PATHOPHYSIOLOGY AND NATURAL HISTORYVALVUILAR HEART DISEASE

Mitral valve prolapse in patients with priorrheumatic fever

NICHOLAS J. LEMBO, M.D., LouIs J. DELL'ITALIA, M.D., MICHAEL H. CRAWFORD, M.D.,JACELYN F. MILLER, R.D.M.S., KENT L. RICHARDS, M.D., AND ROBERT A. O'ROURKE, M.D.

ABSTRACT It is known that rheumatic heart disease frequently results in isolated mitral regurgitationwithout concomitant mitral stenosis, especially in countries with a high prevalence of rheumatic fever.However, more recent surgical pathologic data also have demonstrated a high incidence of mitral valveprolapse in cases of rheumatic heart disease, which suggests that rheumatic fever may be a cause ofmitral valve prolapse. To determine whether this association of mitral valve prolapse and rheumaticheart disease is present in a stable clinic population, we studied 30 patients who had an apical systolicmurmur and a well-documented history of rheumatic fever with dynamic auscultation, two-dimensionalechocardiography, and pulsed Doppler examinations. Twenty of the 30 patients (67%) had findings onphysical examination consistent with isolated mitral regurgitation and 25 patients (84%) had mitralregurgitation by Doppler examination. Echocardiography demonstrated mitral valve prolapse in 24patients (80%), whereas only one of the total study group had echocardiographic findings consistentwith mitral stenosis. We conclude that (1) the presence of an isolated systolic murmur in patients witha history of rheumatic fever frequently represents pure mitral regurgitation secondary to mitral valveprolapse and (2) postinflammatory changes in valvular tissue resulting from rheumatic fever may bethe etiology of mitral valve prolapse in these patients.Circulation 77, No. 4, 830-836, 1988.

RHEUMATIC HEART DISEASE was considered amajor cause of isolated mitral regurgitation in theUnited States when rheumatic fever was a major healthhazard,1-5 and this remains the predominant valvularsequela today in countries where rheumatic fever is stillprevalent.6' 7 This contrasts with a current series fromWaller et al.,8 who report nonrheumatic conditions asthe cause of isolated mitral regurgitation in 97% ofpatients requiring mitral valve replacement. Because ofthis observation and the declining incidence of rheu-matic fever in the United States over the past 20 years,rheumatic heart disease is now considered a very rarecause of mitral regurgitation unless associated withmitral stenosis or aortic valve dysfunction.9 However,Tomaru et al.'0 and Marcus et al.11 have recentlyreported that valvular regurgitation caused by mitral

From the Department of Medicine, Division of Cardiology, Univer-sity of Texas Health Science Center and Veterans Administration Hos-pital, San Antonio.

Supported in part by NIH Research Training Grant T32-HL07350from the NHLBI and by the Veterans Administration.

Address for correspondence: Nicholas J. Lembo, M.D., AndreasGruentzig Cardiovascular Center, Emory University Hospital, SuiteF606, 1364 Clifton Road, NE, Atlanta, GA 30322.

Received Nov. 18, 1986; revision accepted Jan. 14, 1988.Presented in part at the 58th Annual Scientific Sessions of the Arner-

ican Heart Association, Washington, DC, 1985.

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valve prolapse may result from postinflammatorychanges, including those after rheumatic fever.We noted an isolated apical systolic murmur in many

of our clinic patients who had a well-documented his-tory of rheumatic fever and were receiving monthlyprophylaxis with penicillin G benzathine (Bicillin).This physical examination finding was suggestive ofmitral regurgitation and appeared consistent with thereports from the older literature in the United States1-5and with recent data from countries with a high inci-dence of rheumatic fever.6 7 However, of greater inter-est was the potential role of mitral valve prolapse in theetiology of mitral regurgitation in patients with a his-tory of rheumatic fever.1' 11 Accordingly, we evalu-ated patients who had a well-documented history ofrheumatic fever and an isolated apical systolic murmurby means of dynamic auscultation, echocardiography,and Doppler examinations to determine whether mitralvalve prolapse was the source of these murmurs.

