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ABSTRACT: Occurrence of sustained microvolt-level T wave alternans (TWA) at a specified heart rate has been suggested to predict life-threatening arrhythmic events, but its prognostic value has not been well established in patients who survived an acute myocardial infarction (AMI). The purpose of this prospective study was to assess the predictive significance of various noninvasive risk indicators of mortality, including TWA, in consecutive post-AMI patients with optimized medical therapy.
In addition to a symptom-limited predischarge exercise test with measurement of TWA, mortality risk was assessed using heart rate variability, 24-hour ECG recordings, baroreflex sensitivity, signal-averaged ECG, QTc interval, QT dispersion, and echocardiographic wall-motion index in 379 consecutive patients. Twenty-six patients (6.9%) died during a mean follow-up of 14 +/- 8 months. Sustained TWA was found in 56 patients (14.7%), none of whom died. Several risk variables, e.g., incomplete TWA test (inability to perform the exercise test or reach the required target heart rate of 105 beats/min), increased QRS duration on signal-averaged ECG, increased QT dispersion, long QTc interval, nondiagnostic baroreflex sensitivity result, and low wall-motion index, predicted all-cause mortality in univariate analyses. In multivariate analysis, the incomplete TWA test was the most significant predictor of cardiac death (relative risk 11.1, 95% confidence interval 2.4 to 50.8; P < 0.01).
Sustained TWA during the predischarge exercise test after AMI does not indicate increased risk for mortality. An incomplete TWA test and several common risk variables provided prognostic information in this post-AMI population.
Journal of Cardiovascular Electrophysiology 06/2001; 12(6):645-52. · 3.06 Impact Factor
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ABSTRACT: Altered heart rate (HR) dynamics precede the spontaneous onset of atrial fibrillation (AF), but the factors related to the perpetuation and duration of paroxysmal AF episodes are not well established. This study was designed to test the hypothesis that HR dynamics preceding the onset of (AF) may influence the duration of AF.
Traditional time and frequency domain HR variability indices, along with a short-term fractal scaling exponent (alpha(1)) and approximate entropy (ApEn), were analyzed in 20-minute intervals before 92 episodes of spontaneous paroxysmal AF in 22 patients without structural heart disease. AF episodes were divided into two groups according to the duration of the arrhythmia episodes.
The high-frequency (HF) spectral component in normalized units (nu) of heart rate variability was higher and low-frequency (LF) component lower before long (> 200 s, n = 41) compared to short (< 200 s, n = 51) AF episodes (HF nu; 40.1 +/- 14.8 vs 31.5 +/- 16.4, P < 0.0001 and LF nu; 59.9 +/- 14.8 vs 68.5 +/- 16.4, P < 0.0001). Short-term scaling exponent values also were lower before long compared to short AF episodes (e.g., alpha(1); 1.12 +/- 0.21 vs 1.24 +/- 0.23, P < 0.0001). Women had a larger number of long AF episodes than men, but the duration of AF was not related to any other clinical or demographic features or antiarrhythmic medication.
Increased HF oscillations and decreased short-term correlation properties of R-R intervals, reflecting altered sympathovagal balance before the onset of AF, predispose to perpetuation of spontaneous arrhythmia episodes in patients with vulnerability to paroxysmal AF and without structural heart disease.
