Fractal analysis of heart rate variability and mortality after an acute myocardial infarction

The recently developed fractal analysis of heart rate (HR) variability has been suggested to provide prognostic information about patients with heart failure. This prospective multicenter study was designed to assess the prognostic significance of fractal and traditional HR variability parameters in a large, consecutive series of survivors of an acute myocardial infarction (AMI). A consecutive series of 697 patients were recruited to participate 2 to 7 days after an AMI in 3 Nordic university hospitals. The conventional time-domain and spectral parameters and the newer fractal scaling indexes of HR variability were analyzed from 24-hour RR interval recordings. During the mean follow-up of 18.4 +/- 6.5 months, 49 patients (7.0%) died. Of all the risk variables, a reduced short-term fractal scaling exponent (alpha(1) <0.65), measured by detrended fluctuation analysis, was the most powerful predictor of mortality (univariate relative risk 5.05, 95% confidence intervals [CI] 2.87 to 8.89, p <0.001). A low scaling exponent alpha(1) predicted death in the patients with and without depressed left ventricular function (p <0.001 and p <0.01, respectively). Several other HR variability parameters also predicted mortality in univariate analyses, but in a multivariate analysis after adjustments for clinical variables and left ventricular ejection fraction, alpha(1) was the most significant independent HR variability index that predicted subsequent mortality (relative risk 3.90, 95% CI 2.03 to 7.49, p <0.001). Short-term fractal scaling analysis of HR variability is a powerful predictor of mortality among patients surviving an acute myocardial infarction.     

Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction

BACKGROUND: Preliminary data suggest that the analysis of R-R interval variability by fractal analysis methods may provide clinically useful information on patients with heart failure. The purpose of this study was to compare the prognostic power of new fractal and traditional measures of R-R interval variability as predictors of death after acute myocardial infarction. METHODS AND RESULTS: Time and frequency domain heart rate (HR) variability measures, along with short- and long-term correlation (fractal) properties of R-R intervals (exponents alpha(1) and alpha(2)) and power-law scaling of the power spectra (exponent beta), were assessed from 24-hour Holter recordings in 446 survivors of acute myocardial infarction with a depressed left ventricular function (ejection fraction 相似文献   

Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.     

Temporal changes and prognostic significance of measures of heart rate dynamics after acute myocardial infarction in the beta-blocking era

Previous studies have shown that indexes describing heart rate (HR) dynamics may predict subsequent deaths of patients after an acute myocardial infarction (AMI). Because beta-blocking (BB) drugs affect both mortality and HR dynamics, the prognostic power of measurements of HR dynamics may have changed in the current era of BB therapy. This study assessed the temporal changes and prognostic significance of time-domain, spectral, and fractal indexes of HR variability along with HR turbulence after an AMI among patients with optimized BB medication. SD of NN intervals, spectral indexes, the short-term fractal scaling exponent (alpha(1)), power-law slope (beta), and turbulence onset and slope were measured in 600 patients at 5 to 7 days after AMI and in 416 patients at 12 months after AMI. In the multivariate analysis, after adjusting for clinical variables, only reduced fractal HR indexes, alpha1 and beta (p <0.01 for both), turbulence onset, and slope (p <0.05 for both), measured at the convalescent phase after AMI, predicted subsequent cardiac death. All time-domain and spectral HR variability indexes and turbulence onset increased significantly during the 12-month period after AMI (p <0.001 for all), whereas the fractal indexes and turbulence slope remained unchanged. Late after AMI, reduced beta (p <0.05) and turbulence slope (p <0.01) were the only independent predictors of cardiac mortality. Traditional time-domain and spectral measurements of HR variability and turbulence onset improved significantly after AMI, whereas the fractal HR dynamics and turbulence slope remained stable. Fractal HR variability and HR turbulence retain their prognostic power in the BB era, when measured either at the convalescent or late phase after AMI.     

Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure

Time-domain measures of heart rate (HR) variability provide prognostic information among patients with congestive heart failure (CHF). The prognostic power of spectral and fractal analytic methods of HR variability has not been studied in the patients with chronic CHF. The aim of this study was to assess whether traditional and fractal analytic methods of HR variability predict mortality among a population of patients with CHF. The standard deviation of RR intervals, HR variability index, frequency-domain indexes, and the short-term fractal scaling exponent of RR intervals were studied from 24-hour Holter recordings in 499 patients with CHF and left ventricular ejection fraction < or =35%. During a mean follow-up of 665 +/- 374 days, 210 deaths (42%) occurred in this population. Conventional and fractal HR variability indexes predicted mortality by univariate analysis. For example, a short-term fractal scaling exponent <0.90 had a risk ratio (RR) of 1.9 (95% confidence interval [CI] 1.4 to 2.5) and the SD of all RR intervals <80 ms had an RR of 1.7 (95% CI 1.2 to 2.1). After adjusting for age, functional class, medication, and left ventricular ejection fraction in the multivariate proportional-hazards analysis, the reduced short-term fractal exponent remained the independent predictor of mortality, RR 1.4 (95% CI 1.0 to 1.9; p <0.05). All HR variability indexes were more significant univariate predictors of mortality in functional class II than in class III or IV. Among patients with moderate heart failure, HR variability measurements provide prognostic information, but all HR variability indexes fail to provide independent prognostic information in patients with the most severe functional impairment.     

Heart Rate Variability in Risk Stratification of Cardiac Patients

Heart rate (HR) variability has been extensively studied in cardiac patients, especially in patients surviving an acute myocardial infarction (AMI) and also in patients with congestive heart failure (CHF) or left ventricular (LV) dysfunction. The majority of studies have shown that patients with reduced or abnormal HR variability have an increased risk of mortality within a few years after an AMI or after a diagnosis of CHF/LV dysfunction. Various measures of HR dynamics, such as time-domain, spectral, and non-linear measures of HR variability have been used in risk stratification. The prognostic power of various measures, except of those reflecting rapid R–R interval oscillations, has been almost identical, albeit some non-linear HR variability measures, such as short-term fractal scaling exponent have provided somewhat better prognostic information than the others. Abnormal HR variability predicts both sudden and non-sudden cardiac death. Because of remodeling of the arrhythmia substrate after AMI, early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events. Future randomized trials using HR variability/turbulence as one of the pre-defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of cardiac patients.     

Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects

OBJECTIVES: The aim of this study was to test the hypothesis that abnormal scaling characteristics of heart rate (HR) predict sudden cardiac death in a random population of elderly subjects. BACKGROUND: An abnormality in the short-term fractal scaling properties of HR has been observed to be related to a risk of life-threatening arrhythmias among patients with advanced heart diseases. The predictive power of altered short-term scaling properties of HR in general populations is unknown. METHODS: A random sample of 325 subjects, age 65 years or older, who had a comprehensive risk profiling from clinical evaluation, laboratory tests and 24-h Holter recordings were followed up for 10 years. Heart rate dynamics, including conventional and fractal scaling measures of HR variability, were analyzed. RESULTS: At 10 years of follow-up, 164 subjects had died. Seventy-one subjects had died of a cardiac cause, and 29 deaths were defined as sudden cardiac deaths. By univariate analysis, a reduced short-term fractal scaling exponent predicted the occurrence of cardiac death (relative risk [RR] 2.5, 95% confidence interval [CI], 1.9 to 3.2, p < 0.001) and provided even stronger prediction of sudden cardiac death (RR 4.1, 95% CI, 2.5 to 6.6, p < 0.001). After adjusting for other predictive variables in a multivariate analysis, reduced exponent value remained as an independent predictor of sudden cardiac death (RR 4.3, 95% CI, 2.0 to 9.2, p < 0.001). CONCLUSIONS: Altered short-term fractal scaling properties of HR indicate an increased risk for cardiac mortality, particularly sudden cardiac death, in the random population of elderly subjects.     

Fractal correlation properties of heart rate dynamics and adverse events in patients with implantable cardioverter-defibrillators.

