Absence of Echocardiographic Abnormalities of the Anterior Mitral Valve Leaflet in Rheumatoid Arthritis LT COL JAMES E. DAVIA, M.D., F.A.C.P., COL MELVIN D. CHEITLIN,
M.D., F.A.C.P.,
COL CARLOS M. de CASTRO, M.D., F.A.C.P., LT COL OLIVER LAWLESS, M.D., and LAWRENCE NIEMI, Washington, D.C.
Thirty-five consecutive patients with classic or definite rheumatoid arthritis underwent echocardiography to evaluate the motion of the anterior mitral valve leaflet. Adequate echocardiograms were obtained in 31 patients. All 31 patients showed normal valve motion and a normal EF slope. If meticulous technique was not observed, a falsely low value for the EF slope was obtained and a normal slope was found when the method was improved. This study shows that echocardiographic abnormalities of the anterior mitral valve leaflet rarely, if ever, occur in patients with rheumatoid arthritis, provided that careful attention to recording method is observed.
CARDIAC INVOLVEMENT in rheumatoid arthritis has been
previously well documented at necropsy (1-8). These studies have shown that the pericardium, coronary arteries, myocardium, and endocardium may be affected. Endocardial involvement is characterized by variable degrees of sclerosis of the valves, especially on the left side of the heart. A recent echocardiographic study in rheumatoid arthritis patients attempted to show abnormal motion of the anterior mitral valve leaflet manifested by a reduced E F slope and explained on the basis of either abnormal valve structure or reduced myocardial compliance ( 9 ) . We report here our results of echocardiographic analysis of anterior mitral valve leaflet motion in 31 patients with rheumatoid arthritis. Patients and Methods Thirty-five consecutive patients with rheumatoid arthritis, who were seen within a 6-week period in the Rheumatology Clinic were evaluated with echocardiography. Echocardiograms adequate for interpretation were unobtainable in 4 patients because of emphysema or extreme obesity, or both, and these patients were not included in the study. Of the remaining 31 patients, 29 had classic rheumatoid arthritis, and 2 had definite rheumatoid arthritis as defined by the American Rheumatism Association (10). Subcutaneous nodules were present in 28 patients, and 29 patients had a positive rheumatoid factor. All of these patients were either severely limited by their arthritis or severely symptomatic and required gold, glucocorticoids, azothrioprine, or combinations of these drugs, and all were thought to require care by subspecialists in rheumatology. It is the pol• From the Cardiology and Rheumatology Services, Walter Reed Army Medical Center, Washington, D . C.
500
Downloaded from https://annals.org by Tulane University user on 01/18/2019
icy of the Cardiology Clinic not to treat severe rheumatoid arthritis. Consequently, all cardiac patients with severe arthritis are seen in the Rheumatology Clinic and thus there is no bias against arthritic cardiac patients, specifically those with mitral valve disease, from entrance into the Rheumatology Clinic. The ages ranged from 9 to 70 years and the mean age was 47.1 years, with a median age of 50 years. There were 19 women and 12 men. The average duration of illness was 7.4 years, with a range of 1 to 28 years. A history and physical examination were done on each patient. Standard 12-lead electrocardiograms were taken on 30 patients, and chest X-rays were available for review in 26 patients. The echocardiograms were obtained with an Ekoline 20A (Smith Kline Instruments, Philadelphia, Pennsylvania) using a 2.2 megaHertz transducer with a 1.2 cm diameter and a 10 cm focus. The transducer was placed in the fourth intercostal space parasternally, and the mitral valve was identified. Appropriate adjustments of the transducer position, damping, reject and gain controls were made until the clearest possible mitral valve complexes with maximum amplitude and velocity were obtained. The echoes were recorded on Polaroid film (Polaroid Corp., Cambridge, Massachusetts) or with a Honeywell strip chart recorder (Honeywell, Inc., Denver, Colorado). Measurements of the EF slope in mm/sec were made on multiple complexes, and the highest value was recorded. Results
