* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
Download the acute-phase heart rate variability in acute coronary syndrome
Survey
Document related concepts
History of invasive and interventional cardiology wikipedia , lookup
Cardiac contractility modulation wikipedia , lookup
Remote ischemic conditioning wikipedia , lookup
Cardiac surgery wikipedia , lookup
Electrocardiography wikipedia , lookup
Coronary artery disease wikipedia , lookup
Transcript
Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS THE ACUTE-PHASE HEART RATE VARIABILITY IN ACUTE CORONARY SYNDROME- THE IMPLICATIONS OF DIFFERENT ANALYSES Ho-Tsung Hsin1,2, Chi-Yu Yang3, Jiann-Shing Shieh4, Pi-Chi Lin1, Liang-Yu Chen1 Abstract Purpose: Heart-rate variability (HRV) is non-stationary. HRV is traditionally analyzed by power spectrum (low / high frequency (LF/HF) ratio). Detrended fluctuation analysis (DFA) deduces HRV to a simple fractal scaling exponent alpha. Previously, HRV studies focused on post-MI and chronic heart failure. The decreased DFA alpha is associated with mortality. The acute-phase HRV has not been elucidated. We intended to evaluate acute-phase HRV of acute coronary syndromes (ACS), in comparison with non-ACS subjects. Methods: Our study had two parts: simulation of acute stress on non-ACS volunteers and the prospective observation in patients of ACS. We assessed 1hour ECG of volunteers taking three designated intensity of exercise and patients in the acute stage of ACS. All ECG data were analyzed by DFA and power spectrum. The results of HRV were evaluated by univariate analysis. Results: The 30 volunteers got elevated DFA alpha while the intensity of exercise increased (0.95 0.050 to 1.07 0.084 to 1.20 0.083, p<0.05). The fractal properties of 33 ACS patients correlated with the complexity of post-MI course (1.004 0.0080 in non-complicated vs. 1.216 0.058 in complicated p <0.05). There was no significance when the fractal scaling exponent was categorized by age, type of ACS and other variables. The LF/HF ratio did not differ in any clinical perspective but between RCA/LCx and LAD groups (4.23 2.34 / 4.987 vs. 1.87 1.06, p<0.05). Conclusions: DFA can be used to study the acute-phase HRV in ACS, while the traditional power spectral analysis failed. The increased value derived from DFA may imply unresolved cardiac stress which demands further attention. Key words: Acute coronary syndrome, Detrended fluctuation, Fractal, Heart-rate variability, Power spectrum Correspondence: Dr. Liang-Yu Chen Cardiovascular Intensive Care Unit, Far-Eastern Memorial Hospital, 14F, No. 29, Sec. 2, Nan-Ya South Rd., Banciao City, Taipei County, Taiwan, 2201 Phone: +886-2-8966-7000 ext.1602; Fax: + 886-2-8966-5138; E-mail: [email protected] National Tainan Institute of Nursing, Tainan City, Taiwan2 Division of Cardiology, Cardiovascular Center, Far-Eastern Memorial Hospital, Taipei, Taiwan3 Department of Mechanical Engineering, Yuan Ze University, Taoyuan, Taiwan4 239 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. Introduction physiologic implications. Heart rate, a biologic signal, bears the inherited nature of being non-stationary. In addition, the dynamics of heart rate, referring to heart rate variability (HRV), vary in different disease status. Traditionally, HRV can be analyzed by several means, such as power spectral analysis (lowfrequency/high frequency ratio), or time-domain analysis (standard deviation of consecutive RR intervals (SDNN)). However, the traditional methods are easily hampered by the variation of signal/ noise components and the results may be misleading. The fractal organization of human HRV is believed to reflect the balance between sympathetic and vagal outflow.1 It can also be used as a reliable indicator of state of the heart.2 Detrended fluctuation analysis (DFA), a mathematic approach to study non-stationary signals, has made HRV much easier understood by qualitatively deducing HRV to a simple fractal scaling exponent (). The DFA of HRV has been used to evaluate the risk of mortality in various patient groups. In selected patients with depressed left ventricular function or heart failure, the decreased