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Circulation. 1996;94:73-82

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(Circulation. 1996;94:73-82.)
© 1996 American Heart Association, Inc.

Articles

Echocardiographic Evaluation of Patients With Acute Rheumatic Fever and Rheumatic Carditis

Ramachandran S. Vasan, MD; Savitri Shrivastava, MD; Manam Vijayakumar, MD; Rajiv Narang, MD; Bradford C. Lister, PhD; Jagat Narula, MD, PhD

From the Department of Cardiology, the All India Institute of Medical Sciences, New Delhi, India (R.S.V., S.S., M.V., R.N.), and Northeastern University, Boston, Mass (B.C.L., J.N.).


*    Abstract
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Background Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis.

Methods and Results Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%.

Conclusions In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.


Key Words: echocardiography • rheumatic heart disease • mitral valve • myocarditis


*    Introduction
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Acute rheumatic fever is a common and serious public health problem in developing countries.1 Focal outbreaks of rheumatic fever within the United States over the last decade have rekindled interest in this disease in the developed countries as well.2 Rheumatic valvular heart disease, an important sequel to rheumatic fever, remains the most common acquired heart disease worldwide1 3 and is the major cause of cardiovascular death during the first five decades of life in developing countries.4 Rheumatic valvular heart disease is associated with considerable disability in children and young adults and imposes a substantial economic burden.1 Prevention of chronic valvular damage is both feasible and cost effective1 if secondary prophylaxis with penicillin is instituted and maintained regularly after an episode of rheumatic fever.5 6 These observations underscore the importance of making a prompt and accurate diagnosis of rheumatic carditis. Several reports have highlighted the utility of echocardiography for the diagnosis of rheumatic carditis7 8 9 10 11 12 and have emphasized its value in defining the mechanisms of valve regurgitation13 14 15 16 17 and heart failure associated with severe attacks of carditis.18 19 20 21 These studies have been limited by the small size of study samples,10 11 12 13 14 15 16 17 18 19 a lack of Doppler color flow imaging,7 9 10 12 16 17 18 19 failure to focus on the mechanisms of valve dysfunction,7 8 9 10 11 12 18 19 and a selection bias (evaluating patients who were undergoing valve surgery).13 14 20 21 The aim of the present study was to prospectively describe the spectrum of cardiac abnormalities in patients with primary or recurrent episodes of acute rheumatic fever by use of two-dimensional and color Doppler echocardiography and to obtain insights into the pathophysiological mechanisms and functional significance of acute rheumatic valvulitis and myocarditis. We also evaluated the utility of echocardiography for the diagnosis of carditis in patients with acute rheumatic fever in whom clinical examination did not indicate any evidence of carditis.


*    Methods
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Patients
One hundred eight consecutive patients with acute rheumatic fever who presented to the cardiac unit of the All India Institute of Medical Sciences over a 30-month period formed the study population. The diagnosis of acute rheumatic fever in these patients was based on the revised Jones' criteria (Table 1Down).22 23 24 25 26 The age of the patients ranged from 5 to 23 years; there were 78 male and 30 female patients. A routine blood count, erythrocyte sedimentation rate, C-reactive protein level, antistreptolysin-O titer, chest radiograph, and ECG were obtained in all patients. Additionally, multiple blood cultures were obtained whenever there was a clinical suspicion of infective endocarditis. Patients who satisfied the criteria for infective endocarditis or who had a history of a prior episode of endocarditis were excluded from the study. Patients with acute rheumatic fever were divided into three groups based on the absence (group 1) or presence (groups 2 and 3) of carditis (Table 1Down). Table 2Down describes the major and minor manifestations of rheumatic fever observed in the three groups of patients with acute rheumatic fever.


