CARDIOMYOPATHY
Prognostic
Features of Children with Idiopathic Dilated Cardiomyopathy
Henry B. Wiles, MD, Patrick D. McArthur, MD, Ashby B. Taylor, MD, Paul C. Gillette, MD, Derek A. Fyfe, MD, John P. Matthews, MD, and Leslie W. Shelton, MD
The presenting features and long-term outcome of 39 children (median age 6.5 months, range 1 day to 16 years) with idiopathic dilated cardiomyopathy (IDC) were reviewed to help determine the appropriate management of these patients. Four outcome groups were identified: those who died, improved, had IDC resolved or received transplants. Presenting clinical features of age, sex, race, congestive heart failure, cardiomegaly, and degree of systolic ventricular dysfunction did not predict final outcome. Left ventricular hypertrophy on the electrocardiogram was seen significantly more often in children who improved than in those who died or in whom IDC resolved (p = 0.662). A rhythm disturbance was also see more often in those who died than in those who survived (p = 0.025). Of 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) resolved. Eighteen of 26 (69%) patients presenting at age I2 years survived, whereas 6 of 10 patients >2 years survived. There were no differences based on age at presentation, in the time to death or time of follow-up. Three patients received orthotopic heart transplants, 1 of whom died from graft failure. Thus, no clinical feature including age at presentation consistently predicts ultimate outcome in children with IDC. (Am J Cardiol 1991;68:1372-1376)
From the South Carolina Children’s Heart Center, Medical University of South Carolina, Charleston; Children’s Hospital, Greenville Hospital System, Greenville; and the Department of Pediatrics, University of South Carolina Medical School, Columbia, South Carolina. Manuscript received April 16,199l; revised manuscript received July 1,1991, and accepted July 5. Address for reprints: Henry B. Wiles, MD, Pediatric Cardiology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425.
1372
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
68
dentifying the cause and managing children with idiopathic dilated cardiomyopathy (IDC) still presents a substantial clinical problem. Although extensive reports of IDC in adults are published,‘-3 only recently have additional reports added necessaryinformation about the presentation and outcome of children with IDC.4m6Areas that require further information are the clinical progressionof IDC, the appropriate use of diagnostic procedures such as endomyocardial biopsy, and the appropriate selection and timing of treatment modalities and transplantation. This report describes the presenting features, diagnostic evaluation and clinical outcome of a relatively large group of children with IDC from an entire state referral population and not just from a tertiary center. This information, combined with other reports, is important to help understand the nature of IDC in children and to establish appropriate management.
I
METHODS Patient selection: Subjects for this study were collected from the records of a state children’s medical center and its consortium hospitals. Records between July 1966 and June 1990 were searchedretrospectively for all patients with IDC as a primary diagnosis.Diagnosis was made on the basis of cardiomegaly or evidcnce of poor left ventricular systolic function by cardiac catheterization, echocardiography or autopsy in all cases.Patients with IDC secondary to arrhythmia or anatomic anomaly were excluded from the study, as were patients with hypertrophic or restrictive cardiomyopathy. Charts of patients with IDC were reviewed for data on age and condition at initial presentationand at latest follow-up. Systolic left ventricular function was measured by the degree of fractional shortening in the minor axis (normal 31 to 42%). Left ventricular size at end-diastole was measured in the minor axis on Mmode recordings. To compare values with those of normal children, a ratio of measuredend-diastolic dimension to the upper normal value for age and size was used. This value was labeled the left ventricular dimension ratio. A ratio of 5 1 indicates a ventricular dimension within 2 standard deviations of the mean. Analysis of data: Each patient was followed until death, resolution of IDC, loss to follow-up, or through NOVEMBER
15, 1991
r
TABLE
I Clinical Features of Children with Dilated Cardiomyopathy At Follow-Up
At Presentation
Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
sex F M F M M M F F F M M F F F M F F M F F F F F M M M M M F F F M M M F F M M M
Age ho) Birth 0.2 0.4 1 5 6 14 16 48 84 144 146 2 3 3 3 4 4 6 7 7 7 7 21 36 48 192 0.15 2 6 6 6 6 27 84 180 144 156 156
CHF + + + + + + f + + + + + + + + + + + + + + + + + + + + + + + + + + + 0 + + + +
Arrhyth. + 0 + 0 0 0 0 0 + + 0 0 0 0 + + 0 0 + 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 + 0 0
LVH
CMCXR*
-
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
0 0 0 + + 0 0 0 0 0 0 + + + + + + + 0 + 0 + + + + 0 0 0 0 0 0 0 0 + 0 + 0 0
*Cardiomegaly defined as cardiothoracic ratio >0.55. Arrhyth. = arrhythmia; CHF = congestive heart failure; CMCXR = cardiamegaly hypertrophy; SF = shorteningfraction; + = positive; 0 = negative; - = not done.
