Single-Lung Transplantation With Atrial Septa1 Defect Repair for Eisenmenger’s Syndrome Patrick M. McCarthy, MD, Eliot R. Rosenkranz, MD, Richard D. White, MD, Thomas W. Rice, MD, Richard Sterba, MD, Rita Vargo, RN, and Atul C. Mehta, MD Departments of Thoracic and Cardiovascular Surgery, Pediatric Cardiology, Pulmonary Medicine, and Diagnostic Radiology, The Cleveland Clinic Foundation, Cleveland, Ohio Heart-lung transplantation has been used successfully for patients with pulmonary vascular disease but its application has been very limited due to the scarcity of donors. We report a patient with Eisenmenger’s syndrome who underwent right single-lung transplantation
with closure of atrial septal defect; postoperative convalescence was uneventful. Serial magnetic resonance imaging examinations demonstrate improved right heart function. (Ann Tkorac Surg 1991;52:300-3)
E
”competition” with status I heart recipients who have a higher priority in the UNOS system. As experience with single-lung transplantation has grown, patients have undergone successful transplantation with pulmonary hypertension secondary to pulmonary fibrosis [3] and sub-
isenmenger’s syndrome is one of the medically untreatable pulmonary vascular diseases for which heart-lung transplantation (H-LTx) has been successfully performed [l, 21. However, the number of H-LTx operations is very limited due to donor organ availability and
Fig I , Preoperntizir cnrdiac condition
(ciiie; trnnsaxinl). Four represeiitative iiiinges froin the cardiac c!ycle d e i t i ~ ~ n strate the follorciing: ( I ) st,ciritdui~ atrial septal deject farrow) 7oith imzrestricted bidirectioiial sklriztiiig, (2) diiniuished coiitractioii of the right z w tricle (RV) from end-diastole (top, left) to em-systole (bottom, left), mid ( 3 ) systolic sigiinl-void jet (large arrowhead) passing f r o m the lezd of the tricuspid valzie (small arrowheads) through the atrial septal defect irito the left ntriuin (LA).
Accepted for publication Dec 31, 1990. Address reprint requests to Dr McCarthy, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Ave, Cleveland, OH 44195-5066.
0 1991 by The Society of Thoracic Surgeons
OOO3-4975/911$3.SO
301
CASE REPORT McCARTHY ET AL EISENMENGERS LUNG TRANSPLANTATION
Ann Thorac Surg 1991;52:30&3
Fig 2 . Preoperative pulmonary arterial condition (spin-echo and cine; transaxial). Compared with the normal-sized ascending aorta (A) the pulmonary arteries are substantially dilated. Abnormal systolic intravascular signal patterns, representing slow blood pow,are best demonstrated within the right central pulmonary artery (asterisk). Specifically, abnormal signal increase compared with the normal signal void in the aorta is noted on the spin-echo image (top). Abnormal signal loss, on the other hand, is noted in contrast to signal enhancement on the cine image (hottom).
