Impairment of heart rate variability during paclitaxel therapy.

BACKGROUND: Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS: Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. RESULTS: The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS: The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

Prediction of short-term outcome in patients with suspected myocardial infarction.

STUDY OBJECTIVE: Although specific cardiac injury markers have enhanced early patient classification, the ECG remains a necessary investigation in the acute phase of chest pain. Combined use of both tests could further improve the diagnostic and prognostic accuracy. METHODS: We studied 311 consecutive patients who came to the emergency department of a regional referral hospital for the differential diagnosis of acute chest discomfort. The admission ECG was classified using an automated interpretation program and tested together with elevated admission creatine kinase isoform MB (CK-MB) and cardiac troponin I (TnI) concentration for prediction of final myocardial injury (44%) and in-hospital mortality (14%). RESULTS: Combining the information from the admission ECG and cardiac markers, the sensitivity for becoming final myocardial injury (maximal CK-MB >/=11 microg/L) was 90% and specificity 61%. The proportion of false-negative results (10%) was independent of symptom duration. Age, positive ECG findings, and increased admission TnI levels were predictive for in-hospital mortality. CONCLUSION: The commonly available biochemical and ECG criteria allow risk stratification of patients with a suspected acute ischemic event. The data analysis can easily be automated and is independent of patient delay.

Computer-assisted electrocardiography in structured diagnosis of acute myocardial infarction.

The purpose of this study was to investigate the applicability of computerized electrocardiogram interpretation in classifying patients with suspected acute myocardial infarction. Computerized acquisition and analysis of the 12-lead electrocardiogram can increase the consistency and reduce the workload of patient classification. The serial electrocardiograms of 311 consecutive patients with suspected myocardial infarction were studied and a new computerized myocardial infarction (CMI) electrocardiographic classification was developed and compared with one commercially available and two manual codes. Statistically, there was almost no correlation between the four ECG codes. Compared with the WHO enzymatic criteria, the sensitivity of the CMI code toward detecting definite and possible infarction was 69.2% and 29.8% with a specificity of 62.1% and 79.7%, respectively. In subjects without previous infarction (n = 214) the sensitivity of the CMI code for definite enzymatic infarction was 71.9% and specificity 77.6%. Substituting the CMI for the Minnesota code had no effect on patient classification by the WHO MONICA criteria in 78% of patients with first infarction. Judged by cardiac macromolecular leakage, all electrocardiographic classifications of possible infarction were poorly correlated with myocardial tissue injury. We have developed a new computerized coding system to detect electrocardiographic myocardial infarction. The structure of the code allows interactive redefinition of criteria to meet user-defined needs. However, because of the weak relationship between electrocardiographic and biochemical criteria of myocardial injury, the role of ECG in the diagnostic classification of acute ischemic syndromes should be re-evaluated.

Antihypertensive treatment and heart rate variability in diabetic patients: role of cardiac autonomic neuropathy.

Optimization of antihypertensive drug therapy continues to be a clinical challenge in patients with diabetes mellitus and its complications. We assessed the interference of autonomic neuropathy with drug effects on heart rate variability in 13 hypertensive diabetic subjects (mean age 48.4 years) during treatment with two blood pressure lowering drugs, metoprolol and enalapril. The baseline findings were compared with those obtained in 24 diabetic subjects without hypertension (mean age 32.5 years) and in 24 non-diabetic hypertensive patients (mean age 47.6 years). Cardiovagal autonomic neuropathy was present in 10/13 (77%) of the hypertensive diabetic group, 14/24 (58%) the non-hypertensive diabetic group and 17/24 (71%) the non-diabetic hypertensive group. Heart rate variation was studied by power spectral analysis using total variability and three different frequency bands (low-frequency 0.025-0.075 Hz, mid-frequency 0.075-0.15 Hz and high-frequency 0.15-0.40 Hz). At baseline, the two hypertensive groups showed significantly smaller mid- and high-frequency heart rate variability compared with the diabetes only group. Age and the presence of cardiovagal autonomic neuropathy were important determinants of variability. Both metoprolol and enalapril reduced blood pressure comparably in hypertensive diabetics while metoprolol also reduced heart rate. Metoprolol decreased heart rate variability at the low-frequency and mid-frequency bands even after correction for the change in heart rate. Heart rate variability was not significantly altered by enalapril. In subjects with hypertension, diabetes and autonomic neuropathy, metoprolol almost abolished all heart rate variability. Therefore, an ACE inhibitor is a more neutral treatment alternative in such patients from the point of view of autonomic cardiac control.

High resolution ECG changes among Finnish pilots.