Annals of Noninvasive Electrocardiology 05/2001; 6(2):134-42. · 1.10 Impact Factor
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ABSTRACT: Cross-sectional studies have suggested that heart rate (HR) variability, analysed using traditional time and frequency domain methods, is related to ageing, but no longitudinal studies have estimated the age dependence of HR fluctuation. This study evaluated temporal age-related changes in 12-h measures of HR variability among 109 patients with coronary artery disease (CAD), who underwent repeat Holter recordings at 32-month intervals. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were determined at the baseline and after 32 months. Changes in HR dynamics were compared with various laboratory variables, exercise data and angiographic progression of CAD. Traditional time and frequency domain measures of HR variability did not change significantly during the follow-up, but the power-law scaling slope decreased from -1.29 +/- 0.20 to -1.36 +/- 0.23 (P<0.01) and the short-term fractal exponent (alpha1) of HR dynamics from 1.29 +/- 0.14-1.22 +/- 0.18 (P<0.001). The approximate entropy value also decreased from 1.00 +/- 0.19 to 0.95 +/- 0.18 (P<0.05). The changes in HR behaviour were not related to demographic data, laboratory values or angiographic progression of CAD. Only a weak correlation was observed between the change in the power-law slope and the baseline glucose value (P<0.05). This longitudinal study shows that the fractal characteristics of HR dynamics and the complexity properties of R-R intervals undergo rapid changes along with ageing, and that fractal and complexity analysis techniques are more sensitive than traditional analysis methods in documenting temporal age-related changes in HR behaviour.
Clinical Physiology 05/2001; 21(3):273-81.
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ABSTRACT: Determinants and intersubject variations of fractal and complexity measures of R-R interval variability were studied in a random population of 200 healthy middle-aged women (age 51 +/- 6 yr) and 189 men (age 50 +/- 6 yr) during controlled conditions in the supine and sitting positions. The short-term fractal exponent (alpha(1)) was lower in women than men in both the supine (1.18 +/- 0.20 vs. 1.12 +/- 0.17, P < 0.01) and sitting position (P < 0.001). Approximate entropy (ApEn), a measure of complexity, was higher in women in the sitting position (1.16 +/- 0.17 vs. 1.07 +/- 0.19, P < 0.001), but no gender-related differences were observed in ApEn in the supine position. Fractal and complexity measures were not related to any other demographic, laboratory, or lifestyle factors. Intersubject variations in a fractal measure, alpha(1) (e.g., 1.15 +/- 0.20 in the supine position, z value 1.24, not significant), and in a complexity measure, ApEn (e.g., 1.14 +/- 0.18 in the supine position, z value 1.44, not significant), were generally smaller and more normally distributed than the variations in the traditional measures of heart rate variability (e.g., standard deviation of R-R intervals 49 +/- 21 ms in the supine position, z value 2.53, P < 0.001). These results in a large random population sample show that healthy subjects express relatively little interindividual variation in the fractal and complexity measures of heart rate behavior and, unlike the traditional measures of heart rate variability, they are not related to lifestyle, metabolic, or demographic variables. However, subtle gender-related differences are also present in fractal and complexity measures of heart rate behavior.
AJP Heart and Circulatory Physiology 04/2001; 280(3):H1400-6. · 3.71 Impact Factor
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ABSTRACT: tk;1Passive head-up tilt and exercise result in specific changes in the spectral characteristics of heart rate (HR) variability as a result of reduced vagal and enhanced sympathetic outflow. Recently analytic methods based on nonlinear system theory have been developed to characterize the nonlinear features in HR dynamics. This study was designed to assess the changes in the fractal and complexity measures of HR behavior during the passive head-up tilt and during exercise. Fractal exponent (alpha(1)) and approximate entropy (ApEn), measures of short-term correlation properties and overall complexity of HR, respectively, along with spectral components of HR variability were analyzed during a passive head-up tilt test (n = 10) and a low-intensity steady-state exercise (n = 20) in healthy subjects. We observed that alpha(1) increased during the tilt test (from 0.85 +/- 0.22 to 1.48 +/- 0.20; P < 0.001) and during the exercise (from 1.00 +/- 0.22 to 1.37 +/- 0. 14; P < 0.001). ApEn also increased during the exercise (from 1.04 +/- 0.11 to 1. 11 +/- 0.08; P < 0.05), but it did not change during the tilt test. The normalized high-frequency spectral component decreased and the low-frequency component increased similarly during both the exercise and the tilt test (P < 0.001 for all). Exercise and passive tilt result in an increase of short-term fractal correlation properties of HR dynamics, which is related to changes in the balance between the low- and high-frequency oscillations in controlled situations. Overall complexity of HR dynamics increases during exercise but not during passive tilt.