sequently for primary pulmonary hypertension. In 1988, the first single-lung transplantation for Eisenmenger’s syndrome was performed in Toronto [4] in a patient who underwent simultaneous closure of a patent ductus arteriosus. This paper reports our experience with single-lung transplantation and atrial septa1 defect (ASD) repair. A 25-year-old woman was admitted to another hospital in November 1989 with fatigue, dyspnea on exertion, palpiTable 1 . Cardiac Findings Before and After Transplantation Variable
Preop
RV EF RV EDV (mL) RV ESV (mL) RV stroke volume (mL) LV stroke volume (mL) LV EF
0.22 158 123 35 36 0.68
1 Month 0.47
77 41
36 64 0.70
3 Months
0.40 87 52 35 49 0.64
tations, right heart failure, pitting edema, ascites, and hepatomegaly. Investigations disclosed a large ASD and systemic pulmonary artery pressures. She was evaluated and accepted for H-LTx at another institution. She was first seen at the Cleveland Clinic in April 1990. She had no signs of right heart failure, but still complained of fatigue, dyspnea, chest pain, and nearsyncope. On examination she had peripheral cyanosis, clubbing, palpable right ventricular heave, loud P,, and split S., The chest roentgenogram was remarkable for dilated pulmonary arteries. Her blood tests, including liver function tests, were within normal limits. A cardiac magnetic resonance imaging examination, consisting of standard static spin-echo imaging and a cine survey of the ventricles [5], confirmed an ostium secundum ASD, marked hypertrophy and dilatation of the right ventricle with overall diminished systolic function, and flow characteristics indicating both bidirectional shunting and moderate to severe tricuspid regurgitation directed through the ASD (Fig 1). Similar magnetic resonance imaging examination of the main and central pulmonary arteries demonstrated moderate to severe dilatation and abnormal systolic intravascular signal consistent with slow flow (Fig 2) [6]. Volumetric measurements obtained before and after transplantation are listed in Table 1. The echocardiogram was consistent with these results. A full cardiopulmonary exercise stress test demonstrated severe impairment of the maximum oxygen uptake (21%predicted) and maximum workload (75 W). Her oxygen saturation at rest was 0.90 and decreased to 0.64 with exertion. She was listed for transplantation on June 27, 1990. On July 8, 1990, a 33-year-old female donor was identified. The donor lung was flushed with modified EuroCollins solution after being infused with prostaglandin El. The heart was excised and used for simultaneous heart transplantation in another recipient at the Cleveland Clinic. Through a right posterolateral thoracotomy the recipient was placed on cardiopulmonary bypass. The heart was protected with cold blood cardioplegia while the 3.5-cm2 ASD was closed through a right atriotomy with a generous autologous pericardial patch. The right lung was transplanted with the heart in the normotherTable 2. Perioperative Data From Right Ventricular Ejection
Fraction Catheter
Time
RV EF
~~
107147
0.17
Post-CPB”
43130
0-12 h 12-24 h 24-48 h 48-72 h
40120
0.19 0.23 0.26 0.26 0.24
Pre-CPB
a
EDV = end-diastolic volume; EF = ejection fraction; ESV = end-systolic volume; LV = left ventricular; RV = right ventricular.
PA (mm Hg)
RV Stroke Volume (mL)
30119 25115 28116
45 40 40 55 57 59
Initial value in operating room off CPB.
CPB = cardiopulmonary bypass; EF = ejection fraction; RV = right ventricular. pulmonary artery;
PA =
302
CASE REPORT McCARTHY ET AL EISENMENGERS LUNG TRANSPLANTATION
Ann Thorac Surg 1991;52:300-3
Fig 3. One-month postoperative cardiac condition (cine; transaxial). Four representative images corresponding to those in Figure 2 demonstrate the following: (2) decrease in size of the right atrium (RA) and right ventricle, which shows evidence of improved ventricular function, (2) absence of a jet of serious tricuspid regurgitation, and ( 3 ) surgical closure of the atrial septa1 defect establishing continuity of the interatrial septum (arrowheads).
mic, beating empty state on full bypass. The graft ischemic time was 2 hours 30 minutes. A pedicle of omentum was wrapped around the bronchial anastomosis. The right ventricular ejection fraction and right ventricular stroke volume were calculated perioperatively using a quadruple-lumen pulmonary artery catheter (Baxter Healthcare, Edwards Critical Care Division, Irvine, CA) [7]. The initial measurement of right ventricular ejection fraction in the operating room (0.17), before transplantation and ASD closure, may not have been accurate owing to right to left shunting through the still patent ASD. After transplantation, the right ventricular ejection fraction and stroke volume increased, while the pulmonary artery pressures dropped (Table 2). The patient was extubated 29 hours postoperatively and on room air by the fourth postoperative day. She was transferred out of the intensive care unit on the sixth postoperative day, and was discharged from the hospital on the 16th day. Daily maintenance immunosuppression consisted of triple-drug therapy including cyclosporin A (intravenous drip for the first 48 hours), azathioprine, and prednisone. Steroids were not withheld after transplantation. Bronchoscopy on the 14th postoperative day showed the bronchial anastomosis was healing normally, and biopsy showed no evidence of lung rejection. Repeat static and dynamic cardiac magnetic resonance imaging examinations performed at 1 and 3 months (see Table 1) showed decreased size of the right atrium and
right ventricle and trivial tricuspid regurgitation (Fig 3) compared with preoperatively, as well as improved pulmonary artery size and flow patterns (Fig 4). Five months after transplantation she is functionally rehabilitated, has had no episodes of lung rejection, and has resumed employment.
