Accuracy of the echocardiographic diagnosis of aortic regurgitation

Accuracy of the Echocardiographic Diagnosis of Aortic Regurgitation

DAVID J. SKORTON, M.D.* JOHN S. CHILD, M.D. JOSEPH K. PERLOFF, M.D. Los Angeles, California

From the Division of Cardiology, Department of Medicine, Center for the Health Sciences, School of Medicine, University of California, Los Angeles, Los Angeles, California. Requests for reprints should be addressed to Dr. John S. Child, Division of Cardiology, UCLA Department of Medicine, 10833 LeConte Avenue, Los Angeles, California 99024. Manuscript accepted March 26, 1980. * Present address: Department of Medicine, University of Iowa, Iowa City, Iowa 52240.

Anterior mitral leaflet diastolic flutter and flutter of contiguous cardiac structures are accepted M-mode echocardiographic signs of aortic regurgitation. Ninety-four subjects (47 normal and 47 with aortic regurgitation on angiography) had echocardiograms evaluated (double-blind) by two observers for the presence of anterior mitral leaflet diastolic flutter or ventricular septal diastolic flutter. For the entire study population, sensitivity was 66 percent for anterior mitral leaflet diastolic flutter, 36 percent for ventricular septal diastolic flutter and 72 percent for diastolic flutter over-all (i.e., present on either or both). Severe chronic aortic regurgitation always revealed anterior mitral leaflet diastolic flutter. Mild to moderate aortic regurgitation without mitral stenosis had an 61 percent sensitivity for over-all diastolic flutter; with mitral stenosis, over-all sensitivity of diastolic flutter was 44 percent. Specificity of anterior mitral leaflet diastolic flutter was 63 percent, of ventricular septal diastolic flutter 96 percent, of diastolic flutter over-all 63 percent. There was no ohserver discordance over diastolic flutter in severe aortic regurgitation, hut 19 percent discordance over diastolic flutter in mild to moderate aortic regurgitation without mitral stenosis, and 31 percent discordance in mild to moderate aortic regurgitation with mitral stenosis. There was 26 percent disagreement over the absence of diastolic flutter in normal subjects, predominantly regarding anterior mitral leaflet diastolic flutter. Predictive value of diastolic flutter was 61 percent when present and 75 percent when absent. We conclude the following: (1) In severe aortic regurgitation, interobserver agreement is good for anterior mitral leaflet diastolic flutter, which is a highly sensitive sign; (2) interobserver agreement is good for ventricular septal diastolic flutter, which is highly specific but insensitive; (3) disagreement was greatest over anterior mitral leaflet diastolic flutter in normal subjects; and, (4) with coexisting mitral stenosis, diastolic flutter is not a sensitive sign. In patients with known aortic regurgitation, the M-mode echocardiogram may exhibit diastolic flutter of anterior and posterior mitral leaflets [l-5]. More recent reports describe diastolic flutter of the ventricular septum and posterior left ventricular wall [6-81. The flutter has been related to the regurgitant jet striking the relevant structures. Despite the utility of M-mode echocardiography in identifying diastolic flutter as a sign of aortic regurgitation, the sensitivity, specificity and predictive value of the sign have not been established. Dillon et al. [l] reported a study of 216 subjects, 64 normal and 152 catheterized patients. There was no evidence of mitral valve flutter in normal subjects or in subjects without angiographically proved aortic regurgitation; the incidence of mitral valve flutter was related to the severity of aortic regurgitation. Similarly, Winsberg et al. [4] in a study of 500 normal

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Figure 1. Representative M-mode echocardiogram in a patient with aortic regurgitation. High frequency uniform flutter is clearly seen on the anterior mitral leaflet’ on the left. The large arrow points to mitral chordae tendineae; in the right mitral echogram, the choidae obscure the E and F points, rendering exact measurement of flutter amplitude difficult. Diastolic flutter on the posterior mitral leaflet causes difficulty in determining the presence of posterior left ventricular endocardial flutter (small arrow).

subjects, found only three examples of equivocal mitral valve diastolic flutter. Higginson et al. [3] studied 50 patients with angiographically proved aortic regurgitation and found that 48 displayed echocardiographic diastolic flutter of the anterior mitral leaflet, 40 displayed flutter of the posterior mitral leaflet, 20 displayed flutter of the left ventricular septal surface and six displayed flutter of the posterior left ventricular endocardium. The presence and character of the flutter showed no correlation with severity of aortic regurgitation or with the presence of an Austin Flint murmur. Diastolic flutter was rarely absent unless the mitral valve was immobile; even then, flutter was often found on the interventricular septum. Because of the inconclusive impressions left by these observations, we believed it desirable to examine in detail the sensitivity, specificity and predictive value of diastolic flutter of the mitral leaflets and ventricular septum, and to define more precisely the clinical utility and application of this sign in the echocardiographic diagnosis of chronic aortic regurgitation. To this end, we undertook a blind review of echocardiograms of normal subjects and of subjects with angiographically-proved aortic regurgitation.