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  		Table 1. Criteria for the Diagnosis of Rheumatic Fever and Carditis in Study Groups


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  		Table 2. Clinical Features and Major Manifestations of Rheumatic Fever (Based on Jones' Criteria) in Patients in the Present Study

Group 1: Patients With Acute Rheumatic Fever Without Clinical Evidence of Carditis
Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis. Twenty-five of these patients presented with typical migratory polyarthritis (Table 2Up); each of these 25 patients had at least two minor manifestations of rheumatic fever along with evidence of recent streptococcal infection (manifested by elevated antistreptolysin-O titer). Subcutaneous nodules were not present in any of these patients. Four patients had a past history of a similar episode of rheumatic polyarthritis; no clinical details of the previous episodes were available. The remaining 3 patients presented with Sydenham's chorea; they did not have minor manifestations of rheumatic fever or evidence of recent streptococcal infection.

Group 2: Patients With a First Attack of Acute Rheumatic Fever With Clinical Evidence of Carditis
Thirty-five patients presented with a "probable first" episode of acute rheumatic fever and clinical evidence of carditis. There was neither a history of a previous attack of rheumatic fever nor echocardiographic stigmata of chronic valvular disease (such as restricted excursion or doming of valve leaflets or significant mitral or aortic stenosis).27 Carditis, evidenced by the presence of murmurs suggestive of valvular regurgitation, constituted a major manifestation in all patients; isolated mitral regurgitation was present in 29, combined mitral and aortic regurgitation in 4, and isolated aortic regurgitation in 2 patients. In addition, congestive heart failure was present in 6 patients and pericarditis in 5 patients. Nineteen patients had one or more major manifestations of rheumatic fever, including arthritis in 18 and subcutaneous nodules in 2 patients. One patient developed chorea during hospital stay (Table 2Up).

Group 3: Patients With Previous Rheumatic Heart Disease With Acute Rheumatic Fever and Clinical Evidence of Active Carditis
Forty-five patients with prior rheumatic heart disease presented with a recurrence of rheumatic fever and clinical evidence of active carditis. All patients had either a history of a previous attack of rheumatic fever or demonstrated echocardiographic stigmata of chronic rheumatic valvular disease.27 The diagnosis of carditis was based on the appearance of a new murmur in 2 patients in whom prior cardiac findings were available, clinical evidence of pericarditis in 5 patients, and unexplained acute onset of congestive heart failure in 18 patients.22 25 In the remaining 20 patients in group 3, one or more noncarditic major manifestations confirmed the diagnosis of rheumatic fever. The diagnosis of rheumatic carditis in these 20 patients was entertained on the basis of the tendency of rheumatic episodes to be mimetic.26 These 20 patients satisfied the WHO criteria for rheumatic fever23 and the 1992 update of the Jones' criteria.24 In addition to the major manifestations (Table 2Up), all patients had elevated antistreptococcal antibody titer along with other minor manifestations of rheumatic fever.

Control Groups
Because the patient population included subjects with and without clinical carditis, two groups of control subjects were enrolled in the present study. Control group A consisted of 25 healthy children free of any disease and matched for age with group 1 patients. This group formed the comparison group for patients with rheumatic fever and no clinical evidence of carditis. Control group B comprised 19 patients with chronic quiescent rheumatic heart disease without clinical evidence of active rheumatic fever or sore throat in the preceding year. These 19 patients were matched with Group 3 patients for severity of valvular lesions and formed the comparison group for Group 3 patients. All 19 patients had normal antistreptococcal antibody titer and had been receiving regular recommended penicillin as a prophylactic for at least 1 year.

Echocardiographic Examination
All patients in groups 1, 2, and 3 underwent echocardiographic examination within 24 to 48 hours of establishment of the diagnosis of acute rheumatic fever and before starting anti-inflammatory treatment. Echocardiographic imaging was performed with ATL Ultramark 8 and 9 machines (Advanced Technology Laboratories, Inc) equipped with 2.5-, 3.5-, and 5-MHz transducers. A standardized cross-sectional and Doppler echocardiographic examination was performed with multiple orthogonal parasternal, apical, and subcostal views with the patient in the left lateral decubitus position. All examinations were recorded on half-inch videotape (VHS) for future analysis.