BACKGROUND: Abundant appearance of late potentials registered by high resolution ECG (HR-ECG) has been shown to predict a risk for cardiac arrhythmia. The aim of this study was to evaluate the appearance of normal and abnormal late potentials in a group of Finnish private and commercial pilots. METHODS: Standard 12-lead ECG and 40-250 Hz band-pass filtered HR-ECG were recorded in 168 healthy male pilots. The following parameters were estimated: the root-mean-square voltage in the terminal 40 ms (RMS40), the total filtered QRS duration (FQRSD) and the duration of terminal high frequency low amplitude signal (HFLAD) of less than 40 microV in the filtered QRS. RESULTS: Age (38 +/- 12 yr) and height (179 +/- 6 cm) had a significant (p < 0.005) and independent association with the total filtered QRS duration. No such correlations were observed for RMS40 or HFLAD. Mean +/- SD for RMS40 was 35.3 +/- 15.4 microV, for FQRSD 114.6 +/- 6.8 ms and for HFLAD 31.0 +/- 7.9 ms. Smokers tended to have longer late potentials (HFLAD) than non-smokers. Fasting blood glucose had a significant (p < 0.05) positive correlation with HFLAD. Serum cholesterol level had no correlation with the HR-ECG parameters. Age and height of the subject were associated with the total QRS duration as follows: FQRSD (ms) = -9.7* log age (yr) + 0.2*height (cm) + 94.6.

Autonomic cardiovascular reflexes in pregnancy. A longitudinal study.

Cardiovascular reflexes were studied in 22 healthy women before they were pregnant, once during each pregnancy trimester and after delivery to evaluate the effect of pregnancy on autonomic control of haemodynamics. The Valsalva manoeuvre, the deep breathing test, the orthostatic test and the isometric handgrip test were used to assess changes in autonomic nervous function. We found that pregnancy altered the heart rate response in the Valsalva manoeuvre, the deep breathing test and the orthostatic tests. The deep breathing difference (p = 0.03) and max/min ratio (p = 0.03) decreased in pregnancy, whereas standing heart rate increased (p < 0.0001). Both the systolic and diastolic blood pressure increased after standing up during pregnancy. The circulatory responses to isometric exercise were not affected by pregnancy. The results show that parasympathetic responsiveness is decreased in pregnancy and that it returns to normal after delivery.

Computer analysis of heart rate variation and breathing movements in fetal lambs.

A quantitative method for studying the frequency-specific relationships between heart rate (HR) and fetal breathing movements (FBM) was developed. The reactivity of periodic HR variation in relation to FBM was investigated by means of power spectral analysis. Seven fetal lambs were studied during the third trimester of gestation using a chronic animal model. HR variability increased at the rate of FBM, as shown by an increase of spectral density at > 0.35 Hz in the HR autospectrum and in the cross-spectrum of HR and respirogram, as well as by an increase in the short-term variability index CVS. FBM were associated with the increased HR variation in all but the lowest frequency bands (0.07-1.0 Hz). Although respiratory sinus arrhythmia was found, only 10 per cent of the total HR variability and 25 per cent of the joint-density of HR and respirogram appeared at > 0.35 Hz during FBM. The greatest variation in both the HR and respirogram spectra appeared at < 0.07 Hz. Although the low-frequency variability of HR and respirogram was simultaneous, it was on the whole not synchronised. The existence of multiple control systems that simultaneously link the cardiac and respiratory control mechanisms to each other in the fetal lamb is postulated.

Cardiovascular autonomic reflexes in mid-pregnancy.

OBJECTIVE: To study the physiological responses to noninvasive cardiovascular autonomic function tests in normal pregnancy. DESIGN: Cardiovascular autonomic responses in 60 women at 22 to 29 weeks gestation and 62 nonpregnant women were investigated using the Valsalva manoeuvre as well as orthostatic, quiet breathing, deep breathing, and isometric handgrip tests. RESULTS: Compared with nonpregnant women, those who were pregnant showed significantly lower heart rate variability during normal breathing and a blunted tachycardic reaction to blowing during the Valsalva manoeuvre. The vagally controlled biphasic heart rate response to standing was also attenuated in the pregnant group. CONCLUSIONS: The cardiovascular responses were blunted in mid-pregnancy indicating a decrease in parasympathetic cardiovascular control.

Changes in autonomic cardiovascular control in mid-pregnancy.