Comment Single-lung transplantation has many advantages over H-LTx aside from the availability and better utilization of donors. By repairing the heart, and not replacing it, several problems are avoided. There is no need for frequent cardiac biopsies after transplantation. There is no risk of cardiac rejection, and the risk of increased immunosuppression (increased infection) during cardiac rejection episodes is avoided. There is no functional disability from the denervated transplanted heart. Finally, the longterm risk of graft atherosclerosis is avoided. Survival after single-lung transplantation has dramatically improved (77% at 1 year, 73% at 2 years [8]), so that it is roughly comparable with the best results after H-LTx. Although survival after H-LTx has been improving in some centers with extensive experience, the 59% 1-year worldwide survival reported by the International Society for Heart Transplantation compares poorly with survival after isolated cardiac transplantation (79% 1-year survival [9]). Therefore, scarce donor hearts may not be well
Ann Thorac Surg
1991:52:300-3
CASE REPORT
MCCARTHY ET AL
EISENMENGER’S LUNG TRANSPLANTATION
303
direct right atrial to pulmonary artery connections (the Fontan concept) suggest that even severe right ventricular dysfunction could be well tolerated if the left ventricular function is normal and the pulmonary vascular resistance decreases to normal in the transplanted lung.
Addendum Ten months postoperatively this patient continues to be well (New York Heart Association class I) and has not had any lung rejection. Another patient with an ASD and Eisenmenger’s syndrome underwent transplantation after this report was submitted and showed similar right heart recovery (right ventricular ejection fraction, 0.18 preoperatively, 0.45 in the operating room and initial 72 hours, and 0.48 at 1 month). A patient with primary pulmonary hypertension who underwent transplantation also showed excellent recovery of right heart function and improved right ventricular ejection fraction (0.23 preoperatively, 0.47 perioperatively, and 0.71 at 1 month).
References
Fig 4 . One-month postoperative pulmonary arterial condition (spinecho and cine; transaxial). Two images corresponding to those in Figure 2 demonstrate the high-intensity fat within the omental flap (arrows) surrounding the region of the anastomosis (arrowhead) of the right central pulmonary artety. There is also evidence of improvement in the size of the pulmonary arteries compared with the ascending aorta and no further evidence of systolic slow blood flow uiithin the right central pulmonary artery.
utilized for H-LTx, except in centers that can attain acceptable survival after H-LTx. Complex congenital heart defects associated with Eisenmenger’s syndrome still require H-LTx because of the complexity associated with repairing these defects. For less complicated congenital defects, however, cardiac repair with single-lung transplantation may be performed with recovery of right heart function. Clinical results after
1. Reitz BA, Wallwork JL, Hunt SA, et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982;306:557-64. 2. McCarthy PM, Starnes VA, Theodore J, Stinson EB, Oyer PE, Shumway NE. Improved survival after heart-lung transplantation. J Thorac Cardiovasc Surg 1990;99:54-60. 3. Grossman RF, Frost A, Zamel N, et al. Results of single-lung transplantation for bilateral pulmonary fibrosis. N Engl J Med 1990;322:727-33. 4. Fremes SE, Patterson GA, Williams WG, et al. Single lung transplantation and closure of patent ductus arteriosus for Eisenmenger’s syndrome. J Thorac Cardiovasc Surg 1990;lOO: 1-5. 5. Sechtem U, Pflugfelder PW, White RD, et al. Cine MR imaging: potential for the evaluation of cardiovascular function. AJR 1987;148:23946. 6 . White RD, Paschal CB, Tkach JA, Carvlin MJ. Functional cardiovascular evaluation by magnetic resonance imaging. Top Magn Reson Imag 1990;2(2):31-48. 7. Dhainaut J, Brunet F, Monsallier JF, et al. Bedside evaluation of right ventricular performance using a rapid computerized thermodilution method. Crit Care Med 1987;15:148-52. 8. Calhoon JH, Grover FD, Gibbons WJ, et al. Single lung transplantation-alternative indications and technique. J Thorac Cardiovasc Surg 1991;101:81&25. 9. Kriett JM, Kaye MP. The registry of the International Society for Heart Transplantation: seventh official report-1990. J Heart Transplant 1990;9:323-30.