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Figure 2. M-mode echocardiogram of diastolic flutter (small arrows) on the interventricular septum and anterior mitral leaflet in a patient with aortic regurgitation. The posterior mitral leaflet is not well seen; a portion of mitral apparatus (chord, annulus or leaflet) is shown by’the large arrow.

METHODS Subjects. The echocardiographic and cineangiographic files of the University of California at Los Angeles, Center for the Health Sciences, were used to obtain the material for this study. Echocardiograms of 47 clinically normal subjects were chosen at random; these subjects were from a population of nonhospitalized volunteers who responded to a request to establish a normal population file. Each subject was carefully assessed by a staff cardiologist and ha’d a normal cardiovascular history and normal physical examination, as well as a normal resting electrocardiogram, normal treadmill exercise test, 24-hour Holter ambulatory electrocardiogram, phonocardiogram and chest roentgenogram. For$seven examples of catheterization-proved aortic regurgitation were obtained. The M-mode echocardiograms from these two groups (normal and catheterization-proved aortic regurgitation) were presented in random fashion independently to two readers. To evaluate intraobserver differences, the procedure was repeated two months later. Technique. Echocardiography: Tracings were obtained with a Smith-Kline Ekoline 20A Ultrasonoscope utilizing a 2.25 megaHertz transducer with a repetition rate of l,OOO/sec and a 10 cm focus. Tracings were recorded with a Honeywell 1856 fiberoptic recorder on Kodak light-sensitive paper at a carefully calibrated paper speed of !% mm/set. Using standard techniques, the transducer was placed in the third, fourth or fifth left parasternal space and ‘a “window” was identified where the transducer was perpendicula; to the chest wall

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without inferior or superior angulation, while directed slightly medially to identify the mitral valve leaflets. The echoes of the interventricular septum and of the left ventricular posterior wall were recorded at the level of the chordae tendineae, i.e., just below the tip of the anterior mitral leaflet. A standard sweep from aorta to left ventricular apex was also performed. Each observer recorded whether or not diastolic fluttering was present on the anterior mitral leaflet [Figure 1)and left ventricular septal surface (Figure 21. Because the posterior mitral leaflet normally lies next to the posterior left ventricular endocardium early in diastole, differentiation of posterior mitral leaflet flutter from flutter of the posterior endocardium was often difficult; therefore, separate posterior leaflet results are not reported. Identification of diastolic flutter was based upon generally accepted published criteria [z]. In addition, total amplitude (in millimeters) of anterior mitral leaflet flutter was estimated at the E and the F points of the anterior mitral leaflet echo. Cardiac catheCardiac Catheterization and Angiography. terization was performed with either the Sones or modified Seldinger technique. The presence and degree of aortic regurgitation were determined by standard thoracic aortography using the criteria of Sellers and associates [g]. Data Compilation and Statistical Analysis. After review of the echocardiograms by two readers, the number of correct and incorrect observations of diastolic fluttering were tabulated. Thoracic aortography was the standard for patients with aortic regurgitation, and meticuluous cardiac auscultation was the standard for normal subjects. Results were evaluated as follows: (1)sensitivity was defined as true-positives/true-positives + false-negatives; (2) specificity was defined as true-negatives/true-negatives + false-positives; (3) predictive value of a positive examination was defined as true-positives/truepositives + false-positives: and (4) predictive value of a negative examination was defined as true-negatives/true-negatives + false-negatives. These calculations were performed on the consensus reading of the two independent observers for each cardiac structure (anterior mitral leaflet, ventricular septum) and for the over-all presence of diastolic flutter (on either or both structures). Intraobserver differences between the two readings two months apart varied by less than 4 percent, and such differences solely involved the presence or absence of flutter of the anterior mitral leaflet in the normal subjects. Interobserver differences (discordance] for the first independent reading were calculated for each structure and for final diagnosis. Final diagnosis was a reading of presence or absence of aortic regurgitation echocardiographically if either or both of the two structures revealed diastolic flutter,

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ET AL.

