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(Circulation. 1995;91:552-554.)
© 1995 American Heart Association, Inc.

Articles

`High Time' for Noninvasive Assessment of Regional Ventricular Diastolic Ischemic Dysfunction

Richard L. Popp, MD

From the Cardiovascular Medicine Division, Department of Medicine, Stanford University School of Medicine, Stanford, Calif.

Key Words: Editorials • ischemia • echocardiography • diastole

	Introduction

Top Introduction The Problem of Characterizing... High-Frame-Rate Echocardiography... References

 
Two-dimensional (2D) tomographic images of the heart first were obtained by ultrasound about 20 years ago. The equipment has been improved gradually, Doppler analysis has been added, and the technique has been accepted widely within the last 10 years. Echocardiographic imaging is used to assess ischemic heart disease by displaying the segmental wall motion abnormalities of acute myocardial infarction, chronic wall motion abnormalities from chronic ischemia or prior infarction, and stress-induced wall motion abnormalities, as well as complications of this condition such as ventricular thrombi, postinfarction ventricular septal defect, ventricular remodeling, and aneurysm formation. The initial diagnosis of coronary artery disease (CAD) now is confirmed commonly by stress echocardiography. Deterioration or lack of the expected improvement in systolic wall motion after exercise or during pharmacological stress, compared with the resting images, labels the patient as having coronary stenosis.¹ Stress echocardiography usually is not analyzed quantitatively. Very experienced expert interpreters are quite accurate in recognizing CAD with this "quantitative" technique with sensitivities exceeding 80% and specificities approximately 90%. Those less expert in the technique do not achieve such good results.² Various approaches to quantitative analysis of echocardiographic images have been attempted to standardize the interpretation of the images, using computer measurement of wall motion.^{3 4} The goal is to provide the equivalent of expert interpretation to those who are less experienced, usually for recognition of patients with ischemic heart disease.

	The Problem of Characterizing Diastolic Function

Top Introduction The Problem of Characterizing... High-Frame-Rate Echocardiography... References

 
Abnormalities of ventricular filling and of myocardial relaxation are sensitive early signs of myocardial ischemia in acute experiments in animals and humans. It is reasonable to assume that good quantitative analysis methods should detect differences between ischemic and nonischemic myocardium very accurately. However, myocardial relaxation and ventricular filling are complex processes, and their analysis in vivo has been a challenge.^{5 6 7 8} Nishimura et al⁷ have stated: "Diastolic filling of the heart. . .is a complex sequence of interrelated events. In order to understand diastolic function each of these factors contributing to filling of the heart must be examined. They include relaxation, passive compliance, atrial contraction, erectile effect of the coronary arteries, viscoelastic properties, ventricular interaction, and pericardial restraint—all of which are interrelated. In addition, diastolic factors are affected by changes in loading conditions and contractility, and they demonstrate nonuniformity in time and space." Additionally, most things we measure to tell us about diastolic function are dependent on the vagaries of the measurement techniques per se. Even the ventricular pressure-volume relation, which has been the "gold standard" for defining ventricular function, is cumbersome to obtain in humans so it is seldom assessed in clinical laboratories.

We usually substitute radionuclide angiography or Doppler ultrasound signals of mitral and pulmonary venous blood flow velocity as the means to measure left ventricular (LV) filling.^{8 9 10} Most available parameters reflect aggregate or global filling of the ventricle, although abnormalities associated with ischemic heart disease and myocardial hypertrophy have been defined using these methods.^{5 8 10} Abnormally delayed LV segmental contraction and relaxation in ischemic heart disease were recognized by angiography in several laboratories nearly 20 years ago (about the time 2D echocardiography was invented). However, measurements based on motion characteristics of subsegments within the ventricle obtained from angiography and other imaging methods were fraught with technical difficulties.^{11 12 13} Brutsaert's⁶ elegant analysis of myocardial relaxation using cells, muscle strips, and extrapolations to the intact ventricle suggested that load, activation-inactivation, and nonuniform distribution of both of these factors in time and space are the three prime elements normally controlling relaxation of cardiac muscle. Further, he has postulated that myocardial ischemia may produce inappropriately increased nonuniformity of relaxation that might increase incoordinate relaxation.⁶ But we have had few easily accessible methods with which to observe such potential effects of ischemia on regional ventricular diastolic function. Radionuclide methods have shown reversal of asynchronous diastolic motion after successful angioplasty,¹² but lack of quantitative echocardiography for similar noninvasive studies has been an impediment for beat-to-beat analysis.

	High-Frame-Rate Echocardiography

Top Introduction The Problem of Characterizing... High-Frame-Rate Echocardiography... References

