Optimal electrocardiographic leads for detecting acute myocardial ischemia.

This study identifies the most sensitive electrocardiographic leads for monitoring ST-segment changes caused by acute coronary ischemia. The data set consisted of 120-lead electrocardiograms (ECGs) digitally recorded during balloon-inflation angioplasty in 3 groups of patients with single-vessel disease (left anterior descending [LAD], 32; right coronary artery [RCA], 36; left circumflex [LCx], 23). The ST deviation was measured in all recorded leads during baseline and ischemic states, and its difference between these 2 states (DeltaST) was calculated at 352 sites and plotted as DeltaST maps. The patients in each group were divided, by means of DeltaST criteria, into subgroups of "responders" and "nonresponders." Mean DeltaSTs for each group/subgroup were calculated and standardized by the corresponding standard deviation (SD); these values were plotted as mean DeltaST and t maps. Sites where extrema of DeltaST occurred most frequently were sought in bootstrap trials, performed in each group/subgroup. The results suggest that the optimal sites for the ischemia-sensitive leads are: V(3) (+) and just below V(8) (-) for LAD-related ischemia; the left iliac crest (+) and above V(3) at the third intercostal space (-) for RCA-related ischemia; and just below V(8) (+) and above V(2) at the third intercostal space (-) for LCx-related ischemia. Three "optimal" bipolar leads using these sites registered, in the responders from the LAD, RCA, and LCx groups, mean DeltaST (+/-SD) of 232 +/- 59, 245 +/- 96 and 158 +/- 91 microV, respectively; the corresponding t values were 15.14, 9.90, and 6.75. In the 12-lead ECG, only lead V(3) approached optimal DeltaST and t values for the LAD responders (187 +/- 61 microV; t = 11.75) and lead III for the RCA responders (191 +/- 76 microV; t = 9.73), but even these values were significantly suboptimal (P = 0.0011 and P = 0.0120, respectively). We found that the "optimal" bipolar leads can be derived, to an excellent approximation, from the 12 standard leads or from 3 EASI leads (with 3 electrodes at Frank's transverse level and 1 on the manubrium), by using precalculated regression coefficients. By means of bootstrap trials, we estimated the mean sensitivity (SE) and the mean positive predictive value (PPV) with which 3 "optimal" vessel-specific leads could identify ischemia related to the LAD, RCA, and LCx arteries, in the test set, as (SE/PPV) 94.7/92.8%, 78.7/80.9%, and 81.5/80.9%. A similar diagnostic performance can be achieved by vessel-specific leads derived from the 12-lead ECG (93.0/93.4%, 76.6/82.0%, and 82.7/77.1%) and, interestingly, from the EASI lead system (97.8/88.4%, 78.0/80.2%, and 76.8/83.2%). Thus, although the "optimal" bipolar leads for detecting ischemia related to each of the 3 coronary arteries were found to require sampling outside the 12-lead ECG, these leads can be derived from the full set of 12 standard leads or--for clinical monitoring applications--from the EASI lead system by using fewer electrodes at convenient locations.

Intravascular hemodynamic factors responsible for progression of coronary atherosclerosis and development of vulnerable plaque.

The initiation, localization, growth, composition, and rupture of intracoronary atheromatous plaque-factors that define the natural history of coronary artery disease-are all dependent on inhomogenieties and irregularities of intracoronary local blood flow and endothelial shear stress. Restenosis of mechanically recanalized coronary arteries may be related in part to similar abnormalities of disturbed local flood flow and shear stress. Low or reversed shear stress leads to plaque development and progression. High shear stress contributes significantly to plaque rupture. Regions of hemodynamic stasis caused by major luminal irregularities may lead to thrombosis and myocardial infarction without plaque rupture. This review outlines the mechanisms that link hemodynamic factors to plaque development and rupture and describes in some detail recently developed techniques that, for the first time, make it possible to determine these factors in vivo in patients during routine cardiac catheterization procedures.

Diagnostic accuracy of derived versus standard 12-lead electrocardiograms.