SF (%)
LVD Ratio
15 -
-
8 -
1.14 1.15 -
13 14 -
1.36 1.61 -
24
1.39
-
-
15 11 25 18 13 17 27 -
1.30 1.15 1.60 1.56 1.33 1.17 1.11 -
17 22 23 9 12
1.89 1.89 1.30 1.81 1.33
9 16 28 14 16 20 23 11 17
1.56 1.35 1.00 1.57 1.92 1.19 1.71 1.08 1.55
14 10 3 20
1.37 1.59 1.55 1.46
Follow-Up (mos) 50 0.03 2 0.75 144 7 3 2 18 4 2 0.73 252 4 108 96 84 194 204 64 10 223 98 23 90 36 22 36 69 84 24 27 28 95 24 30 24 22 1
an chest roentgenography;
the most recent clinic visit. Only 3 patients were lost to follow-up 2, 7 and 15 years after initial diagnosis. Patients were grouped by outcome-deceased, improved, IDC resolved or heart transplantation. To be classified as “resolved,” a patient had to be clinically asymptomatic, be taking no cardiac medications, have no cardiomegaly (cardiothoracic ratio 2 years (n = 10) *Excludes
,.-,
in Children*
~
I.-I
.-I
12 (33) 8 (31)
24 (67) 18 (69)
15 (43) 12 (46)
9 (25) 6 (23)
4 (40)
6 (60)
3 (30)
3 (30)
transplants.
L
at presentation was 6.5 months (range 1 day to 16 years). At presentation 26 (67%) were 52 years old and 13 (33%) were >2 years old. Follow-up and outcome: The demographic data previously listed include all 39 patients. Of the 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) had IDC resolved. Mean time to death was 19 months (mean f standard deviation 40 months, range 1 day to 12 years). Time to death was not signilicantly different for those who presented at _2 years of age. Mean follow-up time for patients who survived was 80 months (k 70 months, range 4 months to 21 years). Eighteen of 26 patients (69%) 52 years at presentation survived, whereas 6 of 10 (60%) patients >2 years at presentation survived (Table II). Actuarial survivorship values at 1 and 5 years are shown in Figure 1. There was no correlation betweensex, race, or age at presentation and survival or resolution. Clinical presentation: Thirty-eight (97%) patients had signs of congestive heart failure. Only 1 patient had syncope.Eighteen patients (5 1%) had a precordial murmur. Serum carnitine levels measured in 15 patients were all normal. There was no significant correlation between outcome and any of the aforementioned features.
Electrocardiography: On presentation, 37 of 38 patients (97%) had an abnormal electrocardiogram (hypertrophy, conduction disturbance, or ST segment and T-wave abnormality), with 16 (42%) showing left ventricular hypertrophy (Table I). When deceasedpatients were comparedwith survivors, left ventricular hypertrophy was seensignificantly less often in those who died (2 of 12 vs 13 of 24, p 2 Years
No. of Pk.
Died (%)
Survived (%)
No.
Died w
Survived (%)
No.
