Abstract
Background and hypothesis: QT interval length is influenced by autonomic nervous activity. In patients with diabetic autonomic neuropathy, both prolongation and shortening of ventricular repolarization has been reported. We studied diabetic and nondiabetic uremic patients to assess the effects of autonomic neuropathy on QT interval length.
Methods: 24‐hour electrocardiogram recordings were performed in 12 diabetic and 11 nondiabetic renal transplantation patients, and in 12 control patients. Mean and corrected QT interval (QTc) during the 24‐h period and intervals at predetermined heart rates at day and night periods were determined. The degree of autonomic neuropathy was assessed with cardiovascular autonomic function tests and measurement of heart rate variability.
Results: In the diabetic group, severe autonomic neuropathy was present; in nondiabetic uremic patients, abnormalities were less severe. Mean QTc interval during 24 h was 444 ± 24,447 ± 21, and 442 ± 19 ms in the diabetic and nondiabetic uremic patients, and in the control groups, respectively, without any between‐group difference. QT and QTc interval length did not differ among the groups when measured at heart rates of 70, 80, 90, or 100 beats/min.
Conclusions: In patients with autonomic failure caused by diabetes and/or uremia, QT interval length cannot be used as a diagnostic indicator of cardiac autonomic neuropathy.
Keywords: autonomic neuropathy, QT interval, diabetes, uremia
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The study was supported by the Academy of Finland and the Sigrid Juselius Foundation, Helsinki, Finland.
References
- 1. Lloyd‐Mostyn RH, Watkins PJ: Defective innervation of heart in diabetic autonomic neuropathy. Br Med J 1975; 3: 15–17 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Ewing DJ, Campbell IW, Clarke BF: The natural history of diabetic autonomic neuropathy. QJ Med 1980; 49: 95–108 [PubMed] [Google Scholar]
- 3. Navarro X, Kennedy WR, Loewenson RB, Sutherland DER: Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction and mortality in diabetes mellitus. Diabetes 1990; 39: 802–806 [DOI] [PubMed] [Google Scholar]
- 4. Ewing DJ, Winney R: Autonomic function in patients with chronic renal failure on intermittent hemodialysis. Nephron 1975; 15: 424–429 [DOI] [PubMed] [Google Scholar]
- 5. Campese VM, Romoff MS, Levitan D, Lane K, Massry SG: Mechanisms of autonomic nervous system dysfunction in uremia. Kidney Int 1981; 20: 246–253 [DOI] [PubMed] [Google Scholar]
- 6. Solders G: Autonomic function tests in healthy controls and in terminal uremia. Acta Neurol Scand 1986; 73: 638–639 [DOI] [PubMed] [Google Scholar]
- 7. Spallone V, Mazzaferro S, Tomei E, Maiello MR, Lungaroni G, Sardella D, Diacinti D, Menzinger G, Coen G: Autonomic neuropathy and secondary hyperparathyroidism in uremia. Nephrol Dial Transplant 1990; (suppl 1): 128–130 [DOI] [PubMed]
- 8. Ahnve S, Vallin H: Influence of heart rate and inhibition of autonomic tone on the QT interval. Circulation 1982; 65: 435–439 [DOI] [PubMed] [Google Scholar]
- 9. Browne KF, Zipes DP, Heger JJ, Prystowsky EN: Influence of the autonomic nervous system on the QT interval in man. Am J Cardiol 1982; 50: 1099–1103 [DOI] [PubMed] [Google Scholar]
- 10. Bexton RS, Vallin HO, Camm AJ: Diurnal variation of the QT interval‐influence of the autonomic nervous system. Br Heart J 1986; 55: 253–258 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Kahn JK, Sisson JC, Vinik AI: QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy. J Clin Endocrinol Metab 1987; 64: 751–754 [DOI] [PubMed] [Google Scholar]
- 12. Bellavere F, Ferri M, Guarini L, Bax G, Piccoli A, Cardone C, Fedele D: Prolonged QT period in diabetic autonomic neuropathy: A possible role in sudden cardiac death? Br Heart J 1988; 59: 379–383 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Ewing DJ, Neilson JMM: QT interval length and diabetic autonomic neuropathy. Diabetic Med 1990; 7: 23–26 [DOI] [PubMed] [Google Scholar]
