- Email: [email protected]
Pregnancy after heterotopic heart transplant removal
Accepted Manuscript Case report Pregnancy after heterotopic heart transplant removal - a case report S. Churchill, L. de Lloyd, H.C. Francis, H Wallis PII: DOI: Reference:
S0959-289X(17)30421-1 https://doi.org/10.1016/j.ijoa.2018.04.003 YIJOA 2673
To appear in:
International Journal of Obstetric Anesthesia
Received Date: Revised Date: Accepted Date:
13 November 2017 10 March 2018 6 April 2018
Please cite this article as: Churchill, S., de Lloyd, L., Francis, H.C., Wallis, H., Pregnancy after heterotopic heart transplant removal - a case report, International Journal of Obstetric Anesthesia (2018), doi: https://doi.org/10.1016/ j.ijoa.2018.04.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Pregnancy after heterotopic heart transplant removal - a case report
2 3
S Churchill1, L de Lloyd1, HC Francis2, H Wallis.3
4
1.
Department of Anaesthetics, University Hospital of Wales, Cardiff
5
2.
Department of Obstetrics, University Hospital of Wales, Cardiff
6
3.
Department of Cardiology, University Hospital of Wales, Cardiff
8
4.
Correspondence to Dr. S. Churchill, Department of Anaesthetics, University Hospital of
9
Wales, Cardiff
7
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
E-mail address: [email protected]
36
ABSTRACT
37
Heterotopic heart transplants were introduced in 1974. The technique allows the patient’s native
38
heart to be preserved in situ, alongside the transplanted heterotopic donor heart.1 We present the
39
case of a nulliparous women who underwent heterotopic heart transplant in infancy, and subsequent
40
explantation of the donor heart eleven years later, when her native heart function recovered.
41
In adulthood the patient attended pre-pregnancy counselling and was awaiting cardiac magnetic
42
resonance imaging when she presented pregnant at 6 weeks-of-gestation. She attended the joint
43
cardiac obstetric and anaesthetic clinic, where she was reviewed monthly and had bi-monthly
44
echocardiograms. At 35 weeks-of-gestation she was admitted to hospital with preeclampsia. After
45
blood pressure control and steroid administration, a category 3 caesarean delivery under spinal
46
anaesthesia was performed. To our knowledge this is the first case report describing pregnancy in a
47
patient with a removed heterotopic heart transplant.
48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70
Keywords: pregnancy, heterotopic heart transplant, preeclampsia, removal of donor heart.
71
Introduction
72
Cardiac transplantation usually involves removal of the diseased native heart and replacement with
73
a donor heart (orthotopic transplantation). In heterotopic transplantation, the diseased native heart is
74
retained in situ, and the donor heart is ‘piggybacked’ alongside it (Fig. 1). Heterotopic heart
75
transplantation is an unusual technique whereby the donor heart functions alongside the native
76
heart, essentially as a ventricular assist device. It was originally introduced to improve safety in the
77
event of acute rejection occurring following orthotopic heart transplantation. With the advent of
78
improved immunosuppressive regimens using cyclosporin, this advantage has been lost and
79
orthotopic heart transplantation is now the technique of choice in most cases. Heterotopic heart
80
transplants are reserved for highly-selected cases, such as an alternative to heart-lung
81
transplantation in patients with severe pulmonary hypertension or in the case of severe donor
82
recipient size mismatch.2,3
83 84
Case report
85
The patient had developed dilated cardiomyopathy in infancy, which led to heart failure that
86
required heterotopic cardiac transplantation at two years of age. The transplant functioned well, but
87
the immunosuppression induced post-transplant lymphoproliferative disease, which relapsed despite
88
treatment with several cycles of chemotherapy. Her native cardiac function recovered over the
89
following years to a point that allowed removal of the heterotopic heart 11 years later. The
90
lymphoproliferative disease resolved once immunosuppression had ceased and her native heart was
91
maintaining adequate function.4
92
She remained under annual review in the congenital cardiac clinic. In adulthood, the patient sought
93
pre-pregnancy counselling and underwent exercise testing, which was sub-optimal because of its
94
limitation by chest tightness. The anaerobic threshold was not reached and she achieved a
95
maximum rate of oxygen consumption (VO2) peak of 29.8 mL/kg/min. Cardiac magnetic resonance
96
imaging (MRI) was requested but had not yet been performed when she presented with a pregnancy
97
at 6 weeks-of-gestation.