 
In this issue of Circulation, a dedicated group of investigators has used a further advance in 2D echocardiography, combined with modern computer techniques, to attempt improvement in recognition of patients with CAD. High-frame-rate echocardiography (HFRE), with digital subtraction of sequential frames, was used to assess the timing of LV outward wall motion in diastole (after the second heart sound) as a marker for regional ischemia due to CAD.¹⁴ Advanced signal processing methods permit ultrasound images to be formed at 17-millisecond intervals, providing a frame rate of 60 frames per second. The conventional systems can sample a very small portion of the adult heart with that speed, but standard images are formed at 30 frames or less per second. The improved time resolution of the new equipment was used to highlight the first outward movement of the LV endocardium in diastole. The authors found they could recognize outward motion in early diastole by frame subtraction, because this method helped identify a coherent change in the position of the ventricular endocardium from one frame to the next in a way not possible with the naked eye. These investigators studied 455 LV segments in 30 normal subjects and 855 segments in 59 patients with CAD. This analysis required human observation of these 1310 segments over a sequence of frames—a daunting task despite the computer assistance. Outward motion of the LV segments occurred during the isovolumic period in all segments of the normal subjects. Wall motion during isovolumic periods has been well documented by angiography, cinefluoroscopy of myocardial markers, and M-mode echocardiography.^{13 15 16} The patients with CAD showed a delay in this initial outward motion, which went beyond the isovolumic period in those segments that were assumed to be ischemic because of angiographic coronary stenosis in the associated vessel. Additionally, there was asynergy of the various segments within the ventricle in patients with CAD as contrasted to the synergy found in normal subjects. By these authors' criteria, HFRE showed high sensitivity (92%) and specificity (81%) for the diagnosis of coronary-involved segments. The test results compare with those expected for stress echocardiography, but the new method does not require a stress intervention.

The authors of this study attempted to validate their method against contrast angiography. This is an imperfect comparison because the angiogram is a projectional image whereas the ultrasound images are tomographic, as the authors point out. Comparisons with most tested indexes of ventricular filling did not correlate with the authors' global or regional relaxation index, but they would not be expected to do so. It is not surprising that there was poor correlation of their results with indexes of ventricular filling that occur after mitral valve opening, such as those assessed by Doppler echocardiography or radionuclide angiography.

The authors of the present work can be commended for their innovative approach to an important clinical problem. HFRE applied to diastole seems to work in identifying patients with ischemic myocardium, and it has the advantage of not requiring a stress intervention. Prior myocardial infarction was present in 37 of the 59 patients, but the technique worked well both in patients with and those without regional systolic wall motion abnormalities. It is a noninvasive method and it looks promising in the current study, which excluded patients with intraventricular conduction delays and included only patients with angina pectoris due to coronary heart disease. The authors point out several technical limitations of this new method, including the current temporal resolution, the sometimes noisy images, the choice of a reference system to minimize the effect of translation of the left ventricle,^{3 4} the problem of decreased recognition of changes in endocardial position when absolute motion is small, comparison of their method against an unproven angiographic parameter, and the probable lack of specificity of HFRE for identifying CAD as opposed to hypertrophic cardiomyopathy or other forms of myopathy.¹⁴

It is most satisfying to use methods if one knows why they work. The relation between systolic and diastolic function is acknowledged, even if it is not visualized by imaging methods in many of these patients with localized CAD. However, the mechanism underlying the documented change in the timing of wall motion during the cardiac cycle is not yet fully defined. Advances in our understanding of cellular mechanisms influencing myocardial contraction and relaxation may help solve the puzzle of why the currently reported phenomena occur. Abnormalities of calcium flux, disturbances of intracellular energy generation, features of cell structure, and other factors are being explored.^{5 17 18} The present work is quite interesting because of the new method it describes, because of its positive results, because of the confirmation of prior work, and because of the questions it raises. Continued improvement of various noninvasive methods to assess ventricular area, ventricular volume, segmental wall motion, and pressure are under way.^{14 19 20} Eventually, some combination of these may lead to better characterization of diastolic function in health and disease. This, in turn, may let us more easily distinguish and grade the severity of ventricular pathologies to design therapies to mitigate the effects of the underlying processes.

	Footnotes

 
Reprint requests to Richard L. Popp, MD, Cardiovascular Medicine Division, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305.

	References

Top Introduction The Problem of Characterizing... High-Frame-Rate Echocardiography... References

 

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8. Bonow RO. Radionuclide angiographic evaluation of left ventricular diastolic function. Circulation. 1991;84(suppl I):I-208-I-215.
   
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10. Nishimura RA, Abel MD, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography, II: clinical studies. Mayo Clin Proc. 1989;64:71-81.
    
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14. Kondo H, Masuyama T, Ishihara K, Mano T, Yamamoto K, Naito J, Nagano R, Kishimoto S, Tanouchi J, Hori M, et al. Digital subtraction high frame rate echocardiography: its use for the detection of regionally impaired left ventricular relaxation in patients with ischemic heart disease. Circulation. 1995;91:304-312. [Abstract/Free Full Text]
    
15. Gibson DG, Prewitt TA, Brown DJ. Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease. Br Heart J. 1976;38:1010-1019. [Abstract/Free Full Text]
    
16. Ingels NB Jr, Fann JI, Daughters GT, Nikolic SD, Miller DC. Left ventricular volume is not constant during isovolumic contraction and relaxation using standard LV models. Circulation. 1994;90(suppl I):I-431. Abstract.
    
17. Varma N, Eberli FR, Apstein CS. Calcium sensitivity of diastolic dysfunction is dissociated in demand ischemia compared to reperfusion, suggesting differing roles for increased myocyte calcium. Circulation. 1994;90(suppl I):I-432. Abstract.
    
18. Zile MR, Buckley JM, Richardson KE, Cooper G, IV. Passive stiffness and viscous damping in the hypertrophied myocyte. Circulation. 1994;90(suppl I):I-432. Abstract.
    
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