- 14. Gonin JM, Kadrofske MM, Schmaltz S, Bastyr EJ, Vinik AI: Corrected Q‐T interval prolongation as diagnostic tool for assessment of cardiac autonomic neuropathy in diabetes mellitus. Diabetes Care 1990; 13: 68–71 [DOI] [PubMed] [Google Scholar]
- 15. Reissell E, Yli‐Hankala A, Orko R, Lindgren L: Sudden cardiorespiratory arrest after renal transplantation in a patient with diabetic autonomic neuropathy and prolonged QT‐mterval. Acta Anaesthesiol Scand 1993; 37: 406–408 [DOI] [PubMed] [Google Scholar]
- 16. Ong JJC, Sarma JSM, Venkataraman K, Levin SR, Singh BN: Circadian rhythmicity of heart rate and QTc interval in diabetic autonomic neuropathy: Implications for the mechanism of sudden death. Am Heart J 1993; 125: 744–752 [DOI] [PubMed] [Google Scholar]
- 17. Murakawa Y, Inoue H, Nozaki A, Sugimoto T: Role of sympathovagal interaction in diurnal variation of QT interval. Am J Cardiol 1992; 69: 339–343 [DOI] [PubMed] [Google Scholar]
- 18. Kawataki M, Kashima T, Toda H, Tanaka H: Relation between QT interval and heart rate. Applications and limitations of Bazett's formula. Electrocardiology 1984; 17: 371–376 [DOI] [PubMed] [Google Scholar]
- 19. Sarma JSM, Sarma RJ, Bilitch M, Katz D, Song SL: An exponential formula for heart rate dependence of QT interval during exercise and cardiac pacing in humans: Re‐evaluation of Bazett's formula. Am J Cardiol 1984; 54: 103–108 [DOI] [PubMed] [Google Scholar]
- 20. Yamasaki Y, Ueda N, Kishimoto M, Tani A, Ishida Y, Kawamori R, Kamada T: Assessment of early stage autonomic nerve dysfunction in diabetic subjects—application of power spectral analysis of heart rate variability. Diabetes Res 1991; 17: 73–80 [PubMed] [Google Scholar]
- 21. Bellavere F, Balzani I, DeMasi G, Carraro M, Carenza P, Cobelli C, Thomaseth K: Power spectral analysis of heart rate variations improves assessment of diabetic cardiac autonomic neuropathy. Diabetes 1992; 41: 633–640 [DOI] [PubMed] [Google Scholar]
- 22. Ziegler D, Dannehl K Mühlen H, Spüler M, Gries FA: Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart rate variation in newly diagnosed IDDM patients. Diabetes Care 1992; 15: 908–911 [DOI] [PubMed] [Google Scholar]
- 23. Ziegler D, Dannehl K Mühlen H, Spüler M, Gries FA: Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy. Diabetic Med 1992; 9: 806–814 [DOI] [PubMed] [Google Scholar]
- 24. Piha SJ: Cardiovascular autonomic reflex tests: Normal responses and age‐related reference values. Clin Physiol 1991; 11; 277–290 [DOI] [PubMed] [Google Scholar]
- 25. Piha SJ: Cardiovascular Autonomic Function Tests. Responses in Healthy Subjects and Determination of the Age‐Related Reference Values. Academic dissertation. Turka, Finland: Publications of the Social Insurance Institution, 1988. [Google Scholar]
- 26. Lepeschkin E, Surawicz B: The measurement of the Q‐T interval of the electrocardiogram. Circulation 1952; 6: 378–388 [DOI] [PubMed] [Google Scholar]
- 27. Bazett HC: An analysis of the time‐relation of electrocardiograms. Heart 1920; 7: 353–370 [Google Scholar]
- 28. Karjalainen J, Viitasalo M Mänttäri M, Manninen V: Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and simple method to adjust QT interval values. J Am Coll Cardiol 1994; 23: 1547–1553 [DOI] [PubMed] [Google Scholar]
- 29. Coghlan JG, Madden B, Norell MN, Ilsley CDJ, Mitchell AG: Paradoxical early lengthening and subsequent linear shortening of the QT interval in response to exercise. Eur Heart J 1992; 13: 1325–1328 [DOI] [PubMed] [Google Scholar]
- 30. Davidowski TA, Wolf S: The QT interval during reflex cardiac adaptation. Circulation 1984; 69: 22–25 [DOI] [PubMed] [Google Scholar]
