Transplant of Rescued Stunned Donor Hearts
Transplant of Rescued Stunned Donor Hearts
Six marginal candidate donors (mean age, 40 ± 13 years; three men) were enrolled (Table 1). The causes of death were head trauma in two, cerebral vascular accident in three, and cardiac arrest in one. Resting echocardiography showed in all a LVEF ≥ 45%, mean value = 51 ± 5%, but multiple risk factors were present: all were heavy smokers, three had elevated cardiac markers, three had central venous pressure > 12 mmHg, three had need for excessive inotropic support, all six had either global or discrete wall motion abnormalities, with WMSI at rest = 1.33 ± 0.25. Stress echocardiography was performed with high-dose dipyridamole (0.84 mg/kg over 6 min).
The stress echo results were abnormal in three donors: WMSI peak = 1.41 ± 0.30, with a flat-negative contractile reserve (Figures 1 and 2) (Additional files 1 and 2). At autopsy study (available in two), the donor with incomplete recovery of apical hypokinesia showed myocardial fibrosis with a mild DCM aspect (Table 1, donor #1); the donor with worsening of apical akinesia (Table 1, donor #3) showed a 90% LAD stenosis, multiple foci of coagulative necrosis associated with diffuse coagulative subendocardial myocytolysis (Figure 3).
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Figure 1.
Donor #2 in Table 1. An example of a stress echocardiogram in a brain-dead potential donor, showing end-diastolic and end-systolic frames at rest and following stress using Dipyridamole (0.84 mg/kg in 6') [see Additional file 1]. Left ventricular interventricular septum and apical wall a-kinesia are shown in parasternal long-axis (panel A) and short-axis (panel B) chamber views. At peak stress an incomplete viability response is shown. The donor was considered unsuitable for heart donation.
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Figure 2.
Donor #3 in Table 1. An example of a stress echocardiogram with fixed abnormalities in a brain-dead potential donor, showing end-diastolic and end-systolic frames at rest and following stress using Dipyridamole. The test was prematurely stopped at 4 min due to severe systemic hypotension; WMSI rest = 1.65; WMSI = 1.71 at stop stress [see Additional file 2]. The pressure volume relation was negative with the ΔESP/ESV value = - 1.7 mmHg/mL/m. The heart was sent to the pathology department for detailed macroscopic and histology examination.
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Figure 3.
The donor heart unsuitable for transplant of Figure 2. A) Macroscopic aspect of donor heart. B) Fibro-lipidic plaque narrowing (≈90%) the lumen of left anterior coronary artery (Mallory trichrome stain; original magnification 25x); in the inset, the corresponding macroscopic sample. C) Focus of myocardial coagulative necrosis (arrow) in the left ventricle (Hematoxylin-Eosin stain; original magnification 200x). D) Subendocardial coagulative myocytolysis (arrow) in the septal myocardium (Hematoxylin-Eosin stain; original magnification: 400x).
The remaining three hearts showed reversible left ventricular resting abnormalities (Figures 4, 5, 6 and 7) (Additional files 3, 4 and 5). WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06. All had positive contractile reserve, with LV elastance increase during stress. These three hearts were transplanted uneventfully and underwent standard post TX coronary, angiography, IVUS and endomyocardial biopsies. The recipients were male, age 53 ± 4 years. No recipient had primary graft failure and all showed normal coronary vessel at 1-month post-TX coronary angiography: left ventricular function was normal at 1 month post-TX (LVEF = 57 ± 6%; WMSI = 1 ± 0). In the EMBs taken for post-transplant rejection status surveillance, no significant ischemic peritransplant injury was noted in two recipients (Table 1, donors #4 and #6) (Figure 6). The recipient of the donor heart with mild left ventricular hypertrophy and reversible septal hypokinesia (Table 1, donor #5) showed at EMBs mild peritransplant injury (Figure 8). The recipients were alive at 12-month median follow-up.
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Figure 4.
Donor #6 of Table 1. Two-dimensional transesophageal echocardiogram recorded immediately after "explosive" subarachnoid hemorrhage accompanied by extreme systolic hypertensive response with systolic blood pressure ≈ 300 mmHg and acute pulmonary edema. The donor had discrete left ventricular dysfunction with hypokinesia involving the inferior and lateral LV walls [see Additional file 3].
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Figure 5.