AJP Heart and Circulatory Physiology 04/2001; 280(3):H1081-7. · 3.71 Impact Factor
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ABSTRACT: Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function.
To understand better the role of NA in cardiovascular homeostasis.
We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz.
The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (+/- SD) baseline level of 17.3+/-6.6 to 34.1+/-20.8 ms/mmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0+/-12.9 to 10.1+/-7.4 during the low NA infusion rate and to 6.2+/-6.2% during the high rate (P < 0.05 and 0.01, respectively).
Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.
Annals of Medicine 04/2001; 33(3):193-200. · 3.52 Impact Factor
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K E Airaksinen
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ABSTRACT: Asymptomatic coronary artery disease and myocardial infarctions are common in diabetic subjects. The available clinical and epidemiological data suggest that the increased incidence of asymptomatic myocardial infarctions and coronary artery disease in diabetic patients mainly reflects accelerated coronary atherosclerosis and the proportion of silent disease relative to symptomatic disease or episodes is not increased in diabetes. In spite of the theoretical background, there is no convincing clinical or epidemiological evidence that diabetic autonomic neuropathy plays a major part in the lack of ischaemic pain. This is not surprising because the mechanisms of silent myocardial ischaemia are complex and controversial even without diabetes.
Diabetologia 03/2001; 44(2):259-66. · 6.81 Impact Factor
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ABSTRACT: Autonomic neuropathy is associated with increased mortality. In patients with primary Sjögren's syndrome (SS), disturbances in the autonomic nervous system have been described using conventional cardiovascular reflex tests. Heart rate variability (HRV) measured from Holter recording has proved to be a reliable and sensitive method in assessing autonomic function and prognosis. We evaluated cardiovascular autonomic function based on HRV in patients with primary SS compared to the general population.
We analyzed HRV from 24 h electrocardiography recordings in 28 patients with primary SS and 28 healthy age and sex-matched population-based controls.
There were no significant differences in time or frequency domains or nonlinear measures of HRV between the groups.
The prevalence of autonomic disturbances is not increased in patients with primary SS compared to the general population.
The Journal of Rheumatology 12/2000; 27(11):2605-10. · 3.69 Impact Factor
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A Ylitalo, K E Airaksinen,
A Hautanen,
M Kupari,
M Carson,
J Virolainen,
M Savolainen,
H Kauma,
Y A Kesäniemi,
P C White,
H V Huikuri
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ABSTRACT: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes.
Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS.
Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction.
In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03).
Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.
Journal of the American College of Cardiology 02/2000; 35(1):194-200. · 14.16 Impact Factor
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ABSTRACT: The objectives of this review are to discuss the diversity of mechanisms that may explain the association between heart rate (HR) variability and mortality, to appraise the clinical applicability of traditional and new measures of HR variability and to propose future directions in this field of research. There is a large body of data demonstrating that abnormal HR variability measured over a 24-h period provides information on the risk of subsequent death in subjects with and without structural heart disease. However, the mechanisms responsible for this association are not completely established. Therefore, no specific therapy is currently available to improve the prognosis for patients with abnormal HR variability. Reduced HR variability has been most commonly associated with a risk of arrhythmic death, but recent data suggest that abnormal variability also predicts vascular causes of death, progression of coronary atherosclerosis and death due to heart failure. A consensus is also lacking on the best HR variability measure for clinical purposes. Time and frequency domain measures of HR variability have been most commonly used, but recent studies show that new analysis methods based on nonlinear dynamics may be more powerful in terms of risk stratification. Before the measurement of HR variability can be applied to clinical practice and used to direct therapy, more precise insight into the pathophysiological link between HR variability and mortality are needed. Further studies should also address the issue of which of the HR variability indexes, including the new nonlinear measures, is best for clinical purposes in various patient populations.
