreich R, Kark JD, von Eckardstein A, Sapoznikov D, Bolte HD (2001) Determinants of short-period heart rate variability in the general population. Cardiology 95:131–138PubMedCrossRefGoogle Scholar
  113. 113.
    Kupper NH, Willemsen G, van den Berg M, de Boer D, Posthuma D, Boomsma DI, de Geus EJ (2004) Heritability of ambulatory heart rate variability. Circulation 110:2792–2796PubMedCrossRefGoogle Scholar
  114. 114.
    Kurokawa J, Tamagawa M, Harada N, Honda S, Bai CX, Nakaya H, Furukawa T (2008) Acute effects of oestrogen on the guinea pig and human IKr channels and drug-induced prolongation of cardiac repolarization. J Physiol 586:2961–2973PubMedCrossRefGoogle Scholar
  115. 115.
    La Rovere MT, Pinna GD, Raczak G (2008) Baroreflex sensitivity: measurement and clinical implications. Ann Noninvasive Electrocardiol 13:191–207PubMedCrossRefGoogle Scholar
  116. 116.
    Laitinen T, Hartikainen J, Vanninen E, Niskanen L, Geelen G, Länsimies E (1998) Age and gender dependency of baroreflex sensitivity in healthy subjects. J Appl Physiol 84:576–583PubMedGoogle Scholar
  117. 117.
    LaMonte CS, Freiman AH (1965) The electrocardiogram after mastectomy. Circulation 32:746–754PubMedCrossRefGoogle Scholar
  118. 118.
    Lanfranchi PA, Gosselin N, Kara T, Jurak P, Somers VK, Denesle R, Petit D, Carrier J, Nadeau R, Montplaisir J (2005) Menopause, hormone replacement and RR and QT modulation during sleep. Sleep Med 6:561–561PubMedCrossRefGoogle Scholar
  119. 119.
    Larsen JA, Tung RH, Sadananda R, Goldberger JJ, Horvath G, Parker MA, Kadish AH (1998) Effects of hormone replacement therapy on QT interval. Am J Cardiol 82:993–995PubMedCrossRefGoogle Scholar
  120. 120.
    Laughlin GA, McEvoy LK, von Mühlen D, Daniels LB, Kritz-Silverstein D, Bergstrom J, Cummins K, Der-Martirosian C, Jassal SK, Barrett-Connor E (2011) Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease. Psychosom Med 73:683–689PubMedCrossRefGoogle Scholar
  121. 121.
    Leaf DA (1990) Women and coronary artery disease. Gender confers no immunity. Postgrad Med 87:55–60PubMedGoogle Scholar
  122. 122.
    Lehmann MH, Yang H (2001) Sexual dimorphism in the electrocardiographic dynamics of human ventricular repolarization: characterization in true domain. Circulation 194:32–38CrossRefGoogle Scholar
  123. 123.
    Leicht AS, Hirning DA, Allen GD (2003) Heart rate variability and endogenous sex hormones during the menstrual cycle in young women. Exp Physiol 88:441–446PubMedCrossRefGoogle Scholar
  124. 124.
    Lepeschkin E, Surawicz B (1953) The duration of Q–U interval and its components in electrocardiograms of normal persons. Am Heart J 46:9–20PubMedCrossRefGoogle Scholar
  125. 125.
    Levy D, Labib SB, Anderson KM, Christiansen JC, Kannel WB, Castelli WP (1990) Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy. Circulation 81:815–820PubMedCrossRefGoogle Scholar
  126. 126.
    Liao D, Barnes RW, Chambless LE, Simpson RJ, Sorlie P, Heiss G, The ARIC Investigators (1995) Age, race, and sex differences in autonomic cardiac function measured by spectral analysis of heart rate variability — The ARIC study. Am J Cardiol 76:906–912PubMedCrossRefGoogle Scholar
  127. 127.
    Liu CC, Kuo TB, Yang CC (2003) Effects of estrogen on gender-related autonomic differences in humans. Am J Physiol Heart Circ Physiol 285:H2188–H2193PubMedGoogle Scholar
  128. 128.
    Liu K, Ballew C, Jacobs DR Jr, Sidney S, Savage PJ, Dyer A, Hughes G, Blanton MM (1989) Ethnic differences in blood pressure, pulse rate, and related characteristics in young adults. The CARDIA study. Hypertension 14:218–226PubMedCrossRefGoogle Scholar
  129. 129.
    Liu S, Yuan S, Kongstad O, Olsson SB (2001) Gender differences in the electrophysiological characteristics of atrioventricular conduction system and their clinical implications. Scand Cardiovasc J 35:313–317PubMedCrossRefGoogle Scholar
  130. 130.
    Liu XK, Katchman A, Drici MD, Ebert SN, Ducic I, Morad M, Woosley RL (1998) Gender difference in the cycle length-dependent QT and potassium currents in rabbits. J Pharmacol Exp Ther 285:672–679PubMedGoogle Scholar
  131. 131.
    Liu XK, Katchman A, Whitfield BH, Wan G, Janowski EM, Woosley RL, Ebert SN (2003) In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits. Cardiovasc Res 57:28–36PubMedCrossRefGoogle Scholar
  132. 132.