Spectral analysis of heart rate variability was used to study autonomic nervous control in mid-pregnancy. Fifty women (age 22-36 years) with singleton pregnancies (mean duration of gestation 27.7 weeks) and 39 non-pregnant female controls (age 21-39 years) were studied using controlled breathing and orthostatic tests. During spontaneous breathing the overall heart rate variability was lower in pregnant subjects indicating a decreased parasympathetic tone at rest. The decreased parasympathetic tone probably counts for the increased heart rate in pregnancy. The parasympathetic efferent capacity of autonomic cardiac control was found to be similar in pregnant and non-pregnant subjects, as no difference was seen during controlled breathing in periodic heart rate variability between the groups. Standing up caused a similar change in low frequency and mid-frequency bands in both groups, but high frequency heart rate variability increased in pregnant subjects and decreased in the controls indicating an increased sympathetic tone at rest in mid-pregnancy.

Do beta-adrenergic blockade and sleep state affect cardiorespiratory control in neonatal lambs? Multivariate autoregressive modeling approach.

Beta-Blockers are used in pregnancy-associated hypertension and in postnatal cardiac arrhythmias, and the neonate may get them in breast milk. We therefore studied the effects of beta-adrenergic medication on interrelations between heart rate (HR), respiration, and arterial blood pressure (aBP) in newborn lambs. The influence of sleep state on these cardiorespiratory interrelations was also examined. HR, aBP, and respiration (based on transthoracic electrical impedance) were recorded and the sleep state was visually documented in five healthy chronically instrumented newborn lambs before the age of 30 d. Propranolol was given (1 mg/kg). Two-min stationary segments of the three signals were analyzed using a multivariate autoregressive model, which yields oscillations of the signals and intersignal relationships as source contributions. The variabilities of aBP and HR were greatest at the low frequencies (less than 0.25 Hz) and so were their intersignal relationships (including baroreflex). The respiratory variability was greatest at the frequencies corresponding to the respiratory rate. During quiet sleep, the variabilities in HR, aBP, and respiration were lowest. The impact of respiratory oscillations on other signals increased but the impact of aBP variability decreased during quiet sleep. beta-Blockade and sleep state affected separately the cardiovascular and respiratory variables and their interrelations. beta-Blockade reduced HR and increased pulse pressure. The overall heart rate variability and the respiratory low-frequency contribution to heart rate variability decreased due to the beta-blockade. We postulate that the beta-adrenergic system is an important regulator of HR and HR variability in neonatal lambs and also of the low-frequency components of the respiratory sinus arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variability in infants subsequently suffering sudden infant death syndrome (SIDS).

To study the role of the autonomic cardiovascular control in SIDS the heart rate variability (HRV) was analysed from 24 tape recordings made from a prospective population-based study on 16 term and one preterm infant suffering SIDS and compared to similar data on 23 control infants matched on birthweight, gestation and postnatal age. The number of regular breathing segments was lower in the SIDS cases than in controls (P = 0.02). No significant differences were found between the SIDS cases and their controls for average heart rate, median breathing rate, indices of overall and beat-to-beat HRV. Neither were significant intergroup differences found when the subjects were divided into neonatal and postneonatal subgroups. Analysis of HRV by power-spectral techniques did not show any significant differences between SIDS cases and controls for the general distribution of power or for the respiratory HRV. Analysis of HRV did not differentiate infants destined to die of SIDS from surviving controls in the same population.

Regulation of heart rate variation by the autonomic nervous system in neonatal lambs.

We studied the role of the autonomic nervous system in the regulation of heart rate variation (HRV) in 12 chronically instrumented neonatal lambs. HRV was quantified from ECG tracings by computing periodic HRV distributions at frequencies of 0.02-1.00 Hz, using power spectral analysis of heart rate, and also by HRV indices. Heart rate declined more during the 1st than the 2nd mo after birth. Multiple regression analysis showed that the heart rate responses to vagal and to beta-adrenergic blockade had an independent negative association both with age and with the initial mean heart rate, whereas the overall HRV response had a positive association with age. Vagal blockade led to a 70-80% decrease in the beat-to-beat HRV in all lambs (p less than 0.001). The overall HRV indices decreased by 40-65% in lambs (less than 30 d old (p less than 0.001) and about 30% in those greater than 30 d old (p less than 0.05). In the power spectrum the greatest decrease was seen in the high-frequency components of HRV. beta-Blockade led to a decrease of about 50% in all HRV (p less than 0.001) in the younger lambs, without frequency selection. In the older lambs, it had no effect on the beat-to-beat HRV, but the overall HRV (coefficient of variance) decreased maximally by 40% (p less than 0.01), with a significant reduction in the low-frequency components of HRV. These results suggest that in the regulation of HRV after birth dual control via the autonomic nervous system is most important. In the older lambs, developmental changes result in precise regulation of the fast heart rate fluctuations mainly by the vagal division, whereas the slow fluctuations are partially regulated by the vagal and beta-adrenergic divisions.

Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy.

