Heart Rate Variabilityin Patients With Diabetes Mellitus, Ischemic Heart Disease, and CongestiveHeart Failure
Bonpei Takase, MD, Akira Kurita, MD, Masayuki Noritake, MD, Akimi Uehata, MD, Toshiharu Maruyama, MD, Hirokazu Nagayoshi, MD, Toshihiko Nishioka, MD, Kyoichi Mizuno, MD, and Haruo Nakamura, MD
Abstract: The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 t 12.6 ms, 43.7 2 15.4 ms, and 34.6 +- 15.8 ms vs 65.6 ? 16.7 ms, p < 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 2 6.5 ms vs 44.2 ? 11.0 ms, p < 0.05). Patients who died suddenly had a significantly lower (p < 0.05) mean SD as compared to survivors: 49 2 7 ms in patients with mild ischemic heart disease, 48 2 15 ms in patients with severe ischemic heart disease, and 23 t 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p < 0.05) than in those who survived (19.0 ? 5.6 ms vs 40.0 2 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%. The mean SD of less than 30 ms reflects either an impaired cardiac autonomic nerve innervation or an imbalance in the autonomic nerve activity, or both. This value of mean SD might be a good marker in clinical practice concerning autonomic dysfunction and poor prognosis in patients with diabetes mellitus, ischemic heart disease, or congestive heart failure. Key words: heart rate variability, diabetes mellitus, ischemic heart disease, congestive heart failure, ambulatory ECG monitoring.
Heart rate variability in various patient subsets has been shown to aid in the prognostication of patients
From The First Department of Internal Medicine, National Defense Medical College, Saitama. Japan.
at risk for sudden cardiac death. I-’ It is postulated that a decrease in the mean of the standard deviation
Reprint requests: Bonpei Takase, MD, St. Louis University, 4144 Lindell Boulevard, Suite 333, St. Louis, MO 63108.
79
80
Journal of Electrocardiology
Vol. 25 No. 2 April 1992
for all 5 minute intervals over 24 hours may reflect underlying abnormal autonomic contro1.3,6 Altered sympathetic and parasympathetic activity in patients with organic or functional impairment of cardiovascular system may play a crucial role in the risk of subsequent untoward cardiac events.’ This method was initially investigated on electrocardiogram (ECG) rhythm strips.’ However, recent advances in ambulatory ECG monitoring software now permit computer-assisted analyses of R-R intervals by means of several sophisticated approaches for the elimination of such confounding factors as ectopic beats and artifacts.‘,‘O However, efficacy of this method has not been validated in repeated analysis or in varied patient cohorts. ’ ’ Therefore, it is the purpose of this investigation to examine the utility of heart rate variability as assessed by 24-hour ambulatory ECG in diabetic patients with and without an autonomic neuropathy, patients with known ischemic heart disease, and patients with congestive heart failure, as compared to normal subjects.
Materials
and Methods
Patients Heart rate variability as calculated from 24-hour ambulatory ECG was obtained in 72 subjects who were classified into 4 groups. Group 1. Patients with non-insulin dependent diabetes mellitus (n = 25) formed the first group. Diabetic patients were examined between January 1, 1989 and December 31, 1989. Patients with technically poor quality recording as well as patients on beta-blocker therapy were excluded from the study. The diabetic patients who exhibited overt signs of either ischemic heart disease or congestive heart failure were also excluded from the study. Patients were classified as to the presence or absence of clinical signs of autonomic neuropathy. Diabetic neuropathy was defined as at least one of the following clinical symptoms: orthostatic hypotension, abnormal sweating, signs of gastroparesis or diarrhea, difficulty in urinating, or sexual impotence. Thirteen (52%) patients in this group had clinical signs of autonomic neuropathy. Selected clinical variables are listed in Table 1. Group 2. The second group consisted of patients with ischemic heart disease who already had a 24-
Table 1. Selected Clinical Data in Patients With and
Without Diabetic Autonomic Neuropathy Diabetics With Autonomic Neuropathy Number of patients Age (years) Duration of diabetes mellitus (years) Complications (+ ) Nephropathy Retinopathy Sensorimotor neuropathy HbAlc (%) Total cholesterol (mg/ml) Mean ropathy.