    Lombardi F (2002) Clinical implications of present physiological understanding of HRV components. Card Electrophysiol Rev 6:245–249PubMedCrossRefGoogle Scholar
  133. 133.
    López L, Wilper AP, Cervantes MC, Betancourt JR, Green AR (2010) Racial and sex differences in emergency department triage assessment and test ordering for chest pain, 1997–2006. Acad Emerg Med 17:801–808PubMedCrossRefGoogle Scholar
  134. 134.
    Lubinski A, Kornacewicz-Jach Z, Wnuk-Wojnar AM, Adamus J, Kempa M, Krolak T, Lewicka-Nowak E, Radomski M, Swiatecka G (2000) The terminal portion of the T wave: a new electrocardiographic marker of risk of ventricular arrhythmias. Pacing Clin Electrophysiol 23:1957–1959PubMedGoogle Scholar
  135. 135.
    Lubinski A, Lewicka-Nowak E, Kempa M, Baczynska AM, Romanowska I, Swiatecka G (1998) New insight into repolarization abnormalities in patients with congenital long QT syndrome: the increased transmural dispersion of repolarization. Pacing Clin Electrophysiol 21:172–175PubMedCrossRefGoogle Scholar
  136. 136.
    Luzier AB, Nawarskas JJ, Añonuevo J, Wilson MF, Kazierad DJ (1998) The effects of gender on adrenergic receptor responsiveness. J Clin Pharmacol 38:618–624PubMedCrossRefGoogle Scholar
  137. 137.
    Macfarlane PW, McLaughlin SC, Devine B, Yang TF (1994) Effects of age, sex, and race on ECG interval measurements. J Electrocardiol 27(Suppl):14–19PubMedCrossRefGoogle Scholar
  138. 138.
    MacLeod RS, Ni Q, Punske B, Ershler PR, Yilmaz B, Taccardi B (2000) Effects of heart position on the body-surface electrocardiogram. J Electrocardiol 33(Suppl):229–237PubMedCrossRefGoogle Scholar
  139. 139.
    Madias JE (2012) Augmentation/attenuation of the QRST complexes and their effects on the QT/QTc: a heretofore overlooked important association. Pacing Clin Electrophysiol 35:1409–1410PubMedCrossRefGoogle Scholar
  140. 140.
    Magnano AR, Holleran S, Ramakrishnan R, Reiffel JA, Bloomfield DM (2002) Autonomic nervous system influences on QT interval in normal subjects. J Am Coll Cardiol 39:1820–1826PubMedCrossRefGoogle Scholar
  141. 141.
    Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH (1993) Female gender as a risk factor for Torsades de Pointes associated with cardiovascular drugs. J Am Med Assoc 270:2590–2597CrossRefGoogle Scholar
  142. 142.
    Malik M (2002) The impression in heart rate correction may lead to artificial observations of drug induced QT interval changes. Pacing Clin Electrophysiol 25:209–216PubMedCrossRefGoogle Scholar
  143. 143.
    Malik M, Acar B, Gang Y, Yap YG, Hnatkova K, Camm AJ (2000) QT dispersion does not represent electrocardiographic interlead heterogeneity of ventricular repolarization. J Cardiovasc Electrophysiol 11:835–843PubMedCrossRefGoogle Scholar
  144. 144.
    Malik M, Färbom P, Batchvarov V, Hnatkova K, Camm AJ (2002) Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart 87:220–228PubMedCrossRefGoogle Scholar
  145. 145.
    Malik M, Hnatkova K, Kowalski D, Keirns JJ, van Gelderen EM (2012) Importance of subject-specific QT/RR curvatures in the design of individual heart rate corrections of the QT interval. J Electrocardiol 45:571–581PubMedCrossRefGoogle Scholar
  146. 146.
    Malik M, Hnatkova K, Novotny T, Schmidt G (2008) Subject-specific profiles of QT/RR hysteresis. Am J Physiol Heart Circ Physiol 295:H2356–H2363PubMedCrossRefGoogle Scholar
  147. 147.
    Malik M, Hnatkova K, Sisakova M, Schmidt G (2008) Subject-specific heart rate dependency of electrocardiographic QT, PQ, QRS intervals. J Electrocardiol 41:491–497PubMedCrossRefGoogle Scholar
  148. 148.
    Malliani A, Pagani M, Lombardi F, Cerutti S (1991) Cardiovascular neural regulation explored in the frequency domain. Circulation 84:482–492PubMedCrossRefGoogle Scholar
  149. 149.
    Mandic S, Fonda H, Dewey F, Le VV, Stein R, Wheeler M, Ashley EA, Myers J, Froelicher VF (2010) Effect of gender on computerized electrocardiogram measurements in college athletes. Phys Sportsmed 38:156–164PubMedCrossRefGoogle Scholar
  150. 150.
    Mangoni AA, Kinirons MT, Swift CG, Jackson SH (2003) Impact of age on QT interval and QT dispersion in healthy subjects: a regression analysis. Age Ageing 32:326–331PubMedCrossRefGoogle Scholar
  151. 151.