shortterm fractal scaling exponent () has been shown to be a strong predictor of cardiac and total mortality.3-6 In addition, the DFA has also been prospectively applied in a consecutive series of survivors of acute myocardial infarction (AMI). The reduced short-term fractal scaling exponent was significantly correlated with mortality in follow-up.7 So far, the studies of HRV by traditional power spectral analysis mostly focused on convalescent or chronic stable phase of specific disease entities, such as survivors of AMI, or patients of chronic compensated heart failure. Moreover, the available literature discusses the application of DFA in HRV are limited in the chronic phase, too.3-7 The physiologic significance of HRV analyzed by above methods in the acute phase of acute coronary syndromes (ACS) is not clear. Therefore, we conduct this study to evaluate the acute-phase HRV in ACS by both power spectral analysis and DFA, and try to clarify their Materials and Methods Acquisition of electrocardiogram The device used to acquire electrocardiogram (ECG) was tailor-made. The acquisition system in this article referred to an industrial personal computer (IPC). The IPC could be connected to any ECG monitor with analogue electric output, such as the polygraphic monitor in the intensive care unit (Fig. 1) or the directcurrent defibrillator. The capturing of ECG worked with a frequency of 400Hz. The captured signals were digitalized and further processed by the software MatLab 6.0, which could translate digitalized ECG into beat-to-beat R-R interval. In addition, a portable single-chip device was designed for ECG acquisition for ambulatory volunteers, in order to capture exercise ECG. The single-chip device took ECG by conventional leads, as that in performing routine treadmill exercise ECG or Holter ECG scanning. Simulation of acute stress The heart variability shall change with different stress, so shall the consequent shortterm fractal scaling exponent (), which was our primary hypothesis. We arranged programmed exercise for 30 subjects without current of past history of ACS. These volunteers were in their sixties and with or without hypertension, diabetes or hyperlipidemia. The percentage of the comorbidities were tried to rival the studied ACS patients. The 30 volunteers bore the portable single-chip ECG device while they were taking activities of specific-intensities after presenting their informed consent. The stress protocol included light, moderate and vigorous activities. All of the subjects took the three designated intensity of activities for 60 minutes, respectively. Sedentary works such as casual reading, internet browsing were regarded as light activities, which rendered less than 3 metabolic equivalents (METs). The activity of moderate stress in this study referred to programmed treadmill exercise, 4 miles 240 Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS Fig. 1. The instrument used in the intensive care unit for ECG acquisition. The industrial personal computer is connected to the polygraphic monitor in the unit and the process is controlled by a laptop. and 1 or 2 of the following parameters: (1) chest pain or dyspnea lasting for more than 30 minutes, and (2) ischemic ECG changes on admission or any later change of ECG caused by AMI. The exclusion criteria were unstable hemodynamics requiring very high dose of intravenous inotropes (defined as an intravenous infusion of dopamine more than 10 microgram/kg/min with or without using additional vasopressive agents, such as norepinephrine, epinephrine and vasopressin), advanced age (>80 year-old), dementia, old or ongoing intracranial process (i.e. old or active cerebrovascular accidents, brain tumor, metabolic encephalopathy, parkinsonism), alcoholism, drug abuse, or any other condition that could impair the subject’s or the family’s capability to give informed consent. In addition, patients of nonamenable cardiac dysrhythmia were also excluded, such as chronic atrial fibrillation, refractory frequent premature atrial or ventricular complex, and malignant arrhythmia requiring immediate resuscitation. Other non-cardiovascular conditions that made the