13 58 -c 11 16.4 f 5.6”
4 11 6 9.8 198.6
(31%) (85%) (46%) 2 1.1 k 43.5
2 SD; * p < 0.05 vs diabetics
without
Diabetics Without Autonomic Neuropathy 12 49 2 16 8.1 f 3.9
1 7 1 9.5 192.5
(8%) (58%) (8%) ? 1.3 f 50.3
autonomic
neu-
hour ambulatory ECG performed. Only those who in addition had a clinical examination within 1 month of the ambulatory ECG were selected. A total of 15 patients fulfilled these criteria. An additional 4 patients who died suddenly within 1 month of a 24-hour ambulatory ECG were enrolled as a separate group. Patients were considered to have died suddenly if death was observed and occurred within 1 hour of the onset of new or more serious symptoms. The tapes of the ambulatory ECGs were then reevaluated for this study. Patients with mild ischemic heart disease (n = 8; age 35-68; mean age 59 + 11 years; 75% men) were defined as those with single-vessel coronary disease (~70% diameter stenosis), left ventricular ejection fraction ?50%, and I Class II Canadian Cardiovascular Society Classiftcation (CCSC) angina pectoris.12 Patients with severe ischemic heart disease (n = 7; age 45-7 1; mean age 62 2 9 years; 53% men) were defined as those with multivessel disease, left ventricular ejection fraction
Bonpei Takase, MD, Akira Kurita, MD, Masayuki Noritake, MD, Akimi Uehata, MD, Toshiharu Maruyama, MD, Hirokazu Nagayoshi, MD, Toshihiko Nishioka, MD, Kyoichi Mizuno, MD, and Haruo Nakamura, MD
Abstract: The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 t 12.6 ms, 43.7 2 15.4 ms, and 34.6 +- 15.8 ms vs 65.6 ? 16.7 ms, p < 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 2 6.5 ms vs 44.2 ? 11.0 ms, p < 0.05). Patients who died suddenly had a significantly lower (p < 0.05) mean SD as compared to survivors: 49 2 7 ms in patients with mild ischemic heart disease, 48 2 15 ms in patients with severe ischemic heart disease, and 23 t 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p < 0.05) than in those who survived (19.0 ? 5.6 ms vs 40.0 2 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%. The mean SD of less than 30 ms reflects either an impaired cardiac autonomic nerve innervation or an imbalance in the autonomic nerve activity, or both. This value of mean SD might be a good marker in clinical practice concerning autonomic dysfunction and poor prognosis in patients with diabetes mellitus, ischemic heart disease, or congestive heart failure. Key words: heart rate variability, diabetes mellitus, ischemic heart disease, congestive heart failure, ambulatory ECG monitoring.
Heart rate variability in various patient subsets has been shown to aid in the prognostication of patients
From The First Department of Internal Medicine, National Defense Medical College, Saitama. Japan.
at risk for sudden cardiac death. I-’ It is postulated that a decrease in the mean of the standard deviation
Reprint requests: Bonpei Takase, MD, St. Louis University, 4144 Lindell Boulevard, Suite 333, St. Louis, MO 63108.
79
80
Journal of Electrocardiology
Vol. 25 No. 2 April 1992
for all 5 minute intervals over 24 hours may reflect underlying abnormal autonomic contro1.3,6 Altered sympathetic and parasympathetic activity in patients with organic or functional impairment of cardiovascular system may play a crucial role in the risk of subsequent untoward cardiac events.’ This method was initially investigated on electrocardiogram (ECG) rhythm strips.’ However, recent advances in ambulatory ECG monitoring software now permit computer-assisted analyses of R-R intervals by means of several sophisticated approaches for the elimination of such confounding factors as ectopic beats and artifacts.‘,‘O However, efficacy of this method has not been validated in repeated analysis or in varied patient cohorts. ’ ’ Therefore, it is the purpose of this investigation to examine the utility of heart rate variability as assessed by 24-hour ambulatory ECG in diabetic patients with and without an autonomic neuropathy, patients with known ischemic heart disease, and patients with congestive heart failure, as compared to normal subjects.
Materials
and Methods
Patients Heart rate variability as calculated from 24-hour ambulatory ECG was obtained in 72 subjects who were classified into 4 groups. Group 1. Patients with non-insulin dependent diabetes mellitus (n = 25) formed the first group. Diabetic patients were examined between January 1, 1989 and December 31, 1989. Patients with technically poor quality recording as well as patients on beta-blocker therapy were excluded from the study. The diabetic patients who exhibited overt signs of either ischemic heart disease or congestive heart failure were also excluded from the study. Patients were classified as to the presence or absence of clinical signs of autonomic neuropathy. Diabetic neuropathy was defined as at least one of the following clinical symptoms: orthostatic hypotension, abnormal sweating, signs of gastroparesis or diarrhea, difficulty in urinating, or sexual impotence. Thirteen (52%) patients in this group had clinical signs of autonomic neuropathy. Selected clinical variables are listed in Table 1. Group 2. The second group consisted of patients with ischemic heart disease who already had a 24-
Table 1. Selected Clinical Data in Patients With and
Without Diabetic Autonomic Neuropathy Diabetics With Autonomic Neuropathy Number of patients Age (years) Duration of diabetes mellitus (years) Complications (+ ) Nephropathy Retinopathy Sensorimotor neuropathy HbAlc (%) Total cholesterol (mg/ml) Mean ropathy.
13 58 -c 11 16.4 f 5.6”
4 11 6 9.8 198.6
(31%) (85%) (46%) 2 1.1 k 43.5
2 SD; * p < 0.05 vs diabetics
without
Diabetics Without Autonomic Neuropathy 12 49 2 16 8.1 f 3.9
1 7 1 9.5 192.5
(8%) (58%) (8%) ? 1.3 f 50.3
autonomic
neu-
hour ambulatory ECG performed. Only those who in addition had a clinical examination within 1 month of the ambulatory ECG were selected. A total of 15 patients fulfilled these criteria. An additional 4 patients who died suddenly within 1 month of a 24-hour ambulatory ECG were enrolled as a separate group. Patients were considered to have died suddenly if death was observed and occurred within 1 hour of the onset of new or more serious symptoms. The tapes of the ambulatory ECGs were then reevaluated for this study. Patients with mild ischemic heart disease (n = 8; age 35-68; mean age 59 + 11 years; 75% men) were defined as those with single-vessel coronary disease (~70% diameter stenosis), left ventricular ejection fraction ?50%, and I Class II Canadian Cardiovascular Society Classiftcation (CCSC) angina pectoris.12 Patients with severe ischemic heart disease (n = 7; age 45-7 1; mean age 62 2 9 years; 53% men) were defined as those with multivessel disease, left ventricular ejection fraction