    Mason JW, Ramseth DJ, Chanter DO, Moon TE, Goodman DB, Mendzelevski B (2007) Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 40:228–234PubMedCrossRefGoogle Scholar
  152. 152.
    Matsukawa T, Sugiyama Y, Watanabe T, Kobayashi F, Mano T (1998) Gender difference in age-related changes in muscle sympathetic nerve activity in healthy subjects. Am J Physiol 275:R1600–R1604PubMedGoogle Scholar
  153. 153.
    Mayuga KA, Thattassery E, Taneja T, Karha J, Subacius H, Goldberger J, Kadish A (2010) Circadian and gender effects on repolarization in healthy adults: a study using harmonic regression analysis. Ann Noninvasive Electrocardiol 15:3–10PubMedCrossRefGoogle Scholar
  154. 154.
    McKenna DS, Ventolini G, Neiger R, Downing C (2006) Gender-related differences in fetal heart rate during first trimester. Fetal Diagn Ther 21:144–147PubMedCrossRefGoogle Scholar
  155. 155.
    Medina-Ravell VA, Lankipalli RS, Yan GX, Antzelevitch C, Medina-Malpica NA, Medina-Malpica OA, Droogan C, Kowey PR (2003) Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization: does resynchronization therapy pose a risk for patients predisposed to long QT or torsade de pointes? Circulation 107:740–746PubMedCrossRefGoogle Scholar
  156. 156.
    Mercuro G, Podda A, Pitzalis L, Zoncu S, Mascia M, Melis GB, Rosano GM (2000) Evidence of a role of endogenous estrogen in the modulation of autonomic nervous system. Am J Cardiol 85:787–789PubMedCrossRefGoogle Scholar
  157. 157.
    Minson CT, Halliwill JR, Young TM, Joyner MJ (2000) Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women. Circulation 101:862–868PubMedCrossRefGoogle Scholar
  158. 158.
    Minson CT, Halliwill JR, Young TM, Joyner MJ (2000) Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives. Circulation 102:1473–1476PubMedCrossRefGoogle Scholar
  159. 159.
    Mohamed MK, El-Mas MM, Abdel-Rahman AA (1999) Estrogen enhancement of baroreflex sensitivity is centrally mediated. Am J Physiol 276:R1030–R1037PubMedGoogle Scholar
  160. 160.
    Molnar J, Zhang F, Weiss J, Ehlert FA, Rosenthal JE (1996) Diurnal pattern of QTc interval: how long is prolonged? J Am Coll Cardiol 27:76–83PubMedCrossRefGoogle Scholar
  161. 161.
    Moss AJ (1993) Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol 72:23B–25BPubMedCrossRefGoogle Scholar
  162. 162.
    Moss AJ (2012) Sex hormones and ventricular tachyarrhythmias in LQTS: new insights regarding antiarrhythmic therapy. Hear Rhythm 9:833–834CrossRefGoogle Scholar
  163. 163.
    Nakagawa M, Ooie T, Takahashi N, Taniguchi Y, Anan F, Yonemochi H, Saikawa T (2006) Influence of menstrual cycle on QT interval dynamics. Pacing Clin Electrophysiol 29:607–613PubMedCrossRefGoogle Scholar
  164. 164.
    Nakagawa M, Takahashi N, Watanabe M, Ichinose M, Nobe S, Yonemochi H, Ito M, Saikawa T (2003) Gender differences in ventricular repolarization: terminal T wave interval was shorter in women than in men. Pacing Clin Electrophysiol 26:59–64PubMedCrossRefGoogle Scholar
  165. 165.
    Nevsky G, Jacobs JE, Lim RP, Donnino R, Babb JS, Srichai MB (2011) Sex-specific normalized reference values of heart and great vessel dimensions in cardiac CT angiography. AJR Am J Roentgenol 196:788–794PubMedCrossRefGoogle Scholar
  166. 166.
    Ng AV, Callister R, Johnson DG, Seals DR (1993) Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 21:498–503PubMedCrossRefGoogle Scholar
  167. 167.
    Nowinski K, Pripp U, Carlstrom K, Landgren BM, Schenck-Gustafsson K, Bergfeldt L (2002) Repolarization measures and their relation to sex hormones in postmenopausal women with cardiovascular disease receiving hormone replacement therapy. Am J Cardiol 90:1050–1055PubMedCrossRefGoogle Scholar
  168. 168.
    Oberman A, Myers AR, Karunas TM, Epstein FH (1967) Heart size of adults in a natural population—Tecumseh, Michigan. Variation by sex, age, height, and weight. Circulation 35:724–733PubMedCrossRefGoogle Scholar
  169. 169.
    O'Brien IA, O'Hare P, Corrall RJ (1986) Heart rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function. Br Heart J 55:348–354PubMedCrossRefGoogle Scholar
  170. 170.
    Okin PM, Devereux RB, Fabsitz RR, Lee ET, Galloway JM, Howard BV (2002) Principal component analysis of the T wave and prediction of cardiovascular mortality in American Indians: the Strong Heart Study. Circulation 105:714–719PubMedCrossRefGoogle Scholar
  171. 171.