Died (%I
Survived (%I
161 23 24 32
57 11 15 17
104 12 9 15
99 10 12 20
32 5 4 5
67 (68) 5 (50) 8 (69) 15 (75)
62 13 12 12
25 6 11 12
37 (60) 7 (54) 1 (8)
(35) (48) (63) (53)
(65) (52) (38) (47)
(32) (50) (33) (25)
(40) (46) (92) (100)
plantation Registry records a worldwide 1-year survival in pediatric patients of approximately 70%. This does not differ from the 67% survival of transplanted patients in this study or the 67% survival of medically treated patients. Until diagnostic evaluation can accurately differentiate between the one-third who die, the one-third who improve and the one-third in whom IDC resolves, timing of transplantation for children with IDC remains a difficult problem. Age: Griffin et al5 reported a difference in outcome dependingon age at presentation.All patients who presented at >2 years of age died, whereas only 25% of patients presentedat 52 years old died. Taliercio et al4 did not discusspatients by age at presentation,but presentedsufficient data to show that 33% of children presenting 12 years of age died, whereas92% of children presenting at >2 years old died. The reports of Greenwood et al7 and Chen et aJ6 however,showedno significant differencesin outcome based on age at presentaDISCUSSION tion (Table III). The study population in this report Outcome: Four follow-up groups of children pre- showed a slightly higher mortality in patients presentsenting with IDC were found: those who died, those ing at >2 years (40 vs 3 1%) but this did not reach who improved after presentation but did not have re- statistical significance. This finding may reflect the fact turn of normal ventricular function, those in whom that this report covered an entire state population and IDC resolved, and those who underwent transplanta- not only patients referred to a tertiary center. tion. The definition for “resolved” was strict and inChest roentgenography and echocardiography: cluded normal left ventricular systolic function, normal Most investigators of IDC in children and adults have heart size, normal electrocardiogram, no clinical symp- found no significant differences in presenting clinical toms and requiring no cardiac ‘medication. The group signs.4-9Heart size at presentation as measured by with transplantation must be considered separately in cardiothoracic ratio on chest roentgenography did not follow-up becausethis surgical procedure drastically al- predict outcome in this study. As with chest roentters the course of IDC. The outcome of the 36 children genography, measurement of left ventricular indexes, who received medical therapy included 33% who died, shortening fraction and end-diastolic dimension on pre42% who improved and 25% in whom IDC resolved. sentation provided no prognostic information. FollowThese numbers correspond closely to the results of up echocardiography near the time of death or long Greenwoodet al7 who reviewed the courseof 161 pedi- term again showed that patients who died had worse atric patients with “primary myocardial disease” (Ta- left ventricular function as measuredby these parameble III). Other studies4-‘jhave shown higher mortality ters. Further prospectivestudy may indicate that how rates of 48 to 63% (Table III). rapid or slow function returns may predict eventual The small number of patients undergoing transplan- outcome. tation in this study does not allow comparison of outElectrocardiography: Studies of adults and children come with those receiving medical therapy alone; how- have shown that atria1 and ventricular arrhythmias are ever, the 1990 International Society of Heart Trans- poor prognostic signsin patients with IDC.5,s Only 15% remaining patient had areas of focal lymphocytic inliltration with myocyte necrosis,representing acute myocarditis. One other patient had an increasednumber of lymphocytes throughout the myocardium but no areas of myocyte necrosis. Treatment: Thirty-six patients receivedonly medical treatment. Thirty-four (94%) were treated with inotropit agents, 21 (58%) with afterload reducers, 6 (17%) with antiarrhythmic drugs, and 2 (6%) with antiinflammatory agents. There was no significant correlation between outcome and type of medical management. Transplantation: Three patients received cardiac transplants (Table I). There were no significant differencesin clinical presentation between the transplant recipients and other patients. One transplant recipient died after 2 cardiac grafts failed, 1 month after diagnosis.
CHILDREN WITH DILATED CARDIOMYOPATHY
1375
of the patients in this study presentedwith ventricular ectopy, and their long-term outcome was worse. The absenceof left ventricular hypertrophy on the presenting electrocardiogram showed a statistically significant difference between death or resolution and improvement. Other reports have noted a similar finding in adultslOJ1but not in children.4 The theory explaining this finding is that myocardial hypertrophy reduceswall stress. This theory applies to the difference seen between patients who died and those who improved, but it does not separatethe patients who died and those who ultimately had a complete resolveof IDC. The patients who had resolution of IDC must have had significantly lessdisease,but no other clinical test at presentation in this series allowed prediction of outcome. Myocarditis: The association of myocarditis and IDC has always been assumed.The clinical cliche that IDC represents“burned out myocarditis” is hardly ever convincingly proved. The number of casesof biopsyprove myocarditis in children presenting with unexplained IDC appearssmall. Lewis et alI2 found no evidenceof myocarditis in 15 children. Leatherbury et al13 obtained biopsy specimensfrom 20 children and found myocarditis in 25%, but 1 of these had sarcoidosisand another had transplacental antinuclear antibodies from maternal systemic lupus erythematosus. These do not represent the typical case of a child presenting with IDC and possible myocarditis. Only 1 of 14 (7%) patients undergoing a biopsy procedure in this study had evidenceof myocarditis by the criteria of Aretz et a1.14 Overall, the incidence of biopsy-proved myocarditis in children presenting with IDC appearsto be 2 to 15%. Study limitations: This report, as with all others, is a retrospective review of patients over a relatively long period of time and has its shortcomings. Diagnostic techniques varied over this time period, so careful attention was paid to help eliminate conditions not representing IDC. Becausewe cannot differentiate the many
1376
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
causesof dilated cardiomyopathy, information on outcome cannot be specifically grouped based on cause. Using chart review, we were unable to gather enough information to track the rate of recovery in patients who survived. The rate of recovery may be the best indicator of ultimate outcome.
