Frequency of valvular regurgitation by color Doppler echocardiography in systemic lupus erythematosus

response.A hypercontractile ventricle with a small end- substance,such as arginine vasopressin,may sensitizethe systolic volume may stimulate receptor discharge by in- mechanoreceptorsand thereby lower the threshold for ducing intraventricular pressure gradients. Within this triggering the vasodepressorresponse. physiologic framework, severalmechanismsmay explain isoproterenol’senhancedability, comparedwith epinephrine, to trigger the vasodepressorresponse.First, isoproterenol has been demonstrated to reduce end-diastolic 1. Almquist A, Goldenberg IF, Milstein S, Chen M, Chen X, HansenR, Gornick Benditt DG. Provocation of bradycardia and hypotensionby isoproterenol volume and increasestroke volume.12This effect on end- CC, and upright posture in patients with unexplained syncope. N Engl J Med diastolic volume would be expected to be greater with 1989;320:346-351. isoproterenol than with epinephrine becauseof the great- 2. Waxman MB, Yao L, Cameron DA, Wald RW, Roseman J. lsoproterenol of vasodepressor-type reaction in vasodepressor-prone persons. Am J er chronotropic effects of isoproterenol. Second,isopro- induction Cardiol 1989;63:58-65. terenol may increase end-diastolic pressureto a greater 3. Fitzpatrick A, Sutton R. Tilting towards a diagnosis in recurrent unexplained Lancet 1989;1:658-660. degreethan epinephrine becauseof a greater shortening 4.syncope. Kenny RA, Bayliss J, Ingram A, Sutton R. Head-up tilt: a useful test for of the diastolic tilling period. Finally, once the vaso- investigating unexplained syncope. Lancer 1986;1:1352-1354. depressorresponseis triggered, isoproterenol may aug- 5. Milstein S, Reyes WJ, Benditt DG. Upright body tilt for evaluation of patients recurrent, unexplained syncope.PACE 1989;12:117-124. ment peripheral vasodilation becauseof its p-2 agonist with 6. Stratton JR, Pfeifer MA, Ritchie JL, Halter JB. Hemodynamic effects of properties,whereasepinephrine may counteract vasodila- epinephrine: concentration-effect study in humans. JAppl Physioll985;58:11991206. tion through its a-agonist effects. EP, Hayter CJ, Barlow ED. Mechanism of acute hypotension The precise role of epinephrine in precipitating vaso- 7.fromSharpey-Schafer fear or nausea. Br Med J 1958:878-X80. depressor syncope remains unknown. Although other 8. Graham DT, Kabler JD, Lunsford L. Vasovagal fainting: a diphasic response. Med 1961;23:492-507. studiesreport increasesin circulating epinephrine in asso- 9.Psychosom Vingerhoets AJJM. Biochemical changes in two subjects succumbing to synco.. ciation with vasodepressorsyncope, the results of this pe. Psychosom Med 1984;46:95-103. study suggest that additional factors are important. 10. ThamesMD. Effect of d- and 1-propranolol on the dischargeof cardiac vagal Am J Physiol 1980;7:H465-H470. Thesefactors may include a marked withdrawal of vagal C11.fibers. Barron KW. BishouVS. The influence of vanal afferents on the left ventricutone in conjunction with an increase in circulating epi- lar contractile response to intracoronary adminizration of catecholamines in the nephrine, which together may lead to a more marked conscious doe. Circ Res 1981:49:159-l 69. 12. Paley WyMcDonald IG, Blumenthal J, Mailhot J. The effects of posture and tachycardia and, in turn, trigger a vasodepressorre- isoproterenol on the velocity of left ventricular contraction in man. J Clin Inuest sponse.It is also possible that a second neurohumoral 1971;50:2283-2293.