    Okin PM, Kligfield P (1995) Gender-specific criteria and performance of the exercise electrocardiogram. Circulation 92:1209–1216PubMedCrossRefGoogle Scholar
  172. 172.
    Okin PM, Xue Q, Reddy S, Kligfield P (2000) Electrocardiographic quantitation of heterogeneity of ventricular repolarization. Ann Noninvasive Electrocardiol 5:79–87CrossRefGoogle Scholar
  173. 173.
    Ostrander LD Jr, Brandt RL, Kjelsberg MO, Epstein FH (1965) Electrocardiographic findings among the adult population of a total natural community, Tecumseh, Michigan. Circulation 31:888–898PubMedCrossRefGoogle Scholar
  174. 174.
    Palmero HA, Caeiro TF, Iosa DJ, Bas J (1981) Baroreceptor reflex sensitivity index derived from Phase 4 of the Valsalva manoeuvre. Hypertension 3:II-134–137Google Scholar
  175. 175.
    Papaioannou VE (2007) Heart rate variability, baroreflex function and heart rate turbulence: possible origin and implications. Hell J Cardiol 48:278–289Google Scholar
  176. 176.
    Parmer RJ, Cervenka JH, Stone RA (1992) Baroreflex sensitivity and heredity in essential hypertension. Circulation 85:497–503PubMedCrossRefGoogle Scholar
  177. 177.
    Pearl W (1996) Effects of gender, age, and heart rate on QT intervals in children. Pediatr Cardiol 17:135–136PubMedCrossRefGoogle Scholar
  178. 178.
    Persky VW, Dyer AR, Stamler J, Shekelle RB, Schoenberger FA (1979) Racial patterns of heart rate in an employed adult population. Am J Epidemiol 110:274–279PubMedGoogle Scholar
  179. 179.
    Pham TV, Robinson RB, Danilo P Jr, Rosen MR (2002) Effects of gonadal steroids on gender-related differences in transmural dispersion of l-type calcium current. Cardiovasc Res 53:752–762PubMedCrossRefGoogle Scholar
  180. 180.
    Pham TV, Sosunov EA, Gainullin RZ, Danilo P Jr, Rosen MR (2001) Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I(k)-blocking drugs. Circulation 103:2207–2212PubMedCrossRefGoogle Scholar
  181. 181.
    Pickering TG, Gribbin B, Sleight P (1972) Comparison of the reflex heart rate response to rising and falling arterial pressure in man. Cardiovasc Res 6:277–283PubMedCrossRefGoogle Scholar
  182. 182.
    Pietila E, Fodstad H, Niskasaari E, Laitinen PP, Swan H, Savolainen M, Kesaniemi YA, Kontula K, Huikuri HV (2002) Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women. J Am Coll Cardiol 40:511–514PubMedCrossRefGoogle Scholar
  183. 183.
    Priori SG, Mortara DW, Napolitano C, Diehl L, Paganini V, Cantu F, Cantu G, Schwartz PJ (1997) Evaluation of the spatial aspects of T-wave complexity in the long-QT syndrome. Circulation 96:3006–3012PubMedCrossRefGoogle Scholar
  184. 184.
    Pueyo E, Smetana P, Caminal P, de Luna AB, Malik M, Laguna P (2004) Characterization of QT interval adaptation to RR interval changes and its use as a risk-stratifier of arrhythmic mortality in amiodarone-treated survivors of acute myocardial infarction. IEEE Trans Biomed Eng 51:1511–1520PubMedCrossRefGoogle Scholar
  185. 185.
    Pueyo E, Smetana P, Laguna P, Malik M (2003) Estimation of QT lag in response to RR changes. J Electrocardiol 36(Suppl):187–190PubMedCrossRefGoogle Scholar
  186. 186.
    Ramaekers D, Ector H, Aubert AE, Rubens A, Van de Werf F (1998) Heart rate variability and heart rate in healthy volunteers. Is the female autonomic nervous system cardioprotective? Eur Heart J 19:1334–1341PubMedCrossRefGoogle Scholar
  187. 187.
    Rashba EJ, Zareba W, Moss AJ, Hall WJ, Robinson J, Locati EH, Schwartz PJ, Andrews M (1998) Influence of pregnancy on the risk for cardiac events in patients with hereditary long QT syndrome. LQTS Investigators. Circulation 97:451–456PubMedCrossRefGoogle Scholar
  188. 188.
    Rautaharju PM, Ge S, Nelson JC, Marino Larsen EK, Psaty BM, Furberg CD, Zhang ZM, Robbins J, Gottdiener JS, Chaves PHM (2006) Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study). Am J Cardiol 97:309–315PubMedCrossRefGoogle Scholar
  189. 189.
    Rautaharju PM, Zhou SH, Wong S, Calhoun HP, Berenson GS, Prineas R, Davignon A (1992) Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 8:690–695PubMedGoogle Scholar
  190. 190.
    Reiley MA, Su JJ, Guller B (1979) Racial and sexual differences in the standard electrocardiogram of black vs white adolescents. Chest 75:474–480PubMedCrossRefGoogle Scholar
  191. 191.