A history of hypertension was obtained in 6 patients and a history of an undocumented myocardial infarction in 1 patient. Three patients complained of occasional palpitations, and 1 patient had chest pain that was atypical for angina pectoris. The cardiovascular examination was entirely normal in 23 patients. A fourth heart sound was heard in 6 patients. A soft systolic ejection murmur was heard at the apex in another patient. Another patient had a grade 2 / 6 systolic ejection murmur at the upper left sternal border and a systolic ejection click. The electrocardiogram was normal in 25 patients. Two patients had nonspecific ST-T changes, and 3 patients had a large negative component of a biphasic P wave in lead V15 suggesting left atrial enlargement. The posteroanterior and lateral chest X-rays were normal in 20 patients. Three patients showed a dilated, tortuous aorta, and another had the same finding together with emphysematous changes in the lung fields. Two other patients had diffuse, reticular patterns in the lung fields. Review of the echocardiograms indicated that all patients had an E F slope equal to or greater than the lower limits Annals of Internal Medicine 83:500-502, 1975
of normal of 70 mm/sec (11). The range was 70 to 184 mm/sec with an average of 106 mm/sec. No abnormalities of anterior mitral leaflet motion were observed. A representative anterior mitral leaflet complex from one patient is shown in Figure 1. Figure 2 shows an abnormally slow EF slope of 50 mm/sec obtained in the first examination in one patient and a normal EF slope of 100 mm/sec in the same patient when better angulation of the transducer was achieved. Discussion
This study has shown normal diastolic motion of the anterior mitral valve leaflet manifested by normal EF slope in 31 consecutive patients with rheumatoid arthritis. This finding indicates that the pathologic process that may involve the mitral valve is not of sufficient magnitude to result in diminished leaflet mobility. Likewise, it also indicates that myocardial involvement is also not severe enough to reduce compliance to the extent that the EF slope would be reduced. The results of this investigation are in contrast to Nomeir and colleagues' study (9) in which 30% of rheumatoid arthritis patients were found to have a diminished EF slope. In an attempt to explain the discrepancy between our results and the findings of Nomeir and coworkers, it is necessary to review the accumulated autopsy data on the pathology of the mitral valve in rheumatoid arthritis. Cruickshank (1) reported that 9 of 100 rheumatoid arthritis patients had fibrous or nonspecific inflammatory changes but in only 3 patients was the valve stenotic. Bonfiglio and Atwater (2) compared the necropsy findings in 47 rheumatoid arthritis patients with 47 age and sex-matched controls. In the rheumatoid arthritis patients there were two cases of "stenotic valvular disease" but no indication of which valves were involved and no information regarding past history of rheumatic fever was given. Also noted was the fact that 70% had some evidence of "valvulitis" of one or more valves without frank stenosis, whereas 74% of the control patients also had similar
Figure 1. Normal motion of the anterior mitral valve leaflet (AMVL) with normal EF slope (arrow) in a 50-year-old woman with classic rheumatoid arthritis of 12 years' duration.
Figure 2, Upper. The anterior mitral valve leaflet (AMVL) in this patient has an EF slope (arrow) of 50 mm/sec. The intraventricular septal echoes are labeled S. Lower. The anterior mitral valve leaflet in the same patient shows a normal EF slope (arrow) of 100 mm/sec after better transducer position was achieved.