98
She was referred to the joint cardiac-obstetric-anaesthetic clinic and was reviewed at 12 weeks-of-
99
gestation. She was asymptomatic from a cardiac perspective (American Heart Association (AHA)
100
functional status 1), took no regular cardiovascular medication and had a normal body mass index
101
of 23 kg/m2. Transthoracic echocardiogram (TTE) showed good overall left ventricular function,
102
with some reduction of radial and longitudinal function of the right ventricle. Electrocardiogram
103
showed sinus tachycardia of 100 beats/min and a partial right bundle-branch block.
104
She gave a history of longstanding wheeze and shortness of breath, with morning expectoration and
105
recurrent chest infections. Her general practitioner had diagnosed asthma and prescribed salbutamol
106
inhalers. She was referred to a respiratory physician during the forced expiratory pregnancy.
107
Spirometry showed a forced expiratory volume in one second (FEV1) of 59% predicted and a
108
forced vital capacity of 70% predicted, with a ratio of 72% suggestive of a mild airflow obstruction
109
without significant reversibility. She was commenced on a fluticasone and salmeterol inhaler.
110
Respiratory symptoms remained stable during pregnancy. A high-resolution computerized
111
tomography scan was requested for after delivery.
112
She had monthly follow-up in the joint clinic, with TTE performed bi-monthly throughout her
113
pregnancy (Table 1). Longitudinal function of the left ventricle was assessed by serial tissue
114
Doppler imaging measurements of the basal lateral wall, recording peak systolic velocity. Right
115
ventricular longitudinal assessment was assessed by measuring tricuspid annular plane systolic
116
excursion (TAPSE).
117
Proteinuria had been identified early in pregnancy and blood results at booking showed a urea of 5
118
mmol/L and creatinine of 60 µmol/L, these being attributed to pre-existing renal disease. At 25
119
weeks-of-gestation the protein/creatinine ratio was elevated at 219 mg/mmol (expressed as mg of
120
protein:mmol creatinine; the normal value <30 mg/mmol). At 35 weeks-of-gestation she was
121
admitted to hospital with a blood pressure of 160/100 mmHg. Hydralazine (5 mg IV) was
122
administered to stabilise her blood pressure and regular nifedipine (10 mg) was commenced. Blood
123
test results at this time showed urea 6.9 mmol/L, creatinine 70 mol/L, haemoglobin 126 g/L and
124
platelet count 246 x109/L. This reflected mild renal impairment but no hepatic or haematological
125
evidence of severe preeclampsia. She received betamethasone for fetal lung maturation. A TTE
126
showed that the left ventricular (LV) ejection fraction had fallen from over 55% to 45%, with
127
reduction in radial and longitudinal right ventricular (RV) function (Fig. 2). The protein-to-
128
creatinine ratio increased to 445 mg/mmol and her renal function deteriorated (urea 8.1 mmol/L,
129
creatinine 95 µmol/L). Although she remained clinically well, the decision was made at 35+6
130
weeks-of-gestation to proceed with a planned caesarean delivery, in view of evolving preeclampsia
131
and the potential for maternal deterioration.
132
The anaesthetic plan was for combined spinal-epidural anaesthesia and invasive arterial blood
133
pressure monitoring. There was to be a low threshold for mechanical uterotonic treatment due to
134
relative contraindications to ergometrine (hypertension) and 15-methyl-prostaglandin F2a (asthma).
135
Uterine tone was to be aided with 5 IU oxytocin as a fractionated, slow IV bolus and a further 40 IU
136
by infusion over four hours, and cautious fluid administration due to the impaired ventricular
137
function and preeclampsia.
138
The patient was severely needle phobic and reported a history of difficulty with IV access. Insertion
139
of the arterial cannula proved difficult and was abandoned at her request. Non-invasive blood
140
pressure was measured every 2.5 minutes. Large bore peripheral intravenous access was
141
established. Epidural catheter insertion also proved difficult and was abandoned after several
142
attempts in favour of single-shot spinal anaesthesia, which was achieved using 2.0 mL hyperbaric
143
bupivacaine 0.5% plus 20 µg intrathecal fentanyl and 100 µg intrathecal morphine. Haemodynamic
144
stability was maintained throughout surgery with an infusion of phenylephrine and a healthy infant
145
was delivered. Prominent vasculature over the lower uterine segment resulted in bleeding to a
146
measured blood loss 1.4 L, which was controlled surgically. She showed no signs of hypovolaemia
147
despite her blood loss and 200 mL IV Hartmann’s solution was infused intraoperatively. Uterine
148
tone was good both intraoperatively and postoperatively and mechanical uterotonics were not
149
required.