with closure of atrial septal defect; postoperative convalescence was uneventful. Serial magnetic resonance imaging examinations demonstrate improved right heart function. (Ann Tkorac Surg 1991;52:300-3)
E
”competition” with status I heart recipients who have a higher priority in the UNOS system. As experience with single-lung transplantation has grown, patients have undergone successful transplantation with pulmonary hypertension secondary to pulmonary fibrosis [3] and sub-
isenmenger’s syndrome is one of the medically untreatable pulmonary vascular diseases for which heart-lung transplantation (H-LTx) has been successfully performed [l, 21. However, the number of H-LTx operations is very limited due to donor organ availability and
Fig I , Preoperntizir cnrdiac condition
(ciiie; trnnsaxinl). Four represeiitative iiiinges froin the cardiac c!ycle d e i t i ~ ~ n strate the follorciing: ( I ) st,ciritdui~ atrial septal deject farrow) 7oith imzrestricted bidirectioiial sklriztiiig, (2) diiniuished coiitractioii of the right z w tricle (RV) from end-diastole (top, left) to em-systole (bottom, left), mid ( 3 ) systolic sigiinl-void jet (large arrowhead) passing f r o m the lezd of the tricuspid valzie (small arrowheads) through the atrial septal defect irito the left ntriuin (LA).
Accepted for publication Dec 31, 1990. Address reprint requests to Dr McCarthy, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Ave, Cleveland, OH 44195-5066.
0 1991 by The Society of Thoracic Surgeons
OOO3-4975/911$3.SO
301
CASE REPORT McCARTHY ET AL EISENMENGERS LUNG TRANSPLANTATION
Ann Thorac Surg 1991;52:30&3
Fig 2 . Preoperative pulmonary arterial condition (spin-echo and cine; transaxial). Compared with the normal-sized ascending aorta (A) the pulmonary arteries are substantially dilated. Abnormal systolic intravascular signal patterns, representing slow blood pow,are best demonstrated within the right central pulmonary artery (asterisk). Specifically, abnormal signal increase compared with the normal signal void in the aorta is noted on the spin-echo image (top). Abnormal signal loss, on the other hand, is noted in contrast to signal enhancement on the cine image (hottom).
sequently for primary pulmonary hypertension. In 1988, the first single-lung transplantation for Eisenmenger’s syndrome was performed in Toronto [4] in a patient who underwent simultaneous closure of a patent ductus arteriosus. This paper reports our experience with single-lung transplantation and atrial septa1 defect (ASD) repair. A 25-year-old woman was admitted to another hospital in November 1989 with fatigue, dyspnea on exertion, palpiTable 1 . Cardiac Findings Before and After Transplantation Variable
Preop
RV EF RV EDV (mL) RV ESV (mL) RV stroke volume (mL) LV stroke volume (mL) LV EF
0.22 158 123 35 36 0.68
1 Month 0.47
77 41
36 64 0.70
3 Months
0.40 87 52 35 49 0.64
tations, right heart failure, pitting edema, ascites, and hepatomegaly. Investigations disclosed a large ASD and systemic pulmonary artery pressures. She was evaluated and accepted for H-LTx at another institution. She was first seen at the Cleveland Clinic in April 1990. She had no signs of right heart failure, but still complained of fatigue, dyspnea, chest pain, and nearsyncope. On examination she had peripheral cyanosis, clubbing, palpable right ventricular heave, loud P,, and split S., The chest roentgenogram was remarkable for dilated pulmonary arteries. Her blood tests, including liver function tests, were within normal limits. A cardiac magnetic resonance imaging examination, consisting of standard static spin-echo imaging and a cine survey of the ventricles [5], confirmed an ostium secundum ASD, marked hypertrophy and dilatation of the right ventricle with overall diminished systolic function, and flow characteristics indicating both bidirectional shunting and moderate to severe tricuspid regurgitation directed through the ASD (Fig 1). Similar magnetic resonance imaging examination of the main and central pulmonary arteries