MethodsPatients. The study population consisted of 30 patients with

a well-documented history of rheumatic fever as determined bychart review, including 23 women and seven men, ages 19 to 54years (mean 31). This group of patients was identified from atotal of 120 clinic patients who were receiving monthly pro-

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phylaxis with intramuscular penicillin for rheumatic fever.These patients were chosen because they had only an apicalsystolic murmur on physical examination. The apical systolicmurmur was pansystolic in nine patients and early, mid, or latesystolic in 21 patients. No patient had a diastolic murmur, andtherefore patients with evidence on physical examination ofmitral stenosis and aortic regurgitation were excluded from thestudy.

Twenty-eight of the 30 patients (93%) had a history of acuterheumatic fever documented by review of admission charts andby strict application of the Jones criteria'2: (1) at least two majorcriteria (n = 26) or (2) one major and two minor (n = 2). Inaddition, all 28 patients had supporting evidence of a precedingstreptococcal infection documented by rising antistreptolysin 0(ASO) titers and/or a positive throat culture for group A ,B-hemolytic streptococci and/or recent scarlet fever (table 1). Inthe remaining two patients, admitted in 1938 and 1949, thehospital laboratory records could not be located. However, thepatient admitted in 1938 presented with carditis, polyarthritis,and fever and developed chorea during her hospitalization. Thepatient admitted in 1949 had polyarthritis, erythema margina-tum, subcutaneous nodules, and fever documented during hos-pitalization. Thus both patients had three major and one minorcriteria and, although supporting evidence of a preceding strep-tococcal infection could not be documented secondary to lostlaboratory records, we believe that both patients had acuterheumatic fever. The mean age of the patient group was 13 yearswhen the diagnosis of acute rheumatic fever was made. Thus thetime from diagnosis of acute rheumatic fever to study dateaveraged 18 years. All study patients were on monthly prophy-laxis with intramuscular benzathine penicillin and none was oncardiac medications. No patients had a history of prior endo-carditis and none had a history of angina pectoris or electro-cardiographic evidence of myocardial infarction. All 30 patientsgave written consent to participate in the study on a formapproved by our institutional review board.

Physical examination. Physical examination was performedindependently by two staff cardiologists who were blinded to theresults of echocardiography and Doppler studies. Physicalexamination was accomplished by having the patient and theauscultators in separate rooms and by having an independent

TABLE 1Documentation of acute rheumatic fever (n = 30)

Jones criteria n %

MajorCarditis 26 87Polyarthritis 30 100Chorea 1 3Erythema marginatum 7 23Subcutaneous nodules 1 3

MinorPrevious history of rheumatic fever 3 10Arthralgia (not used if polyarthritis present) 0 0Fever 29 97Elevated sedimentation rate, C-reactive protein, or

leukocytosis 20 67Prolonged PR interval 11 37

Supporting evidence of streptococcal infectionElevated ASO titer 24 80Positive throat culture for /-hemolytic strep. 1033Recent scarlet fever 5 17At least one of the above 28 93

observer place an electronic stethoscope (Andries Stethoscope,Andries Tek, Austin, TX) on the chest wall and direct the variousmaneuvers. Systolic murmurs were graded from I to VI with thepatients resting in the left lateral decubitus position.'3 Subse-quently, commonly used bedside maneuvers were used to deter-mine the origin of the systolic murmur. These included isometrichandgrip, amyl nitrite inhalation, respiration, Valsalva maneu-ver, squatting and standing, leg elevation, cycle length changes,and transient arterial occlusion.'4' 15 Mitral regurgitation wasdiagnosed when the murmur intensity decreased with amylnitrite, increased with transient arterial occlusion, and increasedwith isometric handgrip. Forward flow murmurs were identifiedwhen murmur intensity increased with amyl nitrite, increasedafter long cycle lengths, and did not change with transientarterial occlusion. Difficulties arose in the case of mitral regur-gitation secondary to mitral valve prolapse where murmur inten-sity may increase after amyl nitrite inhalation and during iso-metric handgrip, thereby yielding a false diagnosis of a forwardflow murmur. In this instance the responses to leg elevation,transient arterial occlusion, and cycle length changes weredeciding factors in determining etiology of the murmurs.