The aim of this study was to determine the prognostic significance of nonlinear and standard heart rate (HR) variability parameters in predicting future adverse events (AEs) in patients with implantable cardioverter-defibrillators. In postinfarction studies, nonlinear measures of HR variability obtained from long-term electrocardiographic recordings have been suggested to be better predictors of adverse outcomes than conventional HR variability measures. Fifty-five high-risk patients with reduced left ventricular function and an implantable cardioverter-defibrillator had a 10-minute, high-resolution electrocardiographic recording after which they were followed for 25 months on average. Implantable cardioverter-defibrillator shock or death was determined as the end point. The SD of all normal-to-normal RR intervals, the square root of the mean squared differences of successive normal-to-normal RR intervals, and the proportion of interval differences of successive normal-to-normal RR intervals >50 ms, low-frequency and high-frequency powers of the power spectrum and their ratio were calculated as conventional measures of HR variability. The short-term scaling exponent (alpha(1)) and approximate entropy were determined as nonlinear measures of HR variability. AEs occurred in 23 patients (42%). Patients with AEs had significantly lower alpha(1) than event-free patients: 0.81 +/- 0.29 (mean +/- SD) versus 1.01 +/- 0.30 (p = 0.02). None of the other HR variability parameters differed significantly between patients with and without AEs. In the Cox proportional-hazards model including age, gender, ejection fraction, occurrence of ventricular tachyarrhythmia before defibrillator implantation, beta-blocker usage, and alpha(1), only alpha(1) was an independent predictor of AEs: hazard ratio 1.20 (95% confidence interval 1.03 to 1.39) for every 0.10 decrease in alpha(1) (p = 0.020). In conclusion, alpha(1) obtained from a 10-minute electrocardiographic recording yields important prognostic information about the risk of AEs in patients with implantable cardioverter-defibrillators.     

Relation of depression to heart rate nonlinear dynamics in patients > or =60 years of age with recent unstable angina pectoris or acute myocardial infarction

Depression is common among older patients and it has been related to a worsened coronary prognosis. The basis for this association is controversial. The aim of this study was to ascertain whether patients with a recent acute coronary event show depression-related changes of heart rate variability (HRV) nonlinear dynamics. Alterations of the HRV have been recently shown to predict mortality in patients recovering from an acute myocardial infarction. In 52 patients > or =60 years (52% women) with recent (within 24 to 72 hours) unstable angina pectoris or myocardial infarction, we obtained conventional time- and frequency-domain HRV measurements, along with nonlinear HRV measurements, including SD of the instantaneous beat-to-beat variability (SD1), scaling exponent alpha1 (alpha1), and approximate entropy (ApEn) from 10-minute RR-interval recordings. We also evaluated the presence of clinical depression and measured its severity by means of a 21-item Hamilton Depression Scale. On admission to the coronary care unit, 19 patients (37%) were depressed; alpha1 was higher (1.23 +/- 0.21 vs 1.03 +/- 0.30, p <0.05), whereas SD1 (10.4 +/- 3.7 vs 14.4 +/- 7.3, p <0.05) and ApEn (0.98 +/- 0.22 vs 1.16 +/- 0.15, p <0.001) were lower in depressed patients. Also, alpha1 increased (r = 0.31, p <0.05) and both SD1 (r = -0.46, p <0.01) and ApEn (r = -0.28, p <0.05) decreased with worsening depressive symptoms. In our sample, depression was associated with increased correlation and decreased complexity of the interbeat interval time series in older adults who had recently developed an acute coronary syndrome.     

Relation of heart rate dynamics to the occurrence of myocardial ischemia after coronary artery bypass grafting

Postoperative myocardial ischemia is a common finding after coronary artery bypass grafting (CABG) and is associated with an adverse short-term clinical outcome. The reasons and pathophysiologic background for the occurrence of ischemia after CABG are not well established. We tested the hypothesis that altered heart rate (HR) behavior precedes the onset of myocardial ischemic episodes in patients after CABG. Time-domain HR variability measurements, along with analysis of Poincaré plots and fractal scaling analysis were assessed in 40 CABG patients from 48-hour postoperative Holter recordings. Twenty patients experienced 195 ischemic episodes during the postoperative course. In the univariate analysis of HR variability measurements of the first postoperative day (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR variability analyzed from the Poincaré plot and the decreased short- and intermediate-term fractal scaling exponents alpha(1) and alpha(2) were significantly associated with ischemia during the study period (p <0.01, p <0.05, and p <0.05, respectively). In the multivariate model, the increased SD1/SD2 ratio of the first POD was the most powerful independent predictor of all possible confounding variables for the occurrence of postoperative ischemia (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval 1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial ischemic episodes in patients after CABG, suggesting that the autonomic nervous system has an important role in the pathogenesis of myocardial ischemia in the postoperative phase of CABG.     