Cardiac Dimensions and Mechanics
Two-dimensionally guided M-mode tracings were obtained, and chamber dimensions and wall thickness were measured with a pair of electronic calipers in accordance with the recommendations of the American Society of Echocardiography.28 Chamber enlargement was identified by comparison of observed measures (indexed for body surface area) with reference values for age-matched normal subjects.29 Fractional shortening of the left ventricle during systole (% FS) was calculated from the left ventricular internal dimensions and used as an index of left ventricular systolic function, as follows:

where LVIDed and LVIDes are the left ventricular internal dimensions at end diastole and end systole, respectively. In our laboratory, a value of FS>28% is considered normal. The left ventricular relative wall thickness, expressed as the ratio of end-diastolic radius to wall thickness (R/Th)30 was calculated as

where IVSed and PWed are the thickness of the interventricular septum and the left ventricular posterior wall at end diastole, respectively.31 The diameter of the mitral valve annulus was measured at end diastole from the apical four-chamber view by use of an inner edge–to–inner edge technique, and three measurements were averaged.32 The aortic annulus was measured at end diastole from the parasternal long-axis view by a similar technique.33 Dilatation of mitral or aortic valve annulus was identified by comparing observed values (indexed for body surface area) with reference values for age-matched subjects.32 33

Valvular Apparatus
The structure of the valves and the subvalvular apparatus (in the case of the mitral valve) and leaflet mobility were carefully evaluated. Valves were examined for the presence of focal or diffuse thickening and leaflet prolapse. Leaflet motion was graded as excessive, normal, or restricted according to whether the location of maximal systolic excursion of any portion of the mitral leaflet extended beyond, to, or below the mitral annular plane on the ventricular side. Prolapse of the mitral valve was defined as the systolic displacement of the coaptation point of mitral valve leaflets posterior to the plane of the mitral valve annulus into the left atrium in the parasternal long-axis and apical four-chamber views.34 Displacement of mitral valve leaflets noted only on the apical four-chamber view was not accepted as prolapse because this may be caused by a nonplanar annulus configuration.35 Prolapse of the aortic valve was identified when the tissue or coaptation point of the aortic valve cusps was shifted downward toward the left ventricular outflow tract during diastole in the parasternal long-axis view.36

Doppler Color Flow Imaging
Doppler color flow imaging was performed with use of a standard velocity color map; green color was added to areas that demonstrated variance in the Doppler signal and thereby served as an index of turbulent flow. Each exam was performed with the use of the shallowest depth and narrowest sector angle capable of encompassing the jet area of regurgitant flow. The optimal gain setting was adjusted by using the maximal gain level possible without signals being introduced outside of flow areas or onto tissues from an adjoining chamber. The cineloop mode was used for systematic analysis of Doppler flow.

Valvular regurgitation was diagnosed when color Doppler flow mapping demonstrated reversed flow away from the valve when the valve was closed; signals of very short duration (<100 ms) detected at the time of valve closure were not regarded as true regurgitation. To differentiate abnormal from physiological regurgitation,37 the high-velocity turbulent jet had to extend beyond the paravalvular region (more than 1 cm) and had to be confirmed by color-guided pulsed Doppler spectral analysis.38 On-line computerized planimetry of the maximal regurgitant jet areas was performed, and the mean of three cardiac cycles was taken. The severity of mitral and aortic regurgitation was graded on the basis of the maximal distance of the regurgitant jet from the valve orifice using the criteria of Helmcke et al39 and Perry et al,40 respectively. The direction of the mitral regurgitant jets was noted in the parasternal long-axis view. Mitral regurgitation jets were classified as posterior, anterior, central, or multidirectional.41 The severity of mitral stenosis was determined by calculation of mitral valve area by computer-assisted planimetry of the mitral orifice (in the short-axis view)42 in patients with significant regurgitation and by the Doppler pressure half-time method43 in those without regurgitation.