- 31. Lau CP, Ward DE: QT hysteresis: The effect of an abrupt change in pacing rate In Clinical Aspects of Ventricular Repolarization (Eds. Burous GS, Schwartz PJ.), p. 175–181. London: Farrand Press; 1989. [Google Scholar]
- 32. Coumel P, Hermida JS, Wennerblöm B, Leenhardt A, Maison‐Blanche P, Cauchemez B: Heart rate variability in left ventricular hypertrophy and heart failure, and the effects of beta‐blockade. A non‐spectral analysis of heart rate variability in the frequency domain and in the time domain. Eur Heart J 1991; 12: 412–422 [DOI] [PubMed] [Google Scholar]
- 33. Langewitz W Rüddel H, Schächinger H: Reduced parasympathetic cardiac control in patients with hypertension at rest and under mental stress. Am Heart J 1994; 127: 122–128 [DOI] [PubMed] [Google Scholar]
- 34. Cook JR, Bigger JT, Kleiger RE, Gleiss JL, Steinman RC, Ronitzky LM: Effect of atenolol and diltiazem on heart period variability in normal persons. J Am Coll Cardiol 1991; 17: 480–484 [DOI] [PubMed] [Google Scholar]
- 35. Sandrone G, Mortara A, Torzillo D, La Rovere MT, Malliani A, Lombardi F: Effects of beta blockers (atenolol or metoprolol) on heart rate variability after acute myocardial infarction. Am J Cardiol 1994; 74: 340–345 [DOI] [PubMed] [Google Scholar]
- 36. Mallamaci F, Zoccali C, Ciccarelli M, Briggs JD: Autonomic function in uremic patients treated by hemodialysis or CAPD and in transplant patients. Clin Nephrol 1986; 25: 175–180 [PubMed] [Google Scholar]
- 37. Ekstrand A, Groop L, Pettersson E, Grönhagen‐Riska C, Laatikainen L, Matikainen E, Seppäläinen A‐M, Laasonen E, Summanen P, Ollus A, Ahonen J: Metabolic control and progression of complications in insulin‐dependent diabetic patients after kidney transplantation. J Int Med 1992; 232: 253–261 [DOI] [PubMed] [Google Scholar]
- 38. Milne JR, Camm AJ, Ward DE, Spurrell RAJ: Effect of intravenous propranolol on QT interval. Br Heart J 1980; 43: 1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Puddu PE, Bernard PM, Chaiman BR, Bourassa MG: QT interval measurement by a computer assisted program: A potentially useful clinical parameter. J Electrocardiol 1982; 15: 15–22 [DOI] [PubMed] [Google Scholar]
- 40. Sarma JSM, Singh N, Schoenbaum MP, Venkataraman K, Singh BN: Circadian and power spectral changes of RR and QT intervals during treatment of patients with angina pectoris with nadolol providing evidence for differential autonomic modulation of heart rate and ventricular repolarization. Am J Cardiol 1994; 74: 131–136 [DOI] [PubMed] [Google Scholar]
- 41. Surawicz B, Knoebel SB: Long QT: Good, bad or indifferent? J Am Coll Cardiol 1984; 4: 398–413 [DOI] [PubMed] [Google Scholar]
- 42. Day CP, McComb JM, Mathews J, Campbell RWF: Reduction in QT dispersion by sotalol following myocardial infarction. Eur Heart J 1991; 12: 423–427 [DOI] [PubMed] [Google Scholar]
- 43. Day CP, McComb JM, Campbell RWF: QT dispersion in sinus beats and ventricular extrasystoles in normal hearts. Br Heart J 1992; 67: 39–41 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Tomaselli GF, Beuckelmann DJ, Calkins HG, Berger RD, Kessler PD, Lawrence JH, Kass D, Feldman AM, Marban E: Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 1994; 90: 2534–2539 [DOI] [PubMed] [Google Scholar]
- 45. Day CP McComb JM, Campbell RWF: QT dispersion: An indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990; 63: 342–344 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Buja G, Miorelli M, Turrini P, Melacini P, Nava A: Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am J Cardiol 1993; 72: 973–976 [DOI] [PubMed] [Google Scholar]
- 47. Barr CS, Naas A, Freeman M, Lang CC, Struthers AD: QT dispersion and sudden unexpected death in chronic heart failure. Lancet 1994; 343: 327–329 [DOI] [PubMed] [Google Scholar]
- 48. Kirvelä M, Yli‐Hankala A, Lindgren L: QT dispersion and autonomic function in diabetic and non‐diabetic patients with renal failure. Br J Anesth 1994; 73: 801–804 [DOI] [PubMed] [Google Scholar]