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Reversal of “inoperable” pulmonary hypertension
Case reports Reversal
of “inoperable”
pulmonary
hypertension
Isamu Kawabori, M.D. Beverly C. Morgan, M.D. Warren G. Guntheroth, M.D. Seattle, Wash.
Severe pulmonary hypertension associated with pulmonary vascular disease has been regarded as a contraindication for surgery in congenital heart disease because of the high operative mortality rate.’ This case report demonstrates the need to follow even those patients presumed to have inoperable heart disease. Changing clinical findings over a period of years in this patient indicated the need for thorough re-evaluation. Case history This child was born at approximately 25 weeks gestation, weighing 740 grams. She had mild idiopathic respiratory distress syndrome, severe apneic episodes, and hyperbilirubinemia. During her initial hospitalization she developed pneumonia. A Grade 216 machinery-type murmur, loudest at the left sternal border in the second intercostal space, was felt to represent a patent ductus arteriosus (PDA), but this murmur was not heard at the time of discharge from the premature nursery at 10 weeks of age. During her second hospitalization at six months of age for pneumonia, a systolic murmur was heard, tachycardia was present, and heart enlargement with normal pulmonary vascular markings was noted on chest x-ray (Fig. 1, A). Her third hospitalization at age six and a half months was again for pneumonia. She was admitted again at 11 months of age, four months following her last episode of recognizable pneumonia, in moderate distress with congestive heart failure. Chest x-ray films showed a few residual signs in the region previously involved with pneumonia and atelectasis (Fig. 1, B). The pulmonary vascularity was normal. Her clinical findings at this time included tachycardia, hepatomegaly, gallop rhythm, Grade l/6 blowing systolic murmur at the left sternal border with diastole remaining clear, and a markedly increased and unsplit second sound in the pulmonic area. There was differential cyanosis of the extremities with acyanotic fingernails From the Division of Pediatric Cardiology, Department of Pediatrics, University of Washington School of Medicine, Seattle, Wash. Supported by a training grant from the United States Public Health Service, HE-05924. Received for publication Aug. 10, 1973.
Reprint requests to: Warren Pediatrics (RD-ZO), University Seattle, Wash. 98195.
G. Guntheroth, of Washington
M.D., Department of School of Medicine,
June, 1975, Vol. 89, No. 6, pp. 775-778
and cyanotic toenails. She was digital&d and given diuretics with good clinical improvement. Cardiac catheterization after improvement revealed a PDA with bidirectional shunting and severe pulmonary hypertension with markedly elevated pmmonary vascular resistance (Table I). The condition was felt to be inoperable because of the pulmonary vascular obstruction and the absence of a significant left-to-right shunt. The social situation was poor and follow-up visits were sporadic. At age 11 months, clubbing was not described, but was observed at 15 and again at 21 months. At 36 months she had only clubbing with no definite cyanosis. Over the years the murmur became progressively louder and pansystolic. At age four years, there was a question of a “spill-over” of the murmur into diastole. She was then lost to follow-up until age six, when her murmur was definitely continuous, and the second sound in the puhnonic area only mildly accentuated. She was admitted for her second catheterization at age seven years, six years after her initial cardiac catheterization. She had a Grade 3/6 continuous murmur typical of a PDA, loudest in the second intercostal space in the left midclavicular line, and had neither cyanosis nor clubbing. Her clinical findings are summarized in Table II; representative chest xrays and ECG are shown in Figs. 1, C and 2. The second cardiac catheterization revealed mildly elevated pulmonary artery pressure, no right-to-left shunt, and a significant left-to-right shunt at the level of the pulmonary artery. At operation, a 6 to 7 mm. PDA was found, divided and oversewn. She tolerated the operation well, had a benign postoperative course, and went home on the fourth postoperative day. Discussion
In infants with or without left-to-right shunts, the pulmonary vascular resistance (PVR) falls in early infancy, but even in large ventricular septal defects, this has occurred by 12 weeks.’ The larger defects with greater severity of symptoms are at risk of progression to even higher PVR.” The very late and relatively marked decrease in PVR in our patient requires further consideration. There are two pieces of data missing from the first cardiac catheterization: the pulmonary artery wedge pressure and the oxygen saturation of the pulmonary vein. The latter was assumed to be 96
American
Heart
Journal
775
Kawabori,
Morgan,
and Guntheroth
Fig. 1. Serial chest x-rays show (left) RUL and LLL pneumonia at six months (Dec. 7, 1964), (middle) LLL atelectasis at 11 months (May 20,1965), and (right) mildly increased pulmonary vascular&y and prominent main pulmonary artery at seven years of age (Aug. 25, 1971).