REFERENCES 1. Johnson RA, Palacios I. Dilated cardiomyopathies of the adult. N Engl J Med 1982;307:1051-1058. 2. Johnson RA, Palacios I. Dilated cardiomyopathies of the adult. N Eng/ J Med 1982;307:1119~1126. 3. Keogh AM, Baron DW, Hickie JB. Prognostic guides in patients with idiopathic or ischemic dilated cardiomyopathy assessedfor cardiac transplantation. Am .I Cardiol 1990;65:903-908. 4. Taliercio CP, Seward JB, Driscoll DJ, Fisher LD, Gersh BJ, Tajik AJ. Idiopathic dilated cardiomyopathy in the young: clinical profile and natural history. J Am Co11 Cardiol 1985;6:1126-1131. 5. Griffin ML, Hernandez A, Martin TC, Goldring D, Bolman RM, Spray TL, Strauss AW. Dilated cardiomyopathy in infants and children. J Am Coil Cardiol 1988;11:139-144. 6. Chen S, Nouri S, Balfour I, Jureidini S, Appleton RS. Clinical profile of congestive cardiomyopathy in children. J Am CON Cardiol 1990;15:189-193. 7. Greenwood RD, Nadas AS, Fyler DC. The clinical course of primary myocardial disease in infants and children. Am Heart J 1976;92:549-560. 8. Hofmann T, Meinertz T, Kasper W, Geibel A, Zehender M, Hohnloser S, Stienen U, Treese N, Just H. Mode of death in idiopathic dilated cardiomyopathy: a multivariate analysis of prognostic determinants. Am Heart J 1988;116: 1455-1463. 9. Romeo F, Pelliccia F, Cianfrocca C, Gallo P, Barilla D, Cristofani R, Reale A. Determination of end-stage idiopathic dilated cardiomyopathy: a multivariate analysis of 104 patients. Clin Cardiol 1989;12:387-392, IQ. Goodwin JF. Congestive and hypertrophic cardiomyopathies: a decade of study. Lancet 1970;1:731-739. 11. Benjamin IJ, Schuster EH, Bulkley BH. Cardiac hypertrophy in idiopathic dilated congestive cardiomyopathy: a clinicopathologic study. Circulation 198 1; 64~442-441. 12. Lewis AB, Niestein HB, Takahashi M, Lurie PR. Findings on endomyocardial biopsy in infants and children with dilated cardiomyopathy. Am J Cardiol 1985;55:143-145. 13. Leatherbury L, Chandra RS, Shapiro SR, Perry LW. Value of endomyocardial biopsy in infants, children and adolescents with dilated or hypertrophic cardiomyopathy and myocarditis. J Am Coil Cardiol 1988;12:1547-1554. 14. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ, Olsen EG, Schoen FJ. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14.
