- Email: [email protected]
Mitral valve prolapse associated with pectus excavatum
404
Clinical and laboratory observattons
insulin regimen. Improved diabetes control was achieved with a lower dose of insulin, presumably because of better absorption from rotated injection sites." The diagnosis of insulin-induced swelling is based on the exclusion of all other major causes of edema, 9 its temporal relationship to improved diabetes control, and its transient and benign nature? ,7,8 Our patient's findings met these criteria because of the absence of evident cardiovascular, renal, or hepatic disease. Insulin in physiologic concentrations has been shown to act directly on the distal nephron of dogs to enhance sodium reabsorption. 4 In normal humans, this effect appears to be independent of changes in filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration? A reduction in urinary sodium excretion and positive sodium balance, leading to weight gain and edema, have been demonstrated in patients with nonketotic diabetes treated with insulin. 2 This reduced sodium clearance has not been explained by decreased urinary glucose excretion or preexisting sodium deficits. Although the incidence of insulin edema is assumed to be rare] the occurrence of positive sodium balance in newly treated diabetes or in patients who vary in degree of compliance may be quite common. The few reports of this phenomenon 7,~ and the exclusion of insulin-induced edema from a differential diagnosis of swelling9,1o may be because edema is generally attributed to congestive failure, vascular insufficiency, or proteinuria, all of which commonly occur in this population. Insulin-induced antinatriuresis can aggravate these more serious abnormalitiesJ 2 Sodium retention and edema may be a transient, untoward effect of the institution or alteration of insulin regimens. The
The Journal of Pediatrics September 1987
differential diagnosis of edema in patients with insulindependent diabetes mellitus should include this entity. REFERENCES
1. VonNoorden C, Isaac S. Die: Zuckerkrankheit. Und ihre behandlung. Berlin: J Springer, 1927:535. 2. Saudek CD, Boulter PR, Knopp RH, Arky RA. Sodium retention accompanying insulin treatment of diabetes mellitus. Diabetes 1974;23:240-6. 3. DeFronzo RA, Cooke RC, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975;55:845-5. 4. DeFronzo RA, Goldberg M, Agus ZS. The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 1976;58:83-90. 5. DeFronzo RA. The effect of insulin on renal sodium metabolism: a review with clinical implications. Diabetologia 1981;21:165-71. 6. Foster DW. Diabetes mellitus. In: Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD, eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw-Hill, 1983;662. 7. Bleach NR, Dunn PJ, Khalafalla ME, McConkey B. Insulin oedema. Br Med J 1979;2:177-8. 8. Lawrence JR, Dunningan MG. Diabetic (insulin) oedema. Br Med J 1979;2:445. 9. Braunwald E. Edema. In: Petersdorf RG, Adams RD, Braunwald E, lsselbacher KJ, Martin JB, Wilson JD, eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw-Hill, 1983:167. 10. Finberg L, Kravath RE, Fleischman AR. Water and electrolytes in pediatrics: physiology, pathophysiology and treatment. Philadelphia: WB Saunders, 1982;108. 1t. Young R J, Hannan W J, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care 1984;7:479-80. 12. Sheehan JP, Sisam DA, Schumacker OP. Insulin-induced cardiac failure. Am J Med 1985;79:I47-8.