Donor #6 of Table 1. The same donor as in Figure 4. Two days after the subarachnoid hemorrhage and after brain death, the donor underwent a transthoracic dipyridamole stress echo (0.84 mg/kg in 6') [see Additional file 4]. Left ventricular lateral wall hypokinesia and inferior wall akinesia are shown in 4-chamber (panel A) and 3-chamber (panel B) views at baseline (left panels). At peak stress a viability response is shown with recovery of lateral and inferior wall motion (right panels). The donor was considered suitable for heart donation and the heart was transplanted.
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Figure 6.
The donor heart of donor #6 (Table 1) after heart transplant. In the figure, images from the first two endomyocardial biopsies (EMBs) performed on the 7 (panel A) and 15 (panel B) days after surgery, where regular myocardium is shown. In the EMBs taken for post-transplant rejection status surveillance, no significant ischemic peritransplant injury was noted, a finding usually seen in biopsies during the first 6 weeks after transplantation.
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Figure 7.
Donor #4 of Table 1. Transthoracic pharmacological stress echo test using dipyridamole (0.84 mg/kg in 6') in a potential donor with prolonged (37 min) cardiac arrest at death [see Additional file 5]. The donor had normal response with normal regional wall motion during pharmacological stress echo. (panel A, 4-chamber views; panel B, 2-chamber views). The pressure/volume relation was positive and the individual was considered a suitable donor.
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Figure 8.
Recipient of donor #5 in Table 1. Ischemic peritransplant injury in the first 4 endomyocardial biopsies (EMBs) taken for post-transplant rejection status surveillance. A (12 day after surgery): generic interstitial oedema; B (19 day after surgery): a focus of peritransplant injury with hypereosinophilic cytoplasm myocites (asterisk) or with coagulative myocytolisis (arrow); C (26 day after surgery): necrotic, evanescent (disappearing) and fragmented myocytes (asterisk); D (36 day after surgery): a focus of resolving peritransplant injury with regional loss of myocytes, loose substitutive connective tissue/granulation tissue and pigment-laden macrophages.
Results
Six marginal candidate donors (mean age, 40 ± 13 years; three men) were enrolled (Table 1). The causes of death were head trauma in two, cerebral vascular accident in three, and cardiac arrest in one. Resting echocardiography showed in all a LVEF ≥ 45%, mean value = 51 ± 5%, but multiple risk factors were present: all were heavy smokers, three had elevated cardiac markers, three had central venous pressure > 12 mmHg, three had need for excessive inotropic support, all six had either global or discrete wall motion abnormalities, with WMSI at rest = 1.33 ± 0.25. Stress echocardiography was performed with high-dose dipyridamole (0.84 mg/kg over 6 min).
Abnormal Stress Echo Response With Fixed or Worsening Wall Motion
The stress echo results were abnormal in three donors: WMSI peak = 1.41 ± 0.30, with a flat-negative contractile reserve (Figures 1 and 2) (Additional files 1 and 2). At autopsy study (available in two), the donor with incomplete recovery of apical hypokinesia showed myocardial fibrosis with a mild DCM aspect (Table 1, donor #1); the donor with worsening of apical akinesia (Table 1, donor #3) showed a 90% LAD stenosis, multiple foci of coagulative necrosis associated with diffuse coagulative subendocardial myocytolysis (Figure 3).
(Enlarge Image)
Figure 1.
Donor #2 in Table 1. An example of a stress echocardiogram in a brain-dead potential donor, showing end-diastolic and end-systolic frames at rest and following stress using Dipyridamole (0.84 mg/kg in 6') [see Additional file 1]. Left ventricular interventricular septum and apical wall a-kinesia are shown in parasternal long-axis (panel A) and short-axis (panel B) chamber views. At peak stress an incomplete viability response is shown. The donor was considered unsuitable for heart donation.
(Enlarge Image)
Figure 2.
Donor #3 in Table 1. An example of a stress echocardiogram with fixed abnormalities in a brain-dead potential donor, showing end-diastolic and end-systolic frames at rest and following stress using Dipyridamole. The test was prematurely stopped at 4 min due to severe systemic hypotension; WMSI rest = 1.65; WMSI = 1.71 at stop stress [see Additional file 2]. The pressure volume relation was negative with the ΔESP/ESV value = - 1.7 mmHg/mL/m. The heart was sent to the pathology department for detailed macroscopic and histology examination.
