Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.     

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   

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.     

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.     

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.     

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.     

Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era

OBJECTIVES: This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI). BACKGROUND: Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use. METHODS: A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI). RESULTS: During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD. CONCLUSIONS: Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.     

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 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.     

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.     

Decreased heart rate variability and its association with increased mortality after acute myocardial infarction

A high degree of heart rate (HR) variability is found in compensated hearts with good function, whereas HR variability can be decreased with severe coronary artery disease, congestive heart failure, aging and diabetic neuropathy. To test the hypothesis that HR variability is a predictor of long-term survival after acute myocardial infarction (AMI), the Holter tapes of 808 patients who survived AMI were analyzed. Heart rate variability was defined as the standard deviation of all normal RR intervals in a 24-hour continuous electrocardiogram recording made 11 +/- 3 days after AMI. In all patients demographic, clinical and laboratory variables were measured at baseline. Mean follow-up time was 31 months. Of all Holter variables measured, HR variability had the strongest univariate correlation with mortality. The relative risk of mortality was 5.3 times higher in the group with HR variability of less than 50 ms than the group with HR variability of more than 100 ms. HR variability remained a significant predictor of mortality after adjusting for clinical, demographic, other Holter features and ejection fraction. A hypothesis to explain this finding is that decreased HR variability correlates with increased sympathetic or decreased vagal tone, which may predispose to ventricular fibrillation.     

Predictors of Long‐Term Risk for Heart Failure Hospitalization after Acute Myocardial Infarction

Background: Data on the value of baseline brain natriuretic peptide (BNP) and autonomic markers in predicting heart failure (HF) hospitalization after an acute myocardial infarction (AMI) are limited. Methods: A consecutive series of patients with AMI without a previous history of HF (n = 569) were followed up for 8 years. At baseline, the patients had a blood sample for determination of BNP, a 24‐hour Holter recording for evaluating heart rate variability (HRV) and heart rate turbulence (HRT), and an assessment of baroreflex sensitivity (BRS) using phenylephrine test. Results: During the follow‐up, 79 (14%) patients were hospitalized due to HF. Increased baseline BNP, decreased HRV, HRT, and BRS had a significant association with HF hospitalization in univariate comparisons (P < 0.001 for all). After adjusting with all the relevant clinical parameters, BNP, HRV, and HRT still significantly predicted HF hospitalization (P < 0.001 for BNP and for the short‐term scaling exponent α₁, P < 0.01 for turbulence slope). In the receiver operator characteristics curve analysis, the area under the curve for BNP was 0.77, for the short‐term scaling exponent α₁ 0.69, for turbulence slope 0.71, and for BNP/standard deviation of all N‐N intervals ratio 0.80. Conclusion: Baseline increased BNP and impaired autonomic function after AMI yield significant information on the long‐term risk for HF hospitalization. Ann Noninvasive Electrocardiol 2010;15(3):250–258     

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.     

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     

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.     

Prognostic significance of risk stratifiers of mortality, including T wave alternans, after acute myocardial infarction: results of a prospective follow-up study

INTRODUCTION: Occurrence of sustained microvolt-level T wave alternans (TWA) at a specified heart rate has been suggested to predict life-threatening arrhythmic events, but its prognostic value has not been well established in patients who survived an acute myocardial infarction (AMI). The purpose of this prospective study was to assess the predictive significance of various noninvasive risk indicators of mortality, including TWA, in consecutive post-AMI patients with optimized medical therapy. METHODS AND RESULTS: In addition to a symptom-limited predischarge exercise test with measurement of TWA, mortality risk was assessed using heart rate variability, 24-hour ECG recordings, baroreflex sensitivity, signal-averaged ECG, QTc interval, QT dispersion, and echocardiographic wall-motion index in 379 consecutive patients. Twenty-six patients (6.9%) died during a mean follow-up of 14 +/- 8 months. Sustained TWA was found in 56 patients (14.7%), none of whom died. Several risk variables, e.g., incomplete TWA test (inability to perform the exercise test or reach the required target heart rate of 105 beats/min), increased QRS duration on signal-averaged ECG, increased QT dispersion, long QTc interval, nondiagnostic baroreflex sensitivity result, and low wall-motion index, predicted all-cause mortality in univariate analyses. In multivariate analysis, the incomplete TWA test was the most significant predictor of cardiac death (relative risk 11.1, 95% confidence interval 2.4 to 50.8; P < 0.01). CONCLUSION: Sustained TWA during the predischarge exercise test after AMI does not indicate increased risk for mortality. An incomplete TWA test and several common risk variables provided prognostic information in this post-AMI population.     