demonstrated moderate to severe dilatation and abnormal systolic intravascular signal consistent with slow flow (Fig 2) [6]. Volumetric measurements obtained before and after transplantation are listed in Table 1. The echocardiogram was consistent with these results. A full cardiopulmonary exercise stress test demonstrated severe impairment of the maximum oxygen uptake (21%predicted) and maximum workload (75 W). Her oxygen saturation at rest was 0.90 and decreased to 0.64 with exertion. She was listed for transplantation on June 27, 1990. On July 8, 1990, a 33-year-old female donor was identified. The donor lung was flushed with modified EuroCollins solution after being infused with prostaglandin El. The heart was excised and used for simultaneous heart transplantation in another recipient at the Cleveland Clinic. Through a right posterolateral thoracotomy the recipient was placed on cardiopulmonary bypass. The heart was protected with cold blood cardioplegia while the 3.5-cm2 ASD was closed through a right atriotomy with a generous autologous pericardial patch. The right lung was transplanted with the heart in the normotherTable 2. Perioperative Data From Right Ventricular Ejection
Fraction Catheter
Time
RV EF
~~
107147
0.17
Post-CPB”
43130
0-12 h 12-24 h 24-48 h 48-72 h
40120
0.19 0.23 0.26 0.26 0.24
Pre-CPB
a
EDV = end-diastolic volume; EF = ejection fraction; ESV = end-systolic volume; LV = left ventricular; RV = right ventricular.
PA (mm Hg)
RV Stroke Volume (mL)
30119 25115 28116
45 40 40 55 57 59
Initial value in operating room off CPB.
CPB = cardiopulmonary bypass; EF = ejection fraction; RV = right ventricular. pulmonary artery;
PA =
302
CASE REPORT McCARTHY ET AL EISENMENGERS LUNG TRANSPLANTATION
Ann Thorac Surg 1991;52:300-3
Fig 3. One-month postoperative cardiac condition (cine; transaxial). Four representative images corresponding to those in Figure 2 demonstrate the following: (2) decrease in size of the right atrium (RA) and right ventricle, which shows evidence of improved ventricular function, (2) absence of a jet of serious tricuspid regurgitation, and ( 3 ) surgical closure of the atrial septa1 defect establishing continuity of the interatrial septum (arrowheads).
mic, beating empty state on full bypass. The graft ischemic time was 2 hours 30 minutes. A pedicle of omentum was wrapped around the bronchial anastomosis. The right ventricular ejection fraction and right ventricular stroke volume were calculated perioperatively using a quadruple-lumen pulmonary artery catheter (Baxter Healthcare, Edwards Critical Care Division, Irvine, CA) [7]. The initial measurement of right ventricular ejection fraction in the operating room (0.17), before transplantation and ASD closure, may not have been accurate owing to right to left shunting through the still patent ASD. After transplantation, the right ventricular ejection fraction and stroke volume increased, while the pulmonary artery pressures dropped (Table 2). The patient was extubated 29 hours postoperatively and on room air by the fourth postoperative day. She was transferred out of the intensive care unit on the sixth postoperative day, and was discharged from the hospital on the 16th day. Daily maintenance immunosuppression consisted of triple-drug therapy including cyclosporin A (intravenous drip for the first 48 hours), azathioprine, and prednisone. Steroids were not withheld after transplantation. Bronchoscopy on the 14th postoperative day showed the bronchial anastomosis was healing normally, and biopsy showed no evidence of lung rejection. Repeat static and dynamic cardiac magnetic resonance imaging examinations performed at 1 and 3 months (see Table 1) showed decreased size of the right atrium and
right ventricle and trivial tricuspid regurgitation (Fig 3) compared with preoperatively, as well as improved pulmonary artery size and flow patterns (Fig 4). Five months after transplantation she is functionally rehabilitated, has had no episodes of lung rejection, and has resumed employment.