150
Postoperatively her blood pressure normalised and antihypertensive therapy was no longer required.
151
She remained haemodynamically stable and was discharged home four days postoperatively, having
152
had cardiology follow-up arranged. Three months after discharge she remained asymptomatic
153
(AHA status 1) but her cardiac function had not recovered to the pre-pregnancy baseline. An
154
echocardiogram at six-months postpartum showed an increased LV diastolic diameter (5 cm), an
155
LV ejection fraction of 49% and mildly impaired RV function (Fig. 2).
156 157
Discussion
158
Compared to orthotopic transplantation, heterotopic heart transplantation, which retains the native
159
heart in situ, may have significant long-term benefits, as recovery of the diseased myocardium at
160
some point in the future remains a possibility. Since explantation, this patient had led a relatively
161
normal life, with good cardiac function, resolution of her lymphoproliferative disease, and no
162
requirement for immunosuppression. To our knowledge this is the first case report describing
163
pregnancy in a patient with an explanted heterotopic heart transplant, after recovery of the native
164
heart.
165
In contrast to patients after removed heterotopic cardiac transplant, pregnancy in women with
166
orthotopic cardiac transplantation is well documented and established, and there are several case
167
series describing maternal and fetal outcomes.5,6 These patients constitute a high-risk group, with
168
specific management challenges.
169
The risk of developing preeclampsia and deteriorating renal function is increased in patients with
170
cardiac transplantation, as is the risk of preterm delivery. The mean gestational age at delivery has
171
been reported as 34 to 35 weeks.5,6 During pregnancy medications with known teratogenicity must
172
be stopped and replaced. It is crucial that adequate immunosuppression is maintained to prevent
173
graft rejection. This can be challenging in the face of altered drug distribution and clearance
174
associated with evolving pregnancy. Maternal death may occur after delivery: in two case series, 4
175
of 22; and 2 of 17 patients respectively, died postnatally.5,6 In these series deaths were due to
176
postpartum haemorrhage (n=1), complications related to atheromatous coronary disease (n=1) and
177
complications related to graft rejection, thought to be related to poor compliance with
178
immunosuppressant medication (n=4).
179
Risk-stratification of pregnancy in a patient with such an unusual cardiac history is difficult due to
180
the lack of a precedent. In this patient, although her heart appeared to function well before
181
pregnancy, its response to the additional cardiovascular demands of pregnancy was unpredictable,
182
given her past history of fulminant heart failure. High-risk cardiac patients should attend for formal
183
pre-pregnancy counselling. This will allow thorough assessment of baseline status, optimisation of
184
management, preparation for pregnancy, and discussion of the potential risks to the mother and her
185
fetus.7,8 Cardiac MRI may assist in this regard and had been requested, but the patient became
186
pregnant before it had been performed.
187
The pregnancy was regarded as high-risk and joint cardiac and obstetric monitoring was instituted
188
early. This facilitated communication between specialists and the formulation of multidisciplinary
189
care plans. It is a model that has been recommended to optimise patient care.9
190
Although her principal pathology was cardiac, our patient had other medical conditions.
191
Cardiopulmonary exercise testing pre-pregnancy was limited by breathlessness and she gave a
192
history of recurrent chest infections, morning expectoration and shortness of breath, which were
193
attributed to poorly-controlled asthma. Lung function tests suggested obstructive airway disease
194
more consistent with bronchiectasis and further investigation was planned postpartum. Chronic lung
195
disease may have been a consequence of the cardiac transplant, immunosuppression and
196
chemotherapy. Despite explantation of the heterotopic heart, her good reported AHA status and
197
cardiac function on TTE, her medical morbidity status was complex and was further complicated by
198
severe needle phobia and challenging venous access.