Reduced respiratory sinus arrhythmia, measured as heart rate variability, is a reliable indicator of autonomic nervous dysfunction, reflecting a damage in vagal cardiac control. The authors studied the heart rate variability (HRV) of nine children treated for acute lymphoblastic leukemia during the different phases of cytostatic treatment utilizing heart rate processing techniques with a computer. The indices of HRV as well as the spectral components of heart rate were examined with special relation to vincristine administration. The heart rate variability was significantly reduced during the vincristine induction phases as compared to the consolidation and maintenance phases without vincristine administration. In particular, the respiratory components of the HRV during deep breathing tests were significantly reduced during vincristine treatment. The authors conclude that the measurement of the HRV is a suitable method for monitoring transient autonomic neuropathy, which these results show to be a frequent complication of vincristine treatment.

Beta-adrenergic control and inter-relationships between heart rate and blood pressure in neonatal lambs.

Our aim was to develop a signal analysis method for revealing interrelationships between heart rate and blood pressure and for displaying the influence of autonomic nervous control on these signals in a chronic lamb model. A chronically instrumented neonatal lamb model was made to record ECG and direct arterial blood pressure (N = 15). Continuous two-minute recordings of blood pressure (BP) and ECG were digitised. The instantaneous heart rate signal (IHR) was derived from the ECG. The IHR and BP signals were bandpass filtered. Autospectra, cross-spectra, coherence spectra and phase spectra for the signals were computed to study the relative magnitudes and inter-relationships of the cardiovascular signals under normal conditions and during beta-adrenergic blockade. It was noted that both in the BP and IHR there were oscillations at the frequency of less than 0.1 Hz and also at the respiratory rate around 0.6 Hz. Beta-blockade reduced the oscillations of the IHR in less than 30-day-old lambs. It did not affect the coherence spectra or the phase lag between the signals. During quiet sleep the variability of blood pressure was decreased. In over-30-day-old-lambs the beta-blockade did not affect the variabilities of the cardiovascular parameters. These findings indicate that in neonatal lambs the sympathetic control system is a major regulator of cardiovascular interactions.

Blood pressure reactivity in patients with neurocirculatory asthenia.

The hemodynamic reactions of 30 young men with neurocirculatory asthenia (NCA) were compared to those of 30 healthy controls in isometric handgrip test, orthostatic test, and cold pressor test in order to study the regulation of the central circulation of NCA patients. The measurements were made using sphygmomanometry, ECG, and impedance cardiography. In the isometric handgrip test the heart rate and the diastolic and mean blood pressure increased slightly more (P less than 0.05) in the NCA group than in the controls. In the NCA group the blood pressure rise was, on average, due to an increase in the peripheral vascular resistance, while in the control group it was caused by an elevation in the cardiac output. In the orthostatic and cold pressor tests the hemodynamic alterations were quite similar in the two groups. It is concluded that the NCA patients have in the orthostatic and cold pressor tests a normal ability to elevate the blood pressure by increasing the peripheral vascular resistance. The lack of rise in the cardiac output during the isometric handgrip test in the NCA group is an abnormal reaction, the reason of which remains to be studied.

Heart-rate variability and SIDS. Examination of heart-rate patterns using an expert system generator.

In a prospective, population-based study, HRV was analyzed from 24-hr tape recordings made on 16 full-term and one preterm infant who had subsequently suffered SIDS and compared to similar data on 23 control infants (n of recordings, 44). In the SIDS group, heart rate was higher, and overall and beat-to-beat HRV (CV, CVS, respectively) were lower, than in the controls, but not significantly. Respiratory rate and respiratory HRV (by spectral analysis) were similar in both groups. Assuming that cardiorespiratory mechanisms of SIDS are multifactorial, we expected that several subgroups would be detected in both test groups. Therefore, the average data for each recording were subsequently examined by means of an expert system generator (ExTran, Intelligent Terminals Ltd., Edinburgh, UK). By rules induced with 25 nodes, the following results were obtained: 16/44 recordings were diagnosed as SIDS on the basis of (1) respiratory rate (RR) less than 33 and CV less than 3.46% (n = 8); (2) RR greater than 33, CVS less than 2.18%, and BW greater than 3,520 g (n = 4); and (3) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, HR greater than 136, and CV greater than 1.89% (n = 4). Seventeen of 44 were considered as non-SIDS when (1) RR was 33-47.4, CVS greater than 2.18%, and RSA less than 74.3 and (2) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, and HR less than 142. The remaining 11 cases required more complicated rules in order to be classified. This study shows that although the trend of increased HR and decreased HRV in the SIDS cases was statistically non-significant, an expert system program may be helpful in defining decision rules to identify cases of SIDS on the basis of cardiorespiratory data.