To compare the diagnostic yield of electrocardiograms (ECGs) recorded by 12 standard leads with that of 12-lead ECGs derived from 3 bipolar EASI leads, we analyzed pertinent ECG data for 290 normal subjects and 497 patients who had had a prior myocardial infarction (MI); the latter group comprised 36 patients with a non-Q MI, 282 patients with a Q-wave MI, and 179 patients with a history of ventricular tachycardia (VT). We first estimated statistically an optimal set of coefficients for deriving the 12 standard leads from EASI leads and assessed this transformation in terms of goodness of fit. To gauge the diagnostic information content of the recorded vs. derived 12-lead ECGs, we performed successively two-group diagnostic classification--based on the Cardiac Infarction Injury Score (CIIS)--separating each of the patient subgroups from the normal group; the classification was repeated for 200 sets of patients selected randomly (with replacement), and the results were plotted as mean receiver operating characteristics. We found that derived 12-lead ECGs correlated well with the recorded ones, and reproduced faithfully the diagnostic features needed for the CIIS. When the CIIS was determined from features of the recorded standard 12 leads, its mean diagnostic performance (assessed in terms of area under the receiver operating characteristics curve) was 0.9004 for detecting non-Q MIs, 0.9546 for Q-wave MIs, and 0.9919 for MIs complicated by a history of VT. When, instead, features of derived 12 leads were used to determine the CIIS, diagnostic performance remained virtually unchanged (at 0.8905, 0.9531, and 0.9906, respectively). We conclude that, in our population, EASI-derived 12-lead ECGs contain nearly the same diagnostic information as standard 12-lead ECGs.

Determination of blood flow and endothelial shear stress in human coronary artery in vivo.

This paper describes a system that permits, for the first time, the in vivo determination of local velocity and endothelial shear stress in the major human coronary arteries. The purpose of the system is to facilitate the study of plaque growth and the relationships between local hemodynamic factors and atherogenesis and restenosis. The three-dimensional anatomy of a segment of the right coronary artery was determined immediately after directional atherectomy via a combination of intracoronary ultrasound and biplane angiography. The highly irregular geometry of the segment was then represented in curvilinear coordinates and a computational fluid dynamics technique was used to investigate the detailed, intravascular velocity profile and shear stress distribution. We found minor flow reversals, significant swirling and a large variation of local velocity and shear stress, both axially and circumferentially, within the artery, even in the absence of significant luminal obstruction. The flow phenomena exhibit characteristics consistent with the focal nature of atherogenesis and restenosis. It is concluded that the technology now exists to determine luminal geometry and local variations in flow fields and endothelial shear stress, in vivo.

Effects of curvature and stenosis-like narrowing on wall shear stress in a coronary artery model with phasic flow.

To gain insight into the details of intracoronary flow we have used computational fluid dynamic techniques to determine the velocity and wall shear stress distributions in both steady- and phasic-flow models of a curved coronary artery with several degrees of stenosis. The steady-flow Reynolds number was 500 and the peak phasic flow Reynolds number was 700. Without stenosis and at 25% (area) stenosis wall shear stress and velocities are higher at the outer wall than the inner wall but retain the same direction as the superimposed flow. At higher stenoses laminar flow separation occurs and the inner wall is exposed to shear stresses that vary widely, both temporally and spatially.

Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study.

BACKGROUND: Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). CONCLUSIONS: The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.

Determinants of heart rate variability.

OBJECTIVES: This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. BACKGROUND: Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. METHODS: The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability. Recordings with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1-h recording time or processed time < 50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis. Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. RESULTS: There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure > or = 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent supraventricular and ventricular premature beats, female gender and systolic blood pressure > or = 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R2 values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. CONCLUSIONS: Age and heart rate must be taken into account when assessing heart rate variability.

Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study.

BACKGROUND: The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/- SD) of 72 +/- 6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are > 50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P < .0001), low-frequency power (P < .0001), high-frequency power (P = .0014), total power (P < .0001), and the standard deviation of total normal RR intervals (P = .0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P < .0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09). CONCLUSIONS: The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors.

A neural network system for detection of atrial fibrillation in ambulatory electrocardiograms.

INTRODUCTION: A neural network classifier has been designed, which is able to distinguish atrial fibrillation (AF) from other supraventricular arrhythmias in ambulatory (Holter) ECGs. METHOD AND RESULTS: The classification algorithm uses a rhythm analysis that considers the ECG to be a time series of RR interval durations. This is combined with an analysis of baseline morphology that considers the morphological characteristics of the non-QRS portions of the waveform. A backpropagation-based neural network has been used as part of the classifier implementation. When applied to a library consisting exclusively of 42,970 examples of AF and other supraventricular rhythm disturbances validated by an experienced cardiologist, the algorithm demonstrated a sensitivity of 82.4% for 10-beat runs of paroxysmal atrial fibrillation (PAF) and a specificity of 96.6%. Since this system has been implemented as a postprocessor to a conventional automated Holter system, operating only on segments of ECG that are known to contain supraventricular arrhythmias rather than ventricular arrhythmias or sinus rhythm, it can be added to most existing Holter processing systems without significantly increasing the average time to process a tape. CONCLUSION: A neural network system has been designed, which can potentially provide, for the first time, an accurate, quantitative technique to determine the natural history of PAF and to evaluate potential treatments for PAF.

Minor recorder imperfections can cause artifacts in the RR interval spectrum derived from Holter recordings.