Fig. 2. Serial ECGL show the changing patterns from RVH and p-pulmonale at six months (Dec. 10, 1964), RVH with “strain” and p-pulmonale at 11 months (May 16, 1965), RVH at three years (June 17,1967), and to CVH at seven years of age (Aug. 25, 1971).
per cent at the time of the first study, which caused the calculated right-to-left shunt to be large, since the saturation in the descending aorta was only 83 per cent. The earpiece oximetry obtained at the conclusion of the catheterization, > 85 per cent, was probably a valid reflection of the saturation in the ascending aorta, and therefore of the pulmonary vein. This would indicate intrapulmonary shunting, and would imply that pulmonary parenchymal disease was a major
776
cause of the pulmonary hypertension. However, as can be seen from the alternate calculations in Table I, using the lower pulmonary vein saturation would still yield a negligible left-to-right shunt and a pulmonary vascular resistance almost equal to the systemic vascular resistance. The calculated net pulmonary vascular resistance for the fkst catheterization done in 1965 is based on an assumed value of 10 mm. Hg for the pulmonary artery wedge pressure. (Unfortunately, this position of the catheter was not achieved during the first procedure.) Judging from the radiologic findings at that time, age 11 months (Fig. 1, B), there was no pulmonary venous hypertension: there were no Kerley’s Blines or relative hypoperfusion of the lower lobes. Calculating the total pulmonary resistance (TPR), the values are extraordinarily high, no matter which saturation of the pulmonary vein is used (Table I). To most clinicians, evidence of the early severity and stability of pulmonary hypertension may be found in the physical and ECG findings. After the first month of life the patient had no continuous murmur until past five years (Table II). The only murmur was a very soft left sternal border murmur in systole. The pulmonic closure was accentuated by six months of age, and remained loud throughout the follow-up period. The ECG’s showed an abnormal degree of right ventricular hypertrophy (RVH) from the first tracing at six months (Fig. 2); by 11 months, there was p-pulmonale in addition. Marked RVH was still present at three years of age, but no ppuhnonale. Combined ventricular hypertrophy
June, 1975, Vol. 89, No. 6
Reversal
I. Cardiac catheterization
Table
Position
196-71-----
RA RV MPA
3’ W/2/4 88/58 70* aorta
8* 47/3/8 46/26 35* 11
!30/52 68*
-~
1971
59
84
12.83
60 59 67
81 82 88
14.01
97
15.44
85 115/85 R8*
97
Femoral Pulmonic/systemic
flow
o.s/lt
ratio
Total pulmonary vascular (dynes, sec. cm. “) Resistance ratio P/S
Table
f Jz content ..- .- .--.__-_
83
Ear oximeter Bra&al
pulmonary puhnonary pulmonary
hypertension
-- ._-.l__-.-Per cent 0, saturation T-1965 ) 1971
svc
tkssuming $k3x!dng lAasuming
pulmonary
results Pressures
PC Descending
of “‘inoperable”
resistance
1.8/l
1.4/1$ s.aso’r 4,160$ l/1.55
287 l/5
vein saturation of 96 per cent. vein saturation of 85 per cent. wedge pressure of 10 mm. Hg.
I I. Clinical findings Cyanosis
Age fir.) l/12 2/12 6112 11/12* l-3/12 l-9/12 2-11/U 4-4/12 6-7/12 7-2/121
Pink Mild Mild
0 0 0 fingers cyanotic toes cyanosis, lips and nails 0 0 0 0
Clubbing 0 0 0 0 Minimal Mild Mild 0 0 0
Murmur
P2
216 continuous 0 2/6 l/6 l-2/6 2/6 2/6 2/6 3/6 316
short LSB systolic short LSB systolic upper-mid LSB systolic 2nd LSB systolic LSB harsh pansystolic moderately harsh ? diastolic continuous continuous _____--
--
f
spillover
T : ;r t f t T T r-r
‘1st catheterization. t2nd catheterization.
