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Program in Cardiac Arrhythmias: Diabetes and Cardiac Autonomic Neuropathy

What is cardiac autonomic neuropathy?

Diabetes is associated with many complications, particularly those that result in heart and kidney disease. Diabetes also affects the body’s nerves. The nerves that control the heart, including its rate and rhythm, are not under voluntary control and are called cardiac autonomic nerves. When these nerves are affected by diabetes, this is called cardiac autonomic neuropathy. Although this condition usually does not cause symptoms, unless severe, it is associated with worse survival.

What are the implications of cardiac autonomic neuropathy in diabetes?
       
Diabetes affects an estimated 23.6 million Americans and 171 million people worldwide, with this number projected to double to 366 million people by the year 2030. One in nine Chicagoans have diabetes. Approximately one in five patients with diabetes has cardiac autonomic neuropathy, and this increases the risk of dying 3.5-fold, making cardiac autonomic neuropathy a significant risk factor for dying from diabetes.
 
What are the current treatments?
 
There are many treatments for diabetes. In a large National Institutes of Health study, called the ACCORD trial, it was shown that intensive control of glucose (blood sugar), blood pressure, and cholesterol do not improve survival in patients with diabetes. There are no known treatments for cardiac autonomic neuropathy despite its associated risk.
 
What are the current challenges in improving outcomes in diabetes?
       
As diabetes is characterized by high blood sugars and is often associated with high blood pressure and high cholesterol, it was thought that intensive control of these factors would improve survival in diabetics. The ACCORD trial shattered this notion and demonstrates that there are likely some other factors that underlay the increased risk of death in diabetes. The race is on to identify these other factors. Cardiac autonomic neuropathy, which can cause serious abnormalities of the heart rhythm, is high on the list of possibilities.
 
How is the Center for Cardiovascular Innovation addressing this problem?
 
Dr. Goldberger is a specialist and established researcher in heart rhythm disorders and the effects of the autonomic nervous system on the heart. He has developed a novel exercise based approach to diagnose cardiac autonomic neuropathy. His team has shown that this approach is more sensitive than currently used methods. They are extending these studies to different groups of patients with diabetes and are proposing to study the effects of an exercise training regimen on cardiac autonomic neuropathy. This groundbreaking work could substantially improve survival in diabetes.