Frequency of Valvular Regurgitation by Color Doppler Echocardiography in Systemic Lupus Erythematosus Katsuaki Enomoto, MD, Yoshikazu Kaji, MD, Takehito Mayumi, MD, Yasuo Tsuda, MD, Shozo Kanaya, MD, Kohei Nagasawa! MD, Takehiko Fujino, MD, and Yoshiyuki Niho, MD e studied valvular regurgitation in patients with W systemiclupus erythematosus(SLE) by color Doppler echocardiography. Because valvular regurgitation

chest x-ray, standard 12-lead electrocardiography, phonocardiography, blood and urine analyses and serum chemistry analysis. Normal subjects comprised 93 womoccurs frequently in normal subjects,1,2we matched the en (18 to 29 years, 23; 30 to 39 years, 43; 40 to 49 years, patients by age with a control group. Furthermore, the 27) who had no history of heart disease, hypertension or samepersonexamined both patients and normal subjects other medical problems, and who underwent blood presusing the same Doppler echocardiographic apparatus. sure measurement, urine analysis, chest x-ray and elecThe patients were 43 women with stable SLE (18 to trocardiography. M-mode, 2-dimensional and Doppler echocardiographic studies were performed with a 29 years, 14; 30 to 39 years, 13; 40 to 49 years, 16). All fulfilled the 1982 American Rheumatism Association SSHl6OA (Toshiba, Tokyo, Japan) using a 2-dimencriteria for the diagnosis of SLE.3 We judged as stable sional transducer (3.75 MHz) and a Doppler transducer patients with SLE whose values of erythrocyte sedimen- (2.5 MHz). Echocardiography was performed on both tation rate and complements were normal or had not patients and normal subjects in the partial left lateral changed for a few months and whose clinical symptoms decubitus position. The flow signal was judged as a did not deteriorate. They underwent echocardiography, regurgitation when .it was observed as a regurgitant jet away from the valve by color Doppler echocardiography and when its duration was >I00 ms by M-mode colorFrom the First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan, and the Institute of Health Sci- flow mapping. The severity of regurgitation was judged ence, Kyushu University, Fukuoka, Japan. Dr. Enomoto’s present adaccording to the classification by distance with pulseddress is the Division of Cardiology, Department of Medicine, University Doppler echocardiography.4-7 Right ventricular systolic of North Carolina, Burnett-Womack Building, Chapel Hill, North pressure was ascertained by measuring the pressure graCarolina 27599-7075. Manuscript received June 5,199O; revised manuscript received September 4, 1990, and accepted September 5. dient between right ventricular and right atria1 systolic THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 15, 1991

209

TABLE

I Clinical Characteristics

Age WI

in Patients with Systemic Lupus Erythematosus

Duration of Disease W

Duration of Steroid TX(yr)

5.5 f 3.6

5.2 i 3.6

Wm (U/ml)

(SLE) and Control Subjects BSA W)

SBP (mm W

DBP (mm Hg)

1.54f0.10

1.56f0.10

114f lllfll

69f13 68i7

18-29

SLE Control

30*5

15

30-39

SLE

9.1 f 2.8

7.5 f 3.6

32+8

1.58f0.12 1.52f0.10

119f9 115zk 10

79 f 10” 72f8

10.0 f 4.8

10.3 f 6.5

33f7

1.58f0.11 1.54f0.10

125614 122+ 14

SO&9 76kll

Control 40-49

SLE Control

* p <0.05 patients vs control subjects. BSA = body surface area: CHso = complement

TABLE

II Echocardiographic

hemolytic

actmty;

DBP = diastok

blood pressure; SBP = systolic blood pressure; TX = therapy.