was first suggested at age four and by seven years seemed established. The relationship of pulmonary parenchymal disease to increased pulmonary vascular resistance is well known (car pulmonale); atelectasis can produce a marked increase in resistance in the involved segment and, in addition, a secondary increase in the total PVR by the effects of hypoxia and hyperpnea.” This patient had idiopathic respiratory distress in the neonatal period and at six months of age had major changes of atelectasis and consolidation on x-ray. Although there was no clinical evidence of acute pulmonary
American
Heart
Journal
disease at the time of cardiac catheterization at 11 months, there was radiographic evidence of residual parenchymal disease. The most unusual aspect of the course of this child’s disease is the very slow regression of PVR, judged from clinical evidence. The most likely explanation for the decline in PVR is the resolution of chronic pulmonary parenchymal abnormalities. The other possible explanation for resolution of this patient’s pulmonary vascular obstruction is spontaneous improvement unrelated to resolving parenchymal disease. This has not been reported previously and must be regarded as an unlikely
777
Kawabori,
Morgan,
and Guntheroth
explanation. Spontaneous closure of the ductus, if that had occurred early in life, might have led to an improvement in PVR, but the ductus was obviously patent. The most likely explanation for the course of events in this patient seems to be slowly resolving parenchymal disease. The importance of these data, regardless of their explanation, lies in the fact that between the ages of 11 months and seven years, the hemodynamics of this patient changed from those associated with’ severe pulmonary hypertension and bidirectional shunting to mild pulmonary hypertension and pure left-to-right shunting. She, therefore, became a candidate for operation, which proved successful, several years after her
778
condition had been judged inoperable. This emphasizes the need for regular follow-up of all patients with congenital heart disease, even those whose conditions are considered inoperable. REFERENCES
.
Ellis, F. H., Jr., Kirklin, J. W., Callahan, J. A., and Wood, E. H.: Patent ductus arteriosus with pulmonary hypertension, J. Thorac. Cardiovasc. Surg. 3 1:268, 1956. Rudolph, A. M.: The changes in circulation after birth, Circulation 41:343, 1971. Hoffman, J. I. E., and Rudolph, A. M.: The natural history of ventricular septal defects in infancy, Am. J. Cardiol. 16:634, 1965. Morgan, B. C., and Guntheroth, W. G.: Pulmonary blood flow and resistance during acute atelectasis in intact dogs, J. Appl. Physiol. 26:609, 1970.
June,
1975, Vol. 89, No. 6
of “inoperable”
pulmonary
hypertension
Isamu Kawabori, M.D. Beverly C. Morgan, M.D. Warren G. Guntheroth, M.D. Seattle, Wash.
Severe pulmonary hypertension associated with pulmonary vascular disease has been regarded as a contraindication for surgery in congenital heart disease because of the high operative mortality rate.’ This case report demonstrates the need to follow even those patients presumed to have inoperable heart disease. Changing clinical findings over a period of years in this patient indicated the need for thorough re-evaluation. Case history This child was born at approximately 25 weeks gestation, weighing 740 grams. She had mild idiopathic respiratory distress syndrome, severe apneic episodes, and hyperbilirubinemia. During her initial hospitalization she developed pneumonia. A Grade 216 machinery-type murmur, loudest at the left sternal border in the second intercostal space, was felt to represent a patent ductus arteriosus (PDA), but this murmur was not heard at the time of discharge from the premature nursery at 10 weeks of age. During her second hospitalization at six months of age for pneumonia, a systolic murmur was heard, tachycardia was present, and heart enlargement with normal pulmonary vascular markings was noted on chest x-ray (Fig. 1, A). Her third hospitalization at age six and a half months was again for pneumonia. She was admitted again at 11 months of age, four months following her last episode of recognizable pneumonia, in moderate distress with congestive heart failure. Chest x-ray films showed a few residual signs in the region previously involved with pneumonia and atelectasis (Fig. 1, B). The pulmonary vascularity was normal. Her clinical findings at this time included tachycardia, hepatomegaly, gallop rhythm, Grade l/6 blowing systolic murmur at the left sternal border with diastole remaining clear, and a markedly increased and unsplit second sound in the pulmonic area. There was differential cyanosis of the extremities with acyanotic fingernails From the Division of Pediatric Cardiology, Department of Pediatrics, University of Washington School of Medicine, Seattle, Wash. Supported by a training grant from the United States Public Health Service, HE-05924. Received for publication Aug. 10, 1973.
Reprint requests to: Warren Pediatrics (RD-ZO), University Seattle, Wash. 98195.