evidence of valvulitis, indicating that this finding is both common and nonspecific (2). In contrast, Lebowitz (3) reported the autopsy results of 62 rheumatoid arthritis patients and noted that sclerosis of the mitral and aortic valves was present in 21%, but in only 6% of the control patients. In only 1 arthritic patient, however, was significant deformity of the mitral valve present. Goehrs, Baggerstoss, and Slocum (4) found mildly stenotic mitral valves in 2 of 36 necropsied rheumatoid arthritis patients, but according to their data it was not possible to rule out a history of rheumatic fever. Thus, it can be seen that stenosis of the mitral valve in rheumatoid arthritis is rare and, in most cases where it was reported, it is not possible to rule out a history of rheumatic fever. Weintraub and Zvaifler (5) have emphasized the difficulty in classifying patients with coexistent joint and heart disease. They point out that there is a spectrum ranging from patients with classic rheumatoid arthritis and valvular disease that is not clearly rheumatic to obvious rheumatic heart disease with chronic joint disease (Jaccoud's arthritis). Between these two extremes are patients with features Davia et a\. • Mitral Valve and Rheumatoid Arthritis
Downloaded from https://annals.org by Tulane University user on 01/18/2019
501
of both rheumatoid and rheumatic heart disease. As an example, they reported a case of a patient who had acute rheumatic fever at age 14, was found to have mitral stenosis at age 33, and developed rheumatoid arthritis with a high rheumatoid factor titer at age 37. It is possible, therefore, that when mitral stenosis is found in a rheumatoid arthritis patient, coexisting rheumatic heart disease may also be present. In Nomeir and associates' study (9), no information is given about the possible history of rheumatic fever. None of the patients in our study had a history of rheumatic fever. Severe myocardial dysfunction may result in a diminished EF slope (12) and could conceivably have been responsible for the decreased EF slope found in Nomeir and associates' study (9), but hemodynamic data that would reflect the presence of reduced compliance were not obtained. In addition, only one patient had congestive symptoms. Pathologic studies indicate that rheumatoid arthritis patients may have a nonspecific myocarditis (1-4), but the functional significance of this histologic abnormality has not been studied hemodynamically. The fact that all of our patients had normal EF slopes speaks against significantly reduced myocardial compliance in rheumatoid arthritis patients. If careful attention is not directed toward recording method, then inaccurate information may be obtained. For instance, if transducer position is not optimal, a falsely positive abnormal EF slope may be recorded (Figure 2). It is not possible to determine if differences in recording method can explain the discrepancy between our results and those of Nomeir and colleagues (9). Nevertheless, it cannot be overemphasized that meticulous technique is mandatory in recording echocardiograms if accurate information is to be obtained.
502
On the basis of our findings and a review of the pathology literature, we conclude that cardiac involvement in rheumatoid arthritis is rarely severe enough to result in abnormalities of mitral valve movement as detected by echocardiography. ACKNOWLEDGMENTS: Received 24 January 1975; revision accepted 7 July 1975. *• Requests tor reprints snould be addressed to JLt. uoi. James ±i. Davia, M.D., OSC Box 93, Walter Reed Army Medical Center, Washington, D.C. 20012. References 1. CRUICKSHANK B: Heart lesions in rheumatoid disease. / Pathol Bacteriol 76:223-240 1958 2. BONFIGLIO T, ATWATER EC: Heart disease in patients with seropositive rheumatoid arthritis. Arch Intern Med 124:714-719, 1969 3. LEBOWITZ WB: The heart in rheumatoid arthritis (rheumatoid disease). Ann Intern Med 58:102-123, 1963 4. GOEHRS HR, BAGGENSTOSS AH, SLOCUM CH: Cardiac lesions in
rheumatoid arthritis. Arthritis Rheum 3:398-308, 1960 5. WEINTRAUB AM, ZVAIFLER NJ: The occurrence of valvular and
myocardial disease in patients with chronic joint deformity. Am J Med 35:145-162, 1963 6. CATHCART ES, SPODICK DH: Rheumatoid heart disease: a study of the incidence and nature of cardiac lesions in rheumatoid arthritis. N Engl J Med 266:959-964, 1962 7. CARPENTER DF, GOLDEN A, ROBERTS WC: Quadrivalular rheu-
matoid heart disease associated with left bundle branch block. Am J Med 43:922-929, 1967 8. KARTEN I: Arteritis, myocardial infarction, and rheumatoid arthritis. JAMA 210:1717-1720, 1969 9. NOMEIR A, TURNER R, WATTS E, et al: Cardiac involvement in
rheumatoid arthritis. Ann Intern Med 79:800-806, 1973 10. ROPES M, BENNETT GA, COBB S, et al: Revision of diagnostic
criteria for rheumatoid arthritis. Arthritis Rheum 2:16-20, 1958 11. SEGAL BL, LIKOFF W, KINGSLEY B: Echocardiography: clinical
application in combined mitral stenosis and mitral regurgitation. Am J Cardiol 19:42-49, 1967 12. SHAH PM, GRAMIAK R, KRAMER DH: Ultrasound localization of
October 2975 • Annals of Internal Medicine • Volume 83 • Number 4
Downloaded from https://annals.org by Tulane University user on 01/18/2019
left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3-11, 1969
M.D., F.A.C.P.,
COL CARLOS M. de CASTRO, M.D., F.A.C.P., LT COL OLIVER LAWLESS, M.D., and LAWRENCE NIEMI, Washington, D.C.