Findings and Frequency of Valvular Regurgitation

Age W

LAD (cm)

LVDd (cm)

LVEF (X)

18-29 SLE Control 30-39

2.9 z! 0.26 3.0 f 0.23

4.5 + 0.32 4.8 f 0.27

74.1 f 4.6 75.6 f 4.1

0 0

SLE

MR(%)

TR(%)

PR (%)

57.1+ 17.4

64.3*’ 21.7

71.4”” 21.7 84.6 a>0

3.2 f 0.40

4.5 f 0.38

77.7 f 4.3

7.7

53.8

92.3**

3.1 f0.21

4.7 f 0.27

76.4 f 4.4

0

34.9

20.9

14.0

SLE

3.2 f 0.51

4.6 f 0.45

77.9 f 5.7

12.5

50.0

68.8

81,3”:2

Control

3.3 LIZ0.31

4.8 f 0.32

76.4f

0

37.0

33.3

22.2

Control 40-49

* p <0.05. * * p
pressure with continuous-wave Doppler echocardiography.8 Right ventricular systolic pressure was then determined by the addition of 10 mm Hg (the assumed systolicpressure of the right atrium) to the pressure gradient. Data are expressed as mean f standard deviation. Student’s t test was used for paired samples. Comparison of subgroup proportions was performed by chi-square analysis with correction for continuity.

m

SLE

0

control

AR

MU

TR

PR

PlGURE 1. incidence of valvular regurgitation in patients and control subjects. AR = aortii regurgitation; MR = mitral regurgitation; PR = pulmonary regurgitation; SLE = systemic lupus erythematosus; TR = tricuspid regurgitation; *p <0.05; +*p
210

AR(%)

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67

3.6

dimension:

LVEF = l&t ventricular

ejection fraction;

MR = mitral regurgitation;

PR = pul-

The durations of disease and of steroid therapy correlatedpositively (Table I). Diastolic pressure was higher in patients than in normal subjects in the fourth decade of life (p <0.05), although there was no signljkant difference in blood pressure between patients and normal subjects in the other age groups. The incidence of mitral, tricuspid and pulmonary regurgitation was higher in patients than in normal subjects (53.5 us 31.2%,p 5 years to lO years. There were no significant differences in age and the duration of disease among patient groups with or without mitral regurgitation. However, the duration of disease was significantly longer in the group with than without tricuspid regurgi-

tation. Age and the duration of disease tended to be longer in the group with than without pulmonary regurgitation. In 4 of 24 patients with tricuspid regurgitation, right ventricular systolic pressure was >30 mm Hg. Mitral valve prolapse was present in 7% (control subjects 5%, difference not signtjicant), mitral valve thickening in 7% and tricuspid valve prolapse in 2% of patients.

It has been reported that Libman-Sacks endocarditis was present in 13 to 50% of patients with SLE at autopSY.~JO However, becauseverrucous vegetationswere 3 to 4 mm in many cases,they had been difficult to detect clinically. Mitral valve thickening could be detected in only 7% of our patients. We have shown that the incidence of mitral, tricuspid and pulmonary regurgitation was higher in patients than in normal subjectsin eachage group, and that the degree of regurgitation was more severein patients than in normal subjects.Mitral regurgitation was detected in about half of the patients in each age group. Doherty and Siegel” reported that the incidenceof Libman-Sacks endocarditis was 26% in the mitral valve and 4.6% in the aortic valve in autopsies of patients with SLE in the steroid era, according to previous reports. In addition, they pointed out valvulitis, tibrosis and mucoid degeneration. Left ventricular chamber sizeof 3 patients with aortic regurgitation wasnot different from that in normal subjects,and their blood pressure values were normal. Therefore, aortic regurgitation was not causedby a changein left ventricular chamber sizeor by hypertension. Although we did not detect endocardial lesions directly, mitral and aortic regurgitation might relate to endocarditis and valvulitis. The higher incidence of mitral regurgitation compared with the frequency of the Libman-Sacks lesion at necropsy might imply that mitral regurgitation in our patients was partly due to physiologic regurgitation, as seenin normal subjects.The absenceof a distinct enlargement of the left atrium or ventricle is consistent with this. Right-sided regurgitation, however, may not be explained by only pathologic valvular changes,becausethe incidence of regurgitation was too high compared with that of Libman-Sacks endocarditis (2.9% in the tricuspid valve and 1.3%in the pulmonic valve) at autopsy.” Gross et all2 found pulmonary vascular lesions in 46.5% of patients with SLE at autopsy and Fayemi13found them in 40% of patients at autopsy. Pulmonary hypertension has been described as one of the causesof pulmonary regurgitation and elevatedright ventricular systolic pressure as one of the causes of tricuspid regurgitation.14 Simonson et all5 reported that right ventricular systolic pressurewas >30 mm Hg in 15% of SLE patients with