Echocardiography. After the physical examination, com-plete two-dimensional echocardiography was performed in eachpatient. Echocardiography was performed with the patient atrest and in the absence of tachycardia or systolic hypertensionat the time of the study. All standard echocardiographic viewswere obtained, including parasternal long- and short-axis viewsas well as apical four- and two-chamber views. Visualization ofall four cardiac valves was attempted, and careful assessmentof each cardiac valve was made to evaluate for stenosis orprolapse. The two criteria required for the diagnosis of mitralvalve prolapse on two-dimensional echocardiography were (1)systolic displacement of the coaptation point of the anterior andposterior leaflets posterior to the mitral annular plane in theparasternal or apical long-axis views and (2) similar displace-ment in the apical four-chamber view.'6 Posterior displacementof the lateral aspects of the mitral leaflets in the apical four-chamber view was not considered adequate for the diagnosis ofprolapse, since this may be caused by a nonplanar anulusconfiguration.'7 The echocardiogram was evaluated by a car-diologist blinded to the results of the physical examination andDoppler study.

Doppler examination. Each individual was examined witha commercially available duplex pulsed Doppler ultrasonoscope(ATL Mark 600 or Ultramark 8) with 2.25 or 3.00 MHz trans-ducers. Since the goal of examination was to identify the pres-ence of mitral regurgitation and exclude the presence of otherlesions, a standard approach was used.'8 Mitral regurgitationwas identified by the presence of abnormal systolic velocitiesin the left atrium adjacent to the mitral valve leaflets.'8 Transientsystolic velocities that were detected only in early systole andthat were confined in the left atrium within 1 cm of the mitralleaflets were considered within normal limits. Mitral regurgi-tation was defined as present if abnormal systolic velocities weredetected greater than 1 cm from the mitral leaflets and werepansystolic or were present in mid to late systole. The apicalfour-chamber view was used to exclude mitral stenosis, aorticregurgitation, and aortic stenosis.l' Right-sided valve lesionsand ventricular septal defect were excluded by criteria describedby Hatle and Angelsen.'9 The Doppler echocardiogram wasevaluated by an experienced cardiologist who did not know theresults of clinical examination.

Control group. Fifty-one control subjects with normal find-ings on physical examination were evaluated to determine theincidence of mitral valve prolapse on echocardiography at ourinstitution. The group consisted of 44 normal volunteers andseven patients from our clinic population receiving prophylaxis

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with penicillin for well-documented rheumatic fever. Of theseseven patients, five had a completely normal findings on physicalexamination and two had a grade I/VI early systolic murmur atthe left sternal border identified as a flow murmur after dynamicauscultation. The echocardiographer was blinded to the historyin this control group. Mitral valve prolapse was diagnosed inthree of the 51 subjects (6%) by the same echocardiographiccriteria described above. None of the seven patients with ahistory of rheumatic fever had mitral valve prolapse on echo-cardiography. However, one patient had a thickened anterior andposterior leaflet of the mitral valve without evidence of mitralstenosis or regurgitation by Doppler examination.

ResultsPhysical examination. Cardiac auscultation by both

cardiologists confirmed that all 30 patients had apicalsystolic murmurs without the presence of diastolicmurmurs. The murmur was judged to be grade I/VI in10 patients (33%), grade LI/VI in 12 patients (40%),and grade IIINVI in eight patients (27%). Origin of themurmur as determined by dynamic auscultation isdepicted in figure 1. Twenty of the 30 patients (67%)were diagnosed as having a murmur compatible withmitral regurgitation: nine were holosystolic murmurs,two early systolic, four mid-systolic, and five late sys-tolic. Three of these patients had mid-systolic clicks:one with a holosystolic murmur, one with a mid-sys-tolic murmur, and one with a late systolic murmur. Innine patients (30%) the murmur was attributed to aorticoutflow turbulence; five of these patients had earlypeaking systolic murmurs and the remaining fourpatients had mid-peaking systolic murmurs. Only onepatient (3%) had a right-sided murmur, which in-creased with inspiration.

Echocardiography. The results from echocardiogra-phy are indicated in figure 2. Twenty-four of the 30patients (80%) had echocardiographic evidence ofmitral valve prolapse without concomitant mitral sten-osis or other valvular disease. Six of these 24 patientshad mild thickening of one or both of the mitral valveleaflets, but no diastolic doming. Only one of the 30

Mitral Regurgitatior(N = 20)67%

te A~~~~~A

Right-Sidedn0- (N = 1)

3%

ortlc Outflow(N = 9)30%

FIGURE 1. Results of cardiac auscultation by bedside maneuvers todifferentiate the murmurs.