Thirty-five consecutive patients with classic or definite rheumatoid arthritis underwent echocardiography to evaluate the motion of the anterior mitral valve leaflet. Adequate echocardiograms were obtained in 31 patients. All 31 patients showed normal valve motion and a normal EF slope. If meticulous technique was not observed, a falsely low value for the EF slope was obtained and a normal slope was found when the method was improved. This study shows that echocardiographic abnormalities of the anterior mitral valve leaflet rarely, if ever, occur in patients with rheumatoid arthritis, provided that careful attention to recording method is observed.
CARDIAC INVOLVEMENT in rheumatoid arthritis has been
previously well documented at necropsy (1-8). These studies have shown that the pericardium, coronary arteries, myocardium, and endocardium may be affected. Endocardial involvement is characterized by variable degrees of sclerosis of the valves, especially on the left side of the heart. A recent echocardiographic study in rheumatoid arthritis patients attempted to show abnormal motion of the anterior mitral valve leaflet manifested by a reduced E F slope and explained on the basis of either abnormal valve structure or reduced myocardial compliance ( 9 ) . We report here our results of echocardiographic analysis of anterior mitral valve leaflet motion in 31 patients with rheumatoid arthritis. Patients and Methods Thirty-five consecutive patients with rheumatoid arthritis, who were seen within a 6-week period in the Rheumatology Clinic were evaluated with echocardiography. Echocardiograms adequate for interpretation were unobtainable in 4 patients because of emphysema or extreme obesity, or both, and these patients were not included in the study. Of the remaining 31 patients, 29 had classic rheumatoid arthritis, and 2 had definite rheumatoid arthritis as defined by the American Rheumatism Association (10). Subcutaneous nodules were present in 28 patients, and 29 patients had a positive rheumatoid factor. All of these patients were either severely limited by their arthritis or severely symptomatic and required gold, glucocorticoids, azothrioprine, or combinations of these drugs, and all were thought to require care by subspecialists in rheumatology. It is the pol• From the Cardiology and Rheumatology Services, Walter Reed Army Medical Center, Washington, D . C.
500
Downloaded from https://annals.org by Tulane University user on 01/18/2019
icy of the Cardiology Clinic not to treat severe rheumatoid arthritis. Consequently, all cardiac patients with severe arthritis are seen in the Rheumatology Clinic and thus there is no bias against arthritic cardiac patients, specifically those with mitral valve disease, from entrance into the Rheumatology Clinic. The ages ranged from 9 to 70 years and the mean age was 47.1 years, with a median age of 50 years. There were 19 women and 12 men. The average duration of illness was 7.4 years, with a range of 1 to 28 years. A history and physical examination were done on each patient. Standard 12-lead electrocardiograms were taken on 30 patients, and chest X-rays were available for review in 26 patients. The echocardiograms were obtained with an Ekoline 20A (Smith Kline Instruments, Philadelphia, Pennsylvania) using a 2.2 megaHertz transducer with a 1.2 cm diameter and a 10 cm focus. The transducer was placed in the fourth intercostal space parasternally, and the mitral valve was identified. Appropriate adjustments of the transducer position, damping, reject and gain controls were made until the clearest possible mitral valve complexes with maximum amplitude and velocity were obtained. The echoes were recorded on Polaroid film (Polaroid Corp., Cambridge, Massachusetts) or with a Honeywell strip chart recorder (Honeywell, Inc., Denver, Colorado). Measurements of the EF slope in mm/sec were made on multiple complexes, and the highest value was recorded. Results