Heart rate variability during the acute phase of myocardial infarction.

BACKGROUND. After acute myocardial infarction (AMI), several abnormalities of the autonomic control to the heart have been described. Heart rate (HR) variability has been used to explore the neural control to the heart. A low HR variability count measured 7-13 days after AMI is significantly related to a poor outcome. Little information is available on HR variability early after AMI and its relation to clinical and hemodynamic data. METHODS AND RESULTS. We studied 54 consecutive patients (42 men and 12 women; mean age, 60.4 +/- 11 years) with evidence of AMI by collecting the 24-hour HR SD from Holter tapes recorded on day 2 or 3. We also measured HR variability in 15 patients with unstable angina and in 35 age-matched normal subjects. HR variability was lower in AMI than in unstable angina patients (57.6 +/- 21.3 versus 92 +/- 19 msec; p less than 0.001) and controls (105 +/- 12 msec; p less than 0.001). Also, HR variability was greater in non-Q-wave than in Q-wave AMI (p less than 0.0001) and in recombinant tissue-type plasminogen activator-treated patients with respect to the rest of the group (p less than 0.02). No difference was found for infarct site. HR variability was significantly related to mean 24-hour HR, peak creatine kinase-MB, and left ventricular ejection fraction (all p less than 0.0001). Patients belonging to Killip class greater than I or who required the use of diuretics or digitalis had lower counts (p less than 0.004, p less than 0.001, and p less than 0.024, respectively). Six patients died within 20 days after admission to the hospital. In these patients, HR variability was lower than in survivors (31.2 +/- 12 versus 60.9 +/- 20 msec; p less than 0.001), and a value less than 50 msec was significantly associated with mortality (p less than 0.025). CONCLUSIONS. HR variability during the early phase of AMI is decreased and is significantly related to clinical and hemodynamic indexes of severity. The causes for the observed changes in HR variability during AMI may be reduced vagal and/or increased sympathetic outflow to the heart. It is suggested that early measurements of HR variability during AMI may offer important clinical information and contribute to the early risk stratification of patients.     

Power-law behavior of heart rate variability in Chagas' disease

Beta slope is a nonlinear index derived from the power-law analysis of 24-hour heart rate variability (HRV); in healthy subjects, the beta index is typically near -1, suggesting a fractal behavior of HRV. There is scarce data on HRV in Chagas' disease. This transversal study intends to describe power-law and linear HRV patterns in different forms of Chagas' disease. Patients and healthy controls (n = 26) without other diseases were submitted to a standardized protocol, including electrocardiography, echocardiography, and 24-hour Holter monitoring. Patients with Chagas' disease were divided into groups according to their left ventricular (LV) systolic function: normal (group 1, n = 85), segmental abnormalities (group 2, n = 49), and reduced ejection fraction (group 3, n = 26). The temporal series were carefully processed to obtain the HRV indexes and beta slope. Despite the differences in the LV systolic function, the 3 groups were comparable in terms of long-term HRV index values. After adjustment for covariates, short-term HRV index values were consistently reduced in the Chagas' disease groups. The beta-index values were also diminished in Chagas' disease groups (group 1: -1.09 +/- 0.03, group 2: -1.11 +/- 0.06; group 3: -1.14 +/- 0.03; and controls: 0.95 +/- 0.03, p <0.001). This breakdown of fractal long-range correlation of RR interval dynamics, a strong predictor of mortality in other cardiomyopathies, may reflect cardiac dysautonomia that may have gone undetected in long-term time-domain analysis. This abnormality may explain the increased risk for arrhythmic sudden death found in Chagas' disease even in the absence of signs of LV dysfunction.     