TABLE III Incidence of Mitral and Tricuspid Regurgitation (Grade L2+), and More Than Mild Pulmonary Regurgitation Patients with Systemic Lupus Erythematosus Age W

MR(%)

TR (%)

PR(%)

18-29 30-39 40-49

7.1 46.2 25.0 25.6

14.3 15.4 43.8 25.6

0 7.7 31.3 14.0

Total Abbreviations

in

as in Table Ii.

tricuspid regurgitation and was higher in patients with SLE than in normal subjects.In our study, 4 of 24 patients with tricuspid regurgitation had a high (>30 mm Hg) right ventricular systolic pressure.The incidence of right-sided regurgitation might relate to pulmonary vascular lesionsand increasedpulmonary arterial pressure. To clarify the relations amongvalvular regurgitation and endocarditis, valvulitis and pulmonary lesions, further investigation is necessary. 1. Kostucki W, Vandenbossche JL, Friart A, Englert M. Pulsed Doppler regurgitant Row patterns of normal valves. Am .I Cardiol 1986;58:309-313. 2. Yoshida K, Yoshikawa J, Shakudo M, Akasaka T, Jyo Y, Takao S, Shiratori K, Koizumi K, Okumachi F, Kato H, Fukaya T. Color Doppler evaluation of valvular regurgitation in normal subjects. Circtdation 1988;78:840-847. 3. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25: 1271-l 277. 4. Abbasi AS, Allen MW, DeCristofaro D, Ungar I. Detection and estimation of the degree of mitral regurgitation by range-gated pulsed Doppler echocardiography. Circulation 1980;61:143-147. 5. Ciobanu M, Abbasi AS, Allen M, Hermer A, Spellberg R. Pulsed Doppler echocardiography in the diagnosis and estimation of severity of aortic insufficiency. Am J Cardiol 1982;49:339-343. 6. Miyatake K, Okamoto M, Kinoshita N, Ohta M, Kozuka T, Sakakibara H, Nimura Y. Evaluation of tricuspid regurgitation by pulsed Doppler and twodimensional echocardiography. Circulation 1982;66:777-784. 7. Akasaka T, Yoshikawa J, Yoshida K, Okumachi F, Koizumi K, Shiratori K, Takao S, Shakudo M, Kato H. Age-related valvular regurgitation: a study by pulsed Doppler echocardiography. Circulation 1987;76:262-265. 8. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984;70:657-662. 9. Kong TQ, Kellum RE, Haserick JR. Clinical diagnosis of cardiac involvement in systemic lupus erythematosus. A correlation of clinical and autopsy findings in thirty patients. Circulation 196%26:7-l 1. 10. Hejtmancik MR, Wright JC, Quint R, Jennings FL. The cardiovascular manifestations of systemic lupus erythematosus. Am Heart J 1964:68:119-130. 11. Doherty NE, Siegel RJ. Cardiovascular manifestations of systemic lupus erythematosus. Am Heart J 1985;110:1257-1265. 12. Gross M, WesterlyJR, Earle RH. Pulmonary alterations in systemic lupus erythematosus. Am Reu Respir Dis 1972;105:572-577. 13. Fayemi AO. Pulmonary vascular disease in systemic lupus erythematosus. Am J Clin Pathol 1976;65:284-290. 14. Braunwald E. Valvular heart disease. In: Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine. Philadelphia: W.B. Saunders, 1988:10721076. 15. Simonson JS, Schiller NB, Petri M, Hellman DB. Pulmonary hypertension in systemic lupus erythematosus. J Rheumatol 1989;16:918-925.

THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 15, 1991

211