    Rijnbeek PR, Witsenburg M, Schrama E, Hess J, Kors JA (2001) New normal limits for the paediatric electrocardiogram. Eur Heart J 22:702–711PubMedCrossRefGoogle Scholar
  192. 192.
    Robbe HW, Mulder LJ, Rüddel H, Langewitz WA, Veldman JB, Mulder G (1987) Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension 10:538–543PubMedCrossRefGoogle Scholar
  193. 193.
    Rodriguez I, Kilborn MJ, Liu XK, Pezzullo JC, Woosley RL (2001) Drug-induced QT prolongation in women during the menstrual cycle. J Am Med Assoc 285:1322–1326CrossRefGoogle Scholar
  194. 194.
    Rosa Brito-Zurita O, Posadas-Romero C, Hermosillo AG, Zamora-González J, Hernández-Ono A, Cardoso-Saldaña G, Torres-Tamayo M (2003) Estrogen effect on heart rate variability in hypertensive postmenopausal women. Maturitas 44:39–48PubMedCrossRefGoogle Scholar
  195. 195.
    Rosano GM, Patrizi R, Leonardo F, Ponikowski P, Collins P, Sarrel PM, Chierchia SL (1997) Effect of estrogen replacement therapy on heart rate variability and heart rate in healthy postmenopausal women. Am J Cardiol 80:815–817PubMedCrossRefGoogle Scholar
  196. 196.
    Russell MW, Law I, Sholinsky P, Fabsitz RR (1998) Heritability of ECG measurements in adult male twins. J Electrocardiol 30(Suppl 1):64–68PubMedCrossRefGoogle Scholar
  197. 197.
    Ryan SM, Goldberger AL, Pincus SM, Mietus J, Lipsitz LA (1994) Gender- and age-related differences in heart rate dynamics: are women more complex than men? J Am Coll Cardiol 24:1700–1707PubMedCrossRefGoogle Scholar
  198. 198.
    Saba S, Link MS, Homoud MK, Wang PJ, Estes NA 3rd (2001) Effect of low estrogen states in healthy women on dispersion of ventricular repolarization. Am J Cardiol 87(354–356):A9–A10Google Scholar
  199. 199.
    Saeki Y, Atogami F, Takahashi K, Yoshizawa T (1997) Reflex control of autonomic function induced by posture change during the menstrual cycle. J Auton Nerv Syst 66:69–74PubMedCrossRefGoogle Scholar
  200. 200.
    Sagie A, Larson MG, Goldberg RJ, Bengston JR, Levy D (1992) An improved method for adjusting the QT interval for heart rate (the Framingham Study). Am J Cardiol 70:797–801PubMedCrossRefGoogle Scholar
  201. 201.
    Saleh TM, Connell BJ (1999) Centrally mediated effect of 17beta-estradiol on parasympathetic tone in male rats. Am J Physiol 276:R474–R481PubMedGoogle Scholar
  202. 202.
    Sarikouch S, Peters B, Gutberlet M, Leismann B, Kelter-Kloepping A, Koerperich H, Kuehne T, Beerbaum P (2010) Sex-specific pediatric percentiles for ventricular size and mass as reference values for cardiac MRI: assessment by steady-state free-precession and phase-contrast MRI flow. Circ Cardiovasc Imaging 3:65–76PubMedCrossRefGoogle Scholar
  203. 203.
    Sato N, Miyake S, Akatsu J, Kumashiro M (1995) Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle. Psychosom Med 57:331–335PubMedGoogle Scholar
  204. 204.
    Savelieva I, Yap YG, Yi G, Guo X, Camm AJ, Malik M (1998) Comparative reproducibility of QT, QT peak, and T peak-T end intervals and dispersion in normal subjects, patients with myocardial infarction, and patients with hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 21:2376–2381PubMedCrossRefGoogle Scholar
  205. 205.
    Scherptong RW, Henkens IR, Man SC, Le Cessie S, Vliegen HW, Draisma HH, Maan AC, Schalij MJ, Swenne CA (2008) Normal limits of the spatial QRS–T angle and ventricular gradient in 12-lead electrocardiograms of young adults: dependence on sex and heart rate. J Electrocardiol 41:648–655PubMedCrossRefGoogle Scholar
  206. 206.
    Schwartz PJ, Stramba-Badiale M (1998) Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 338:1709–1714PubMedCrossRefGoogle Scholar
  207. 207.
    Schwartz PJ, Wolf S (1978) QT interval prolongation as predictor of sudden death in patients with myocardial infarction. Circulation 57:1074–1077PubMedCrossRefGoogle Scholar
  208. 208.
    Shimizu W, Antzelevitch C (1998) Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of beta-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes. Circulation 98:2314–2322PubMedCrossRefGoogle Scholar
  209. 209.
    Shimizu W, Tsuchioka Y, Karakawa S, Nagata K, Mukai J, Yamagata T, Matsuura H, Kajiyama G, Matsuura Y (1994) Differential effect of pharmacological autonomic blockade on some electrophysiological properties of the human ventricle and atrium. Br Heart J 71:34–37PubMedCrossRefGoogle Scholar
  210. 210.