Spectral analysis of the heartbeat (RR) interval is a powerful tool for noninvasively assessing the autonomic nervous system. In addition, it may prove to be valuable in stratifying patients at risk for cardiac death. The authors report on a case in which spectral analysis of the RR interval exhibited harmonically related peaks within the physiological range that defied physiological explanation. Analysis showed that these peaks resulted from a subtle abnormality of the Holter recorder that was not apparent in the observed electrocardiogram. Since this type of abnormality can be produced by either minor damage or a manufacturing error in any brand of Holter recorder, the RR interval spectrum derived form a Holter electrocardiogram should always be critically examined for this particular artifact.

Quantitative detection of regional left ventricular contraction abnormalities by two-dimensional echocardiography. I. Analysis of methods.

Different approaches to the quantification of regional left ventricular (LV) function from two-dimensional echocardiographic (2-D echo) images were assessed for their ability to optimize interobserver reproducibility in a heterogeneous patient population and to minimize the variability of regional function observed in a homogeneous normal population. Areas, hemiaxis and perimeter measurements were examined, as were the effect of the degree of image subdivision into halves, quadrants or octants. Each approach was also tested using both a fixed and a floating frame of reference for the definition of a regional-axis system. The area method was consistently superior to either linear method in optimizing both reproducibility and variability. Reproducibility decreased inversely with the degree of subdivision. The axis-system frame of reference had no effect on reproducibility. The floating-axis system yielded the same variability as the fixed system for short-axis sections at the mitral valve level, but slightly less variability for a papillary muscle level section. We conclude that area-based methods are superior for the evaluation of regional LV function with 2-D echo, but the degree of subdivision of the image and the frame of reference chosen do not greatly affect reproducibility or variability and should be chosen based on their performance in a well-defined clinical population.

Quantitative detection of regional left ventricular contraction abnormalities by two-dimensional echocardiography. II. Accuracy in coronary artery disease.

The quantitative approaches to the assessment of regional left ventricular (LV) function described in the preceding paper were applied in a well-defined population of patients with coronary artery disease. Two groups were chosen by electrocardiographic and angiographic criteria: group 1 had infarction and regional wall motion abnormalities and group 2 had no infarction and normal wall motion. Sensitivity to detect wall motion defects, specificity to correctly categorize normal segments, and overall predictive accuracy were evaluated for each two-dimensional echocardiographic approach. In addition, the ability of each method to localize regional contraction defects properly was evaluated. Area methods yielded better predictive accuracy than linear methods (87-95% vs 76-84%). No significant differences in accuracy were noted between quadrant and octant approaches. The fixed external-axis system was superior to a floating one for localizing contraction defects. We conclude that an area-based method, using a fixed-axis system and either octant or quadrant image subdivision, provides the best combination of predictive accuracy in categorizing LV segments as normal or abnormal and the greatest ability to localize LV regional abnormalities.

A system for quantitative evaluation of left ventricular function with two-dimensional ultrasonography.

Phased-array ultrasonic imaging systems produce real-time sectional images of the left ventricle. To quantify left ventricular function, a light-pen-based system was developed using a minicomputer to analyze the geometry of ultrasound images and measure left ventricular volume, ejection fraction, and regional contraction. System accuracy was evaluated by comparing measurements abtained from left ventricular cineangiograms at cardiac catheterization on a series of 25 patients to echocardiographic left ventricular long- and short-axis linear dimensions (r = 0.92, S.E.E. = 0.67 cm), end-diastolic volume (r = 0.84, S.E.E. = 45 cm3), and ejection fraction (r = 0.80, S.E.E. = 0.10). Five patients from the study population with electrocardiographically documented transmural myocardial infarcts had regional contraction abnormalities detected by this analytic approach. Quantitative application of two-dimensional echocardiography appears to be a useful noninvasive method of evaluating left ventricular ejection fraction and has potential to define regional contraction abnormalities objectively.

Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiography. A comparison of cineangiographic and radionuclide techniques.

Five different algorithms for determining left ventricular (LV) ejection fraction (EF) and volumes from two-dimensional echocardiographic examination (TDE) were compared with standard methods for obtaining EF and volume from x-ray cineangiography (cine) and EF from radionuclide ventriculography (RVG) in 35 patients. Although all methods correlated positively, the degree of correlation varied with the algorithm used. For EF determination, TDE algorithms (especially those using multiple planes of section) were superior to unidimensional algorithms commonly used with M-mode echocardiography. The best algorithm (modified Simpson's rule) correlated well enough with cine EF (r = 0.78; SEE 0.097) and RVG EF (r = 0.75; SEE 0.087) to make clinically useful estimates. TDE volumes also correlated meaningfully with cine end-diastolic and end-systole volumes (r = 084; n = 70) but were associated with a large standard error of the estimate (43 ml) and offered less advantage over unidimensional volume estimates. Quantitative application of TDE appears to be a useful noninvasive method of evaluating LVEF, but is not as useful for estimating LV volumes.