NOVEMBER 15, 1991
Prognostic
Features of Children with Idiopathic Dilated Cardiomyopathy
Henry B. Wiles, MD, Patrick D. McArthur, MD, Ashby B. Taylor, MD, Paul C. Gillette, MD, Derek A. Fyfe, MD, John P. Matthews, MD, and Leslie W. Shelton, MD
The presenting features and long-term outcome of 39 children (median age 6.5 months, range 1 day to 16 years) with idiopathic dilated cardiomyopathy (IDC) were reviewed to help determine the appropriate management of these patients. Four outcome groups were identified: those who died, improved, had IDC resolved or received transplants. Presenting clinical features of age, sex, race, congestive heart failure, cardiomegaly, and degree of systolic ventricular dysfunction did not predict final outcome. Left ventricular hypertrophy on the electrocardiogram was seen significantly more often in children who improved than in those who died or in whom IDC resolved (p = 0.662). A rhythm disturbance was also see more often in those who died than in those who survived (p = 0.025). Of 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) resolved. Eighteen of 26 (69%) patients presenting at age I2 years survived, whereas 6 of 10 patients >2 years survived. There were no differences based on age at presentation, in the time to death or time of follow-up. Three patients received orthotopic heart transplants, 1 of whom died from graft failure. Thus, no clinical feature including age at presentation consistently predicts ultimate outcome in children with IDC. (Am J Cardiol 1991;68:1372-1376)
From the South Carolina Children’s Heart Center, Medical University of South Carolina, Charleston; Children’s Hospital, Greenville Hospital System, Greenville; and the Department of Pediatrics, University of South Carolina Medical School, Columbia, South Carolina. Manuscript received April 16,199l; revised manuscript received July 1,1991, and accepted July 5. Address for reprints: Henry B. Wiles, MD, Pediatric Cardiology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425.
1372
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
68
dentifying the cause and managing children with idiopathic dilated cardiomyopathy (IDC) still presents a substantial clinical problem. Although extensive reports of IDC in adults are published,‘-3 only recently have additional reports added necessaryinformation about the presentation and outcome of children with IDC.4m6Areas that require further information are the clinical progressionof IDC, the appropriate use of diagnostic procedures such as endomyocardial biopsy, and the appropriate selection and timing of treatment modalities and transplantation. This report describes the presenting features, diagnostic evaluation and clinical outcome of a relatively large group of children with IDC from an entire state referral population and not just from a tertiary center. This information, combined with other reports, is important to help understand the nature of IDC in children and to establish appropriate management.
I
METHODS Patient selection: Subjects for this study were collected from the records of a state children’s medical center and its consortium hospitals. Records between July 1966 and June 1990 were searchedretrospectively for all patients with IDC as a primary diagnosis.Diagnosis was made on the basis of cardiomegaly or evidcnce of poor left ventricular systolic function by cardiac catheterization, echocardiography or autopsy in all cases.Patients with IDC secondary to arrhythmia or anatomic anomaly were excluded from the study, as were patients with hypertrophic or restrictive cardiomyopathy. Charts of patients with IDC were reviewed for data on age and condition at initial presentationand at latest follow-up. Systolic left ventricular function was measured by the degree of fractional shortening in the minor axis (normal 31 to 42%). Left ventricular size at end-diastole was measured in the minor axis on Mmode recordings. To compare values with those of normal children, a ratio of measuredend-diastolic dimension to the upper normal value for age and size was used. This value was labeled the left ventricular dimension ratio. A ratio of 5 1 indicates a ventricular dimension within 2 standard deviations of the mean. Analysis of data: Each patient was followed until death, resolution of IDC, loss to follow-up, or through NOVEMBER
15, 1991
r
TABLE
I Clinical Features of Children with Dilated Cardiomyopathy At Follow-Up
At Presentation
Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
sex F M F M M M F F F M M F F F M F F M F F F F F M M M M M F F F M M M F F M M M
Age ho) Birth 0.2 0.4 1 5 6 14 16 48 84 144 146 2 3 3 3 4 4 6 7 7 7 7 21 36 48 192 0.15 2 6 6 6 6 27 84 180 144 156 156
CHF + + + + + + f + + + + + + + + + + + + + + + + + + + + + + + + + + + 0 + + + +
Arrhyth. + 0 + 0 0 0 0 0 + + 0 0 0 0 + + 0 0 + 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 + 0 0
LVH
CMCXR*
-
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
0 0 0 + + 0 0 0 0 0 0 + + + + + + + 0 + 0 + + + + 0 0 0 0 0 0 0 0 + 0 + 0 0
*Cardiomegaly defined as cardiothoracic ratio >0.55. Arrhyth. = arrhythmia; CHF = congestive heart failure; CMCXR = cardiamegaly hypertrophy; SF = shorteningfraction; + = positive; 0 = negative; - = not done.