A history of hypertension was obtained in 6 patients and a history of an undocumented myocardial infarction in 1 patient. Three patients complained of occasional palpitations, and 1 patient had chest pain that was atypical for angina pectoris. The cardiovascular examination was entirely normal in 23 patients. A fourth heart sound was heard in 6 patients. A soft systolic ejection murmur was heard at the apex in another patient. Another patient had a grade 2 / 6 systolic ejection murmur at the upper left sternal border and a systolic ejection click. The electrocardiogram was normal in 25 patients. Two patients had nonspecific ST-T changes, and 3 patients had a large negative component of a biphasic P wave in lead V15 suggesting left atrial enlargement. The posteroanterior and lateral chest X-rays were normal in 20 patients. Three patients showed a dilated, tortuous aorta, and another had the same finding together with emphysematous changes in the lung fields. Two other patients had diffuse, reticular patterns in the lung fields. Review of the echocardiograms indicated that all patients had an E F slope equal to or greater than the lower limits Annals of Internal Medicine 83:500-502, 1975
of normal of 70 mm/sec (11). The range was 70 to 184 mm/sec with an average of 106 mm/sec. No abnormalities of anterior mitral leaflet motion were observed. A representative anterior mitral leaflet complex from one patient is shown in Figure 1. Figure 2 shows an abnormally slow EF slope of 50 mm/sec obtained in the first examination in one patient and a normal EF slope of 100 mm/sec in the same patient when better angulation of the transducer was achieved. Discussion
This study has shown normal diastolic motion of the anterior mitral valve leaflet manifested by normal EF slope in 31 consecutive patients with rheumatoid arthritis. This finding indicates that the pathologic process that may involve the mitral valve is not of sufficient magnitude to result in diminished leaflet mobility. Likewise, it also indicates that myocardial involvement is also not severe enough to reduce compliance to the extent that the EF slope would be reduced. The results of this investigation are in contrast to Nomeir and colleagues' study (9) in which 30% of rheumatoid arthritis patients were found to have a diminished EF slope. In an attempt to explain the discrepancy between our results and the findings of Nomeir and coworkers, it is necessary to review the accumulated autopsy data on the pathology of the mitral valve in rheumatoid arthritis. Cruickshank (1) reported that 9 of 100 rheumatoid arthritis patients had fibrous or nonspecific inflammatory changes but in only 3 patients was the valve stenotic. Bonfiglio and Atwater (2) compared the necropsy findings in 47 rheumatoid arthritis patients with 47 age and sex-matched controls. In the rheumatoid arthritis patients there were two cases of "stenotic valvular disease" but no indication of which valves were involved and no information regarding past history of rheumatic fever was given. Also noted was the fact that 70% had some evidence of "valvulitis" of one or more valves without frank stenosis, whereas 74% of the control patients also had similar
Figure 1. Normal motion of the anterior mitral valve leaflet (AMVL) with normal EF slope (arrow) in a 50-year-old woman with classic rheumatoid arthritis of 12 years' duration.
Figure 2, Upper. The anterior mitral valve leaflet (AMVL) in this patient has an EF slope (arrow) of 50 mm/sec. The intraventricular septal echoes are labeled S. Lower. The anterior mitral valve leaflet in the same patient shows a normal EF slope (arrow) of 100 mm/sec after better transducer position was achieved.
