Economic evaluation of exercise-based cardiac rehabilitation in patients with a recent acute coronary syndrome.

Health care decision-making requires evidence of the cost-effectiveness of medical therapies. We evaluated the cost-effectiveness of exercise-based cardiac rehabilitation (ECR) implemented according to guidelines. All the patients (n = 204) had experienced a recent acute coronary syndrome and were randomized to a 1-year ECR (n = 109) or usual care (UC) group (n = 95). The patients' health-related quality of life was followed using the 15D instrument and health care costs were collected from electronic health registries. The cost-effectiveness of ECR was estimated based on intervention and health care costs and quality-adjusted life years (QALYs) gained. The total average cost per patient was lower in ECR than in UC. The incremental cost was divided by the baseline-adjusted incremental QALYs (0.045), yielding an incremental cost-effectiveness ratio of -€24511/QALYs. A combined endpoint of mortality, recurrent coronary event, or hospitalization for a heart failure occurred for five patients in ECR and 16 patients in UC (HR 3.9, 95% CI 1.4-10.6, P = 0.004, relative risk reduction 73%, number needed to treat eight). ECR is a dominant treatment option and decreases the occurrence of adverse cardiac events. These results are useful for decision-making when planning optimal utilization of resources in Finnish health care.

Effect of controlled hypoglycaemia on sympathetic skin response in patients with Type 1 diabetes and control subjects.

AIM: To evaluate the quantity and mechanism of sudomotor function during euglycaemia and hypoglycaemia using sympathetic skin responses in patients with Type 1 diabetes and control subjects. METHODS: Sympathetic skin responses were measured in 16 patients with diabetes without neuropathy and in eight control subjects during euglycaemic and hypoglycaemic clamp. RESULTS: During hypoglycaemia, the number of repetitive synchronous sympathetic skin responses significantly increased in both groups (P<0.05), and this increase was significantly associated with the hypoglycaemia and sweating. CONCLUSIONS: During hypoglycaemia the number of repetitive synchronous sympathetic skin responses was related to increased sweating according to the hypoglycaemic symptom score. This is best explained by central nervous system reactions. The sympathetic skin responses of the patients with Type 1 diabetes had a weaker correlation with hypoglycaemia and its symptoms, which was possibly attributable to an adaptation or a dysfunction of the patients' sudomotor pathways.

Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. METHODS AND RESULTS: The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis. CONCLUSIONS: Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

Temporal dynamics of the circadian heart rate following low and high volume exercise training in sedentary male subjects.

PURPOSE: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown. METHODS: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period. RESULTS: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day). CONCLUSIONS: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Characteristics of "malignant" vs. "benign" electrocardiographic patterns of early repolarization.

The electrocardiographic (ECG) pattern of early repolarization (ER) has historically been regarded as a benign ECG variant, but during the past few years, this concept has been challenged based on multiple reports linking the ER pattern with an increased risk of sudden cardiac death. Although the mechanistic basis of ventricular arrhythmogenesis in patients with ER pattern is still incompletely understood, there is increasing information about the ECG and phenotype characteristics of "malignant" vs. "benign" patterns of ER. This review presents the current evidence of markers of "benign" and a more severe nature of ER.

Characteristics of women with ischemic sudden cardiac death.

BACKGROUND: Sudden cardiac death (SCD) is a significant mode of death causing 15-20% of all deaths in high-income countries. Coronary artery disease (CAD) is the most common cause of SCD in both sexes, and SCD is often the first manifestation of underlying CAD in women. This case-control study aimed to determine the factors associated with SCD due to CAD in women. METHODS: The study group consisted of women with CAD-related SCD (N = 888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017. All SCDs underwent medicolegal autopsy. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N = 610). To compare these groups, we used medical records, autopsy findings, echocardiograms, and electrocardiograms (ECGs). RESULTS: Subjects with SCD were older (73.2 ± 11.3 vs. 68.8 ± 8.0, p < 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6%, p = 0.045) compared to control patients. The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9% vs. 41.4% in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6% vs. 2.4% in CAD controls, p < 0.001). Left ventricular hypertrophy (LVH) was more common finding in SCD subjects (70.9% vs. 55.1% in controls, p < 0.001). Various electrocardiographic abnormalities were more common in subjects with SCD, including higher heart rate, atrial fibrillation, prolonged QTc interval, wide or fragmented QRS complex and early repolarization. The prevalence of Q waves and T inversions did not differ between the groups. CONCLUSIONS: Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with CAD-related SCD. These results suggest that untreated CAD with concomitant myocardial disease is an important factor in SCD in women.

Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with ischemic SCD.Untreated CAD with concomitant myocardial disease is an important factor in SCD among women.Improvements in the diagnosis and management of ischemic cardiomyopathy are likely to reduce the SCD burden in women.

Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population.

BACKGROUND: Short-QT syndrome is an inherited disorder characterized by a short QT interval and an increased risk of sudden cardiac death. The clinical significance of a short QT interval observed in a randomly recorded ECG is not known. Therefore, we assessed the prevalence and prognostic significance of a short QT interval in a general population. METHODS AND RESULTS: QT intervals were measured from the 12-lead ECGs of 10 822 randomly selected middle-aged subjects (5658 males, mean age 44+/-8.4 years) enrolled in a population study and followed up for 29+/-10 years. The end points were all-cause and cardiovascular mortality. In addition to Bazett's method (corrected QT interval, or QTc), the Fridericia (QTfc) and nomogram (QTnc) methods were used to correct the QT interval for heart rate. The cutoff values for short QT intervals were defined as 320 ms (very short) and 340 ms (short). The prevalence of QT interval <320 ms based on QTc, QTfc, and QTnc was 0.10%, 0.08%, and 0.06%, and the prevalence of QT interval <340 ms was 0.4%, 0.3%, and 0.3%, respectively. The majority of subjects with short QT intervals were males. All-cause or cardiovascular mortality did not differ between subjects with a very short or short QT interval and those with normal QT intervals (360 to 450 ms). There were no sudden cardiac deaths, aborted sudden cardiac deaths, or documented ventricular tachyarrhythmias among subjects with a QTfc <340 ms. CONCLUSIONS: A short QT interval does not appear to indicate an increased risk for all-cause or cardiovascular mortality in middle-aged nonreferral, community-based individuals.

High plasma leptin levels are associated with impaired diastolic function in patients with coronary artery disease.

BACKGROUND AND AIMS: Obese subjects have elevated leptin levels, which have been associated with increased risk of cardiovascular events. Because leptin has direct cellular effects on various tissues, we tested the hypothesis that leptin levels are associated with cardiac structure or function in patients with coronary artery disease (CAD). METHODS AND RESULTS: The study population consisted of 1 601 CAD patients, of whom 42% had type 2 diabetes mellitus. Plasma leptin was measured in fasted state and an echocardiography performed. Leptin levels were not related to LV dimensions or LV ejection fraction (NS for all), but higher leptin levels were associated with elevated E/E' (9.43 vs. 11.94 in the lowest and the highest leptin quartile, respectively; p=0.018 for trend). Correspondingly, a decreasing trend was observed in E/A (1.15 vs. 1.06; p=0.037). These associations were independent of obesity and other relevant confounding variables. CONCLUSION: We conclude that elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables. Leptin may be one of the mechanistic links explaining the development of congestive heart failure in obese subjects.

Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory.

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

Dynamic behavior and autonomic regulation of ectopic atrial pacemakers.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Altered complexity and correlation properties of R-R interval dynamics before the spontaneous onset of paroxysmal atrial fibrillation.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Natriuretic peptides and mortality after stroke.

BACKGROUND AND PURPOSE: Measurement of natriuretic peptides provides prognostic information in various patient populations. The prognostic value of natriuretic peptides among patients with acute stroke is not known, although elevated peptide levels have been observed. METHODS: A series of 51 patients (mean age, 68+/-11 years) with first-ever ischemic stroke underwent a comprehensive clinical examination and measurements of plasma atrial natriuretic peptides (N-ANP) and brain natriuretic peptides (N-BNP) in the acute phase of stroke. The patients were followed-up for 44+/-21 months. Risk factors for all-cause mortality were assessed. Control populations, matched for gender and age, consisted of 51 patients with acute myocardial infarction (AMI) and 25 healthy subjects. RESULTS: Plasma concentrations of N-ANP (mean+/-SD, 988+/-993 pmol/L) and N-BNP (751+/-1608 pmol/L) in the stroke patients were at the same level as those in the AMI patients (NS for both), but significantly higher than those of the healthy subjects (358+/-103 pmol/L, P<0.001 and 54+/-26 pmol/L, P<0.01, respectively). Elevated levels of N-ANP and N-BNP predicted mortality after stroke (risk ratio [RR] 4.3, P<0.01 and RR 3.9, P<0.01, respectively) and after AMI (P<0.05), and remained independent predictors of death after stroke even after adjustment for age, diabetes, coronary artery disease, and medication (RR 3.9, P<0.05 and RR 3.7, P<0.05, respectively). CONCLUSIONS: Plasma levels of natriuretic peptides are elevated in the acute phase of stroke and predict poststroke mortality.

Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty.

OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty protect against ischemia-induced ventricular ectopy. BACKGROUND: Most sudden cardiac deaths are caused by fatal ventricular arrhythmias precipitated by early myocardial ischemia of acute coronary occlusion. In animals, a preceding 3- to 5-min coronary occlusion protects against malignant ventricular arrhythmias during a subsequent prolonged coronary occlusion. Whether such an antiarrhythmic effect caused by ischemic preconditioning occurs in humans is not known. METHODS: To assess the effects of a preceding, brief vessel occlusion-reperfusion cycle on the occurrence of ventricular ectopy, continuous electrocardiographic, heart rate and blood pressure recordings were performed in 156 patients before and during two identical balloon occlusions of a coronary artery (mean 111 s) separated by a 5-min equilibration period. RESULTS: The occluded vessel was the left anterior descending coronary artery in 94 patients, the left circumflex branch in 29 patients and the right coronary artery in 33 patients. Balloon occlusion of a coronary artery caused ventricular ectopy in 24 patients. The incidence of ventricular ectopy was higher during the first occlusion than during the second occlusion (21 patients [13.5%] vs. 11 patients [7%], p = 0.02). In 13 patients, ventricular ectopy was observed only during the first occlusion; in 8 patients during both occlusions; and in 3 patients only during the second occlusion. Bigeminal or repetitive ectopic beats were observed in eight patients during the first coronary occlusion and in four patients during the second occlusion. Atrial premature beats occurred during the first occlusion in three patients, but in none of the patients during the second occlusion. The 24 patients with ventricular ectopy during coronary occlusion had milder stenosis than the rest of the patients (mean [+/- SD] 74 +/- 12% vs. 81 +/- 12%, p = 0.01). The 13 patients with ventricular ectopy only during the first occlusion did not, however, differ significantly with respect to any clinical or angiographic features from the rest of the patients with ventricular ectopy. There were no significant differences in the signs of myocardial ischemia or hemodynamic variables between the sequential occlusions. CONCLUSIONS: A preceding, short vessel occlusion-reperfusion cycle seems to increase the electrical stability of ischemic myocardium.

Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction.

OBJECTIVES: The aim of this study was to estimate the value of QT dispersion measurement from the standard 12-lead electrocardiogram (ECG) in identifying patients susceptible to reentrant ventricular tachyarrhythmias after a previous myocardial infarction. BACKGROUND: Variability in QT interval duration on the different leads of the 12-lead ECG has been proposed as an indicator of risk for ventricular arrhythmias in different clinical settings, but the value of QT dispersion measurement in identifying patients at risk for reentrant ventricular tachyarrhythmias after myocardial infarction is not known. METHODS: The QT interval duration, QT dispersion and clinical and angiographic variables were compared between 30 healthy subjects; 40 patients with a previous myocardial infarction but no history of arrhythmic events or inducible ventricular tachycardia during programmed electrical stimulation; and 30 postinfarction patients with a history of cardiac arrest (n = 12) or sustained ventricular tachycardia (n = 18) and inducible, sustained monomorphic ventricular tachycardia by electrical stimulation. RESULTS: Dispersion of the corrected QT interval (QTc) differed significantly between the study groups and was significantly increased in patients with susceptibility to ventricular tachyarrhythmias ([mean +/- SD] 104 +/- 41 ms) compared with that in both healthy subjects (38 +/- 14 ms, p < 0.001) and postinfarction patients with no susceptibility to arrhythmias (65 +/- 31 ms, p < 0.001). Maximal QT interval duration was also prolonged in the group with arrhythmias compared with that in the other groups (p < 0.001). Multivariate analysis, including clinical and angiographic variables, QT dispersion and maximal QT interval, showed that QT dispersion was the independent factor that most effectively identified the patient groups with and without susceptibility to ventricular tachyarrhythmias (p < 0.001). CONCLUSIONS: Increased QT dispersion is related to susceptibility to reentrant ventricular tachyarrhythmias, independent of degree of left ventricular dysfunction or clinical characteristics of the patient, suggesting that the simple, noninvasive measurement of this interval from a standard 12-lead ECG makes a significant contribution to identifying patients at risk for life-threatening arrhythmias after a previous myocardial infarction.