patient excluded were immediate per hour in speed and a 5% incline, which offered 3 to 7 METs. The vigorous one was defined as treadmill exercise at 4 miles per hour in speed and a 10% incline, and the intensity of stress was believed to be 7-10 METs. 8 During each course of designated activity, the single-chip ECG acquisition device recoded the ECG signal. Study of ACS patients This is a prospective observational study conducted in the coronary care unit of a medical center. A consecutive series of patients of acute coronary syndrome admitted to the unit were screened after obtaining their informed consent. During the period of 2 months, we enrolled 33 eligible patients and their ECG data. The acute coronary syndromes referred to unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). The diagnosis of the acute coronary syndrome was based on an elevation of myocardial enzymes up to more than 2 times the upper limit that could not be attributable to any other condition, 241 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. series. The root-mean-square fluctuations of integrated and detrended time series is measured at different observational windows and plotted against the size of the observational window on a log-log scale. The slope of the root-mean-square line relating log F(n) to log n determines the scaling exponent (self-similarity parameter)-. Two equations could summarize the above words: surgical indication, pregnancy and terminal stage of malignancy. In addition, the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee. Every eligible patient was put on routine polygraphic monitoring after being admitted to the unit. The IPC was connected to the bed-side polygraphic monitor and a one-hour ECG acquisition was carried out within 48 hours of admission. The short-time acquisition of ECG, referring to “one-hour” in our study, is justified by the mathematic basis described below and another HRV study adopting “Chaos theory”9. As we adopted early-invasive strategy to treat acute coronary syndromes in this institute, all of the enrolled ACS patients had undergone percutaneous coronary intervention before the ECG acquisition. The therapy for acute coronary syndromes complied with the latest ACC/AHA/ ESC treatment guidelines for either unstable angina/non-ST elevation or ST-elevation myocardial infarction. In other words, dedicated drug therapy such as aspirin, clopidogrel, anti-coagulants, beta-blocker, angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin receptor blocker (ARB), and statins were administered accordingly, unless contraindicated. 1) the least square line 2) the detrended fluctuation analysis The advantages of DFA over conventional methods are that it permits the detection of longrange correlations embedded in a seemingly nonstationary time series and also avoids the spurious detection of apparent long-range correlations that are an artifact of non-stationarity. The DFA method has been tested on control time series that consist of long-range correlations with superposition of a non-stationary external trend.12 The advantage of this mathematic model renders the convenience that it needs only 1000 RR interval (in other words less than 18 minutes for a subject with HR of 60/min) to suffice the analysis of the instant HRV.11 The transformation of ECG signal to RR-intervals and final DFA () is exemplified in Fig. 2, one of our ACS patient’s data. The measured frequency was 400 Hz. The detrended fluctuation analysis (DFA)the fractal scaling exponent () The ECG data of sinus beats, which meant “edited data” were used for the DFA.10,11 The computational details of DFA are well demonstrated by Dr. Peng and his colleagues. 