3~ flutter

e

pa%ents with aortic regurgitati& and mitral stenosis. Top, diastolic flutter can be seen on both the anterior mitral leaflet and the interventricular septum. Bottom, in contrast, diastolic flutter is seen only on the left interventricular septal (IVS) surface and not on the mitral valve.

RESULTS

had aortic regurgitation of mild to moderate severity [Figure 3). The results of the consensus readings are summarized in Table I. For the entire study population with aortic regurgitation, sensitivity was 66 percent (31 true-positive.431 true-positives -I-16 false-negatives, or 31 of 47) for an-

Sensitivity and Specificity of Diastolic Flutter. Sensitivity and specificity of diastolic flutter as a sign of aortic regurgitation were determined for left-sided cardiac structures singly and in various combinations. Subgroups of angiographically severe (3+ to 4+) aortic regurgitation (15 patients], mild to moderate aortic regurgitation without coexisting mitral stenosis (16 patients] and mild to moderate aortic regurgitation with coexisting mitral stenosis (16 patients) were also compared. Those patients with coexisting mitral stenosis all

terior mitral leaflet flutter, and 36 percent (16 truepositive/l6 true-positives + 28 false-negatives, or 16 of 44) for ventricular septal flutter. Because three patients had technically unsatisfactory left septal endocardial recordings, only 44 appears in the denominator, as opposed to 47 for the anterior mitral leaflet. Over-all sensitivity of diastolic flutter of the anterior mitral leaflet was 83 percent (eight false-positives] and of the ventricular septum 98 percent (one false-positive]. Over-all specificity of the sign was 83 percent.

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TABLE I

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TABLE II

Parameters of Accuracy of Diastolic Flutter in Aortic Regurgitation AML-DF

VS-DF

ET AL.

DF-Overall

Sensftivftyof Diastolic Flutter

Ail AR (n = 47) Severe AR (n = 15) Moderate AR without MS (n = 16) Moderate AR with MS

66 (31147) 36 (lW44) 100 (15/15)

100 (15/15)

47 (8/14)

21 (3/14)

81 (13/16)

19 (33116)

31 (5/16)

44 (7116)

Specificity and Predictive Value ot Dfastofk Flutter 83 (39147) 79 (31139) 71 (39155)

83 (39/47) 81 (34143) 75 (39/52)

98 (46f47) 94 (16f17) 62 (46174)

NOTE: AR = aortic regurgitation. MS = mitral stenosis. AML-DF = anterior mitral feaffetdiastolfc flut$r; VS-DF = ventricular septafdiastolic flutter; DF-over-aff = over-ail usefulness of diastolic flutter for diagnosis when diastolic flutter is found on either the anterior miWaf leaflet or the ventricular septum, or on both slructures. Values are presented as percenta@% and; in parentheses, the absolute number for numerator/denominator for the particular statistical index.

Contingency table analysis of the statistical significance of the detection of diastolic flutter is shown in

Table II for all’patients with aortic regurgitation and for the subset with severe aortic regurgitation, and Table III for those with aortic regurgitation with and without mitral stenosis. For all patients with aortic re~tation, detection of diastolic flutter on either of the two structures (or both] was statistically significant; this was even more evident in the subset iNith severe aortic regurgitation. If patients with less than severe aortic regurgitation are considered, the presence or absence of mitral stenosis is an important factor in the likelihood of de-

TABLE III

Present Absent

Present Absent

Present Absent

Contingency Table Analysis of Value of Diastolic Flutter in Patients Wlth and W~t~u~ Mitral Stenosis

ModerateAR

ModerateAR

(no MS) (n = 16) NL AR

(with MS) (n = 16) NL AR

AYL43F 13 9 3 38 X2 = 20.3, p
9 3 38 13 X2 = 0.001, p = NS 5

1

11 46 X2 = 11.8. p
8 39 p <0.02

NOTE: AMLDF = anterior mitral feaffetdfastofic flutter; AR = aortic regurgitation: NL = normal; MS = mitral stenosis; NS = not significant.