The mechanisms of mitral regurgitation were determined on the basis of the presence or absence of leaflet prolapse, annular dilatation, restriction of leaflet mobility, left ventricular dilatation, and left ventricular systolic dysfunction.44 45 The mechanism of aortic regurgitation was determined on the basis of the presence of or absence of leaflet prolapse, annular dilatation, and leaflet retraction.

Pericardial Effusion
Pericardial effusion was diagnosed by standard echocardiographic criteria.46

Treatment and Follow-up Examinations
Patients with rheumatic carditis and congestive heart failure were treated with steroids (along with dietary salt restriction, digoxin, diuretics, and converting enzyme inhibitors), whereas patients with carditis but without congestive heart failure were treated with aspirin.47 All group 1 patients were treated with aspirin. Injectable benzathine penicillin G for secondary prophylaxis was initiated or regulated at the time of the index attack in all patients.

Patients in groups 1 and 2 were followed up prospectively. Follow-up of group 3 patients was not part of the study protocol. Repeat clinical and echocardiographic examinations were routinely scheduled in all patients at 3 and 6 months after the index attack to study the evolution of valvular lesions and left ventricular contractility indexes. All repeat echocardiographic examinations were performed by the same operator with the same ultrasound machine and with similar gain settings.

Statistical Methods
All echocardiographic studies were interpreted by the same observer (R.S.V.) with a random sequencing of studies; the observer was blinded to all clinical information. Intraobserver variability for cardiac measurements was assessed at the conclusion of the study; variability was <5% for left ventricular dimensions, annular diameter, and wall-thickness measurements.

The clinical features of the three groups of patients and their baseline echocardiographic measurements were compared by one-way ANOVA (performed by B.C.L.); the Tukey multiple-range test was used to identify which of the three group means was significantly different from the others. Categorical data in the three groups at the time of the index attack were compared by use of the {chi}2 test. Control group A was compared with patient group 1 for the prevalence of valvular regurgitation, structural valve abnormalities, and left ventricular function. Control group B was compared with patient group 3 for the presence of valve abnormalities and left ventricular systolic function. The comparison of repeated echocardiographic measures within group 2 was performed by use of the multifactorial ANOVA procedure for repeated measures (Statgraphics version 6.0), with patient and time serving as the main factors. The Tukey multiple-range test was used to identify which group of observations (0, 3, and 6 months) was significantly different from the others. All reported probability values are two-sided, and a probability value less than .05 was considered statistically significant.


*    Results
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Echocardiograms that were technically of good quality were obtained in all patients. The echocardiographic features are shown in Tables 3Down and 4Down. There was no mortality in the 108 patients with acute rheumatic fever, and none of them underwent cardiac surgery during the episode of acute rheumatic fever.


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  		Table 3. Two-dimensional Echocardiographic Findings in Patients With Rheumatic Fever


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  		Table 4. Doppler Color Flow Imaging Findings in Patients With Acute Rheumatic Fever1

Valve Morphology
The mitral valve was most commonly involved both in patients with a first episode of carditis as well as in those with a recurrent attack (groups 2 and 3). Aortic valve involvement was more common in patients with recurrent carditis (18 [40%] of 45 patients compared with 6 [17%] of 35 patients with a first episode of rheumatic carditis; {chi}2=4.9, P=.03). Diffuse thickening of the mitral valve leaflets was a universal feature in group 3 but was also seen in 40% of patients with a first attack of carditis. Valve prolapse was infrequent. Prolapse of the anterior mitral leaflet was observed in only 3 (8.6%) of the patients in group 2 and in 6 (13%) of the patients in group 3 ({chi}2=0.45, P=.72). Prolapse of the right aortic cusp was noted in 2 patients, one each from groups 2 and 3.