Journal of the American College of Cardiology 01/2000; 34(7):1878-83. · 14.16 Impact Factor
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ABSTRACT: Trigger mechanisms for the onset of paroxysmal atrial fibrillation (AF) in patients without structural heart disease are not well established. New analysis methods of heart rate (HR) variability based on nonlinear system theory may reveal features and abnormalities in R-R interval behavior that are not detectable by traditional analysis methods. The purpose of this study was to reveal possible alterations in the dynamics of R-R intervals before the spontaneous onset of paroxysmal AF.
Traditional time and frequency domain HR variability indices, along with the short-term scaling exponent alpha(1) and approximate entropy (ApEn), were analyzed in 20-minute intervals before 92 episodes of spontaneous, paroxysmal AF in 22 patients without structural heart disease. Traditional HR variability measures showed no significant changes before the onset of AF. A progressive decrease occurred both in ApEn (1.09+/-0.26 120 to 100 minutes before AF; 0.88+/-0.24 20 to 0 minutes before AF; P<0.001) and in alpha(1) (1.01+/-0.28 120 to 100 minutes before AF, 0.89+/-0.28 20 to 0 minutes before AF; P<0.05) before the AF episodes. Both ApEn (0. 89+/-0.27 versus 1.02+/-0.30; P<0.05) and alpha(1) (0.91+/-0.28 versus 1.27+/-0.21; P<0.001) were also lower before the onset of AF compared with values obtained from matched healthy control subjects.
A decrease in the complexity of R-R intervals and altered fractal properties in short-term R-R interval dynamics precede the spontaneous onset of AF in patients with no structural heart disease. Further studies are needed to determine the physiological correlates of these new, nonlinear HR variability measures.
Circulation 11/1999; 100(20):2079-84. · 14.74 Impact Factor
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ABSTRACT: Heart rate (HR) variability reflects the neural regulation of normal pacemaker tissue, but the autonomic nervous regulation of abnormal atrial foci originating outside the sinus node has not been well characterized. We compared the HR variability of tachycardias originating from the ectopic foci and the sinus node.
R-R-interval variability was analyzed from 24-hour Holter recordings in 12 patients with incessant ectopic atrial tachycardia (average HR 107+/-14 bpm), 12 subjects with sinus tachycardia (average HR 106+/-9 bpm), and 24 age- and sex-matched subjects with normal sinus rhythm (average HR 72+/-8 bpm). Time- and frequency-domain HR variability measures, along with approximate entropy, short- and long-term correlation properties of R-R intervals (exponents alpha(1) and alpha(2)), and power-law scaling (exponent beta), were analyzed. Time- and frequency-domain measures of HR variability did not differ between subjects with ectopic and sinus tachycardia. Fractal scaling exponents and approximate entropy were similar in sinus tachycardia and normal sinus rhythm, but the short-term scaling exponent alpha(1) was significantly lower in ectopic atrial tachycardia (0.71+/-0.16) than in sinus tachycardia (1.16+/-0.13; P<0.001) or normal sinus rhythm (1.19+/-0.11; P<0.001). Abrupt prolongations in R-R intervals due to exit blocks from the ectopic foci or instability in beat-to-beat R-R dynamics were the major reasons for altered short-term HR behavior during ectopic tachycardias.
HR variability obtained by time- and frequency-domain methods does not differ between ectopic and sinus tachycardias, which suggests that abnormal atrial foci are under similar long-term autonomic regulation as normal pacemaker tissue. Short-term R-R-interval dynamics are altered toward more random behavior in ectopic tachycardia, which may result from a specific autonomic disturbance or an intrinsic abnormality of ectopic atrial pacemakers.