Mitral valve prolapse associated with pectus excavatum Robert C. S h a m b e r g e r , MD, K e n n e t h J. W e l c h , MD, a n d S t e p h e n P. Sanders, MD From the Departments, of Surgery and Cardiology, The Children's Hospital and Harvard Medical School, Boston
Mitral valve prolapse occurs in patients with narrow anteroposterior chest diameters, 1 anterior chest wall deforSubmitted for publication Jan. 12, 1987; accepted April 21, 1987. Reprint requests: Robert C. Shamberger, MD, Department of Surgery, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
mities, and scoliosis. 2-4 One prospective study in adults demonstrated mitral valve prolapse by echocardiogram in six of 33 patients (18%) with pectus excavatum, 5 and a French study identified mitral valve prolapse in 11 (65%) of 17 patients with pectus excavatum. 6 Anterior Compression of the heart against the vertebral column by the depressed sternum, with resulting deformity of the mitral
Volume 111 Number 3
anulus, has been proposed as the cause of mitral valve prolapse in these patients. 7 The natural history of mitral valve prolapse in these patients and the effect of repair of the chest wall deformity have not been studied; thus we examined a group of patients with pectus excavatum and mitral valve prolapse to define the effect of surgical correction of the chest wall deformity on mitral valve prolapse. METHODS From December 1976 to December 1985, we evaluated 429 patients (329 male) for primary repair of pectus exeavatum. In 80 patients, a preoperative M-mode echocardiogram (57 patients), two-dimensional echocardiogram (15 patients), or combined study (eight patients) was obtained because of auscultatory findings of mid-systolic click (11 patients), unusually prominent systolic murmur relative to the systolic murmur frequently present in patients with pectus excavatum, 7 or particularly severe pectus deformity. Fifty-seven of the patients were male. Ages ranged from 2 to 41 years (mean 14.3 years). All echocardiograms were obtained in a standard manner with the patient supine, sitting, or standing, using an Irex Continue Trace System (Irex Corp., Ramsey, N.J.), an ultrasound imaging system (Model 77020A, HewlettPackard Co., Waltham, Mass.), or Mark 600 Cardio Series, (Advanced Technology Laboratories, Inc., Bellevue, Wash.). Criteria used to define mitral valve prolapse for M-mode studies were those proposed by Markiewicz et al. 8 Criteria for two-dimensional studies were systolic arching of the mitral leaflets in the parasternal long-axis view, posterior systolic bowing in the apical four-chamber view, or systolic coaption of both leaflets at or behind the plane of the mitral anulus.9 Patients were considered to have mitral valve prolapse if these criteria were achieved in the supine or sitting position, but not if a Valsalva maneuver or standing was required to elicit them. Studies were performed or reviewed by one of us (S.P.S.). RESULTS No evidence for mitral valve prolapse was demonstrated by echocardiogram in 45 patients. Thirty-five patients met the criteria for mitral valve prolapse (Table I). Only one patient had mild mitral regurgitation by Doppler study, and did not undergo surgical repair of the pectus deformity; mitral regurgitation was not present on follow-up study. Two patients had Marfan syndrome with associated aortic root dilation and aortic valve regurgitation, and were excluded from the study. Seven patients did not undergo surgical repair of the chest wall deformity. Five of these seven were available for follow-up study after an interval of 5 months to 5 years, and in one patient, the mitral valve prolapse could no longer be demonstrated.
Clinical and laboratory observations
405
T a b l e I. Results in patients with mitral valve prolapse and pectus excavatum Marfan syndrome No surgical repair Surgical repair No postoperative study Resolution of mitral valve prolapse Persistent mitral valve prolapse
2 7 26 3 t0 13
Table II. Preoperative electrocardiographic findings in patients with mitral valve prolapse and pectus excavatum Incomplete right bundle branch block Probable left ventricular hypertrophy Left atrial enlargement Left-axis deviation Right atrial enlargement Complete right bundle branch block Occasional premature ventricular contractions Within normal limits No ECG available
10 6 5 4 2 2 1 9 6
Twenty-six patients with mitral valve prolapse underwent surgical repair; of these, 23 were available for postoperative studies. Mitral valve prolapse was not demonstrable on the postoperative echocardiogram in 10 of these 23 patients (study obtained 7 months to 9.7 years after surgery, median 4.1 years); the remaining 13 patients had persistent mitral valve prolapse (study obtained 6 months to 5.8 years after surgerY, median 1.6 years). There was no significant difference between the ages of the groups in which mitral valve prolapse resolved (mean _+ SD 13.6 + 6.9 years) or persisted (mean 17.7 _+ 5.8 years, Student t test P >0.25). Seven of the 10 patients with resolution of mitral valve prolapse were younger than 16 years of age when chest wall repair was performed; only four of the 13 patients with persistent prolapse were younger than 16 years. No significant difference was present between resolution of mitral valve prolapse in patients who underwent operations versus those who did not (chi-square test for a 2 X 2 table, P >0.25). Preoperative 12-lead electrocardiograms were obtained in 30 of the 36 patients with mitral valve prolapse. Minor abnormalities were noted in 21 patients (Table II). Twenty-four-hour monitoring was not done. Patients with mitral valve prolapse operated on for pectus excavatum have been followed up for a mean of 3.8 years (range 6 months to 9.7 years). Cerebrovascular accidents, infective endocarditis, or sudden death did not occur in this series. Prophylactic antibiotics were recommended for all dental and surgical procedures while the identifying murmur, clicks, or prolapse by echocardiogram persisted:
406
Clinical and laboratory observations
DISCUSSION Mitral valve prolapse is a common clinical entity with a frequency in the general population of 5% to 7% 1~ II and a frequency of 1% in a pediatric population? 2 The clinical challenge remains to define which patients in this large population are at significant risk for the major complications of mitral valve prolapse. A recent study suggests that patients with redundant mitral valve leaflets are at much greater risk for complications than are patients with nonredundant valves? 3 Others have suggested that prognosis is best related to extent of mitral regurgitation. 14 Jeresaty 15 has proposed dividing patients wit h mitral valve prolapse into those with primary myxomatous degeneration of the valvular apparatus and those with a secondary form and reduced left ventricular volumes. Cheng 16 defined these two populations as those with "too m u c h " valve apparatus or "too littie" cavity size. MitraI valve prolaps e associated with pectus exeavatum could be classified as a secondary form according to both of these schema. The suggestion has been made that such patients are at a much lower risk for complications than are patients with the primary form of the disease. Resolution of thi s question must await study of a larger group of patients. In our population of 33 patients (excluding two patients with Marfan syndrome), no episodes Of infective endocarditis, cerebral embolism, major ventricular arrhythmia, or sudden death have occurred. N o specific abnormalities were identified on standard 12-lead electrocardiograms, but 24-hour electrocardiographic monitoring or exercise testing is required to document the arrhythmias described in patients with mitral valve prolapse. The frequent association of a systolic murmur in patients with pectus excavatum has been attributed to turbulent flow Within the ventricle and pulmonary outflow tract. Angiographic studies have defined diminished ventricular volumes and limited cardiac output, 17 which are normalized after chest wall reconstruction28.j9 The frequency of mitral valve prolapse identified in our population may have been larger if all patients had been examined with echocardiography. The mid-systolic click may be absent or may be concealed by the prominent systolic murmur at the left sternal border. 4 In addition, 5% to 7% of patients have "silent" mitral valve prolapse and no audible murmurs or clicks. Resolution of mitral valve prolapse has been demonstrated after surgical closure of an atrial septal defect. It has also been reported after revascularization in patients with coronary artery insufficiency in whom papillary muscle dysfunction resulting f r o m ischemia was proposed
The Journal of Pediatrics September 1987
as the cause of the valvular dysfunction. In our patients, mitral valve prolapse could not be demonstrated in 43% of the patients after surgical correction of the chest wall deformity. W h a t effect the resolution of echocardiographically defined mitral valve prolapse will have on its natural history and serious complications can be established only by further follow-up studies. REFERENCES*
1. Schutte JE, Gaffney FA, Blend L, et al. Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 1981;71:533. 2. Bisset GS III, Schwartz DC, Meyer RA, et al. Clinical spectrum and long-term follow-up of isolated mitral valve prolapse in 119 children. Circulation 1980;62:423. 3. Bon Tempo CP, Ronan JA Jr, de Leon AC Jr, et al. Radiographic appearance of the thorax in systolic click-late systolic murmur syndrome. Am J Cardiol 1975;36:27. 4. Salomon J, Shah PM, Heinle RA: Thoracic skeletal abnormalities in idiopathic mitral valve prolapse. Am J Cardiol 1975;36:32. 5. Udoshi MB, Shah A, Fisher VJ, Dolgin M. Incidence of mitral valve prolapse in subjects with thoracic skeletal abnormalities: a prospective study. Am Heart J 1979;97:303. 6. Saint-Mezard G, Duret JC, Chanudet X, et al. Prolapsus valvulaire mitral et pectus excavatum: association fortuite ou groupement syndromique? La Presse Med 1986;15:439. 7. Welch KJ. Chest wall deformities. In: Holder TM, Ashcraft K W , eds. Pediatric surgery. PhiladelPhia: WB Saunders, 1980:162. 8. Markiewicz W, Stoner J, London E, et al. Mitral valve prolapse in one hundred presumably healthy young females. Circulation 1976;53:464. 9. Alpert MA, Carney R J, Flaker GC, et al. Sensitivity and specificity of two-dimensional echocardiographic signs of mitral valve prolapse. Am J Cardiol 1984;54:792. 10. Procacci PM, Savran SV, Schreiter SL, et al. Prevalence of clinical mitral-valve prolapse in 1169 young women. N Engl J Med 1976;294:1086. 11. Savage DD, Garrison R J, Devereux R B, et al. Mitral valve prolapse in the general population. I. Epidemiologic features: the Framingham study. Am Heart J 1983;106:571. 12. Warth DC, King ME, Cohen JM, et al. Prevalence of mitral valve prolapse in normal children. J Am Coll Cardiol 1985; 5:1173. 13. Nishimura RA, McGoon MD, Shub C, et aI. Echocardiographically documented mitral-valve prolapse: long-term followup Of 237 patients. N Engl J Med 1985;313:1305. 14. Wynne J. Mitral-valve prolapse. N Engl J Med 1986;314: 577. 15. Jeresaty RM. Mitral ballooning: a possible mechanism of mitral insufficiency in diseases associated with reduced endsystolic volume of the left ventricle. Chest 1971;60:114. 16. Cheng TO. The click-murmur syndrome: a medical pendulum and a unifying concept. Chest 1976;70:569. *List of references shortened at request of the Editor.