12,13 In short, the DFA is a novel mathematic analysis developed to elucidate long-range continuous non-stationary signals, especially biological ones. It has been successfully applied in analyzing electroencephalogram (EEG), waves of respiratory motion, ECG and even the complex sequences of humane DNA.13-15 The conceptual simplification of DFA can refer to that moving window of size n is used to study how the fluctuation F(n) grows with n for the inter-beat interval time The power spectral analysis ECG by frequency domain The power spectrum is a quantity widely used to measure correlations in a time series, which measures the relative frequency content of a signal. The HRV data was measured by fast-Fourier transform analysis in 2 frequency bands: 0.04 to 0.15 Hz (low frequency, LF), and 0.15 to 0.40 Hz (high frequency, HF). LF and HF components were computed over the entire 1-hour recording interval. The LF/HF ratio was calculated accordingly. 242 Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS Fig. 2. The plots of transforming ECG data to DFA , exemplified by one of the ACS patients. The slope is the DFA . Statistical analysis The analysis was done with Statistical Package for Social Sciences software (SPSS 12.0 for Windows). The DFA () has been proved to be normally distributed by Dr. Tapanainen’s work.7 The baseline characteristics were compared by univariate analysis. The chi-square test was used for categorical variables, and the comparison of continuous variables was done by 2-tail t test. A p value <0.05 was considered statistically significant. rival in age, gender and co-morbidities. The percentages of taking specific prescription were also similar, except for anti-platelet agents and statins. Other demographics and clinical profiles were listed in Table 1. Acute stress simulation The baseline resting HRV of the 30 volunteers resulted in a fractal exponent () = 0.95 0.050. The value during exercise of moderate-intensity was 1.07 0.084, and it increased to 1.20 0.083 as the volunteers took vigorous exercises. (p< 0.05). On the other hand, the LF/HF ratio did not show any trend at all (2.83 1.74 to 5.49 2.30 to 4.39 1.29). (Fig. 3) Results Basic demographics The 30 non-ACS volunteers were 66.5 5.2 year-old on average. The ACS patients were 62.2 12.8 year-old. The group of simulation and the studied ACS patients were tried to be Study on ACS patients During a period of 2 months, we enrolled 243 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. Table 1. Clinical variables of the ACS patients and non-ACS subjects Age (year-old) Gender: male/female Co-morbidity Hypertension Diabetes mellitus Hyperlipidemia Current smoker Current drug Aspirin Clopidogrel Statin Beta-blocker ACS patients n=33 (%) Non-ACS subjects n=30 (%) P value 66.5 5.2 26/7 62.2 12.8 24/6 NS* NS (75.6%) (33.3%) (51.5%) (54.5%) 24 (80%) 9 (30%) 15 (50%) 15 (50%) NS NS NS NS 33 (100%) 33 (100%) 24 (72%) 25 (75.6%) 9 (30%) 0 (0%) 15 (50%) 21 (70%) P<0.05 P<0.05 P<0.05 NS 25 11 17 18 *NS: not significant Fig. 3. The power spectral LF/HF ratio and fractal scaling exponent of the 30 healthy volunteers during different intensities of exercise. (The 2nd data of LF/HF was truncated as the standard deviation surpassed the range.) DFA: deterended fluctuation analysis LF: low frequency HF: high frequency MET: metabolic equivalent 244 Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS was 83 10.3/min. The mean arterial pressure was 73 9.8 mmHg. There was no in-hospital mortality in this cohort. In Table 2, we illustrated the summary of HRV both by DFA and power 33 eligible patients and their ECG data of acute coronary syndromes. The acquisition of ECG was done at around 26.8 2.1 hours after admission to the unit. The heart rate during ECG acquisition Table 2. The results of HRV analyzed by DFA and power spectrum in ACS patients by different categories DFA () LF/HF ratio Age (No. of patients) 65 y/o (24) > 65 y/o (9) P Value 1.031 0.113 2.82 1.93 0.660 0.662 1.009 0.144 2.46 1.96 Type of Acute Coronary Syndromes (No. of patients) DFA () LF/HF ratio STEMI (18) 1.008 0.122 3.03 1.83 NSTEMI (8) 1.045 0.163 2.03 2.01 UA (7) 1.070 0.046 0.91 0.58 0.722 0.230 Number of diseased coronary arteries (No. of patients) DFA () LF/HF ratio 1 VD (10) 1.023 0.053 2.28 1.03 2 VD (9) 1.070 0.160 3.05 2.90 3 VD (9) 1.003 0.135 2.51 2.18 LM (5) 1.006 0.177 1.67 1.01 0.838 0.774 Killip IV (1) 0.937 2.24 0.479 0.908 Killip classification of AMI (No. of patients) DFA () LF/HF ratio Killip I (14) 0.999 0.317 3.20 2.00 Killip II (7) 1.005 0.367 3.36 1.43 Killip III (4) 1.081 0.120 3.90 2.96 Left ventricular ejection fraction (No. of patients) DFA () LF/HF ratio < 50% (8) 0.973 0.099 2.67 2.01 50% (25) 1.061 0.112 2.63 1.81 0.070 0.962 Infarct-related artery (No. of patients) DFA () LF/HF ratio LAD (18) 1.005 0.106 1.87 1.06 RCA (14) 1.058 0.176 4.23 2.34 LCx (1) 0.998 4.987 0.440 0.029* Complicated (6) 1.216 0.058 3.00 1.58 <0.001 0.662 Post-MI course (No. of patients) DFA () LF/HF ratio Non-complicated (27) 1.004 0.080 2.76 1.85 *The significance exists between LAD and no-LAD categories. 