Circulation 10/1999; 100(13):1416-22. · 14.74 Impact Factor
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K E Airaksinen
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ABSTRACT: In spite of recent advances in secondary prevention, sudden cardiac death has remained a major public health problem as the majority of fatalities occur in subjects without a history of severe heart disease. Abrupt rupture of a vulnerable plaque resulting in thrombotic occlusion of a coronary artery is a common cause of sudden death in this population. Coronary occlusion does not, however, invariably lead to sudden death but may cause acute myocardial infarction or exacerbation of chest pain. Extensive studies in experimental animals and increasing clinical evidence indicate that autonomic nervous activity has a significant role in modifying the clinical outcome. Sympathetic hyperactivity favours the genesis of life-threatening ventricular tachyarrhythmias while vagal activation exerts an antifibrillatory effect. Strong afferent stimuli from the ischaemic myocardium impair arterial baroreflex and may lead to dangerous haemodynamic instability. Studies with a human angioplasty model have shown that there is wide interindividual variation in the type and severity of autonomic reactions during the early phase of abrupt coronary occlusion, a critical period for out-of-hospital cardiac arrest. The site of the occlusion is not a significant determinant of the reactions, whereas the severity of a coronary stenosis, adaptation or ischaemic preconditioning, beta-blockade and gender seem to affect the autonomic reactions and occurrence of complex ventricular arrhythmias. Clinical and angiographic factors are, however, poor predictors of autonomic reactions in an individual patient. Recent studies have documented a hereditary component for autonomic function, and genetic factors may also modify the clinical manifestations of acute coronary occlusion.
Annals of Medicine 09/1999; 31(4):240-5. · 3.52 Impact Factor
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H V Huikuri,
V Jokinen,
M Syvänne,
M S Nieminen, K E Airaksinen,
M J Ikäheimo,
J M Koistinen,
H Kauma,
A Y Kesäniemi,
S Majahalme,
K O Niemelä,
M H Frick
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ABSTRACT: Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.
Arteriosclerosis Thrombosis and Vascular Biology 09/1999; 19(8):1979-85. · 6.37 Impact Factor
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ABSTRACT: The purpose of this study was to calculate the prevalence of ectopic atrial tachycardia in a population of young asymptomatic males and to assess its natural course both in asymptomatic subjects and in symptomatic hospital patients.
12-lead electrocardiograms (ECG) of 3554 consecutive males applying for a pilot's licence were analysed. ECGs of symptomatic arrhythmia patients at two university hospitals were also analysed. A repeat ECG was taken in cases of ectopic atrial tachycardia to assess the natural course of this arrhythmia. Twelve out of 3554 asymptomatic subjects (prevalence 0.34%) and 17 out of 3700 symptomatic arrhythmia patients (prevalence 0.46%) had ECG evidence of ectopic atrial tachycardia. A repeat ECG was obtained after a mean follow-up of 8+/-3 years in asymptomatic subjects and 7+/-3 years in symptomatic patients. After the follow-up, seven (26%) out of 27 patients were still in a similar ectopic atrial rhythm, 10 (37%) showed a change in P wave morphology and 10 (37%) were in sinus rhythm. Heart rate was significantly slower (mean rate 81+/-19 vs 109+/-17 beats. min-1) in the repeat ECGs.
Asymptomatic ectopic atrial tachycardia is not an uncommon finding in a population of young males. The majority of patients show slowing of heart rate in the course of time, either with restoration of sinus rhythm or with a change in P wave morphology, suggesting that the ectopic foci undergo gradual degeneration with time.
European Heart Journal 06/1999; 20(9):694-700. · 10.48 Impact Factor
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ABSTRACT: Experimental studies suggest that autonomic mechanisms are important in the genesis of ischemia-induced malignant ventricular arrhythmias, but the role of the autonomic nervous system in human arrhythmogenesis is not well known. To assess whether heart rate variability (HRV) predicts the occurrence of ventricular arrhythmias during acute coronary artery occlusion, we performed continuous electrocardiographic, heart rate, and blood pressure recordings before and during a 2-minute balloon occlusion of a stenotic coronary artery in 252 patients with no baseline ventricular premature complexes (VPCs). The ranges of nonspecific responses in heart rate and blood pressure were determined by analyzing a control group of 19 patients with no ischemia during a 2-minute balloon inflation in a totally occluded coronary artery. Balloon occlusion of a coronary artery was stopped because of complex, i.e., bigeminal or repetitive, VPCs in 14 patients, and solitary (<5) VPCs were observed in an additional 19 patients. During coronary occlusion, HRV increased (p <0.001) and heart rate decreased (p <0.05) in patients with no VPCs, whereas an opposite tendency to reduction in HRV (p = 0.08) was observed in patients with complex VPCs. Complex VPCs were observed in 5 (42%) of the 12 patients with a significant coronary occlusion-induced decrease in HRV, in 7 (3.5%) of 200 patients with no change in HRV, but in none of the 40 patients with a significant increase in HRV (p <0.001). Baseline HRV did not predict the occurrence of VPCs during coronary occlusion. Logistic regression analysis identified the decrease in HRV (p <0.001) to be the only independent predictor of complex VPCs. In conclusion, coronary occlusion-induced increase in HRV seems to protect against occurrence of complex ventricular arrhythmias during the early phase of abrupt coronary occlusion, suggesting that vagal activation may modify the outcome of acute coronary events in patients with coronary artery disease.
