Cardiovascular autonomic neuropathy: clinical manifestations and measurement

A number of prospective studies have demonstrated an increased mortality am ong diabetic patients with cardiovascular autonomic neuropathy (CAN). The o verall mortality rates over periods up to 10 years were similar to 27% in d iabetic patients with CAN detected by reduced heart rate variability (HRV) compared with 5% in those without evidence of CAN. However, it must be kept in mind that reduced HRV is an independent indicator of poor prognosis in the absence of diabetes, as a consequence of common cardiovascular diseases such Is coronary artery disease myocardial infarction, and heart failure, Besides reduced HRV, the clinical manifestations of CAN include fixed heart rate, increased resting heart rate, sinus tachycardia, orthostatic hypoten sion,vith systolic blood pressure fall greater than or equal to 30 mmHg, po ssibly increased susceptibility to silent myocardial ischemia/infarction. r educed circadian rhythm of heart rate and bleed pressure, abnormal hormonal regulation to standing and exercise, antibodies to autonomic tissue (vagal nerve, sympathetic ganglia), denervation hypersensitivity to a and beta-ad renergic agonists, inadequate increase in heart rate/blood pressure exercis e, reduced left ventricular diastolic filling/ejection fraction, intraopera tive cardiovascular instability, corrected QT interval prolongation, and in creased QT dispersion. Today, sensitive and early assessment of CAN is poss ible by means of noninvasive autonomic function tests (AFTs), including tim e domain (statistical. analysis) and frequency domain (spectral analysis) i ndices of HRV, aiming at prevention of the advanced stages. However, a gene rally accepted standardization of the various test procedures is needed. De spite this problem, it is estimated that CAN can be detected by abnormal AF Ts in at least one-quarter of type 1 and one-third of type 2 diabetic patie nts. In some cases, autonomic dysfunction may be present at the time of man ifestation of both type 1 and type 2 diabetes. There is increasing evidence suggesting that the statistical, geometric, frequency domain, and nonlinea r (Poincare plot) measures of 24-h HRV could be more sensitive and reliable in detecting CAN when compared with AFTs. Moreover, W-h recording of HRV p rovides insights into abnormal patterns of circadian rhythms modulated by s ympathovagal activity. Recent studies using cardiac radionuclide imaging te chniques have quantified myocardial adrenergic dysinnervation by diminished uptake of the norepinephrine analogs [I-123]metaiadobenzylguanidine or [C- 11]hydroxyephedrine. These methods provide a unique and sensitive tool for direct assessment of the pathophysiology and progression of early sympathet ic innervation detects not accessible to indirect autonomic function testin g. The prognostic significance of these defects and that of reduced measure s of 24-h HRV in CAN need to be determined in large-scale prospective clini cal trials.