Selected Bibliography

  1. Goldberger J, Ahmed M, Parker M, Kadish A: Assessment of effects of autonomic stimulation and blockade on the signal averaged electrocardiogram. Circulation 89:1656-1664, 1994.
  2. Goldberger J, Ahmed M, Parker M, Kadish A: Dissociation of heart rate variability from parasympathetic tone. Am J Physiol 266:H2152-H2157, 1994.
  3. Ahmed M, Kadish A, Parker M, Goldberger J: Effect of physiologic and pharmacologic adrenergic stimulation on heart rate variability. J Am Coll Cardiol 24:1082-1090, 1994.
  4. Cheema A, Ahmed M, Kadish A, Goldberger J: Effects of autonomic stimulation and blockade on the signal averaged P wave duration. J Am Coll Cardiol 26:497-502, 1995.
  5. Ahmed M, Kadish A, Goldberger J: Autonomic effects on the QT interval. Annals Noninvasive Electrocardiol 1:44-53, 1996.
  6. Goldberger J, Kim Y, Ahmed M, Kadish A: Effect of graded increases in parasympathetic tone on heart rate variability. J Cardiovasc Electrophysiol 7:594-602, 1996.
  7. Burke J, Goldberger J, Ehlert F, Kruse J, Parker M, Kadish A: Gender differences in heart rate before and after autonomic blockade: evidence against an intrinsic gender effect. Am J Med 100:537-543, 1996.
  8. Ahmed M, Kadish A, Goldberger J: Autonomic effects on noise recorded during signal averaged electrocardiography. Pacing Clin Electrophysiol 20:1796-1799, 1997.
  9. Kim Y, Ahmed M, Kadish A, Goldberger J: Characterization of the factors that determine the effect of sympathetic stimulation on heart rate variability. Pacing Clin Electrophysiol 20:1936-1946, 1997.
  10. Burke J, Ehlert F, Kruse J, Parker M, Goldberger J, Kadish A: Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults. Am J Cardiol 79:178-181, 1997.
  11. Goldberger J: Sympathovagal balance: how should we measure it? Am J Physiol 276(4 Pt 2):H1273-H1280, 1999.
  12. Challapalli S, Kadish A, Horvath G, Goldberger J: Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability. J Cardiovasc Electrophysiol 10(9):1192-1199, 1999.
  13. Goldberger JJ, Challapalli S, Tung R, Parker MA, Kadish AH: Relationship of heart rate variability to parasympathetic effect. Circulation 103:1977-1983, 2001.
  14. Taneja T, Larsen J, Goldberger J, Kadish A: Age, gender and autonomic tone effects on surface electrocardiographic indices of ventricular repolarization. Ann Noninvasive Electrocardiol 6:290-297, 2001.
  15. Kannankeril P, Goldberger J: Parasympathetic effects on cardiac electrophysiology during exercise and recovery. Am J Physiol 282:H2091-H2098, 2002.
  16. Kannankeril P, Le F, Kadish A, Goldberger J: Parasympathetic effects on heart rate recovery after exercise. J Invest Med 52(6):394-401, 2004.
  17. Goldberger JJ, Le FK, Lahiri M, Kannankeril PJ, Ng J, Kadish AH: Assessment of parasympathetic reactivation after exercise. Am J Physiol 290:H2446-H2452, 2006.
  18. Endres S, Mayuga KA, de Cristofaro A, Taneja T, Goldberger JJ, Kadish AH: Age and gender difference in ST height at rest and after double autonomic blockade in normal adults. Ann Noninvasive Electrocardiol 11:253-258, 2006.
  19. Sundaram S, Carnethon M, Polito K, Kadish AH, Goldberger JJ: Autonomic effects on QT-RR interval dynamics after exercise. Am J Physiol 294:490-497, 2008.
  20. Banthia S, Ng J, Chicos A, Molitch M, Kadish A, Goldberger JJ: Early detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus. Circulation 118(18):S648, 2008.
  21. Chicos AB, Kannankeril PJ, Kadish AH, Goldberger JJ: Parasympathetic effects on cardiac electrophysiology during exercise and recovery in patients with left ventricular dysfunction. Am J Physiol 297:H743-749, 2009.
  22. Ng J, Sundaram S, Kadish AH, Goldberger JJ: Autonomic effects on the spectral analysis of heart rate variability after exercise. Am J Physiol 297(4):H1421-1428, 2009.
  23. Ulphani JS, Cain JH, Inderyas F, Gordon D, Gikas PV, Shade G, Mayor D, Arora R, Kadish AH, Goldberger JJ: Quantitative analysis of parasympathetic innervation of the porcine heart. Heart Rhythm 7(8):1113-1119, 2010.
  24. Laing ST, Gluckman TJ, Weinberg KM, Lahiri MK, Ng J, Goldberger JJ: Autonomic effects of exercise-based cardiac rehabilitation. J Cardiopulm Rehabil Prev. 2010.
  25. Bergner DW, Goldberger JJ: Diabetes mellitus and sudden cardiac death:what are the data? Cardiol J 17(2):117-129, 2010.
  26. Bergner DW, Goldberger JJ: Autonomic determinants of early heart rate recovery after exercise differs in type 2 diabetes mellitus. Circulation 120(18): S634, 2010.
  27. Wang NC, Chicos A, Banthia B, Bergner DW, Lahiri MK, Ng J, Subacius H, Kadish AH, Goldberger JJ: Persistent sympathoexcitation long after submaximal exercise in subjects with and without coronary artery disease. Am J Physiol 301(3):H912-920, 2011.
 
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