SF (%)
LVD Ratio
15 -
-
8 -
1.14 1.15 -
13 14 -
1.36 1.61 -
24
1.39
-
-
15 11 25 18 13 17 27 -
1.30 1.15 1.60 1.56 1.33 1.17 1.11 -
17 22 23 9 12
1.89 1.89 1.30 1.81 1.33
9 16 28 14 16 20 23 11 17
1.56 1.35 1.00 1.57 1.92 1.19 1.71 1.08 1.55
14 10 3 20
1.37 1.59 1.55 1.46
Follow-Up (mos) 50 0.03 2 0.75 144 7 3 2 18 4 2 0.73 252 4 108 96 84 194 204 64 10 223 98 23 90 36 22 36 69 84 24 27 28 95 24 30 24 22 1
an chest roentgenography;
the most recent clinic visit. Only 3 patients were lost to follow-up 2, 7 and 15 years after initial diagnosis. Patients were grouped by outcome-deceased, improved, IDC resolved or heart transplantation. To be classified as “resolved,” a patient had to be clinically asymptomatic, be taking no cardiac medications, have no cardiomegaly (cardiothoracic ratio 2 years (n = 10) *Excludes
,.-,
in Children*
~
I.-I
.-I
12 (33) 8 (31)
24 (67) 18 (69)
15 (43) 12 (46)
9 (25) 6 (23)
4 (40)
6 (60)
3 (30)
3 (30)
transplants.
L
at presentation was 6.5 months (range 1 day to 16 years). At presentation 26 (67%) were 52 years old and 13 (33%) were >2 years old. Follow-up and outcome: The demographic data previously listed include all 39 patients. Of the 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) had IDC resolved. Mean time to death was 19 months (mean f standard deviation 40 months, range 1 day to 12 years). Time to death was not signilicantly different for those who presented at _2 years of age. Mean follow-up time for patients who survived was 80 months (k 70 months, range 4 months to 21 years). Eighteen of 26 patients (69%) 52 years at presentation survived, whereas 6 of 10 (60%) patients >2 years at presentation survived (Table II). Actuarial survivorship values at 1 and 5 years are shown in Figure 1. There was no correlation betweensex, race, or age at presentation and survival or resolution. Clinical presentation: Thirty-eight (97%) patients had signs of congestive heart failure. Only 1 patient had syncope.Eighteen patients (5 1%) had a precordial murmur. Serum carnitine levels measured in 15 patients were all normal. There was no significant correlation between outcome and any of the aforementioned features.
Electrocardiography: On presentation, 37 of 38 patients (97%) had an abnormal electrocardiogram (hypertrophy, conduction disturbance, or ST segment and T-wave abnormality), with 16 (42%) showing left ventricular hypertrophy (Table I). When deceasedpatients were comparedwith survivors, left ventricular hypertrophy was seensignificantly less often in those who died (2 of 12 vs 13 of 24, p 2 Years
No. of Pk.
Died (%)
Survived (%)
No.
Died w
Survived (%)
No.
Died (%I
Survived (%I
161 23 24 32
57 11 15 17
104 12 9 15
99 10 12 20
32 5 4 5
67 (68) 5 (50) 8 (69) 15 (75)
62 13 12 12
25 6 11 12
37 (60) 7 (54) 1 (8)
(35) (48) (63) (53)
(65) (52) (38) (47)
(32) (50) (33) (25)
(40) (46) (92) (100)
plantation Registry records a worldwide 1-year survival in pediatric patients of approximately 70%. This does not differ from the 67% survival of transplanted patients in this study or the 67% survival of medically treated patients. Until diagnostic evaluation can accurately differentiate between the one-third who die, the one-third who improve and the one-third in whom IDC resolves, timing of transplantation for children with IDC remains a difficult problem. Age: Griffin et al5 reported a difference in outcome dependingon age at presentation.All patients who presented at >2 years of age died, whereas only 25% of patients presentedat 52 years old died. Taliercio et al4 did not discusspatients by age at presentation,but presentedsufficient data to show that 33% of children presenting 12 years of age died, whereas92% of children presenting at >2 years old died. The reports of Greenwood et al7 and Chen et aJ6 however,showedno significant differencesin outcome based on age at presentaDISCUSSION tion (Table III). The study population in this report Outcome: Four follow-up groups of children pre- showed a slightly higher mortality in patients presentsenting with IDC were found: those who died, those ing at >2 years (40 vs 3 1%) but this did not reach who improved after presentation but did not have re- statistical significance. This finding may reflect the fact turn of normal ventricular function, those in whom that this report covered an entire state population and IDC resolved, and those who underwent transplanta- not only patients referred to a tertiary center. tion. The definition for “resolved” was strict and inChest roentgenography and echocardiography: cluded normal left ventricular systolic function, normal Most investigators of IDC in children and adults have heart size, normal electrocardiogram, no clinical symp- found no significant differences in presenting clinical toms and requiring