A less frequent but more distinctive finding was the observation of focal nodular thickening of the tips and bodies of the leaflets (Fig 1Down). These valve nodules were observed in 9 (26%) of 35 patients in group 2 (on the mitral valve alone in 7 patients and on the mitral and tricuspid leaflets in 2 patients). Valve nodules were equally frequent in group 3 and were present in 10 (22%) of 45 patients (on the mitral valve alone in 7, the mitral and aortic valve in 2, and the mitral and tricuspid valve in 1 patient; {chi}2=0.86, P=.44 compared with group 2). Valve nodules measured about 3 to 5 mm, had a different echogenicity compared with the valve leaflets, and were present in multiple views throughout the cardiac cycle. These nodules did not exhibit the chaotic mobility characteristic of the vegetations of infective endocarditis, and they disappeared on follow-up (see below).



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  		Figure 1. Top, Schematic representation. The anterior mitral valve leaflet (AML) shows focal nodular thickening of the tip and distal part of its body. Compare with the normal, thin appearance of the posterior mitral leaflet (PML). Mild nodular thickening of the aortic valve (AoV) cusps can also be seen. The posterior echo-free space signifies the presence of a small pericardial effusion. Bottom, Two-dimensional echocardiogram (end-diastolic frame from the parasternal long-axis view) of a patient with a first attack of rheumatic fever with carditis. IVS indicates interventricular septum; LA, left atrium; LV, left ventricle; and LVPW, left ventricular posterior wall.

Cardiac valves were normal in 26 (93%) of 28 subjects in group 1. Two patients, one with polyarthritis and another with Sydenham's chorea, demonstrated focal nodularity of the anterior mitral leaflet tip. None of the control subjects (groups A and B) had valve nodules. Valve prolapse was not identified in any patient in group 1.

Valve Regurgitation
None of the 28 subjects in group 1 had abnormal regurgitant flow detected on Doppler color flow examination. Trivial mitral regurgitation was detected in 8 subjects (29%), trivial pulmonary regurgitation in 6 (21%), and trivial aortic regurgitation in 2 patients (7%). These regurgitant jets were localized to the region immediately below the valve (<1 cm) and were felt to represent "physiological" regurgitation. The two patients in this group with echocardiographic evidence of mitral valve nodules had normal Doppler color flow imaging studies. The proportion of subjects with physiological regurgitation was similar to that in age-matched healthy children (control group A).

The prevalence and severity of valvular regurgitation in patients with acute rheumatic carditis is shown in Table 4Up. Mitral regurgitation was the most common Doppler echocardiographic feature of both first episodes (group 2, 94%) and recurrences of rheumatic carditis (group 3, 84%). The severity of mitral regurgitation was greater in recurrences of carditis (group 3, 31%; group 2, 8.5%; {chi}2=5.98, P=.026). The mitral regurgitation jets most often were directed posterolaterally (70%), but central (16%), anterior (12%), and multiple (2%) jets were also seen. Aortic regurgitation was a less common feature.

In patients with a recurrence of carditis and mitral regurgitation (n=38), the most common identifiable mechanisms of mitral regurgitation were ventricular dilatation (74%), restricted leaflet mobility (37%), annular dilatation (21%), and leaflet prolapse (16%). More than one mechanism was operative in several patients (Table 5Down). The direction of the regurgitant jet varied depending on the relative degree of restriction of the mitral leaflets. Patients with equal restriction of both leaflets had central jets, whereas those with a greater degree of restriction of the posterior leaflet had posteriorly directed regurgitant jets because the more mobile anterior leaflet overrode the posterior mitral leaflet (and vice versa).


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  		Table 5. Mechanisms of Mitral Regurgitation in Acute Rheumatic Carditis

In patients with a first attack of carditis and mitral regurgitation (n=33), left ventricular dilatation was the most common identifiable mechanism of mitral regurgitation (54%). Mitral annular dilatation (12%) and mitral valve prolapse (9%) were infrequent in these patients. In 13 patients (39%) in this group, the exact mechanism of mitral regurgitation was unclear.

Improper coaptation of aortic valve leaflets without prolapse or annular dilatation was the most common mechanism of aortic regurgitation both in first and in recurrent attacks of carditis. Aortic leaflet retraction was seen in patients with recurrent carditis (group 3). Aortic valve prolapse with annular dilatation was noted in two of 24 subjects (one each in groups 2 and 3) with aortic regurgitation and was associated with a severe degree of valvular regurgitation.