245 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. subject is believed to be 1.0 0.1.17,18 In our study, the value of the volunteers before exercise was 0.95 0.050, which was compatible with the published data. In other words, the equality of our value to that in the literature preliminarily validated the authenticity of our study protocol. By applying stepwise programmed exercise, we found that the more intensive the physical stress, the larger the value (0.95 0.050 increased to 1.07 0.084 and then up to 1.20 0.084). This phenomenon explicitly indicates that the short-term fractal scaling exponent () increased with the increment of the acute stress. On the other hand, the LF/HF ratio did not show any consistent trend of variation in stress simulation (2.83 1.74 to 5.49 2.30 to 4.39 1.29), which failed to demonstrate its usefulness in evaluating acute stress. spectral analysis in different categories of acute coronary syndromes. As far as power spectrum is concerned, the only significance existed in the category of infarct-related artery (IRA). The LF/ HF ratio is significantly higher in RCA (right coronary artery)/ LCx (left circumflex artery) group than LAD (left anterior descending artery) group (4.23 2.34/ 4.987 vs. 1.87 1.06, p= 0.029). Regarding the DFA of HRV, the univariate analyses based on age, type of ACS, number of diseased coronary vessels, IRA, and Killip classification, did not show statistical significance between groups. On the other hand, if we took the perspective of post-MI complications, referring to post-MI angina and recurrent cardiogenic lung edema (defined by aggravated lung congestion on chest roentgenogram, or requiring increased or re-instituting intravenous diuretics), there were 6 cases bearing the fractal scaling exponent = 1.216 0.058. Those who experienced smooth post-MI course presented the result of their HRV by DFA () = 1.004 0.080 (p<0.001). Implications of HRV by different analyses Regarding the application of HRV as prognostic factors in patients of acute coronary syndromes, all of the analyses, such as SDNN, power spectrum, predicted mortality when the HRV was measured in the convalescent phase after an AMI. 19-25 However, there are some arguments that these traditional HRV parameters are able to predict mortality in the univariate analysis, but the power is weakened after adjustment for the clinical variables and left ventricular function.7 The original studies showing the association between the reduced heart rate variability and mortality rates were from the pre-thrombolytic era.19,20 With the advent of modern pharmacologic therapy and coronary revascularization, the mortality is much lowered. In addition, the power spectral analysis using LF/HF ratio has inherited flaws: the calculation is based on the assumption that the studied signal is stationary. If deliberately applied, the power spectrum would lead to misleading results in analyzing non-stationary signals. In controlled external contexts with fixed respiratory rate, the short-term fractal scaling exponent () of DFA is closely related to LF/HF ratio.26 However, the correlation becomes weaker in “free-running” ambulatory conditions. This change is ascribed Discussion First of all our study focused on clarifying the physiologic implications of the short-term fractal scaling exponent () of acute phase HRV. Our intention was to imply unresolved cardiac stress in ACS patients in acute stage by analyzing the 1-hour ECG at a specific time point. The study protocol and preliminary result were ever published elsewhere.16 Secondly, we compared different analyses, DFA and power spectral analysis in studying acute-phase HRV, and found that power spectral