832

Mitral Valve ProlapseWlthout Mltrul Stenosis -

(N = 24)80%

Mitral Valve ProlapseWith Mlid Mltral Stenosts

1 (N = 1)3%

Norrnal- (N = 5)

17%

FIGURE 2. Results of two-dimensional echocardiography, interpretedwith criteria for mitral valve prolapse as described in Methods.

patients (3%) with mitral valve prolapse had mild thick-ening of both mitral valve leaflets with doming con-sistent with mild mitral stenosis. This patient also hadthickening of the aortic valve leaflets but no evidenceof aortic stenosis at cardiac catheterization. Only fivepatients (17%) had normal echocardiograms.

Doppler examination. Pulsed Doppler examinationdemonstrated isolated mild-to-moderate (detected inthe mid-left atrium) mitral regurgitation in 25 of the 30patients (84%) (figure 3). One patient had moderatetricuspid regurgitation (3%). Four patients (13%) hadnormal findings on Doppler examination, without evi-dence of regurgitant or stenotic valvular lesions andventricular or atrial septal defects. The one patient whohad evidence of mild mitral stenosis on two-dimen-sional echocardiography had mitral valve orifice veloc-ities at the upper limit of normal and had normal aorticvalve orifice velocity.

Combined results of physical examination, echocardio-graphy, and Doppler studies. The combined results ofphysical examination, echocardiography, and Dopplerstudies are shown in figure 4. Mitral regurgitation wasdiagnosed by physical examination in 20 patients andby Doppler in 25 patients. Echocardiography demon-strated mitral valve prolapse without mitral stenosis orother valvular disease in 24 patients. Fifteen patientswith mitral regurgitation diagnosed both by physicalexamination and Doppler had mitral valve prolapse onechocardiography. Twenty-two of 24 patients (92%)with mitral valve prolapse on echocardiography hadmitral regurgitation present by physical examinationand/or Doppler. Examples of representative two-di-mensional and Doppler echocardiograms are providedin figure 5.

Mitral Regurgitation(N = 25) -

84% A

Tricuspid Regurgitation(N = 1)3%

(N = 4)13%

FIGURE 3. Results of pulsed Doppler recordings as described inMethods.

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Physical Examination: 2 ' 2 Echocardiography:Mitral Regurgitation. | Mitrci Valve Prolopse

(N 20) 15 / Wthout Mitral Stenosis2 / 6(N =24)

Doppler.Mitrl Regurgitation

(N = 25)FIGURE 4. Combined results of physical examination, echocardio-graphy, and pulsed Doppler studies.

DiscussionHistorically, there has been considerable contro-

versy regarding isolated mitral regurgitation inpatients with a history of rheumatic fever. Many of theinitial pathologic and clinical studies concluded thatisolated mitral regurgitation of rheumatic origin wasexceedingly rare unless accompanied by mitral sten-osis. However as early as 1926, Sprague and Whitetchallenged this view and suggested that isolated mitralregurgitation of rheumatic origin was a distinct clin-ical entity, indicating that it was not a necropsy findingbecause it was rarely if ever fatal. In 1960, Jhaveri etal.4 reported that 56 of 300 adult patients (18.6%)with a history of rheumatic fever had isolated mitralregurgitation on physical examination. These patientsremained asymptomatic for a mean follow-up of 18years. The authors concluded that patients with ahistory of rheumatic fever and only apical systolicmurmurs have a benign type of mitral regurgitation

with a good prognosis barring recurrent rheumaticfever or bacterial endocarditis. Other investigatorshave reported a similar benign prognosis for patientswith a history of rheumatic mitral regurgitation.5' 8, 20However, all of these studies were based on physicalexamination findings and did not include cardiaccatheterization, echocardiography, or Doppler con-firmation.