Left Ventricular Function and Clinical-Echocardiographic Correlations
Left ventricular systolic function was normal in all group 1 patients and in the majority of patients in groups 2 and 3. No significant differences were observed in the mean values of fractional shortening between the three groups of patients (group 1, 36±4%; group 2, 36±5%; group 3, 36±5%). In addition, there were no differences in mean values of fractional shortening when the patient groups were compared with their corresponding control groups (control group A, 36±5%; control group B, 40±8%; P=NS). Congestive heart failure was more common in patients with recurrent carditis (group 3, 40%; group 2, 17%; {chi}2=4.9, P=.03). All patients with congestive heart failure had hemodynamically significant valvular regurgitation or stenoses. Fig 2Down displays the relations between clinical heart failure, echocardiographic fractional shortening, and valvular abnormalities. Left ventricular fractional shortening was reduced in 10 patients, 5 each in groups 2 and 3 ({chi}2=0.141, P=NS). Eight of these 10 patients had hemodynamically significant valve lesions (3 with severe mitral stenosis and 5 with severe mitral regurgitation). Fractional shortening was normal in 19 (79%) of 24 patients with congestive heart failure.



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  		Figure 2. Interrelations of congestive heart failure (CHF), ventricular fractional shortening (FS), and valvular disease in 80 patients with acute rheumatic carditis. Twenty-four of 80 patients had CHF, and 19 (79%) of these had normal FS of the left ventricle; all 5 patients with CHF and reduced FS had significant valvular lesions. Ten of 80 patients had reduced FS, and 8 of these had significant valvular disease. These figures suggest that CHF in rheumatic carditis usually occurs because of valvular lesions. Ventricular function remains intact in rheumatic carditis; when encountered, reduced FS is usually associated with significant valvular lesions. MR indicates mitral regurgitation; MS, mitral stenosis.

Left ventricular dilatation was more common in patients with recurrence of carditis (31 of 45 patients) compared with patients with a first attack of carditis (18 of 35 patients; {chi}2=2.529, P=.164). In group 3 patients, left ventricular dilatation was invariably associated with valvular regurgitation of a moderate or severe degree. Three patients in group 2, however, had left ventricular dilatation with mild mitral regurgitation. Mean indexed values of left ventricular end-diastolic and end-systolic dimensions and left atrial size did not differ significantly between groups 2 and 3 but were significantly larger than corresponding values for group 1. Mitral and aortic valve annular dimensions did not differ significantly among the three groups.

Pericardial Involvement
Pericardial effusion was noted in 10 patients (5 each in groups 2 and 3), of whom only 4 had an audible rub. Conversely, 6 of 10 patients (3 each in groups 2 and 3) with a clinically audible pericardial rub did not have evidence of a pericardial effusion on echocardiographic examination. None of the patients in group 1 had evidence of pericardial effusion on the echocardiogram.

Follow-up Examinations
Follow-up was obtained in 25 group 1 patients (89%). None of these patients had evidence of any significant valvular regurgitation at the end of 6 months. Left ventricular function remained normal and mitral valve nodules disappeared in the two subjects in whom these nodules were recorded at the time of the initial examination.

Follow-up was available in 23 (66%) of 35 group 2 patients. Serial evaluation revealed a progressive decrease in left ventricular end-diastolic dimensions (P=.008) and in the R/Th ratio (P=.0002); mean measurements of left ventricular end-diastolic dimensions and R/Th were similar at 3 months (4.24 cm and 2.83, respectively) and 6 months (4.21 cm and 2.79, respectively; P=NS compared with values at 3 months) after the index attack of rheumatic fever but were significantly less than corresponding measurements at baseline (4.37 cm and 3.06, respectively). There was no significant change in serial measures of fractional shortening (baseline, 36%; 3 months, 35%; 6 months, 36%; P=.86) and left atrial dimensions. Valve nodules disappeared in all patients who had valve nodules at the initial examination and who were available for a follow-up examination. Color flow imaging demonstrated disappearance of mitral regurgitation in 2 patients (9%) with mild mitral regurgitation in the index attack. Valvular regurgitation remained unchanged in 16 (69%) of 23 patients and decreased by one or more grades in another 5 patients (22%).