G. Guntheroth, of Washington
M.D., Department of School of Medicine,
June, 1975, Vol. 89, No. 6, pp. 775-778
and cyanotic toenails. She was digital&d and given diuretics with good clinical improvement. Cardiac catheterization after improvement revealed a PDA with bidirectional shunting and severe pulmonary hypertension with markedly elevated pmmonary vascular resistance (Table I). The condition was felt to be inoperable because of the pulmonary vascular obstruction and the absence of a significant left-to-right shunt. The social situation was poor and follow-up visits were sporadic. At age 11 months, clubbing was not described, but was observed at 15 and again at 21 months. At 36 months she had only clubbing with no definite cyanosis. Over the years the murmur became progressively louder and pansystolic. At age four years, there was a question of a “spill-over” of the murmur into diastole. She was then lost to follow-up until age six, when her murmur was definitely continuous, and the second sound in the puhnonic area only mildly accentuated. She was admitted for her second catheterization at age seven years, six years after her initial cardiac catheterization. She had a Grade 3/6 continuous murmur typical of a PDA, loudest in the second intercostal space in the left midclavicular line, and had neither cyanosis nor clubbing. Her clinical findings are summarized in Table II; representative chest xrays and ECG are shown in Figs. 1, C and 2. The second cardiac catheterization revealed mildly elevated pulmonary artery pressure, no right-to-left shunt, and a significant left-to-right shunt at the level of the pulmonary artery. At operation, a 6 to 7 mm. PDA was found, divided and oversewn. She tolerated the operation well, had a benign postoperative course, and went home on the fourth postoperative day. Discussion
In infants with or without left-to-right shunts, the pulmonary vascular resistance (PVR) falls in early infancy, but even in large ventricular septal defects, this has occurred by 12 weeks.’ The larger defects with greater severity of symptoms are at risk of progression to even higher PVR.” The very late and relatively marked decrease in PVR in our patient requires further consideration. There are two pieces of data missing from the first cardiac catheterization: the pulmonary artery wedge pressure and the oxygen saturation of the pulmonary vein. The latter was assumed to be 96
American
Heart
Journal
775
Kawabori,
Morgan,
and Guntheroth
Fig. 1. Serial chest x-rays show (left) RUL and LLL pneumonia at six months (Dec. 7, 1964), (middle) LLL atelectasis at 11 months (May 20,1965), and (right) mildly increased pulmonary vascular&y and prominent main pulmonary artery at seven years of age (Aug. 25, 1971).
Fig. 2. Serial ECGL show the changing patterns from RVH and p-pulmonale at six months (Dec. 10, 1964), RVH with “strain” and p-pulmonale at 11 months (May 16, 1965), RVH at three years (June 17,1967), and to CVH at seven years of age (Aug. 25, 1971).
per cent at the time of the first study, which caused the calculated right-to-left shunt to be large, since the saturation in the descending aorta was only 83 per cent. The earpiece oximetry obtained at the conclusion of the catheterization, > 85 per cent, was probably a valid reflection of the saturation in the ascending aorta, and therefore of the pulmonary vein. This would indicate intrapulmonary shunting, and would imply that pulmonary parenchymal disease was a major
776
cause of the pulmonary hypertension. However, as can be seen from the alternate calculations in Table I, using the lower pulmonary vein saturation would still yield a negligible left-to-right shunt and a pulmonary vascular resistance almost equal to the systemic vascular resistance. The calculated net pulmonary vascular resistance for the fkst catheterization done in 1965 is based on an assumed value of 10 mm. Hg for the pulmonary artery wedge pressure. (Unfortunately, this position of the catheter was not achieved during the first procedure.) Judging from the radiologic findings at that time, age 11 months (Fig. 1, B), there was no pulmonary venous hypertension: there were no Kerley’s Blines or relative hypoperfusion of the lower lobes. Calculating the total pulmonary resistance (TPR), the values are extraordinarily high, no matter which saturation of the pulmonary vein is used (Table I). To most clinicians, evidence of the early severity and stability of pulmonary hypertension may be found in the physical and ECG findings. After the first month of life the patient had no continuous murmur until past five years (Table II). The only murmur was a very soft left sternal border murmur in systole. The pulmonic closure was accentuated by six months of age, and remained loud throughout the follow-up period. The ECG’s showed an abnormal degree of right ventricular hypertrophy (RVH) from the first tracing at six months (Fig. 2); by 11 months, there was p-pulmonale in addition. Marked RVH was still present at three years of age, but no ppuhnonale. Combined ventricular hypertrophy
June, 1975, Vol. 89, No. 6
Reversal
I. Cardiac catheterization
Table
Position
196-71-----
RA RV MPA
3’ W/2/4 88/58 70* aorta
8* 47/3/8 46/26 35* 11
!30/52 68*
-~
1971
59
84
12.83
60 59 67
81 82 88
14.01
97
15.44
85 115/85 R8*
97
Femoral Pulmonic/systemic
flow
o.s/lt
ratio
Total pulmonary vascular (dynes, sec. cm. “) Resistance ratio P/S
Table
f Jz content ..- .- .--.__-_
83
Ear oximeter Bra&al
pulmonary puhnonary pulmonary
hypertension
-- ._-.l__-.-Per cent 0, saturation T-1965 ) 1971
svc
tkssuming $k3x!dng lAasuming
pulmonary
results Pressures
PC Descending
of “‘inoperable”
resistance
1.8/l
1.4/1$ s.aso’r 4,160$ l/1.55
287 l/5
vein saturation of 96 per cent. vein saturation of 85 per cent. wedge pressure of 10 mm. Hg.