The American Journal of Cardiology 04/1999; 83(7):1000-5. · 3.37 Impact Factor
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ABSTRACT: Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.
The American Journal of Cardiology 03/1999; 83(6):885-9. · 3.37 Impact Factor
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ABSTRACT: We tested whether acute coronary occlusion interferes with arterial baroreceptor control of heart rate in humans.
Subnormal baroreflex sensitivity (BRS) is an important risk indicator for sudden death. Animal research indicates that both chronic myocardial infarction and acute coronary occlusion impair baroreflex modulation of heart rate.
We measured RR interval prolongation after phenylephrine-induced systolic pressure increases before and during 2-min coronary occlusions in 47 patients (27 men) undergoing clinically indicated single-vessel coronary angioplasty for stenoses in the proximal or midportion of the vessel causing >50% reduction in the arterial diameter, with normal antegrade flow (33 anterior descending, 10 circumflex, 4 right coronary artery). A control group of 11 patients treated for chronic total occlusion of a coronary artery was assessed to evaluate nonspecific changes in baroreflex function during a 2-min balloon inflation in the occluded artery.
The BRS decreased from 5.2+/-3.8 (mean+/-SD) to 4.1+/-3.5 ms x mm Hg(-1) (p=0.01) during the coronary occlusion in the 28 patients with preserved arterial baroreceptor control of heart rate-that is, adequate blood pressure responses and correlation coefficients of the slopes both in baseline and during coronary occlusion. The same phenylephrine dose increased systolic pressure less during than before coronary artery occlusion (21+/-21 versus 36+/-16 mm Hg, p < 0.0001), and in 6 patients it failed to prevent systolic pressure reduction during occlusion. Correlation coefficients of the baroreflex regressions decreased from 0.81+/-0.27 to 0.47+/-0.44 (p < 0.0001) during coronary artery occlusion in the 41 patients with adequate systolic pressure rises in both phenylephrine tests, and the association between RR intervals and rising systolic pressures was lost in 13 patients during coronary occlusion. Balloon inflation in a chronic total occlusion of a coronary artery did not cause significant changes in BRS (from 5.3+/-4.0 to 5.2+/-3.7 ms x mm Hg(-1)), correlation coefficient of the slope or phenylephrine-induced pressure rise.
Our study shows that abrupt coronary occlusion impairs baroreflex modulation of vagal and sympathetic nervous outflow in humans.
Journal of the American College of Cardiology 12/1998; 32(6):1641-7. · 14.16 Impact Factor
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ABSTRACT: Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.
American Journal of Hypertension 07/1998; 11(6 Pt 1):649-58. · 3.18 Impact Factor
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ABSTRACT: The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects.
A random sample of 347 subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (< -1.50) was the best univariate predictor of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to 17.0; P<.0001). After adjusting for age and sex and including all univariate predictors of mortality in the proportional hazards analysis, ie, measures of HR variability, history of heart disease, functional class, smoking, medication, and blood cholesterol and glucose concentrations, all-cause mortality was predicted only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42 to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted relative risk, 2.84; P=.0001) but not cancer or other causes of death.
Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.
Circulation 06/1998; 97(20):2031-6. · 14.74 Impact Factor