Volume 111 Number 3
17. Diaz FV, Pelous AN, Vald6s FG, et al. Peetus excavatum: hemodynamic and electrocardiographic considerations. Am J Cardiol 1962;10:272. 18. Beveggtrd S. Postural circulatory changes at rest and during exercise in Patients with funnel chest, with special reference to factors affecting the stroke volume. Acta Med Scand 1962; 171:695.
Clinical and laboratory observations
407
19. Beiser GD, Epstein SE, Stampfer M, et al. Impairment of cardiac function in patients with pectus excavatum, with improvement after operative correction. N Engl J Med 1972;287:267.
Management of coronary artery disease in Hutchinson-Gilford syndrome John D. Dyck, MD, Tirone E. David, MD, Bruce Burke, MD,
Gary D. Webb, MD, Mark A. Henderson, MD, and Rodney S. Fowler, MD From the Divisions of Cardiology, The Hospital for Sick Children, and Toronto General Hospital, the Division of Cardiovascular Surgery, Toronto Western Hospital, and the Faculty of Medicine, University of Toronto, Ontario, C a n a d a
Hutchinson-Gilford s y n d r o m e (progeria) is characterized by severe growth r e t a r d a t i o n (which often leads to diagnosis in the first 2 years of life) and by the general appearance of p r e m a t u r e aging. Also of note are the loss of subcutaneous fat a n d hair, a b n o r m a l dentition, enlargem e n t a n d restricted mobility of the joints, characteristic facies and habitus, a n d p r e m a t u r e severe atherosclerosis) The most frequent causes of mortality, which occurs at a m e a n age of 13.4 years, are congestive h e a r t failure and acute myocardial infarction. 2 W e report, to our knowledge, the first patient with progeria to undergo coronary angiography, saphenous and internal m a m m a r y a r t e r y to coronary artery bypass surgery, and percutaneous t r a n s t u m i n a l angioplasty. Informed written consent for publication was obtained. CASE REPORT The patient, a 14-year-old white girl, was born at 43 weeks gestation to a 26-year-old gravida 1 mother and nonconsanguinous 38-year-old father. The pregnancy was complicated by hyperemesis, and the labor and delivery by fetal distress, nuchal cord, and hypoplastic infarcted placenta. The infant's birth weight was 2800 g. At 8 months of age the patient weighed 5.9 kg and was admitted to hospital for examination because of failure to thrive. No specific abnormalities could be demonstrated. At 18 months of age Submitted for publication Sept. 30, 1986; accepted April 14, 1987. Reprint requests: John D. Dyck, MD, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
she weighed 7.7 kg, and a tentative diagnosis of progeria was made on the basis of descriptive features. Over the ensuing years the classic signs and clinical course developed. Repeated IQ testing demonstrated bright normal intelligence. Significant debility has resulted from orthopedic complications and from cardiovascular disease. At ages 7 and 9 years the patient had two separate episodes of transient right-sided hemiplegia, and she continues to have episodic vertigo. Carotid angiography on two occasions has demonstrated severe atherosclerotic disease of the vertebral system and complete occlusion of the left internal carotid artery. Chest pain radiating to the left arm and relieved by sublingual nitroglycerin, but initially unaccompanied by electrocardiographic changes or cardiac enzyme elevations, first appeared at 9 years of age. The subsequent course has been that of progressive angina pectoris, with a documented myocardial infarction at 11 years of age. At the time of admission to hospital the patient was 14 years of age and weighed 13.8 kg. She was experiencing 20 to 30 episodes of chest pain each day, and was limited to bed and wheelchair. Her medications included sublingual nitroglycerin (with each episode of chest pain), isosorbide dinitrate, propranolol, diltiazem, digoxin, and acetylsalicylic acid. She had no sexual development, decreased subcutaneous fat, craniofacial disproportion with micrognathia, complete alopecia, prominent scalp veins, abnormal dentition, bilateral cataracts, coxa valga, prominent joints with decreased range of motion, "'sclerodermatous'" brown spotted skin, thin lips, a thin high-pitched voice, and dystrophic nails. There was a right-sided carotid bruit, audible $3, grade 2/6 ejection systolic murmur along the left sternal border, and grade 3/6 pansystolic murmur at the apex and radiating to the left axilla, consistent with mitral regurgitation. A chest roentgenogram was within normal limits, and an ECG