analysis could not reach a consistent trend in detecting probable stress while DFA could. Acute stress simulation The simulation of acute stress on the heart is maneuvered by imposing different intensity of physical exertion on age- and co-morbiditymatched volunteers without ACS. The fractal scaling exponent () of a healthy and tranquil 246 Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS to that the DFA provides precise information on the scaling properties of heart rate fluctuations over highly segmented time windows, whereas power spectral analysis only vaguely represent HRV in summated time windows.27 The “acute stress” may offer too “narrow” a time window (only 1 hour in our study) and too “non-stationary” a signal (the ACS is still evolving) for the power spectrum to take effective. In our study, the only difference of LF/HF ratio resided in different IRA (RCA/LCx vs. LAD: 4.23 2.34/ 4.987 vs. 1.87 1.06, p= 0.029). Inferior wall MI related to RCA/LCx occlusion is well renowned to have Bezold-Jarisch reflex, which comes from enhanced vagal modulation.28 Physiologically, HF components of HRV represent the activity of vagal outflow, but it is dramatically influenced by respiration. On the other hand, the LF components indicate the mixed modulation of both sympathetic and parasympathetic nerves.29 As a consequence, the enhanced LF/HF ratio in the IRA group of RCA/LCx could not conform to the vagal-dominant nature of inferior wall MI, implying that a LF/HF ratio is of poor clinical significance. with angina pectoris without prior MI were significantly higher, in comparison with agematched healthy controls (1.34 0.15 vs. 1.11 .. 0.12, p< 0.001). Dr. Ma kikallio concluded that the short-term fractal scaling exponent () performed better than other HRV parameters on differentiating patients with active coronary artery diseases (CAD) from healthy subjects, but it was not related to the clinical or angiographic severity of CAD.30 The preliminary conclusion reached by our simulation of acute stress on heart is .. compatible with that of Dr. Ma kikalli’s study. In our patients of acute coronary syndromes, increased value (1.216 0.058) was observed in 6 complicated cases of recurrent cardiogenic lung edema during hospitalization. All the other patients experienced non-complicated postrevascularization course and had the value close to subjects free from ACS (1.004 0.080). The difference of the short-term fractal scaling exponent () between the complicated and noncomplicated patients was statistically significant. The fractal properties of HRV in our patients were not influenced by the type of acute coronary syndromes, the number of diseased coronary vessels, the infract-related artery, and mostinterestingly, the predetermined Killip class of acute myocardial infarction. We may preclude the only one case of Killip IV, and the shortterm scaling exponent did not differ between patients of Killip I, II and III (0.999 0.119 vs. 0.984 0.317 vs. 1.080 0.243, p>0.05). This observation may conform to the experience of our daily practice, in which a majority of the AMI patients would experience an event-free stay after successful revascularization of the IRA, regardless of the Killip classification. Based on the hypothesis built by the acute stress simulation, the DFA probably discloses sort of ongoing cardiac stress, despite the patient is kept rest and the heart has been successfully revascularized. The on-going cardiac stress resulted in the increment of value and the clinical manifestation of acute cardiogenic lung edema. The implication of increased DFA () Previously, the reduced scaling exponent () is found to provide prognostic information among patients with depressed left ventricular systolic function.3-6 The role of the scaling exponent has been broadened to play as a risk stratifier of mortality beyond the patients with impaired left ventricular function to more general postMI populations7. Those studies demonstrated that a reduced short-term scaling exponent (<1.0) predicted pots-MI mortality in follow-up. Differently, our study concerned the unresolved acute-phase stress of ACS on heart, not the mortality in