*    Discussion
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 *Discussion
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Echocardiographic Characteristics of Acute Rheumatic Valvulitis
Valvular thickening was commonly seen in patients with rheumatic carditis. Valve thickening with the first attack of rheumatic carditis may be due to valvulitis48 or may reflect the effects of clinically inapparent prior episodes of rheumatic fever. Approximately one of every four patients with rheumatic carditis demonstrated the echocardiographic presence of focal nodular thickening of valve leaflets. These nodules were found on the body and the tips of the mitral valve leaflets most often, did not have any independent chaotic motion, and disappeared on follow-up. Furthermore, these nodules were not observed in patients with chronic rheumatic heart disease. We speculate that these nodules may represent the echocardiographic equivalents of the verrucae seen universally at autopsy in patients who died of acute rheumatic fever48 and noted macroscopically at surgery in a substantial proportion of patients subjected to valve surgery during the acute phase of carditis.49 The negative blood cultures (obtained in some patients), the absence of any vascular or immunologic phenomena in all patients, and the lack of any chaotic, independent motion of these nodules make it unlikely that these nodules represent infected vegetations. Furthermore, the diagnosis of infective endocarditis could be rejected in all patients by use of standard criteria.50 Marantic endocarditis or nonspecific vegetations48 appear to be a less likely explanation for these observations, as none of our patients had severe malnutrition and the nodules disappeared on follow-up. Such nodules have not been reported previously in echocardiographic studies of patients with rheumatic fever7 8 9 10 11 12 13 14 15 16 17 18 19 ; a specific focus on valve morphology in the present study and regional differences in the severity of rheumatic carditis51 may be possible explanations. The observation of these nodules as an isolated abnormality in two patients with no clinical evidence of carditis and without any valve regurgitation is interesting. The evidence at present is not sufficient to recommend this morphological abnormality as a marker of possible subclinical carditis or a precursor of valvular stenoses.

Prevalence and Mechanisms of Valvular Regurgitation in Acute Rheumatic Carditis
Mitral regurgitation was the most common Doppler echocardiographic feature of both a first episode and recurrences of rheumatic carditis. Associated aortic valve involvement was a less common feature. These findings are consistent with clinical observations in patients with rheumatic fever.52 53 The severity of valve regurgitation was greater in recurrences of carditis, possibly owing to repeated attacks of valvulitis that culminated in greater valvular damage and because of the self-perpetuating nature of regurgitant lesions.

Ventricular dilatation and restriction of leaflet mobility were the most common mechanisms of mitral regurgitation in patients with a recurrence of rheumatic carditis. In patients with a first attack of carditis, ventricular dilatation was the most common identifiable mechanism of mitral regurgitation. This is consistent with the view expressed in older literature that valve regurgitation in the initial attack of carditis is related more to myocardial involvement than to valvulitis.54 55

Valve prolapse and annular dilatation were uncommon mechanisms of valvular regurgitation in our patients with rheumatic carditis. These findings are in contrast to prior reports based on patients subjected to cardiac surgery.13 14 49 A selection bias inherent in surgical series, evaluation of different disease spectra,56 and differing criteria for carditis and valvular prolapse are possible explanations for these differences. Prior studies13 used a combination of clinical and pathological criteria for carditis; some of these patients may be classified as having chronic rheumatic heart disease by clinical criteria alone.57 The use of apical four-chamber views to diagnose mitral valve prolapse may also explain the increased prevalence of this entity in prior studies.58 Our findings are in accord with pathological observations of the mitral valve that suggest that annular dilatation is rare in rheumatic mitral regurgitation.59 60 61 The frequent disappearance of mitral regurgitation on follow-up5 62 also indicates that reversible functional mechanisms (such as left ventricular dilatation) rather than relatively permanent structural alterations (such as annular dilatation) may be operative in the pathogenesis of mitral regurgitation during a first attack of carditis. The role of systolic dysfunction of the annulus (in the absence of dilatation) was not investigated in the present study and merits further study given the predilection of inflammatory activity for valve annuli.63