    Sicouri S, Antzelevitch C (1991) A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Circ Res 68:1729–1741PubMedCrossRefGoogle Scholar
  211. 211.
    Silvetti MS, Drago F, Ragonese P (2001) Heart rate variability in healthy children and adolescents is partially related to age and gender. Int J Cardiol 81:169–174PubMedCrossRefGoogle Scholar
  212. 212.
    Simon T, Mary-Krause M, Funck-Brentano C, Jaillon P (2001) Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II). Circulation 103:375–380PubMedCrossRefGoogle Scholar
  213. 213.
    Simonson E, Blackburn H, Puchner TC, Ribeiro F, Meja M (1960) Sex differences in the electrocardiograms. Circulation 22:598–601CrossRefGoogle Scholar
  214. 214.
    Sims C, Reisenweber S, Viswanathan PC, Choi BR, Walker WH, Salama G (2008) Sex, age, and regional differences in l-type calcium current are important determinants of arrhythmia phenotype in rabbit hearts with drug-induced long QT type 2. Circ Res 102:e86–e100PubMedCrossRefGoogle Scholar
  215. 215.
    Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D (1999) Heritability of heart rate variability: the Framingham Heart Study. Circulation 99:2251–2254PubMedCrossRefGoogle Scholar
  216. 216.
    Singh JP, Larson MG, O'Donnell CJ, Tsuji H, Corey D, Levy D (2002) Genome scan linkage results for heart rate variability (the Framingham Heart Study). Am J Cardiol 90:1290–1293PubMedCrossRefGoogle Scholar
  217. 217.
    Sinnreich R, Friedlander Y, Luria MH, Sapoznikov D, Kark JD (1999) Inheritance of heart rate variability: the Kibbutzim Family Study. Hum Genet 105:654–661PubMedCrossRefGoogle Scholar
  218. 218.
    Sinnreich R, Friedlander Y, Sapoznikov D, Kark JD (1998) Familial aggregation of heart rate variability based on short recordings: the Kibbutzim Family Study. Hum Genet 103:34–40PubMedCrossRefGoogle Scholar
  219. 219.
    Smetana P, Batchvarov V, Hnatkova K, John Camm A, Malik M (2003) Sex differences in the rate dependence of the T wave descending limb. Cardiovasc Res 58:549–554PubMedCrossRefGoogle Scholar
  220. 220.
    Smetana P, Batchvarov VN, Hnatkova K, Camm AJ, Malik M (2002) Sex differences in repolarization homogeneity and its circadian pattern. Am J Physiol Heart Circ Physiol 282:H1889–H1897PubMedGoogle Scholar
  221. 221.
    Smetana P, Batchvarov VN, Hnatkova K, Camm AJ, Malik M (2004) Ventricular gradient and nondipolar repolarization components increase at higher heart rate. Am J Physiol Heart Circ Physiol 286:H131–H136PubMedCrossRefGoogle Scholar
  222. 222.
    Smetana P, Schmidt A, Zabel M, Hnatkova K, Franz M, Huber K, Malik M (2011) Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components. J Electrocardiol 44:301–308PubMedCrossRefGoogle Scholar
  223. 223.
    Smit AA, Timmers HJ, Wieling W, Wagenaar M, Marres HA, Lenders JW, van Montfrans GA, Karemaker JM (2002) Long-term effects of carotid sinus denervation on arterial blood pressure in humans. Circulation 105:1329–1335PubMedCrossRefGoogle Scholar
  224. 224.
    Smyth HS, Sleight P, Pickering GW (1969) Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. Circ Res 24:109–121PubMedCrossRefGoogle Scholar
  225. 225.
    Stein PK, Kleiger RE, Rottman JN (1997) Differing effects of age on heart rate variability in men and women. Am J Cardiol 80:302–305PubMedCrossRefGoogle Scholar
  226. 226.
    Stramba-Badiale M, Locati EH, Martinelli A, Courville J, Schwartz PJ (1997) Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur Heart J 18:1000–1006PubMedCrossRefGoogle Scholar
  227. 227.
    Stramba-Badiale M, Spagnolo D, Bosi G, Schwartz PJ (1995) Are gender differences in QTc present at birth? Am J Cardiol 75:1277–1278PubMedCrossRefGoogle Scholar
  228. 228.
    Surawicz B, Parikh SR (2002) Prevalence of male and female patterns of early ventricular repolarization in the normal ECG of males and females from childhood to old age. J Am Coll Cardiol 40:1870–1876PubMedCrossRefGoogle Scholar
  229. 229.
    Sutliff WD, Holt E (1925) The age curve of pulse rate under basal conditions. Arch Intern Med 35:225–241CrossRefGoogle Scholar
  230. 230.
    Tan JKB, Guo KWQ, Hsu LF (2011) Palpitations and narrow-complex tachycardia. Singap Med J 52:241–245Google Scholar
  231. 231.