Effect of beta-blockade on heart rate variability in patients with coronary artery disease.

OBJECTIVES: This study assessed the effects of beta-blockade on heart rate variability in patients with coronary artery disease and determined whether the effects of metoprolol in a controlled-release formulation and atenolol differ with regard to electrocardiographic measures of cardiac autonomic control. BACKGROUND: Low heart rate variability is common in coronary artery disease and is associated with increased mortality. Beta-adrenergic blocking drugs may increase heart rate variability in healthy subjects, but there is limited knowledge of whether they are able to modify heart rate variability in patients with uncomplicated coronary artery disease. METHODS: In a randomly allocated, double-blind crossover study with three 2-week treatment periods, 200 mg of controlled-release metoprolol once a day, 100 mg of atenolol once a day or placebo once a day were administered in 18 male patients with stable coronary artery disease. The 24-h heart rate variability was measured in both the time and frequency domains. RESULTS: Beta-blockade induced a significant increase in heart rate variability, but no significant differences were found between atenolol and metoprolol. The average 24-h high frequency power increased by 64% after atenolol and by 62% after metoprolol. The root-mean-square successive difference of normal RR intervals increased by 70% after atenolol and by 62% after metoprolol, and the standard deviations of RR intervals increased by 20% and 16%, respectively. Beta-blockade had no significant effects on the amplitude of the circadian rhythm of heart rate variability, although both metoprolol and atenolol blunted the abrupt decrease of high frequency power after arousal. CONCLUSIONS: Beta-blockade by metoprolol and atenolol enhance the heart rate variability in patients with coronary artery disease. This may contribute to the protective effects of beta-blockade in ischemic heart disease.

Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction.

OBJECTIVES: The purpose of this research was to study possible abnormalities in the beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. BACKGROUND: Analysis of approximate entropy of time series data provides information on the complexity of both deterministic and random processes. It has been proposed that regularity or loss of complexity of RR interval dynamics may be related to pathologic states, but this hypothesis has not been well tested in cardiovascular disorders. METHODS: Approximate entropy and conventional time and frequency domain measures of RR interval variability were compared between 40 healthy subjects with no evidence of heart disease and 40 patients with coronary artery disease and a previous Q wave myocardial infarction. The groups were matched with respect to age, and cardiac medication was discontinued in the patients with coronary artery disease before the 24-h electrocardiographic recordings. RESULTS: Approximate entropy was significantly higher in the postinfarction patients (1.21 +/- 0.18 [mean +/- SD]) than in the healthy subjects (1.05 +/- 0.11, p < 0.001), whereas the standard deviation of RR intervals (63 +/- 19 vs. 86 +/- 23 ms, p < 0.001) and the very low, low and high frequency spectral components were lower (p < 0.01, p < 0.001, p < 0.05, respectively). Approximate entropy was not related to the time domain or the spectral components of heart rate variability and was more commonly abnormal in postinfarction patients (62.5%) than any linear measure (from 20% to 42.5%) when the 90% percentile of the values obtained for healthy subjects was defined as the normal range for each measure. CONCLUSIONS: Despite reduced linear measures of heart rate variability, the unpredictability or randomness of beat to beat heart rate dynamics is increased in patients with a previous myocardial infarction. Complexity analysis of RR interval dynamics may provide useful information on abnormalities in heart rate behavior that are not easily detected by the commonly used moment statistics.

Heart rate variability and dispersion of QT interval in patients with vulnerability to ventricular tachycardia and ventricular fibrillation after previous myocardial infarction.