Usefulness of granulocyte colony-stimulating factor in patients with a large anterior wall acute myocardial infarction to prevent left ventricular remodeling (the rigenera study)

Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention.     

Reversal of deteriorated fractal behavior of heart rate variability by beta-blocker therapy in patients with advanced congestive heart failure

INTRODUCTION: The slope of the power spectrum in heart rate variability (HRV) reflects the fractal or scaling behavior in HR dynamics and recently was confirmed as an independent predictor of postmyocardial infarction survival. Whether or not the new measurement in HRV foresees the functional evolution in patients with advanced congestive heart failure treated by beta blockers is unclear. METHODS AND RESULTS: Sequential 24-hour Holter ECG recordings were obtained at baseline, and 1 and 3 months after addition of atenolol therapy for advanced congestive heart failure in 10 patients. The slope and intercept of the regression line of power-law behavior, the short- and intermediate-term of detrended fluctuated analysis (DFA), the approximate entropy (ApEn), and the standard frequency spectra of the 24-hour HRV were compared sequentially as well as with those in 12 age-matched normal controls. The results showed that the slope (-1.70 +/- 0.45 vs -1.22 +/- 0.21; P < 0.05) and the intercept (5.11 +/- 0.46 vs 5.62 +/- 0.24; P < 0.05) of the regression line of power-law behavior and the short-term DFA (for 4 to 11 beats) (0.78 +/- 0.18 vs 1.13 +/- 0.21; P < 0.05) increased after 3 months of atenolol treatment. However, the change in intermediate-term DFA (>11 beats) and ApEn was not apparent (1.24 +/- 0.21 vs 1.22 +/- 0.15 and 1.34 +/- 0.14 vs 1.36 +/- 0.11; both P > 0.05). The evolution of the slope or intercept of the regression line of the HRV power spectrum did not correlate with the echocardiographic or clinical cardiac function, or with the frequency spectral components of the HRV (P > 0.05). CONCLUSION: Additional beta-blocker therapy upregulated the fractal behavior control of the HRV in patients with advanced congestive heart failure. The improvement was independent of subjective and objective global cardiac performance.     

Clinical significance and prognostic importance of left ventricular hypertrophy in non-Q-wave acute myocardial infarction

Left ventricular (LV) hypertrophy is known to be an independent risk factor for cardiac death, but its significance in non-Q-wave acute myocardial infarction (AMI) has not been assessed previously. In a randomized diltiazem-placebo-controlled therapeutic trial of non-Q-wave AMI confirmed by creatine kinase-MB (CK-MB), 126 of 544 patients (23%) exhibited LV hypertrophy using standard voltage criteria. Compared to patients without LV hypertrophy, patients with LV hypertrophy were significantly older (65 vs 60 years, p less than 0.0001) and had smaller peak adjusted CK levels (490 +/- 376 vs 666 +/- 726 IU/liter, p less than 0.001) than patients without LV hypertrophy. Patients with and without LV hypertrophy did not differ significantly in acute mortality during hospitalization, progression to Q waves, reinfarction by CK-MB criteria or angina associated with transient electrocardiographic changes. Compared with patients without LV hypertrophy, those patients with non-Q-wave AMI and LV hypertrophy had a 2-fold higher incidence of reinfarction (24 vs 12%, p less than 0.005) and death (19 vs 9%, p = 0.044) during the first year of follow-up. Multivariate regression analysis revealed that the relative risk of death and reinfarction during the initial year after AMI was increased by a factor of 1.7 and 2.1 among patients with LV hypertrophy, respectively. It was therefore concluded that, although patients with LV hypertrophy and non-Q-wave AMI have smaller enzymatic infarcts and the same short-term prognosis as do patients without LV hypertrophy, their reinfarction and mortality rates are significantly increased during the first year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of prodromal angina pectoris and white blood cell count on outcome of patients with acute myocardial infarction