Comment Single-lung transplantation has many advantages over H-LTx aside from the availability and better utilization of donors. By repairing the heart, and not replacing it, several problems are avoided. There is no need for frequent cardiac biopsies after transplantation. There is no risk of cardiac rejection, and the risk of increased immunosuppression (increased infection) during cardiac rejection episodes is avoided. There is no functional disability from the denervated transplanted heart. Finally, the longterm risk of graft atherosclerosis is avoided. Survival after single-lung transplantation has dramatically improved (77% at 1 year, 73% at 2 years [8]), so that it is roughly comparable with the best results after H-LTx. Although survival after H-LTx has been improving in some centers with extensive experience, the 59% 1-year worldwide survival reported by the International Society for Heart Transplantation compares poorly with survival after isolated cardiac transplantation (79% 1-year survival [9]). Therefore, scarce donor hearts may not be well
Ann Thorac Surg
1991:52:300-3
CASE REPORT
MCCARTHY ET AL
EISENMENGER’S LUNG TRANSPLANTATION
303
direct right atrial to pulmonary artery connections (the Fontan concept) suggest that even severe right ventricular dysfunction could be well tolerated if the left ventricular function is normal and the pulmonary vascular resistance decreases to normal in the transplanted lung.
Addendum Ten months postoperatively this patient continues to be well (New York Heart Association class I) and has not had any lung rejection. Another patient with an ASD and Eisenmenger’s syndrome underwent transplantation after this report was submitted and showed similar right heart recovery (right ventricular ejection fraction, 0.18 preoperatively, 0.45 in the operating room and initial 72 hours, and 0.48 at 1 month). A patient with primary pulmonary hypertension who underwent transplantation also showed excellent recovery of right heart function and improved right ventricular ejection fraction (0.23 preoperatively, 0.47 perioperatively, and 0.71 at 1 month).
References
Fig 4 . One-month postoperative pulmonary arterial condition (spinecho and cine; transaxial). Two images corresponding to those in Figure 2 demonstrate the high-intensity fat within the omental flap (arrows) surrounding the region of the anastomosis (arrowhead) of the right central pulmonary artety. There is also evidence of improvement in the size of the pulmonary arteries compared with the ascending aorta and no further evidence of systolic slow blood flow uiithin the right central pulmonary artery.
utilized for H-LTx, except in centers that can attain acceptable survival after H-LTx. Complex congenital heart defects associated with Eisenmenger’s syndrome still require H-LTx because of the complexity associated with repairing these defects. For less complicated congenital defects, however, cardiac repair with single-lung transplantation may be performed with recovery of right heart function. Clinical results after
1. Reitz BA, Wallwork JL, Hunt SA, et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982;306:557-64. 2. McCarthy PM, Starnes VA, Theodore J, Stinson EB, Oyer PE, Shumway NE. Improved survival after heart-lung transplantation. J Thorac Cardiovasc Surg 1990;99:54-60. 3. Grossman RF, Frost A, Zamel N, et al. Results of single-lung transplantation for bilateral pulmonary fibrosis. N Engl J Med 1990;322:727-33. 4. Fremes SE, Patterson GA, Williams WG, et al. Single lung transplantation and closure of patent ductus arteriosus for Eisenmenger’s syndrome. J Thorac Cardiovasc Surg 1990;lOO: 1-5. 5. Sechtem U, Pflugfelder PW, White RD, et al. Cine MR imaging: potential for the evaluation of cardiovascular function. AJR 1987;148:23946. 6 . White RD, Paschal CB, Tkach JA, Carvlin MJ. Functional cardiovascular evaluation by magnetic resonance imaging. Top Magn Reson Imag 1990;2(2):31-48. 7. Dhainaut J, Brunet F, Monsallier JF, et al. Bedside evaluation of right ventricular performance using a rapid computerized thermodilution method. Crit Care Med 1987;15:148-52. 8. Calhoon JH, Grover FD, Gibbons WJ, et al. Single lung transplantation-alternative indications and technique. J Thorac Cardiovasc Surg 1991;101:81&25. 9. Kriett JM, Kaye MP. The registry of the International Society for Heart Transplantation: seventh official report-1990. J Heart Transplant 1990;9:323-30.