Left Ventricular Systolic Function and Heart Failure in Acute Rheumatic Carditis
The majority of patients with rheumatic carditis have normal left ventricular systolic function. Congestive heart failure was more common in patients with a recurrence of carditis. All patients with congestive heart failure had hemodynamically significant valvular lesions, and a majority had normal left ventricular systolic function. Patients with a reduced fractional shortening had significant valvular lesions. These observations concur with recent reports21 25 that suggest that valvular disease, as opposed to myocardial dysfunction, is the mechanism of congestive heart failure in rheumatic carditis. The infrequent occurrence of congestive heart failure in first attacks of carditis (in which the valve lesions are less severe) strengthens this hypothesis. Three patients with mitral stenosis were noted to have a low value of fractional shortening in the present study. An association between mitral valve stenosis and reduced ventricular fractional shortening has been reported previously64 65 ; it may represent the combined effects of elevated ventricular afterload, posterobasal left ventricular fibrosis, and right ventricular volume overload.

Role of Doppler Echocardiography in the Identification of Acute Rheumatic Carditis in Patients Without Clinical Evidence of Carditis
Patients with rheumatic fever but without clinical evidence of carditis did not demonstrate significant valvular regurgitation at the time of the index attack or on short-term follow-up. This finding is in contrast to previous reports that have suggested an incremental yield in the diagnosis of rheumatic carditis with the use of Doppler echocardiography.7 8 9 10 11 12 The careful exclusion of physiological regurgitation in the present study, varying instrument gain settings,66 a referral bias inherent in a study performed at a tertiary-care facility, and the meticulous initial clinical evaluation in the present study (owing to the specific a priori objective of assessment of the diagnostic utility of echocardiography) may be possible explanations for these differences. Our observations strengthen the recent American Heart Association recommendation24 67 to exercise caution when interpreting isolated Doppler abnormalities in the absence of clinical findings.

Study Limitations
The present study was conducted in a tertiary-care referral center; the diagnostic utility of Doppler echocardiography in the diagnosis of rheumatic carditis in a primary-care setting remains to be assessed. The use of fractional shortening as a measure of left ventricular systolic performance may not be entirely appropriate, since it is significantly influenced by changes in the loading conditions and assesses only the basal portion of the left ventricle; a normal fractional shortening in the face of severe mitral regurgitation may not indicate normal myocardial contractility but may simply reflect a decreased ventricular afterload.68 Investigation of the mechanisms of mitral regurgitation is limited by a lack of information regarding chordal length, annular systolic excursion, or papillary muscle function and by the use of a transthoracic window. Our observations on serial echocardiographic observations are also limited by the less-than-complete follow-up, especially in group 2 patients.

Conclusions
In patients with rheumatic carditis, the mitral valve is most frequently involved and mitral regurgitation is the most common finding on Doppler color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. In one fourth of patients with rheumatic carditis, we observed valve nodules that may represent the echocardiographic equivalent of rheumatic verrucae. The present study failed to reveal any incremental role of echocardiography and Doppler color flow imaging in the diagnosis of carditis in rheumatic fever without clinical evidence of carditis.


*    Acknowledgments
 
The authors wish to acknowledge Dr K.C. Goswami, MD, for his assistance in this study.


*    Footnotes
 
Reprint requests to Dr. Savitri Shrivastava, Escorts Heart Institute and Research Center, Okhla Rd, Delhi-110025, India.

Received August 3, 1995; revision received December 14, 1995; accepted December 21, 1995.


*    References
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