Cardiovascular autonomic neuropathy (CAN)

Cardiac autonomic neuropathy (CAN) is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes.

• there have been recommended five simple tests, the cardiac autonomic reflex tests, to establish the diagnosis (1):
  • 1) heart rate variability (HRV) with deep breathing
  • 2) HRV lying to standing
  • 3) the Valsalva manoeuvre;
  • 4) postural fall in blood pressure; and
  • 5) blood pressure response to sustained handgrip
    
    
  • a single abnormal test may indicate early CAN, and three positive tests are recommended for a definitive diagnosis (1,2)
    
    
• prevalence data are highly dependent on the diagnostic criteria, type of tests and normative data sets used, age, and gender
  • rates are reported as high as 35% in type 1 DM and 44% in type 2 DM, with a prevalence rate of up to 60% in longstanding diabetics (3)
    
    
• association with increased mortality risk
  • older studies have shown 5-year mortality rates as high as 16-50 % in T1DM and T2DM, with a high proportion attributed to sudden cardiac death (4,5)
  • more recently published meta-analysis included 2,900 subjects with diabetes reported a pooled relative risk of mortality of 3.45 (95 % CI, 2.66-4.47) in patients with CAN (6)
    
    
• progression of CAN usually begins with parasympathetic denervation, followed by sympathetic tone enhancement and eventually sympathetic denervation
  • resting tachycardia is often the presenting sign (ranging from 100 to 130 bpm)
    • as CAN progresses in severity then there is a decrease in heart rate
  • baroreflex sensitivity
    • in subclinical CAN will initially have abnormalities in HRV - this is then followed by changes in baroreflex sensitivity (1)
    • in advanced CAN, orthostasis will result secondary to sympathetic denervation along with impaired baroreflex sensitivity and decreased noradrenaline response to change in posture

Management:

• seek expert advice
  • weight loss in obese diabeticss and aerobic exercise for patients with both type 1 and type 2 DM has been shown to improve HRV and cardiac autonomic functionality (1,2)
  • early and comprehensive glycaemic control is believed to help prevent diabetic complications and potentially reverse CAN symptoms (1,2)
  • pharmaceutical management of HRV is controversial - there is no definitive treatment - agents considered include beta blockers, digoxin, verapamil and ACE inhibitors
    • treatment of orthostatic hypotension is required in general only when patients are symptomatic

Reference:

• Ewing DJ et al. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8 (5):491-498.
• Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014; 5 (1):17-39.
• Pop-Busui R. What do we know and we do not know about cardiovascular autonomic neuropathy in diabetes? J Cardiovasc Transl Res 2012; 5: 463-468.
• Navarro X, Kennedy WR, Sutherland DE. Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation. Diabetologia. 1991; 34(Suppl 1):S108-S112.
• Ewing DJ, Campbell IW, Clarke BF. Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. Annals of Internal Medicine. 1980; 92:308-311.
• Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003; 26:1895-1901