Selzer and Katayama21 in 1972 reported the firstlarge series of 230 consecutive cases of isolated mitralregurgitation in which the majority of patients (92%)were evaluated with cardiac catheterization. Theyreported that 88 (39%) of the 230 patients had mitralregurgitation secondary to a rheumatic etiology. Theidentification of a rheumatic etiology was based ondescription of the valve on surgical inspection in 61(69%) of the 88 patients and on a history of rheumaticfever in the remaining 27 patients (31 %). Other inves-tigators also report a very high incidence of puremitral regurgitation in children in Mexico and India,where rheumatic fever remains a major healthhazard.6' 7 This contrasts with recent studies byWaller et al.,8 who reported their findings in 97patients over 30 years of age undergoing mitral valvereplacement for isolated severe mitral regurgitation.Their analysis of the excised mitral valves includedmeasured mitral valve area and annular circumfer-ence. In this series mitral valve prolapse with orwithout ruptured chordae was considered the mostcommon etiology, accounting for 60% of isolatedsevere mitral regurgitation requiring valve replace-

FIGURE 5. Example of an echocardiogram showing mitral valve prolapse (A) and a Doppler recording showing mitralregurgitation (B) from an asymptomatic 19-year-old man. He had acute rheumatic fever at the age of 7 years, manifested bya new mitral regurgitation murmur, marked cardiomegaly on chest x-ray, and both right- and left-sided heart failure. He alsohad polyarthritis, fever, first-degree atrioventricular block, and a positive throat culture for group A P-hemolytic streptococci.Currently on physical examination, he has a grade II/VI holosystolic murmur at the apex, which radiates to the axilla.

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ment. Coronary artery disease accounted for 30%,followed by infective endocarditis (5%) and rheu-matic heart disease (3%). Thus they concluded thatnonrheumatic conditions accounted for 97% ofpatients requiring mitral valve replacement for iso-lated severe mitral regurgitation. However, five of the60 patients defined as having mitral valve prolapse hadprior histories of acute rheumatic fever but were notclassified as having mitral regurgitation secondary toa rheumatic etiology. More importantly, microscopicexamination was not performed to determine whethermyxomatous proliferative changes were present.The microscopic diagnosis of mitral valve prolapse

due to myxomatous proliferation requires that thespongiosa extend into the replace part of the fibrosa.This results in a loss of fibrous tissue and accumulationof mucopolysaccharides that weakens the central por-tion of the fibrosa and enables cusp expansion andchordal elongation to occur.22 However, there are mul-tiple causes of mitral valve prolapse that are not relatedto myxomatous proliferation, such as ischemia,trauma, hypertrophic cardiomyopathy, and bacterialendocarditis.23

Tomaru et al.10 recently described a new entity ofpostinflammatory mitral valve prolapse. They evalu-ated 27 patients with mitral valve prolapse whorequired mitral valve replacement for valvular regur-gitation. Thirteen of the 27 (48%) excised mitral valveson microscopic examination revealed classic myxoma-tous changes. However, the remaining 14 valves (52%)demonstrated fibrosis with vascularization and scat-tered infiltration of round cells, including lymphocytesand plasmacytes without prominent myxomatous pro-liferation of the spongiosa. They postulated that thesechanges were caused by a postinflammatory processassociated with chronic inflammation. Furthermore,there was a history of rheumatic fever only in patientswith this inflammatory type ofmitral valve prolapse andin none of the patients with myxomatous prolapse.They concluded that mitral valve prolapse is producednot only by myxomatous changes but also by postin-flammatory changes resulting from rheumatic fever. Inaddition, gross inspection of the valves demonstrateda greater mean surface area of anterior and posteriorvalve leaflets and a larger mitral annular dimension inboth myxomatous and postinflammatory prolapsewhen compared with normal hearts. This finding ques-tions the validity of the conclusions of Waller et al.8that attribute the majority of surgical mitral regurgi-tation to myxomatous changes based on gross valvularinspection without microscopic examination.

In another recent report, Marcus et al.1` presented

834

their findings in 61 patients with active rheumaticcarditis requiring surgical correction of severe mitralregurgitation. Fifty-seven of these patients (93%) hadmarked prolapse of the anterior mitral valve leaflet onechocardiography, and at surgery mitral valve prolapsewas found in all 57 patients. Among these 57, mitralannular dilatation was found in 54 (95%), chordalelongation in 50 (88%), and chordal rupture in four(17%). Fibrosis and retraction of the mitral leaflettissue was noted in only eight of the 61 patients (13%)at surgery. The authors concluded that anterior mitralvalve leaflet prolapse is the most common valvularabnormality in patients with severe mitral regurgitationcaused by active rheumatic carditis. These resultsagree with the findings of Chauvaud et al.24 in childrenfrom Mediterranean countries and Northern Africa,where rheumatic fever is still prevalent.