(Enlarge Image)
Figure 3.
The donor heart unsuitable for transplant of Figure 2. A) Macroscopic aspect of donor heart. B) Fibro-lipidic plaque narrowing (≈90%) the lumen of left anterior coronary artery (Mallory trichrome stain; original magnification 25x); in the inset, the corresponding macroscopic sample. C) Focus of myocardial coagulative necrosis (arrow) in the left ventricle (Hematoxylin-Eosin stain; original magnification 200x). D) Subendocardial coagulative myocytolysis (arrow) in the septal myocardium (Hematoxylin-Eosin stain; original magnification: 400x).
Normal Stress Echo Response With Improvement in Wall Motion
The remaining three hearts showed reversible left ventricular resting abnormalities (Figures 4, 5, 6 and 7) (Additional files 3, 4 and 5). WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06. All had positive contractile reserve, with LV elastance increase during stress. These three hearts were transplanted uneventfully and underwent standard post TX coronary, angiography, IVUS and endomyocardial biopsies. The recipients were male, age 53 ± 4 years. No recipient had primary graft failure and all showed normal coronary vessel at 1-month post-TX coronary angiography: left ventricular function was normal at 1 month post-TX (LVEF = 57 ± 6%; WMSI = 1 ± 0). In the EMBs taken for post-transplant rejection status surveillance, no significant ischemic peritransplant injury was noted in two recipients (Table 1, donors #4 and #6) (Figure 6). The recipient of the donor heart with mild left ventricular hypertrophy and reversible septal hypokinesia (Table 1, donor #5) showed at EMBs mild peritransplant injury (Figure 8). The recipients were alive at 12-month median follow-up.
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Figure 4.
Donor #6 of Table 1. Two-dimensional transesophageal echocardiogram recorded immediately after "explosive" subarachnoid hemorrhage accompanied by extreme systolic hypertensive response with systolic blood pressure ≈ 300 mmHg and acute pulmonary edema. The donor had discrete left ventricular dysfunction with hypokinesia involving the inferior and lateral LV walls [see Additional file 3].
(Enlarge Image)
Figure 5.
Donor #6 of Table 1. The same donor as in Figure 4. Two days after the subarachnoid hemorrhage and after brain death, the donor underwent a transthoracic dipyridamole stress echo (0.84 mg/kg in 6') [see Additional file 4]. Left ventricular lateral wall hypokinesia and inferior wall akinesia are shown in 4-chamber (panel A) and 3-chamber (panel B) views at baseline (left panels). At peak stress a viability response is shown with recovery of lateral and inferior wall motion (right panels). The donor was considered suitable for heart donation and the heart was transplanted.
(Enlarge Image)
Figure 6.
The donor heart of donor #6 (Table 1) after heart transplant. In the figure, images from the first two endomyocardial biopsies (EMBs) performed on the 7 (panel A) and 15 (panel B) days after surgery, where regular myocardium is shown. In the EMBs taken for post-transplant rejection status surveillance, no significant ischemic peritransplant injury was noted, a finding usually seen in biopsies during the first 6 weeks after transplantation.
(Enlarge Image)
Figure 7.
Donor #4 of Table 1. Transthoracic pharmacological stress echo test using dipyridamole (0.84 mg/kg in 6') in a potential donor with prolonged (37 min) cardiac arrest at death [see Additional file 5]. The donor had normal response with normal regional wall motion during pharmacological stress echo. (panel A, 4-chamber views; panel B, 2-chamber views). The pressure/volume relation was positive and the individual was considered a suitable donor.
(Enlarge Image)
Figure 8.
Recipient of donor #5 in Table 1. Ischemic peritransplant injury in the first 4 endomyocardial biopsies (EMBs) taken for post-transplant rejection status surveillance. A (12 day after surgery): generic interstitial oedema; B (19 day after surgery): a focus of peritransplant injury with hypereosinophilic cytoplasm myocites (asterisk) or with coagulative myocytolisis (arrow); C (26 day after surgery): necrotic, evanescent (disappearing) and fragmented myocytes (asterisk); D (36 day after surgery): a focus of resolving peritransplant injury with regional loss of myocytes, loose substitutive connective tissue/granulation tissue and pigment-laden macrophages.