I I. Clinical findings Cyanosis
Age fir.) l/12 2/12 6112 11/12* l-3/12 l-9/12 2-11/U 4-4/12 6-7/12 7-2/121
Pink Mild Mild
0 0 0 fingers cyanotic toes cyanosis, lips and nails 0 0 0 0
Clubbing 0 0 0 0 Minimal Mild Mild 0 0 0
Murmur
P2
216 continuous 0 2/6 l/6 l-2/6 2/6 2/6 2/6 3/6 316
short LSB systolic short LSB systolic upper-mid LSB systolic 2nd LSB systolic LSB harsh pansystolic moderately harsh ? diastolic continuous continuous _____--
--
f
spillover
T : ;r t f t T T r-r
‘1st catheterization. t2nd catheterization.
was first suggested at age four and by seven years seemed established. The relationship of pulmonary parenchymal disease to increased pulmonary vascular resistance is well known (car pulmonale); atelectasis can produce a marked increase in resistance in the involved segment and, in addition, a secondary increase in the total PVR by the effects of hypoxia and hyperpnea.” This patient had idiopathic respiratory distress in the neonatal period and at six months of age had major changes of atelectasis and consolidation on x-ray. Although there was no clinical evidence of acute pulmonary
American
Heart
Journal
disease at the time of cardiac catheterization at 11 months, there was radiographic evidence of residual parenchymal disease. The most unusual aspect of the course of this child’s disease is the very slow regression of PVR, judged from clinical evidence. The most likely explanation for the decline in PVR is the resolution of chronic pulmonary parenchymal abnormalities. The other possible explanation for resolution of this patient’s pulmonary vascular obstruction is spontaneous improvement unrelated to resolving parenchymal disease. This has not been reported previously and must be regarded as an unlikely
777
Kawabori,
Morgan,
and Guntheroth
explanation. Spontaneous closure of the ductus, if that had occurred early in life, might have led to an improvement in PVR, but the ductus was obviously patent. The most likely explanation for the course of events in this patient seems to be slowly resolving parenchymal disease. The importance of these data, regardless of their explanation, lies in the fact that between the ages of 11 months and seven years, the hemodynamics of this patient changed from those associated with’ severe pulmonary hypertension and bidirectional shunting to mild pulmonary hypertension and pure left-to-right shunting. She, therefore, became a candidate for operation, which proved successful, several years after her
778
condition had been judged inoperable. This emphasizes the need for regular follow-up of all patients with congenital heart disease, even those whose conditions are considered inoperable. REFERENCES
.
Ellis, F. H., Jr., Kirklin, J. W., Callahan, J. A., and Wood, E. H.: Patent ductus arteriosus with pulmonary hypertension, J. Thorac. Cardiovasc. Surg. 3 1:268, 1956. Rudolph, A. M.: The changes in circulation after birth, Circulation 41:343, 1971. Hoffman, J. I. E., and Rudolph, A. M.: The natural history of ventricular septal defects in infancy, Am. J. Cardiol. 16:634, 1965. Morgan, B. C., and Guntheroth, W. G.: Pulmonary blood flow and resistance during acute atelectasis in intact dogs, J. Appl. Physiol. 26:609, 1970.
June,
1975, Vol. 89, No. 6