chronic follow-up. According to the result of acute stress simulation in our study, we preliminarily elucidate the physiologic background of the short-term scaling exponent: the acute stress would make the scaling exponent () higher. Dr. Tulppo in his delicate study also showed the higher the sympathetic tone, the higher the alpha value.29 The scaling exponents in symptomatic patients Limitation of this study 247 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. questions on your competing interest form are all No and there have nothing to declare. This is a single-institute observational study, which has limited significance as inherited. In addition, the scale is too small, which made the receiver’s operating curve (ROC) out-of-thequestion. We also acknowledged that this study was designed to elucidate the relationship between “unresolved stress” and HRV. Therefore, higher event rate than that in general population may be inevitable. However, it is not our initiative to evaluate the DFA among general populations, but test it in patients with probable stress. In addition, the number of Killip IV myocardial infarction is too small to be taken in to account. We should take caution in the preliminary conclusion that the short-term fractal scaling exponent did not correlate with the pre-determined Killip classification. Due to the limited number of subjects, we were unable to perform multivariate analysis. It is also impossible to clarify the influence of beta-blocker, inotropes and DM on HRV. Further expansion of the case number is desired in the future. References 01. Tulppo MP, Kiviniemi AM, Hautala AJ, et al. Physiological background of the loss of fractal heart rate dynamics. Circulation 2005;112:314-319. 02. Acharya UR, Kannathal N, Sing OW, et al. Heart rate analysis in normal subjects of various age groups. Biomed Eng Online 2004;3:24. .. 03. Ma kikallio T, Hojberg S, Kober L, et al. Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. Am J Cardiol 1999;83:836-839. .. 04. Huikuri HV, Ma kikallio TH, Peng CK, et al. DIAMOND Study Group. Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction. Circulation 2000;101: 47-53. .. 05. Ma kikallio TH, Huikuri HV, Hintze U et al. DIAMOND Study Group (Danish Investigations of Arrhythmia and Mortality ON Dofetilide). Fractal analysis and timeand frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure. Am J Cardiol 2001;87: 178-182. .. .. 06. Perkio ma ki JS, Zareba W, Daubert JP, et al. Fractal correlation properties of heart rate dynamics and adverse events in patients with implantable cardioverterdefibrillators. Am J Cardiol 2001;88:17-22. 07. Tapanainen JM, Thomsen PEB, Kober L et al. Fractal Analysis of Heart Rate Variability and Mortality after an Acute Myocardial Infarction. Am J Cardiol 2002; 90:347-352. 08. Ainsworth BE, Haskell WL, Leon AS. Compendium of physical activities: classification of energy costs of human activities. Medicine and Science in sports and Exercise 1993;25:71-80. 09. Krstacic G, Krstacic A, Smalcelj A et al. The “Chaos Theory” and nonlinear dynamics in heart rate variability analysis: does it work in short-time series in patients with coronary heart disease. Ann Noninvasive Electrocardiol 2007;12:130-136. 10. Peng CK, Havlin S. Stanley HE, et al. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos 1995;5: 82-87 11. Stanley HE, Amarala LAN, Goldberger A, Havlina S, Ivanova PCh, Peng CK. Statistical physics and physiology: Monofractal and multifractal approaches. Physica A 1999;270:309-324. Conclusion In Short, abnormal HRV in chronic stage is proved to be associated with increased mortality. However, we did not know how acute stress influences the HRV until the ushering of DFA. Our study implied the probable failure of power spectral analysis (LF/HF ratio) in dealing with acute-phase HRV. On the other hand, our study indicated that elevated acute stress resulted in an increased short-term fractal exponent (). Clinically speaking, the increased DFA () value more than 1.0 probably implies that there should be sort of unresolved cardiac stress, which demands further attention. Acknowledgement This study was supported by grants of FarEastern Memorial Hospital (FEMH-95-C-029). Statement of conflict of interest All authors declare that the answer to the 248 Taiwan Crit. Care Med.2010;11:239-250 Different analyses of acute-phase HRV in ACS 22. Fei L, Copie X, Malik M, et al. Short- and longterm assessment of heart rate variability for risk stratification after acute myocardial infarction. Am J Cardiol 1996;77:681-684. 