In the present investigation the diagnosis of mitralregurgitation on physical examination was based on theresults of dynamic auscultation. In most cases Dopplerexamination corroborated the physical examinationfindings; however, Doppler studies detected mitralregurgitation more often than the physical examina-tion. This was not surprising, since the murmur ofmitral regurgitation secondary to mitral valve prolapsemay behave similarly to an aortic outflow murmurduring dynamic auscultation.14 25 Specifically, theapical systolic murmur of mitral valve prolapse mayincrease in response to amyl nitrite inhalation, leadingto a false diagnosis of a flow murmur especially whena click is not present. This may explain the morefrequent diagnosis of mitral regurgitation by Dopplerexamination when compared with the physical exam-ination. Also, Doppler may be more sensitive for thedetection of mitral regurgitation. Therefore our find-ings are consistent with those of Steinfield et al.,26 whoreported that 34 of 184 patients with acute rheumaticfever had evidence on physical examination of a mid-to-late systolic murmur or a click during their fol-low-up, which did not include an echocardiographic orDoppler examination.

In the present investigation, the results of echo-cardiography provide complementary data to therecent surgical pathologic series.8' 21 These studiescannot be directly compared because they includepatients with severe mitral regurgitation in the sur-gical series and patients with mild-to-moderate mitralregurgitation in our study. Nonetheless, we foundmitral valve prolapse, adhering to strict echocardio-graphic criteria, in 22 of 28 patients with mitral regur-gitation documented by physical examination or Dop-pler in the absence of stenosis or other valvular

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disease. In addition, the majority of cases in ourseries involved the anterior leaflet of the mitral valve,which was also consistent with the recent surgicalseries. However, the mean age of our study group wasyounger (31 years) than that of the group reported byTomaru et al.10 (43 years). Our patients may representa subgroup with early mitral regurgitation caused byrheumatic heart disease. It is also feasible that theymay have gained some protective effect from regularmonthly prophylaxis with penicillin. At this time, itis unknown whether long-term prophylaxis for rheu-matic fever will prevent further valvular inflamma-tion in this subset of patients as suggested by Tomkinset al.27

There are several potential limitations to the presentinvestigation. Hemodynamic and angiographic assess-ments are lacking because all of our patients wereasymptomatic, and this would have exposed thesepatients to unnecessary risks. However, echocardio-graphy combined with Doppler has a very high sen-sitivity and specificity in the detection of mitral regur-gitation in patients with valvular heart disease.28 In thepresent study, 23 of the 30 patients were women, whichis not surprising because rheumatic mitral valve diseaseand clinical evidence of mitral valve prolapse are morecommon in women. In a control population with nor-mal findings on physical examination, including bothnormal volunteers and patients with a well-documentedhistory of rheumatic fever, the echocardiographic inci-dence of mitral valve prolapse was only 6%. Thereforewe do not believe that the high incidence of prolapsein the study group was attributable to a low echocar-diographic threshold for identifying prolapse. Whetherthese patients had mitral valve prolapse before theirattack of acute rheumatic fever is an issue that cannotbe resolved completely without surgical pathologicdocumentation ruling out myxomatous proliferationwithin the valve. However, the common echocardio-graphic findings of thickened valve leaflets with pro-lapse of the anterior rather than posterior leaflet aremore consistent with the surgical description in therecent reports as opposed to myxomatous mitral valveprolapse.

The results of the present investigation are con-sistent with those of numerous other studies, showingthat the presence of a systolic murmur in patients witha past history of rheumatic fever frequently representsisolated mitral regurgitation without mitral stenosis.However, the cause of mitral regurgitation in thispatient population is often mitral valve prolapse. Ourfindings support the theory of an inflammatory eti-ology of mitral valve prolapse proposed by Tomaru et

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al.'0 and Marcus et al."1 in patients with a history ofrheumatic fever. Whether long-term prophylaxis forrheumatic fever will prevent further valvular inflam-mation in these patients is currently unknown. Weplan to follow these patients on a long-term basis todetermine the progression of prolapse and regurgita-tion, as well as the development of mitral stenosis.

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regurgitation and mitral stenosis. Am Heart J 1: 629, 1925-262. Movitt MD, Gerstl B: Pure mitral insufficiency of rheumatic origin

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N J Lembo, L J Dell'Italia, M H Crawford, J F Miller, K L Richards and R A O'RourkeMitral valve prolapse in patients with prior rheumatic fever.

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