BACKGROUND: Elevation of white blood cell (WBC) count at admission is associated with adverse outcome after acute myocardial infarction (AMI). Prodromal angina, by the mechanism of ischemic preconditioning, improves left ventricular (LV) function and survival after reperfusion therapy in patients with AMI. Recent experimental studies have reported that preconditioning has anti-inflammatory effect. METHODS: This study consisted of 598 patients with first anterior wall AMI who underwent coronary angiography within 12 h after symptom onset. WBC count was measured at the time of hospital admission. Prodromal angina was defined as angina occurring within 24 h before the onset of AMI. Serial measurements of LV ejection fraction (EF) were obtained before reperfusion therapy and before discharge in 421 patients (71%). RESULTS: High WBC count (>10.2 x 103/mm3, n=297) was associated with higher 30-day mortality (8% vs. 4%, p=0.02) and lower predischarge LVEF (51+/-15% vs. 57+/-14%, p<0.001), although there was no significant difference in acute LVEF (47+/-10% vs. 49+/-11%, p=0.07). High WBC count was an independent predictor of 30-day mortality (p=0.009) and predischarge LVEF (p=0.002). Prodromal angina was associated with lower 30-day mortality (3% vs. 7%, p=0.02) and preserved predischarge LVEF (57+/-15% vs. 53+/-14%, p=0.006). Patients with prodromal angina had lower WBC count (10.0+/-3.3 x 10(3)/mm3 vs. 11.0+/-3.9 x 10(3)/mm3, p=0.001) and prodromal angina was an independent predictor of WBC count (p<0.001). CONCLUSIONS: Elevation of WBC count and lack of prodromal angina were associated with impaired LV function and mortality after reperfusion in patients with AMI. Prodromal angina might have contributed to favorable outcome after AMI through its anti-inflammatory effect.     

Autonomic Markers as Predictors of Nonfatal Acute Coronary Events after Myocardial Infarction

Background: Autonomic markers, such as heart rate variability (HRV), heart rate turbulence (HRT), and baroreflex sensitivity (BRS) provide information on the risk of all‐cause mortality after an acute myocardial infarction (AMI), but their value in predicting nonfatal cardiac events is not well known. Methods: A consecutive series of 675 patients with an AMI were followed up to 30 months. At baseline, the patients underwent a 24‐hour Holter recording, and assessment of BRS using phenylephrine test. Several parameters of HRV and HRT were determined. Results: After the follow‐up, 98 patients (15%) had a nonfatal acute coronary event. Among the studied variables, the short‐term scaling exponent alpha1 (P = 0.002), power‐law slope beta (P = 0.008), low‐frequency component of HRV power spectrum (P < 0.001), turbulence slope (P < 0.001), and BRS (P < 0.001) had the strongest association with the occurrence of nonfatal acute coronary events in univariate comparisons. After adjustment with relevant clinical variables (such as age, gender, ejection fraction, functional class, medication, diabetes) in the Cox proportional hazards model, alpha1 and beta remained as statistically significant predictors of nonfatal acute coronary events (HR = 2.0 [1.2–3.2, 95% CIs, P = 0.006] for alpha1 ≤ 1.025), (HR = 1.9 [1.2–3.1, P = 0.008] for beta ≤–1.507). Conclusion: Several autonomic markers provide information on the risk of recurrent nonfatal coronary events after an AMI. Altered fractal heart rate behavior seems to be the strongest independent predictor of such events.     

Clinical significance of acute-phase endothelin-1 in acute myocardial infarction patients treated with direct coronary angioplasty.

BACKGROUND: The aim of the present study was to investigate the relationship between plasma concentrations of endothelin (ET)-1 and clinical outcome (including mortality) and left ventricular (LV) systolic function in acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 110 consecutive first-AMI patients who were successfully reperfused by primary coronary intervention. Plasma ET-1 concentrations were evaluated 24 h from onset and the patients were divided into 2 groups according to the median value, either a high group (H group: > or = 2.90 pg/ml plasma ET-1; n = 55) or low group (L group: < 2.90 pg/ml plasma ET-1; n = 55). Major complications and LV systolic function were monitored in the 2 groups. Both highly sensitive C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP) showed a significant positive correlation with ET-1 (BNP: r = 048, p < 0.0001, hs-CRP: r = 0.43, p < 0.001). Chronic stage left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI) were significantly poorer in the H group (LVEF: 51+/-15% vs 60+/-13%, p = 0.003, LVEDVI: 74+/-19 ml/m2 vs 66+/-14 ml/m2, p < 0.05). There were significantly more major complications in the H group than in the L group (cardiogenic shock: 18% vs 5%, p = 0.04; cardiac death: 13% vs 0%, p < 0.01). CONCLUSIONS: In the setting of AMI, plasma ET-1 concentrations may be closely related to LV systolic dysfunction and poor patient outcome, including mortality.     