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SevereAR patients (n = 15) vs. NL (n = 47) AR NL

AML-DF Present Absent

(n = 16) Specificity Predictive (+) Predictive (-)

Ail AR patients (n = 47) vs. NL (n = 47) AR NL

72 (34147)

81(13/16)

Contingency Table Analysis of Diastolic Flutter in All Patients With Aortic Regurgitation and of Patlents With Severe Aortic Regurgitation

Present Absent

Present Absent

31 8 16 39 X2 = 23.2, p
15 9 0 38 x* = 31.3, p <0.0001 8 6

1 48

X2 = 26.0, p
NOTE: AML-DF = anterior mitral ieafietdiastofic flutter; AR = aorfic r~urgitation: NL = normal.

tection of diastolic flutter on the anterior mitral leaflet; detection of ventricular septal flutter is uninfluenced. Because ventricular septal diastolic flutter is less commonly detected in any patient with aortic regurgitation than is anterior mitral leaflet diastolic flutter, the overall usefulness of diastolic flutter is less in patients with coexistent mitral stenosis. Predictive Value of Diastolic Flutter. Predictive value of diastolic flutter as a diagnostic sign was calculated as stated ii “methods”; the results appear in Table I. For anterior mitral leaflet flutter, predictive value of a positive test was 79 percent, and of a negative test 71 percent. The corresponding predictive values for ventricular septal flutter were 94 percent (positives and 62

TABLE IV

Interobserver Dfscordanca (expressed as percent disagreement between readers) for the Initial Independent Reading AML-DF

Severe AR Moderate AR without MS ModerateAR with MS Ail AR

Patients with AR 0 7 19 13 13

FlnafDX

0 19

19

37

13 13 Normal SubJects

17

23% Final Dlagnosls AR patients Normal subjects

VS-OF

2% 17% 26 %

NOTE: AML-DF = anterior mitral feaffetdiastofic flutter; VS-DF = ventricular septaldfastofic flutter; MS = mitral stenosis.

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figure 4. False-positive mitral valve flutter. Ttiis subject was normal, yet, as indicated by the arrow, there is fine, high frequency flutter on the anterior mitral leaflet. IVS = interventricular septum.

Flgure 5. False-negative mitral valve echogram in a patient with aortic regurgitation. As indicated by the arrow, no diastolic flutter can be recognized on the anterior mitral leaflet. IVS = interventricular septum.

percent (negative]. Over-all, diastolic flutter had a predictive value of 81 percent when positive and 75 percent when negative. Measured AmpIitude of Mitral Leaflet Flutter. Normal subjects exhibited mean amplitudes of “flutter” (when judged to be present) of 3 mm at the E point and 2.3 mm at the F point. Patients with aortic regurgitation exhibited mean amplitude of flutter of 4.2 mm at the E point and 3.7 mm at the F point. Because these differences approximated the technical (axial) resolution of M-mode echocardiography (1mm], they were not considered significant. Moreover, measurement of total amplitude of anterior mitral leaflet flutter at the E and F points was difficult in many patients because of either multiple or thick echoes in rheumatic valvular heart disease, superimposition of chordae tendineae or inability to distinguish flutter amplitude from extraneous echoes in the region of the anterior mitral leaflet (Figure 11. Interobserver discordance. Interobserver discordance was calculated as discussed in “Methods,” and the results appear in Table IV. For the subgroup of 15 patients with severe aortic regurgitation, anterior mitral leaflet flutter was found in all cases by both readers. Thus, there was no discordance for either over-all diagnosis or anterior mitral leaflet flutter in this subgroup. In the group of 16 patients with mild to moderate aortic regurgitation without coexisting mitral stenosis, over-all disagreement regarding final diagnosis was 18 percent (i.e., in three of 16 cases, one reader or the other noted no evidence of flutter on any structure]. In the

group of 16 patients with mild to moderate aortic regurgitation without coexisting mitral stenosis, disagreement occurred in 31 percent (five of 16 cases) regarding final diagnosis. Over-all disagreement regarding the diagnosis of aortic regurgitation using diastolic flutter on either of the two structures was 17 percent (eight of 47 cases] for the total group of patients. In normal subjects, there was disagreement over the presence of diastolic flutter 26 percent of the time (12 of 47 normal subjects): this almost entirely represented disagreement over anterior mitral leaflet “flutter.” COMMENTS