evidence of valvulitis, indicating that this finding is both common and nonspecific (2). In contrast, Lebowitz (3) reported the autopsy results of 62 rheumatoid arthritis patients and noted that sclerosis of the mitral and aortic valves was present in 21%, but in only 6% of the control patients. In only 1 arthritic patient, however, was significant deformity of the mitral valve present. Goehrs, Baggerstoss, and Slocum (4) found mildly stenotic mitral valves in 2 of 36 necropsied rheumatoid arthritis patients, but according to their data it was not possible to rule out a history of rheumatic fever. Thus, it can be seen that stenosis of the mitral valve in rheumatoid arthritis is rare and, in most cases where it was reported, it is not possible to rule out a history of rheumatic fever. Weintraub and Zvaifler (5) have emphasized the difficulty in classifying patients with coexistent joint and heart disease. They point out that there is a spectrum ranging from patients with classic rheumatoid arthritis and valvular disease that is not clearly rheumatic to obvious rheumatic heart disease with chronic joint disease (Jaccoud's arthritis). Between these two extremes are patients with features Davia et a\. • Mitral Valve and Rheumatoid Arthritis
Downloaded from https://annals.org by Tulane University user on 01/18/2019
501
of both rheumatoid and rheumatic heart disease. As an example, they reported a case of a patient who had acute rheumatic fever at age 14, was found to have mitral stenosis at age 33, and developed rheumatoid arthritis with a high rheumatoid factor titer at age 37. It is possible, therefore, that when mitral stenosis is found in a rheumatoid arthritis patient, coexisting rheumatic heart disease may also be present. In Nomeir and associates' study (9), no information is given about the possible history of rheumatic fever. None of the patients in our study had a history of rheumatic fever. Severe myocardial dysfunction may result in a diminished EF slope (12) and could conceivably have been responsible for the decreased EF slope found in Nomeir and associates' study (9), but hemodynamic data that would reflect the presence of reduced compliance were not obtained. In addition, only one patient had congestive symptoms. Pathologic studies indicate that rheumatoid arthritis patients may have a nonspecific myocarditis (1-4), but the functional significance of this histologic abnormality has not been studied hemodynamically. The fact that all of our patients had normal EF slopes speaks against significantly reduced myocardial compliance in rheumatoid arthritis patients. If careful attention is not directed toward recording method, then inaccurate information may be obtained. For instance, if transducer position is not optimal, a falsely positive abnormal EF slope may be recorded (Figure 2). It is not possible to determine if differences in recording method can explain the discrepancy between our results and those of Nomeir and colleagues (9). Nevertheless, it cannot be overemphasized that meticulous technique is mandatory in recording echocardiograms if accurate information is to be obtained.
502
On the basis of our findings and a review of the pathology literature, we conclude that cardiac involvement in rheumatoid arthritis is rarely severe enough to result in abnormalities of mitral valve movement as detected by echocardiography. ACKNOWLEDGMENTS: Received 24 January 1975; revision accepted 7 July 1975. *• Requests tor reprints snould be addressed to JLt. uoi. James ±i. Davia, M.D., OSC Box 93, Walter Reed Army Medical Center, Washington, D.C. 20012. References 1. CRUICKSHANK B: Heart lesions in rheumatoid disease. / Pathol Bacteriol 76:223-240 1958 2. BONFIGLIO T, ATWATER EC: Heart disease in patients with seropositive rheumatoid arthritis. Arch Intern Med 124:714-719, 1969 3. LEBOWITZ WB: The heart in rheumatoid arthritis (rheumatoid disease). Ann Intern Med 58:102-123, 1963 4. GOEHRS HR, BAGGENSTOSS AH, SLOCUM CH: Cardiac lesions in
rheumatoid arthritis. Arthritis Rheum 3:398-308, 1960 5. WEINTRAUB AM, ZVAIFLER NJ: The occurrence of valvular and
myocardial disease in patients with chronic joint deformity. Am J Med 35:145-162, 1963 6. CATHCART ES, SPODICK DH: Rheumatoid heart disease: a study of the incidence and nature of cardiac lesions in rheumatoid arthritis. N Engl J Med 266:959-964, 1962 7. CARPENTER DF, GOLDEN A, ROBERTS WC: Quadrivalular rheu-
matoid heart disease associated with left bundle branch block. Am J Med 43:922-929, 1967 8. KARTEN I: Arteritis, myocardial infarction, and rheumatoid arthritis. JAMA 210:1717-1720, 1969 9. NOMEIR A, TURNER R, WATTS E, et al: Cardiac involvement in
rheumatoid arthritis. Ann Intern Med 79:800-806, 1973 10. ROPES M, BENNETT GA, COBB S, et al: Revision of diagnostic
criteria for rheumatoid arthritis. Arthritis Rheum 2:16-20, 1958 11. SEGAL BL, LIKOFF W, KINGSLEY B: Echocardiography: clinical
application in combined mitral stenosis and mitral regurgitation. Am J Cardiol 19:42-49, 1967 12. SHAH PM, GRAMIAK R, KRAMER DH: Ultrasound localization of
October 2975 • Annals of Internal Medicine • Volume 83 • Number 4
Downloaded from https://annals.org by Tulane University user on 01/18/2019
left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3-11, 1969