    Tanaka M, Sato M, Umehara S, Nishikawa T (2003) Influence of menstrual cycle on baroreflex control of heart rate: comparison with male volunteers. Am J Physiol Regul Integr Comp Physiol 285:R1091–R1097PubMedGoogle Scholar
  232. 232.
    Taneja T, Mahnert BW, Passman R, Goldberger J, Kadish A (2001) Effects of sex and age on electrocardiographic and cardiac electrophysiological properties in adults. Pacing Clin Electrophysiol 24:16–21PubMedCrossRefGoogle Scholar
  233. 233.
    Tank J, Baevski RM, Fender A, Baevski AR, Graves KF, Ploewka K, Weck M (2000) Reference values of indices of spontaneous baroreceptor reflex sensitivity. Am J Hypertens 13:268–275PubMedCrossRefGoogle Scholar
  234. 234.
    Tank J, Jordan J, Diedrich A, Stoffels M, Franke G, Faulhaber HD, Luft FC, Busjahn A (2001) Genetic influences on baroreflex function in normal twins. Hypertension 37:907–910PubMedCrossRefGoogle Scholar
  235. 235.
    Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Eur Heart J 17:354–381CrossRefGoogle Scholar
  236. 236.
    Trepanier-Boulay V, St-Michel C, Tremblay A, Fiset C (2001) Gender-based differences in cardiac repolarization in mouse ventricle. Circ Res 89:437–444PubMedCrossRefGoogle Scholar
  237. 237.
    Umetani K, Singer DH, McCraty R, Atkinson M (1998) Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol 31:593–601PubMedCrossRefGoogle Scholar
  238. 238.
    Uusitalo AL, Vanninen E, Levalahti E, Battie MC, Videman T, Kaprio J (2007) Role of genetic and environmental influences on heart rate variability in middle-aged men. Am J Physiol Heart Circ Physiol 293:H1013–H1022PubMedCrossRefGoogle Scholar
  239. 239.
    Valverde ER, Biagetti MO, Bertran GR, Arini PD, Bidoggia H, Quinteiro RA (2003) Developmental changes of cardiac repolarization in rabbits. Implications for the role of sex hormones. Cardiovasc Res 57:625–631PubMedCrossRefGoogle Scholar
  240. 240.
    van Oosterom A, Hoekema R, Uijen GJ (2000) Geometrical factors affecting the interindividual variability of the ECG and the VCG. J Electrocardiol 33(Suppl):219–227PubMedCrossRefGoogle Scholar
  241. 241.
    Vasan RS, Larson MG, Levy D, Evans JC, Benjamin EJ (1997) Distribution and categorization of echocardiographic measurements in relation to reference limits: the Framingham Heart Study: formulation of a height- and sex-specific classification and its prospective validation. Circulation 96:1863–1873PubMedCrossRefGoogle Scholar
  242. 242.
    Vaturi M, Weisenberg D, Yedidya I, Shapira Y, Nevzorov R, Monakier D, Sagie A (2012) Does gender affect the rates of abnormal exercise stress echocardiography in patients with asymptomatic severe aortic stenosis. J Heart Valve Dis 21:31–36PubMedGoogle Scholar
  243. 243.
    Verrier RL, Antzelevitch C (2004) Autonomic aspects of arrhythmogenesis: the enduring and the new. Curr Opin Cardiol 19:2–11PubMedCrossRefGoogle Scholar
  244. 244.
    Viitasalo M, Oikarinen L, Swan H, Vaananen H, Glatter K, Laitinen PJ, Kontula K, Barron HV, Toivonen L, Scheinman MM (2002) Ambulatory electrocardiographic evidence of transmural dispersion of repolarization in patients with long-QT syndrome type 1 and 2. Circulation 106:2473–2478PubMedCrossRefGoogle Scholar
  245. 245.
    Virtanen I, Polo O, Polo-Kantola P, Kuusela T, Ekholm E (2000) The effect of estrogen replacement therapy on cardiac autonomic regulation. Maturitas 37:45–51PubMedCrossRefGoogle Scholar
  246. 246.
    Voss A, Busjahn A, Wessel N, Schurath R, Faulhaber HD, Luft FC, Dietz R (1996) Familial and genetic influences on heart rate variability. J Electrocardiol 29(Suppl):154–160PubMedCrossRefGoogle Scholar
  247. 247.
    Vrtovec B, Starc V, Meden-Vrtovec H (2001) The effect of estrogen replacement therapy on ventricular repolarization dynamics in healthy postmenopausal women. J Electrocardiol 34:277–283PubMedCrossRefGoogle Scholar
  248. 248.
    Watanabe N, Kobayashi Y, Tanno K, Miyoshi F, Asano T, Kawamura M, Mikami Y, Adachi T, Ryu S, Miyata A, Katagiri T (2004) Transmural dispersion of repolarization and ventricular tachyarrhythmias. J Electrocardiol 37:191–200PubMedCrossRefGoogle Scholar
  249. 249.
    White M, Courtemanche M, Stewart DJ, Talajic M, Mikes E, Cernacek P, Vantrimpont P, Leclerc D, Bussières L, Rouleau JL (1997) Age- and gender-related changes in endothelin and catecholamine release, and in autonomic balance in response to head-up tilt. Clin Sci (Lond) 93:309–316Google Scholar
  250. 250.