In this study we examined the sensitivity, specificity and predictive value of diastolic flutter of the anterior mitral leaflet and ventricular septum in the diagnosis of chronic aortic regurgitation. In previous studies these signs were generally found to be highly sensitive and specific for aortic regurgitation [l-4]. Because these investigations were not conducted in a blinded fashion-with the echocardiographer unaware of the clinical diagnosis-the accuracy of the sign was not established. Furthermore, our own day to day readings of echocardiograms identified the presence of flutter in some normal subjects (Figure 4, and the absence of flutter in some patients with proved aortic regurgitation (Figure 5). We were, therefore, prompted to investigate the reliability of echocardiographic diastolic flutter by having two readers independently interpret echocardiograms without knowing whether tracings were from normal

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subjects or from patients with catheterization proved aoritc regurgitation (Figure 5). In mild to moderate aortic regurgitation, diastolic flutter over-all (on either of the two structures or both) proved to be a relatively sensitive sign, except in the setting of mitral stenosis. Anterior mitral leaflet flutter, often identified in normal subjects, was relatively nonspecific. Left ventricular septal flutter was seldom identified (i.e., insensitive) but, when present, was likely to indicate aortic regurgitation (i.e., predictive). When comparing the initial results of two readers, interobserver discordance was minimal in severe chronic aortic regurgitation, moderate in all lesser degrees of aortic regurgitation and moderately severe in normal subjects. Intraobserver variation on the other hand was small (14 percent]. What accounts for these results? We identified a number of problems relevant to flutter as a sign on M-mode echocardiograms. Because of superimposed chordae tendineae, echoes between the E and F points were often slightly “blurred,” sometimes appearing as “flutter” in normal subjects. When comparing the measured amplitude of flutter in patients with known aortic regurgitation to that of normal subjects, the differences were slight and approximated the axial resolution of the technique. Some helpful observations were gathered to improve the ac-

ET AL

curacy of these echocardiographic signs. Ventricular septal flutter was often found in true aortic regurgitation only high on the septum and was more difficult to appreciate below the left ventricular outflow tract. Thus, an adequate “standard” sweep from aorta to left ventricular apex was useful. The spurious “flutter” often seen in normal subjects was inconsistent, i.e., seldom present on every cardiac cycle. Finally, when ventricular septal flutter was identified, the probability of true aortic regurgitation was high. This observation was particularly useful in patients with coexisting mitral stenosis. In summary, diastolic flutter of the anterior mitral leaflet proved to be a reliable sign of severe (angiographically 3+ to 4+) chronic aortic regurgitation. In mild to moderate aortic regurgitation, except when mitral stenosis was present, anterior mitral leaflet flutter was a relatively sensitive sign. Diastolic flutter of the ventricular septum was infrequent, but when identified, predicted aortic regurgitation with high probability. Finally, anterior mitral leaflet “flutter” was sometimes identified in normal subjects, indicated less specificity than previously believed. These observations on diastolic flutter now permit discriminating interpretation of this frequently used echocardiographic sign.

REFERENCES 1.

Dillon JC, Haine CL, Chang S, Feigenbaum H: Significance of mitral fluttering in patients with aortic insufficiency [abstract]. Clin Res 1970; 18: 304. 2. Feigenbaum H: Echocardiography; 2nd ed. Philadelphia: Lea & Febiaer. 1976: 131-132.137. 3. Higginsoi LA, et al.: In: Felner JM, Schlant KC, eds. Echocardiography. New YorkGrune & Stratton, 1976: 182. 4. Winsberg F, Gabor GE, Hernberg JG. Weiss B: Fluttering of the mitral valve in aortic insufficiencv. Circulation 1976; 41: 225-229.

5. 6.

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Hernberg J, Weiss B, Keegan A: The ultrasonic recording of aortic valve motion. Radiology 1970; 94: 361-368. Cope GD, Kisslo JA, Johnson ML, Myers S: Diastolic vibration

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of the interventricular septum in aortic insufficiency. Circulation 1975; 51: 589-593. 7. Friedewald VE. Futral JE, Kinard SA, Phillins B: Oscillations of the interventricular septum in aortic insufficiency (abstract). 1 Clin Ultrasound 1974; 2: 229. 8. D’Cruz I,Cohen HC, Prabhu R, Ayabe T, Glick G: Flutter of left ventricular structures in patients with aortic regurgitation, with soecial reference to oatients with associated mitral stenosis. A-m Heart J 1976; 92:684-691. 9. Sellers RD, Levy MJ, Amplatz K, Lillehei CW: Left retrograde cardioangiography in acquired cardiac disease. Technic, indications, and interpretations in 790 cases. Am I Cardiol 1964; 14: 437-451. -

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