23. La Rovere MT, Bigger JT Jr, Marcus FI, et al. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 1998;351:478-484. 24. Zuanetti G, Neilson J, Latini R, et al. Prognostic significance of heart rate variability in post-myocardial infarction patients in the fibrinolytic era: the GISSI-2 results. Circulation 1996;94:432-436. 25. Lombardi F, Sandrone G, Mortara A et al. Linear and nonlinear dynamics of heart rate variability after acute myocardial infarction with normal and reduced left ventricular ejection fraction. Am J Cardiol 1996; 77:1283-1288. .. 26. Tulppo MP, Hughson R, Ma kikallio T, et al. Effects of exercise and passive head-up tilt on fractal and complexity properties of heart rate dynamics. Am J Physiol 2001;280:H1081-H1087. .. .. 27. Ma kikallio TH, Huikuri H, Ma kikallio A et al. Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects. J Am Coll Cardiol 2001;37:1395-1402. 28. Kawasaki T, Azuma A, Kuribayashi T et al. Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium. Heart 2006;92:325330. 29. Tulppo MP, Kiviniemi AM, Hautala AJ, et al. Physiological background of the loss of fractal heart rate dynamics. Circulation. 2005;112:314-319. .. 30. Ma kikallio TH, Ristimae T, Airaksinen KEJ, et al. Heart rate dynamics in patients with stable angina pectoris and utility of fractal and complexity measures. Am J Cardiol 1998;81:27-31. 12. Peng CK, Buldyrev SV, Havlin S, et al. On the mosaic organization of DNA sequences. Phys Rev 1994;49: 1691-1695. 13. Buldyrev SV, Goldberger AL, Havlin S et al. Longrange correlation properties of coding and noncoding DNA sequences: GenBank analysis. Phys Rev 1995; 51:5084-5091. 14. Buldyrev SV, Goldberger AL, Havlin S, et al. Fractal landscapes and molecular evolution: Modeling the myosin heavy chain gene family. Biophys J 1993; 65:2673-2679. 15. Ossadnik SM, Buldyrev SV, Goldberger AL et al. Correlation approach to identify coding regions in DNA sequences. Biophys J 1994;67:64-70. 16. Hsin HT, Yang CY, Yeih DF, et al. The detrended fluctuation analysis of acute-phase heart-rate variability in acute coronary syndromes - A pilot study. Int J Cardiol 2010;140:252-255. 17. Stanley HE, Amaral LAN, Goldberger AL, et al. Statistical physics and physiology: Monofractal and multifractal approaches. Phys A 1999;270:309-324. 18. Goldberger AL, Amaral LAN, Hausdorff JM, et al. Fractal dynamics in physiology: Alterations with disease and aging. PNAS 2002;99:2466-2472. 19. Kleiger R, Miller J, Bigger J Jr, et al. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987;89:256-262. 20. Bigger J Jr, Fliess G, Steinmann R, et al. Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation 1992;85:164171. 21. Hartikainen J, Malik M, Staunton A, et al. Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction. J Am Coll Cardiol 1996;28:296-304. 249 Taiwan Crit. Care Med.2010;11:239-250 Ho-Tsung Hsin et al. !"#$!%&'()- !"#$ 1,2 I= 3 I= 4 I= 1 I= 1 !"HRV !"#$%&HRV !"#power spectrum !"#$%&'()*+,-./012345 detrended fluctuation analysisDFA HRV !"#$%&' alpha ! HRV !"#$%&'()*+,-./0&1234-5678 alpha !"#$%&'()*+,-HRV !"#$%&'() !"#$%&ACS !ACS !"#$%&'()*HRV !"# !"#$%&'() ACS !"#$%&'()*+ ACS !"#$%&'()*+,- ACS !"#$%&'()* !"#$%&'( ACS !"#$%&'()*+,-. DFA power spectrum !"#$%&'()*+, 30 ACS !"#$ DFA alpha !"#$%& 0.95 0.050 to 1.07 0.084 to 1.20 0.083, p< 0.05 ACS alpha !"#$%&'()*+,-. !"# 1.004 0.0080 vs. !" 1.216 0.058, p<0.05 alpha !"#$%&' ACS !"#$%&'()*+power spectrum !"#$%&'()* !RCA/LCx 4.23 2.34/ 4.987 vs. LAD1.87 1.06, p<0.05 !" DFA !"# ACS ! HRV !"# !"#$%&'()*+,-DFA alpha !"#$%&'()* !"#$%&'()*+, ! Acute coronary syndrome, Detrended fluctuation, Fractal, Heart-rate variability, Power spectrum ! !" 220 !"#$%$& 2 29 !"#$%&'()*+, 1 02-8966-7000 ext.1602 !+ [email protected] !"#$%&' 2 !"#$%&##'() 3 !"#$%&'()*+ 4 250 !