199 200
It is well recognized that pregnancy in patients after cardiac transplantation is associated with an
201
increased risk of developing preeclampsia.10 Despite removal of the donor heart, it is likely that this
202
risk remained elevated. This patient was noted to have proteinuria early in the pregnancy, attributed
203
to her complex medical history, which included relapsing lymphoproliferative disease and multiple
204
cycles of chemotherapy. She also carried the morbidity burden of a previous cardiac transplant and
205
it is unknown whether risk reduces to that of the baseline population after explantation. Low-dose
206
aspirin started early in pregnancy may reduce the likelihood of developing preeclampsia in those at
207
high risk and administration is recommended by the National Institute of Health and Care
208
Excellence (NICE) for patients recognized to be at increased risk of developing the condition.11,12
209
Whether aspirin warrants consideration in patients with the risk factor of cardiac transplantation is
210
of interest, particularly as patients with vulnerable myocardium are at high risk of sustaining
211
morbidity as a result of preeclampsia. Studies exploring this area would be useful.
212
Although an appropriately managed vaginal delivery may be preferable to maintain cardiac
213
stability, the patient had made it clear throughout the antenatal period that she wished for a
214
caesarean delivery.13 The plan for delivery was to administer combined spinal-epidural anaesthesia,
215
with low-dose spinal and an epidural top-up, and with continuous blood pressure monitoring. This
216
was not possible and blood pressure was measured intermittently due to maternal request. The
217
epidural catheter component could not be achieved, so single-shot spinal anaesthesia was
218
administered, with careful maternal positioning to minimize aortocaval compression. It is of note
219
that ‘plan A’ may not be feasible, but it remains important that the principles of management are
220
maintained. Continuous spinal anaesthesia may have been an appropriate alternative choice,
221
however this technique is not in use at our institution.
222
We aimed to avoid fluid overload whilst maintaining venous return and ventricular filling. Fluid
223
was infused judiciously, as discrete small boluses with review, to avoid a hypervolaemic state.
224
Although there is a risk of oxytocin causing vasodilation and hypotension, the patient experienced
225
no cardiovascular compromise from a carefully fractionated, slow IV bolus of 5 units of oxytocin,
226
followed by an infusion. Ergometrine and 15-methyl-prostaglandin F2a were relatively
227
contraindicated and, as bleeding was rapidly controlled surgically, were not required.
228
Although she remained well, the fact that TTE performed three months after delivery did not show
229
recovery of LV function to pre-pregnancy levels is a reminder that pregnancy can have long term
230
deleterious effects on the vulnerable myocardium. At her first postpartum appointment the
231
importance of reliable contraception was discussed. She was strongly advised to undergo detailed
232
pre-pregnancy assessment and counselling before considering further pregnancy.
233
In conclusion, this case illustrates that high-risk cardiac patients should be referred for pre-
234
pregnancy counselling. Referral to a specialized high-risk joint cardiac, obstetric and anaesthetic
235
clinic should occur at an early stage in the pregnancy. Transthoracic echocardiography is a useful
236
and sensitive monitor of cardiac function in this setting. Women becoming pregnant after an
237
explanted heterotopic heart transplant may remain within the cardiac transplantation cohort in terms
238
of risks of developing preeclampsia and renal dysfunction. There should be a low threshold for
239
delivery of patients presenting with pre-existing cardiac disease and superimposed preeclampsia,
240
particularly after 34 weeks’ gestation.
241 242 243 244
245
References
246 247
1. Newcomb AE, Esmore DS, Rosenfeldt FL, Richardson M, Marasco SF. Heterotopic heart
248
transplantation: an expanding role in the twenty-first century? Ann Thorac Surg 2004;78:1345-50
249 250
2. Kadner A, Chen RH, Adams DH. Heterotopic heart transplantation: experimental development
251
and clinical experience. Eur J Cardiothoracic Surg 2000;17:474-81.
252 253
3. Jahanyar J, Koerner MM, Ghodsizad A, Loebe M, Noon GP. Heterotopic heart transplantation:
254
The United States experience. Heart Surg Forum 2014;17:E132-40.
255 256
4. Tsang V, Yacoub M, Sridharan S, et al. Late donor cardiectomy after paediatric heterotopic
257
cardiac transplantation. Lancet 2009;374:L387-92.
258 259
5. Bhagra CJ, Bhagra SK, Donado A, Butt T, Forrest L, MacGowan GA, Parry G. Pregnancy in
260
cardiac transplant recipients. Clin Transplant 2016;30:1059-65.
261 262
6. D’Souza R, Soete E, Silversides CK, et al. Pregnancy outcomes following cardiac
263
transplantation. J Obstet Gynaecol Can 2017 Nov 15. pii: S1701-2163(17)30416-4. doi:
264
10.1016/j.jogc.2017.08.030.
265 266
7. Ruys T, Cornette J, Roos Hesselink JW. Pregnancy and delivery in cardiac disease. J Cardiol
267
2013;61:107–12.