Effects and Significance of Premature Beats on Fractal Correlation Properties of R‐R Interval Dynamics

Background: Premature beats (PBs) have been considered as artifacts producing a bias in the traditional analysis of heart rate (HR) variability. We assessed the effects and significance of PBs on fractal scaling exponents in healthy subjects and patients with a recent myocardial infarction (AMI). Methods: Artificial PBs were first generated into a time series of pure sinus beats in 20 healthy subjects and 20 post‐AMI patients. Thereafter, a case‐control approach was used to compare the prognostic significance of edited and nonedited fractal scaling exponents in a random elderly population and in a post‐AMI population. Detrended fluctuation analysis (DFA) was used to measure the short‐term (α₁) and long‐term (α₂) fractal scaling exponents. Results: Artificial PBs caused a more pronounced reduction of α₁ value among the post‐AMI patients than the healthy subjects, for example, if >0.25% of the beats were premature a >25% decrease in the α₁ was observed in post‐AMI patients, but 4% of the premature beats were needed to cause a 25% reduction in α₁ in healthy subjects. Both edited (1.01 ± 0.31 vs 1.19 ± 0.27, P < 0.01) and unedited α₁ (0.71 ± 0.33 vs 0.89 ± 0.36, P < 0.05) differed between the patients who died (n = 42) and those who survived (n = 42) after an AMI. In the general population, only unedited α₁ differed significantly between survivors and those who died (0.96 ± 0.19 vs 0.83 ± 0.27, P < 0.05). Conclusions: Unedited premature beats result in an increase in the randomness of short‐term R‐R interval dynamics, particularly in post‐AMI patients. Premature beats must not necessarily be edited when fractal analysis is used for risk stratification.     

Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion

OBJECTIVES: We sought to evaluate and compare recently suggested parameters of reperfusion after angioplasty in acute myocardial infarction (AMI) for risk stratification during long-term follow-up. BACKGROUND: Abnormal myocardial perfusion has a detrimental impact on survival. Several parameters of reperfusion have been evaluated in controlled study populations for risk stratification. METHODS: In 253 consecutive patients undergoing intervention in AMI on a native coronary vessel, angiographic myocardial blush grade (MBG), corrected TIMI (thrombolysis in myocardial infarction) frame count (CTFC) and persistent ST-segment elevation (STE) were determined to evaluate reperfusion. This was a high-risk population, including referral for treatment failure at a primary center in 29.2%, failed thrombolysis in 22.1% and cardiogenic shock in 13.4% of cases. RESULTS: In addition to age, patient referral, LBBB and heart rate on admission, MBG 0 to 1 (odds ratio [OR] = 3.23, p < 0.001), CTFC (OR = 1.01, p = 0.015) and persistent STE >2 leads (OR = 3.46, p = 0.010) were univariate predictors of mortality during a 22.1 +/- 15.6 months follow-up. Myocardial blush grade 0 to 1 (OR = 2.17, p = 0.033) and persistent STE (OR = 3.61, p = 0.017) persisted as independent predictors of mortality, whereas CTFC failed. Differences in mortality between reperfusion groups at 30 days remained throughout the complete follow-up. In sequential Cox models, the predictive power of clinical data alone for mortality (model chi-squared 55.8) was strengthened by adding MBG (model chi-squared 64.2) and ECG postintervention (model chi-squared 69.2). CONCLUSIONS: Myocardial blush grade 0 to 1 and persistent STE are independent predictors for long-term mortality after angioplasty in AMI. Corrected TIMI frame count is a less powerful predictor. Combining both parameters to consider quality of reperfusion in the myocardium at risk and extent of the infarct zone increases the predictive power.     

Prognostic utility of comparative methods for assessment of ST-segment resolution after primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial

OBJECTIVE: This study was done to assess and compare the prognostic significance of multiple methods for measuring ST-segment elevation resolution (STR) following primary percutaneous coronary intervention (PCI). BACKGROUND: Resolution of ST-segment elevation (STE) is a powerful predictor of both infarct-related artery patency and mortality in acute myocardial infarction (AMI). Recent thrombolytic studies have suggested that simple measures of STR may be as powerful as more complex algorithms. The optimal method of assessing STR following primary PCI has not been studied. METHODS: We analyzed 700 patients with technically adequate baseline and post-PCI electrocardiograms from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Five methods were used to assess STR: 1) summed %STR across multiple leads (SigmaSTR); 2) %STR in the single lead with maximum baseline STE (MaxSTR); 3) absolute maximum STE before the procedure; 4) absolute maximum STE after intervention (MaxSTPost); and 5) a categorical variable based upon MaxSTPost (High Risk). RESULTS: At 30 days, SigmaSTR, MaxSTR, and MaxSTPost all correlated strongly with mortality (p = 0.004, p = 0.005, and p < 0.0001, respectively) and the combined end point of mortality or reinfarction (p = 0.001, p = 0.001, and p < 0.0001). At one year, SigmaSTR and MaxSTPost correlated with mortality (p = 0.04, p = 0.0001), reinfarction (p = 0.02, p = 0.0015), and the combined end point (p = 0.02, p < 0.0001). By multivariate analysis, only the simpler measures of MaxSTPost and High Risk categorization independently predicted all outcomes at both time points. CONCLUSIONS: The STR following primary PCI in AMI correlates strongly with mortality and reinfarction, independent of target vessel patency. The simple measure of the maximal residual degree of STE after primary PCI is a strong independent predictor of both survival and freedom from reinfarction at 30 days and 1 year.