no cardiac ‘medication. The group signs.4-9Heart size at presentation as measured by with transplantation must be considered separately in cardiothoracic ratio on chest roentgenography did not follow-up becausethis surgical procedure drastically al- predict outcome in this study. As with chest roentters the course of IDC. The outcome of the 36 children genography, measurement of left ventricular indexes, who received medical therapy included 33% who died, shortening fraction and end-diastolic dimension on pre42% who improved and 25% in whom IDC resolved. sentation provided no prognostic information. FollowThese numbers correspond closely to the results of up echocardiography near the time of death or long Greenwoodet al7 who reviewed the courseof 161 pedi- term again showed that patients who died had worse atric patients with “primary myocardial disease” (Ta- left ventricular function as measuredby these parameble III). Other studies4-‘jhave shown higher mortality ters. Further prospectivestudy may indicate that how rates of 48 to 63% (Table III). rapid or slow function returns may predict eventual The small number of patients undergoing transplan- outcome. tation in this study does not allow comparison of outElectrocardiography: Studies of adults and children come with those receiving medical therapy alone; how- have shown that atria1 and ventricular arrhythmias are ever, the 1990 International Society of Heart Trans- poor prognostic signsin patients with IDC.5,s Only 15% remaining patient had areas of focal lymphocytic inliltration with myocyte necrosis,representing acute myocarditis. One other patient had an increasednumber of lymphocytes throughout the myocardium but no areas of myocyte necrosis. Treatment: Thirty-six patients receivedonly medical treatment. Thirty-four (94%) were treated with inotropit agents, 21 (58%) with afterload reducers, 6 (17%) with antiarrhythmic drugs, and 2 (6%) with antiinflammatory agents. There was no significant correlation between outcome and type of medical management. Transplantation: Three patients received cardiac transplants (Table I). There were no significant differencesin clinical presentation between the transplant recipients and other patients. One transplant recipient died after 2 cardiac grafts failed, 1 month after diagnosis.
CHILDREN WITH DILATED CARDIOMYOPATHY
1375
of the patients in this study presentedwith ventricular ectopy, and their long-term outcome was worse. The absenceof left ventricular hypertrophy on the presenting electrocardiogram showed a statistically significant difference between death or resolution and improvement. Other reports have noted a similar finding in adultslOJ1but not in children.4 The theory explaining this finding is that myocardial hypertrophy reduceswall stress. This theory applies to the difference seen between patients who died and those who improved, but it does not separatethe patients who died and those who ultimately had a complete resolveof IDC. The patients who had resolution of IDC must have had significantly lessdisease,but no other clinical test at presentation in this series allowed prediction of outcome. Myocarditis: The association of myocarditis and IDC has always been assumed.The clinical cliche that IDC represents“burned out myocarditis” is hardly ever convincingly proved. The number of casesof biopsyprove myocarditis in children presenting with unexplained IDC appearssmall. Lewis et alI2 found no evidenceof myocarditis in 15 children. Leatherbury et al13 obtained biopsy specimensfrom 20 children and found myocarditis in 25%, but 1 of these had sarcoidosisand another had transplacental antinuclear antibodies from maternal systemic lupus erythematosus. These do not represent the typical case of a child presenting with IDC and possible myocarditis. Only 1 of 14 (7%) patients undergoing a biopsy procedure in this study had evidenceof myocarditis by the criteria of Aretz et a1.14 Overall, the incidence of biopsy-proved myocarditis in children presenting with IDC appearsto be 2 to 15%. Study limitations: This report, as with all others, is a retrospective review of patients over a relatively long period of time and has its shortcomings. Diagnostic techniques varied over this time period, so careful attention was paid to help eliminate conditions not representing IDC. Becausewe cannot differentiate the many
1376
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
causesof dilated cardiomyopathy, information on outcome cannot be specifically grouped based on cause. Using chart review, we were unable to gather enough information to track the rate of recovery in patients who survived. The rate of recovery may be the best indicator of ultimate outcome.
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