Clinical and laboratory observattons
insulin regimen. Improved diabetes control was achieved with a lower dose of insulin, presumably because of better absorption from rotated injection sites." The diagnosis of insulin-induced swelling is based on the exclusion of all other major causes of edema, 9 its temporal relationship to improved diabetes control, and its transient and benign nature? ,7,8 Our patient's findings met these criteria because of the absence of evident cardiovascular, renal, or hepatic disease. Insulin in physiologic concentrations has been shown to act directly on the distal nephron of dogs to enhance sodium reabsorption. 4 In normal humans, this effect appears to be independent of changes in filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration? A reduction in urinary sodium excretion and positive sodium balance, leading to weight gain and edema, have been demonstrated in patients with nonketotic diabetes treated with insulin. 2 This reduced sodium clearance has not been explained by decreased urinary glucose excretion or preexisting sodium deficits. Although the incidence of insulin edema is assumed to be rare] the occurrence of positive sodium balance in newly treated diabetes or in patients who vary in degree of compliance may be quite common. The few reports of this phenomenon 7,~ and the exclusion of insulin-induced edema from a differential diagnosis of swelling9,1o may be because edema is generally attributed to congestive failure, vascular insufficiency, or proteinuria, all of which commonly occur in this population. Insulin-induced antinatriuresis can aggravate these more serious abnormalitiesJ 2 Sodium retention and edema may be a transient, untoward effect of the institution or alteration of insulin regimens. The
The Journal of Pediatrics September 1987
differential diagnosis of edema in patients with insulindependent diabetes mellitus should include this entity. REFERENCES
1. VonNoorden C, Isaac S. Die: Zuckerkrankheit. Und ihre behandlung. Berlin: J Springer, 1927:535. 2. Saudek CD, Boulter PR, Knopp RH, Arky RA. Sodium retention accompanying insulin treatment of diabetes mellitus. Diabetes 1974;23:240-6. 3. DeFronzo RA, Cooke RC, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975;55:845-5. 4. DeFronzo RA, Goldberg M, Agus ZS. The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 1976;58:83-90. 5. DeFronzo RA. The effect of insulin on renal sodium metabolism: a review with clinical implications. Diabetologia 1981;21:165-71. 6. Foster DW. Diabetes mellitus. In: Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD, eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw-Hill, 1983;662. 7. Bleach NR, Dunn PJ, Khalafalla ME, McConkey B. Insulin oedema. Br Med J 1979;2:177-8. 8. Lawrence JR, Dunningan MG. Diabetic (insulin) oedema. Br Med J 1979;2:445. 9. Braunwald E. Edema. In: Petersdorf RG, Adams RD, Braunwald E, lsselbacher KJ, Martin JB, Wilson JD, eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw-Hill, 1983:167. 10. Finberg L, Kravath RE, Fleischman AR. Water and electrolytes in pediatrics: physiology, pathophysiology and treatment. Philadelphia: WB Saunders, 1982;108. 1t. Young R J, Hannan W J, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care 1984;7:479-80. 12. Sheehan JP, Sisam DA, Schumacker OP. Insulin-induced cardiac failure. Am J Med 1985;79:I47-8.