OBJECTIVES: This study was designed to compare QT dispersion measured from the standard 12-lead electrocardiogram and 24-h heart rate variability in patients with vulnerability to either ventricular tachycardia or ventricular fibrillation after a previous myocardial infarction. BACKGROUND: Increased QT interval dispersion and reduced heart rate variability have been shown to be associated with vulnerability to ventricular tachyarrhythmias, but the data have mainly been pooled from patients with presentation of stable ventricular tachycardia and ventricular fibrillation. METHODS: QT dispersion and time domain and two-dimensional vector analysis of heart rate variability were studied in 30 survivors of ventricular fibrillation with a previous myocardial infarction and with inducible unstable ventricular tachyarrhythmia by programmed electrical stimulation and in 30 postinfarction patients with clinical and inducible stable monomorphic sustained ventricular tachycardia. Both of these patient groups were matched, with respect to age, gender and left ventricular ejection fraction, with an equal number of postinfarction control patients without a history of arrhythmic events or inducible ventricular tachyarrhythmia and arrhythmia-free survival during a follow-up period of 2 years. Forty-five age-matched healthy subjects served as normal control subjects. RESULTS: Standard deviation of all sinus intervals and long-term continuous RR interval variability analyzed from Poincaré plots were reduced in patients with vulnerability to ventricular fibrillation (p < 0.001 for both), but not in patients with ventricular tachycardia (p = NS for both), compared with postinfarction control subjects. Corrected QT (QTc) dispersion was significantly broader both in patients with ventricular fibrillation (p < 0.001) and in those with ventricular tachycardia (p < 0.05) than in matched postinfarction control subjects. Heart rate variability performed better than QTc dispersion in predicting vulnerability to ventricular fibrillation. CONCLUSIONS: Increased QT dispersion is associated with vulnerability to both ventricular tachycardia and ventricular fibrillation. Low heart rate variability is specifically related to susceptibility to ventricular fibrillation but not to stable monomorphic ventricular tachycardia, suggesting that the autonomic nervous system modifies the presentation of life-threatening ventricular arrhythmias.

Gender difference in autonomic and hemodynamic reactions to abrupt coronary occlusion.

OBJECTIVES: We sought to determine whether there are gender-related differences in autonomic and hemodynamic responses to abrupt coronary occlusion. BACKGROUND: The risk of sudden death before hospital admission is higher in men with an acute myocardial infarction. The reasons for this gender-related difference are not well understood. Cardiovascular autonomic regulation modifies the outcome of acute coronary events, and there are gender differences in the autonomic regulation of heart rate (HR) in normal physiologic circumstances. METHODS: We analyzed the changes in HR, HR variability and blood pressure and the occurrence of ventricular ectopic beats during a 2-min coronary occlusion in 140 men and 65 women referred for single-vessel coronary angioplasty. The ranges of nonspecific responses were determined by analyzing a control group of 19 patients with no ischemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS: Women more often had ST segment changes (p < 0.01) and chest pain (p < 0.05) during the occlusion. Significant bradycardia or increase in HR variability as a sign of vagal activation occurred more often in women than in men (31% vs. 13%, p < 0.01 and 25% vs. 11%, p < 0.05, respectively). Coronary occlusion also more often caused (28% vs. 11%, p < 0.01) a decrease in blood pressure in women. The most pronounced female preponderance was in the incidence of Bezold-Jarisch-type reaction (i.e., simultaneous bradycardia and decrease in blood pressure [16% vs. 0.7%, p < 0.0001]). Logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia identified female gender to be an independent predictor of bradycardic reactions (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.7, p < 0.01), hypotensive reactions (OR 2.6, 95% CI 1.1 to 6.0, p < 0.05) and Bezold-Jarisch-type response (OR 22.2, 95% CI 2.5 to 200, p < 0.01). Significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats emerged as having borderline significance (OR 0.4, CI 0.1 to 1.1, p = 0.07). CONCLUSIONS: Vagal activation is more common in women than in men during abrupt coronary occlusion and may have beneficial antiarrhythmic effects, modifying the outcome of acute coronary events.

Arterial baroreflex impairment in patients during acute coronary occlusion.

OBJECTIVES: We tested whether acute coronary occlusion interferes with arterial baroreceptor control of heart rate in humans. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study shows that abrupt coronary occlusion impairs baroreflex modulation of vagal and sympathetic nervous outflow in humans.