    Wilson FN, McLeod AG, Barker PS (1931) The T deflection of the electrocardiogram. Trans Assoc Am Phys 46:29–38Google Scholar
  251. 251.
    Wilson PW, Evans JC (1993) Coronary artery disease prediction. Am J Hypertens 6:309S–313SPubMedCrossRefGoogle Scholar
  252. 252.
    Wolf MM, Varigos GA, Hunt D, Sloman JG (1978) Sinus arrhythmia in acute myocardial infarction. Med J Aust 2:52–53PubMedGoogle Scholar
  253. 253.
    Wolk R, Mazurek T, Lusawa T, Wasek W, Rezler J (2001) Left ventricular hypertrophy increases transepicardial dispersion of repolarisation in hypertensive patients: a differential effect on QTpeak and QTend dispersion. Eur J Clin Invest 31:563–569PubMedCrossRefGoogle Scholar
  254. 254.
    Wolk R, Stec S, Kulakowski P (2001) Extrasystolic beats affect transmural electrical dispersion during programmed electrical stimulation. Eur J Clin Invest 31:293–301PubMedCrossRefGoogle Scholar
  255. 255.
    Wu J, Kors JA, Rijnbeek PR, van Herpen G, Lu Z, Xu C (2003) Normal limits of the electrocardiogram in Chinese subjects. Int J Cardiol 87:37–51PubMedCrossRefGoogle Scholar
  256. 256.
    Wu Y, Anderson ME (2002) Reduced repolarization reserve in ventricular myocytes from female mice. Cardiovasc Res 53:763–769PubMedCrossRefGoogle Scholar
  257. 257.
    Xia Y, Liang Y, Kongstad O, Liao Q, Holm M, Olsson B, Yuan S (2005) In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine. Hear Rhythm 2:162–169CrossRefGoogle Scholar
  258. 258.
    Xiao L, Zhang L, Han W, Wang Z, Nattel S (2006) Sex-based transmural differences in cardiac repolarization and ionic-current properties in canine left ventricles. Am J Physiol Heart Circ Physiol 291:H570–H580PubMedCrossRefGoogle Scholar
  259. 259.
    Yamasaki Y, Kodama M, Matsuhisa M, Kishimoto M, Ozaki H, Tani A, Ueda N, Ishida Y, Kamada T (1996) Diurnal heart rate variability in healthy subjects: effects of aging and sex difference. Am J Physiol 271:H303–H310PubMedGoogle Scholar
  260. 260.
    Yan GX, Antzelevitch C (1998) Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 98:1928–1936PubMedCrossRefGoogle Scholar
  261. 261.
    Yang H, Elko P, Fromm BS, Baga JJ, Pires LA, Schuger CD, Steinman RT, Lehmann MH (1997) Maximal ascending and descending slopes of the T waves in men and women. J Electrocardiol 30:267–276PubMedCrossRefGoogle Scholar
  262. 262.
    Yildirir A, Kabakci G, Akgul E, Tokgozoglu L, Oto A (2002) Effects of menstrual cycle on cardiac autonomic innervation as assessed by heart rate variability. Ann Noninvasive Electrocardiol 7:60–63PubMedCrossRefGoogle Scholar
  263. 263.
    Yildirir A, Kabakci G, Yarali H, Aybar F, Akgul E, Bukulmez O, Tokgozoglu L, Gurgan T, Oto A (2001) Effects of hormone replacement therapy on heart rate variability in postmenopausal women. Ann Noninvasive Electrocardiol 6:280–284PubMedCrossRefGoogle Scholar
  264. 264.
    Zabel M, Acar B, Klingenheben T, Franz MR, Hohnloser SH, Malik M (2000) Analysis of 12-lead T-wave morphology for risk stratification after myocardial infarction. Circulation 102:1252–1257PubMedCrossRefGoogle Scholar
  265. 265.
    Zabel M, Malik M, Hnatkova K, Papademetriou V, Pittaras A, Fletcher RD, Franz MR (2002) Analysis of T wave morphology from the 12-lead ECG for prediction of long term prognosis in male US veterans. Circulation 105:1066–1070PubMedCrossRefGoogle Scholar
  266. 266.
    Zhang Y, Ouyang P, Post WS, Dalal D, Vaidya D, Blasco-Colmenares E, Soliman EZ, Tomaselli GF, Guallar E (2011) Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 174:403–411PubMedCrossRefGoogle Scholar
  267. 267.
    Zhang ZM, Prineas RJ, Case D, Soliman EZ, Rautaharju PM, ARIC Research Group (2007) Comparison of the prognostic significance of the electrocardiographic QRS/T angles in predicting incident coronary heart disease and total mortality (from the atherosclerosis risk in communities study). Am J Cardiol 100:844–849PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Wilhelminenspital der Stadt WienViennaAustria
  2. 2.St. Paul’s Cardiac Electrophysiology and St. George’sUniversity of LondonLondonUK
  3. 3.SurreyUK

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