Mitral valve prolapse associated with pectus excavatum Robert C. S h a m b e r g e r , MD, K e n n e t h J. W e l c h , MD, a n d S t e p h e n P. Sanders, MD From the Departments, of Surgery and Cardiology, The Children's Hospital and Harvard Medical School, Boston
Mitral valve prolapse occurs in patients with narrow anteroposterior chest diameters, 1 anterior chest wall deforSubmitted for publication Jan. 12, 1987; accepted April 21, 1987. Reprint requests: Robert C. Shamberger, MD, Department of Surgery, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
mities, and scoliosis. 2-4 One prospective study in adults demonstrated mitral valve prolapse by echocardiogram in six of 33 patients (18%) with pectus excavatum, 5 and a French study identified mitral valve prolapse in 11 (65%) of 17 patients with pectus excavatum. 6 Anterior Compression of the heart against the vertebral column by the depressed sternum, with resulting deformity of the mitral
Volume 111 Number 3
anulus, has been proposed as the cause of mitral valve prolapse in these patients. 7 The natural history of mitral valve prolapse in these patients and the effect of repair of the chest wall deformity have not been studied; thus we examined a group of patients with pectus excavatum and mitral valve prolapse to define the effect of surgical correction of the chest wall deformity on mitral valve prolapse. METHODS From December 1976 to December 1985, we evaluated 429 patients (329 male) for primary repair of pectus exeavatum. In 80 patients, a preoperative M-mode echocardiogram (57 patients), two-dimensional echocardiogram (15 patients), or combined study (eight patients) was obtained because of auscultatory findings of mid-systolic click (11 patients), unusually prominent systolic murmur relative to the systolic murmur frequently present in patients with pectus excavatum, 7 or particularly severe pectus deformity. Fifty-seven of the patients were male. Ages ranged from 2 to 41 years (mean 14.3 years). All echocardiograms were obtained in a standard manner with the patient supine, sitting, or standing, using an Irex Continue Trace System (Irex Corp., Ramsey, N.J.), an ultrasound imaging system (Model 77020A, HewlettPackard Co., Waltham, Mass.), or Mark 600 Cardio Series, (Advanced Technology Laboratories, Inc., Bellevue, Wash.). Criteria used to define mitral valve prolapse for M-mode studies were those proposed by Markiewicz et al. 8 Criteria for two-dimensional studies were systolic arching of the mitral leaflets in the parasternal long-axis view, posterior systolic bowing in the apical four-chamber view, or systolic coaption of both leaflets at or behind the plane of the mitral anulus.9 Patients were considered to have mitral valve prolapse if these criteria were achieved in the supine or sitting position, but not if a Valsalva maneuver or standing was required to elicit them. Studies were performed or reviewed by one of us (S.P.S.). RESULTS No evidence for mitral valve prolapse was demonstrated by echocardiogram in 45 patients. Thirty-five patients met the criteria for mitral valve prolapse (Table I). Only one patient had mild mitral regurgitation by Doppler study, and did not undergo surgical repair of the pectus deformity; mitral regurgitation was not present on follow-up study. Two patients had Marfan syndrome with associated aortic root dilation and aortic valve regurgitation, and were excluded from the study. Seven patients did not undergo surgical repair of the chest wall deformity. Five of these seven were available for follow-up study after an interval of 5 months to 5 years, and in one patient, the mitral valve prolapse could no longer be demonstrated.
Clinical and laboratory observations
405
T a b l e I. Results in patients with mitral valve prolapse and pectus excavatum Marfan syndrome No surgical repair Surgical repair No postoperative study Resolution of mitral valve prolapse Persistent mitral valve prolapse
2 7 26 3 t0 13
Table II. Preoperative electrocardiographic findings in patients with mitral valve prolapse and pectus excavatum Incomplete right bundle branch block Probable left ventricular hypertrophy Left atrial enlargement Left-axis deviation Right atrial enlargement Complete right bundle branch block Occasional premature ventricular contractions Within normal limits No ECG available
10 6 5 4 2 2 1 9 6
Twenty-six patients with mitral valve prolapse underwent surgical repair; of these, 23 were available for postoperative studies. Mitral valve prolapse was not demonstrable on the postoperative echocardiogram in 10 of these 23 patients (study obtained 7 months to 9.7 years after surgery, median 4.1 years); the remaining 13 patients had persistent mitral valve prolapse (study obtained 6 months to 5.8 years after surgerY, median 1.6 years). There was no significant difference between the ages of the groups in which mitral valve prolapse resolved (mean _+ SD 13.6 + 6.9 years) or persisted (mean 17.7 _+ 5.8 years, Student t test P >0.25). Seven of the 10 patients with resolution of mitral valve prolapse were younger than 16 years of age when chest wall repair was performed; only four of the 13 patients with persistent prolapse were younger than 16 years. No significant difference was present between resolution of mitral valve prolapse in patients who underwent operations versus those who did not (chi-square test for a 2 X 2 table, P >0.25). Preoperative 12-lead electrocardiograms were obtained in 30 of the 36 patients with mitral valve prolapse. Minor abnormalities were noted in 21 patients (Table II). Twenty-four-hour monitoring was not done. Patients with mitral valve prolapse operated on for pectus excavatum have been followed up for a mean of 3.8 years (range 6 months to 9.7 years). Cerebrovascular accidents, infective endocarditis, or sudden death did not occur in this series. Prophylactic antibiotics were recommended for all dental and surgical procedures while the identifying murmur, clicks, or prolapse by echocardiogram persisted:
406
Clinical and laboratory observations
DISCUSSION Mitral valve prolapse is a common clinical entity with a frequency in the general population of 5% to 7% 1~ II and a frequency of 1% in a pediatric population? 2 The clinical challenge remains to define which patients in this large population are at significant risk for the major complications of mitral valve prolapse. A recent study suggests that patients with redundant mitral valve leaflets are at much greater risk for complications than are patients with nonredundant valves? 3 Others have suggested that prognosis is best related to extent of mitral regurgitation. 14 Jeresaty 15 has proposed dividing patients wit h mitral valve prolapse into those with primary myxomatous degeneration of the valvular apparatus and those with a secondary form and reduced left ventricular volumes. Cheng 16 defined these two populations as those with "too m u c h " valve apparatus or "too littie" cavity size. MitraI valve prolaps e associated with pectus exeavatum could be classified as a secondary form according to both of these schema. The suggestion has been made that such patients are at a much lower risk for complications than are patients with the primary form of the disease. Resolution of thi s question must await study of a larger group of patients. In our population of 33 patients (excluding two patients with Marfan syndrome), no episodes Of infective endocarditis, cerebral embolism, major ventricular arrhythmia, or sudden death have occurred. N o specific abnormalities were identified on standard 12-lead electrocardiograms, but 24-hour electrocardiographic monitoring or exercise testing is required to document the arrhythmias described in patients with mitral valve prolapse. The frequent association of a systolic murmur in patients with pectus excavatum has been attributed to turbulent flow Within the ventricle and pulmonary outflow tract. Angiographic studies have defined diminished ventricular volumes and limited cardiac output, 17 which are normalized after chest wall reconstruction28.j9 The frequency of mitral valve prolapse identified in our population may have been larger if all patients had been examined with echocardiography. The mid-systolic click may be absent or may be concealed by the prominent systolic murmur at the left sternal border. 4 In addition, 5% to 7% of patients have "silent" mitral valve prolapse and no audible murmurs or clicks. Resolution of mitral valve prolapse has been demonstrated after surgical closure of an atrial septal defect. It has also been reported after revascularization in patients with coronary artery insufficiency in whom papillary muscle dysfunction resulting f r o m ischemia was proposed
The Journal of Pediatrics September 1987
as the cause of the valvular dysfunction. In our patients, mitral valve prolapse could not be demonstrated in 43% of the patients after surgical correction of the chest wall deformity. W h a t effect the resolution of echocardiographically defined mitral valve prolapse will have on its natural history and serious complications can be established only by further follow-up studies. REFERENCES*
1. Schutte JE, Gaffney FA, Blend L, et al. Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 1981;71:533. 2. Bisset GS III, Schwartz DC, Meyer RA, et al. Clinical spectrum and long-term follow-up of isolated mitral valve prolapse in 119 children. Circulation 1980;62:423. 3. Bon Tempo CP, Ronan JA Jr, de Leon AC Jr, et al. Radiographic appearance of the thorax in systolic click-late systolic murmur syndrome. Am J Cardiol 1975;36:27. 4. Salomon J, Shah PM, Heinle RA: Thoracic skeletal abnormalities in idiopathic mitral valve prolapse. Am J Cardiol 1975;36:32. 5. Udoshi MB, Shah A, Fisher VJ, Dolgin M. Incidence of mitral valve prolapse in subjects with thoracic skeletal abnormalities: a prospective study. Am Heart J 1979;97:303. 6. Saint-Mezard G, Duret JC, Chanudet X, et al. Prolapsus valvulaire mitral et pectus excavatum: association fortuite ou groupement syndromique? La Presse Med 1986;15:439. 7. Welch KJ. Chest wall deformities. In: Holder TM, Ashcraft K W , eds. Pediatric surgery. PhiladelPhia: WB Saunders, 1980:162. 8. Markiewicz W, Stoner J, London E, et al. Mitral valve prolapse in one hundred presumably healthy young females. Circulation 1976;53:464. 9. Alpert MA, Carney R J, Flaker GC, et al. Sensitivity and specificity of two-dimensional echocardiographic signs of mitral valve prolapse. Am J Cardiol 1984;54:792. 10. Procacci PM, Savran SV, Schreiter SL, et al. Prevalence of clinical mitral-valve prolapse in 1169 young women. N Engl J Med 1976;294:1086. 11. Savage DD, Garrison R J, Devereux R B, et al. Mitral valve prolapse in the general population. I. Epidemiologic features: the Framingham study. Am Heart J 1983;106:571. 12. Warth DC, King ME, Cohen JM, et al. Prevalence of mitral valve prolapse in normal children. J Am Coll Cardiol 1985; 5:1173. 13. Nishimura RA, McGoon MD, Shub C, et aI. Echocardiographically documented mitral-valve prolapse: long-term followup Of 237 patients. N Engl J Med 1985;313:1305. 14. Wynne J. Mitral-valve prolapse. N Engl J Med 1986;314: 577. 15. Jeresaty RM. Mitral ballooning: a possible mechanism of mitral insufficiency in diseases associated with reduced endsystolic volume of the left ventricle. Chest 1971;60:114. 16. Cheng TO. The click-murmur syndrome: a medical pendulum and a unifying concept. Chest 1976;70:569. *List of references shortened at request of the Editor.