Effects of Carvedilol on Heart Rate Dynamics in Patients with Congestive Heart Failure

Background: Patients with congestive heart failure (CHF) have alterations in the traditional and nonlinear indices of heart rate (HR) dynamics, which have been associated with an increased risk of mortality. This study was designed to test the effects of carvedilol, a nonselective beta‐blocker with alpha‐1 blocking properties, on HR dynamics in patients with CHF. Methods: We studied 15 patients with CHF secondary to ischemic or idiopathic cardiomyopathy who met the following inclusion criteria: NYHA functional class II‐III, optimal conventional medical therapy, normal sinus rhythm, left ventricular ejection fraction (LVEF) of < 40%, and resting systolic blood pressure greater than 100 mmHg. The 6‐minute corridor walk test, estimation of LVEF, and 24‐hour Holter recording were performed at baseline and after 12 weeks of therapy with carvedilol. Traditional time and frequency domain measures and short‐term fractal scaling exponent of HR dynamics were analyzed. Results: After 12 weeks of therapy with carvedilol, the mean LVEF improved significantly (from 0.27 ± 0.08 to 0.38 ± 0.08, P < 0.001). The average HR decreased significantly (from 86 ± 11 to 70 ± 8 beats/min, P < 0.001). The mean distance traveled in the 6‐minute walk test increased significantly (from 177 ± 44 to 273 ± 55 m, P < 0.01). The frequency‐domain indices (HF and LF), the time domain indices (rMSSD and PNN5), and the short‐term fractal scaling exponent increased significantly. The scaling exponent increased particularly among the patients with the lowest initial values (< 1.0), and the change in the fractal scaling exponent correlated with the change in ejection fraction (r = 0.63, P < 0.01). Conclusion: Carvedilol improves time and frequency domain indices of HR variability and corrects the altered scaling properties of HR dynamics in patients with CHF. It also improves LVEF and functional capacity. These specific changes in HR behavior caused by carvedilol treatment may reflect the normalization of impaired cardiovascular neural regulation of patients with CHF. A.N.E. 2002;7(2):133–138     

Power-law behavior of beat-rate variability in monolayer cultures of neonatal rat ventricular myocytes

It is known that extracardiac factors (nervous, humoral, and hemodynamic) participate in the power-law behavior of heart-rate variability. To assess whether intrinsic properties of cardiac tissue might also be involved, beat-rate variability was studied in spontaneously beating cell cultures devoid of extracardiac influences. Extracellular electrograms were recorded from monolayer cultures of neonatal rat ventricular myocytes under stable incubating conditions for up to 9 hours. The beat-rate time series of these recordings were examined in terms of their Fourier spectra and their Hurst scaling exponents. A non-0 Hurst exponent was found in 21 of 22 preparations (0.29+/-0.09; range, 0.11 to 0.45), indicating the presence of fractal self-similarity in the beat-rate time series. The same preparations exhibited power-law behavior of the power spectra with a power-law exponent of -1.36+/-0.24 (range, -1.04 to -1.96) in the frequency range of 0.001 to 1 Hz. Furthermore, it was found that the power-law exponent was nonstationary over time. These results indicate that the power-law behavior of heart-rate variability is determined not only by extracardiac influences but also by components intrinsic to cardiac tissue. Furthermore, the presence of power-law behavior in monolayer cultures of cardiomyocytes suggests that beat-rate variability might be determined by the complex nonlinear dynamics of processes occurring at the level of the cellular network, eg, interactions among a large number of cell oscillators or metabolic regulatory systems.