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17. Diaz FV, Pelous AN, Vald6s FG, et al. Peetus excavatum: hemodynamic and electrocardiographic considerations. Am J Cardiol 1962;10:272. 18. Beveggtrd S. Postural circulatory changes at rest and during exercise in Patients with funnel chest, with special reference to factors affecting the stroke volume. Acta Med Scand 1962; 171:695.
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19. Beiser GD, Epstein SE, Stampfer M, et al. Impairment of cardiac function in patients with pectus excavatum, with improvement after operative correction. N Engl J Med 1972;287:267.
Management of coronary artery disease in Hutchinson-Gilford syndrome John D. Dyck, MD, Tirone E. David, MD, Bruce Burke, MD,
Gary D. Webb, MD, Mark A. Henderson, MD, and Rodney S. Fowler, MD From the Divisions of Cardiology, The Hospital for Sick Children, and Toronto General Hospital, the Division of Cardiovascular Surgery, Toronto Western Hospital, and the Faculty of Medicine, University of Toronto, Ontario, C a n a d a
Hutchinson-Gilford s y n d r o m e (progeria) is characterized by severe growth r e t a r d a t i o n (which often leads to diagnosis in the first 2 years of life) and by the general appearance of p r e m a t u r e aging. Also of note are the loss of subcutaneous fat a n d hair, a b n o r m a l dentition, enlargem e n t a n d restricted mobility of the joints, characteristic facies and habitus, a n d p r e m a t u r e severe atherosclerosis) The most frequent causes of mortality, which occurs at a m e a n age of 13.4 years, are congestive h e a r t failure and acute myocardial infarction. 2 W e report, to our knowledge, the first patient with progeria to undergo coronary angiography, saphenous and internal m a m m a r y a r t e r y to coronary artery bypass surgery, and percutaneous t r a n s t u m i n a l angioplasty. Informed written consent for publication was obtained. CASE REPORT The patient, a 14-year-old white girl, was born at 43 weeks gestation to a 26-year-old gravida 1 mother and nonconsanguinous 38-year-old father. The pregnancy was complicated by hyperemesis, and the labor and delivery by fetal distress, nuchal cord, and hypoplastic infarcted placenta. The infant's birth weight was 2800 g. At 8 months of age the patient weighed 5.9 kg and was admitted to hospital for examination because of failure to thrive. No specific abnormalities could be demonstrated. At 18 months of age Submitted for publication Sept. 30, 1986; accepted April 14, 1987. Reprint requests: John D. Dyck, MD, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
she weighed 7.7 kg, and a tentative diagnosis of progeria was made on the basis of descriptive features. Over the ensuing years the classic signs and clinical course developed. Repeated IQ testing demonstrated bright normal intelligence. Significant debility has resulted from orthopedic complications and from cardiovascular disease. At ages 7 and 9 years the patient had two separate episodes of transient right-sided hemiplegia, and she continues to have episodic vertigo. Carotid angiography on two occasions has demonstrated severe atherosclerotic disease of the vertebral system and complete occlusion of the left internal carotid artery. Chest pain radiating to the left arm and relieved by sublingual nitroglycerin, but initially unaccompanied by electrocardiographic changes or cardiac enzyme elevations, first appeared at 9 years of age. The subsequent course has been that of progressive angina pectoris, with a documented myocardial infarction at 11 years of age. At the time of admission to hospital the patient was 14 years of age and weighed 13.8 kg. She was experiencing 20 to 30 episodes of chest pain each day, and was limited to bed and wheelchair. Her medications included sublingual nitroglycerin (with each episode of chest pain), isosorbide dinitrate, propranolol, diltiazem, digoxin, and acetylsalicylic acid. She had no sexual development, decreased subcutaneous fat, craniofacial disproportion with micrognathia, complete alopecia, prominent scalp veins, abnormal dentition, bilateral cataracts, coxa valga, prominent joints with decreased range of motion, "'sclerodermatous'" brown spotted skin, thin lips, a thin high-pitched voice, and dystrophic nails. There was a right-sided carotid bruit, audible $3, grade 2/6 ejection systolic murmur along the left sternal border, and grade 3/6 pansystolic murmur at the apex and radiating to the left axilla, consistent with mitral regurgitation. A chest roentgenogram was within normal limits, and an ECG