268 269
8. Canobbio MM, Warnes CA, Aboulhosn J, et al. Management of pregnancy in patients with
270
complex congenital heart disease: A scientific statement for healthcare professionals from the
271
American Heart Association. Circulation 2017;135:e50-e87.
272 273
9. Knight M, Nair M, Tuffnell D, et al (eds). on behalf of MBRRACE-UK. Saving lives, improving
274
mothers’ care - surveillance of maternal deaths in the UK 2012-14 and lessons learned to inform
275
maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity
276
2009-14. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2016. Available at:
277
https://www.npeu.ox.ac.uk. Accessed March 21, 2017.
278
279
10. Abdalla M, Mancini D. Management of pregnancy in the post cardiac transplant patient. Semin
280
Perinatol 2014;38:318-25.
281 282
11. Moore GS, Allshouse AA, Post AL, Galan HL, Heybourne KD. Early Initiation of low-dose
283
aspirin for reduction in preeclampsia risk in high risk women: a secondary analysis of the MFMU
284
High-Risk Aspirin Study. J Perinatol 2015;35:328-31.
285 286
12. National Institute of Health and Care Excellence (NICE) Guidance, Hypertension in pregnancy:
287
diagnosis and management. Clinical guideline [CG107]. https://www.nice.org.uk>guidance.
288 289 290
Accessed March 21, 2018.
291
delivery in patients with adult congenital heart disease? Interact Cardiovasc Thorac Surg
292
2013;17:144-150.
293 294
13. Asfour V, Murphy M, Attia R. Is vaginal delivery or caesarian section the safer mode of
Heterotopic heart transplant anatomy SVC
KEY LVd Left ventricle, donor PAd Pulmonary artery, donor Ad Aortic root, donor
SVC RV AA PA RV
PA
Ad
Superior vena cava Right ventricle Aortic arch Pulmonary artery Right ventricle
PAd
RA LVd
295 296
AA
RV
Gestation
LV ejection
LV end-diastolic RV
RV end-
fraction (%)
diameter (cm)
TAPSE
diastolic
(mm)
diameter (cm)
Pre-pregnancy
55
4.7
10
19 weeks
> 55
4.6
20
35 + 6/7 weeks
45
4.9
13
3 mth post-
45
4.9
16
3.1
3.9
partum 297
Fig. 2: Transthoracic echocardiography performed throughout pregnancy
298 299
TAPSE: Tricuspid Annular Plane Systolic Excursion (normal range 15 – 20 mm). LV: Left
300
ventricular. RV: Right ventricular
301 302
GESTATION
303
LV ejection
LV end diastolic RV
RV end
fraction (%)
diameter (cm)
TAPSE
diastolic
(mm)
diameter (cm)
Pre-pregnancy
55
4.7
10
19 weeks
> 55
4.6
20
35+6 weeks
45
4.9
13
3/12 post-partum 45
4.9
16
3.1
3.9
Figure 2: transthoracic echocardiography performed throughout pregnancy
304 305
KEY:
306
TAPSE, Tricuspid Annular Plane Systolic Excursion, normal range 15 – 20 mm
307
LV Left ventricular
308
RV Right ventricular
309 310
311
Highlights
312 313 314
This patient received heterotopic cardiac transplantation in childhood
315 316
Native cardiac function recovered allowing explantation of the donor heart
317 318
This report describes pregnancy after removal of a heterotopic heart transplant
319 320
Pregnancy after explantation of a heterotopic heart transplant is high-risk
321 322 323 324
Care should be within a joint high-risk cardiac, obstetric, anaesthetic environment
S0959-289X(17)30421-1 https://doi.org/10.1016/j.ijoa.2018.04.003 YIJOA 2673
To appear in:
International Journal of Obstetric Anesthesia
Received Date: Revised Date: Accepted Date:
13 November 2017 10 March 2018 6 April 2018
Please cite this article as: Churchill, S., de Lloyd, L., Francis, H.C., Wallis, H., Pregnancy after heterotopic heart transplant removal - a case report, International Journal of Obstetric Anesthesia (2018), doi: https://doi.org/10.1016/ j.ijoa.2018.04.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Pregnancy after heterotopic heart transplant removal - a case report
2 3
S Churchill1, L de Lloyd1, HC Francis2, H Wallis.3
4
1.
Department of Anaesthetics, University Hospital of Wales, Cardiff
5
2.
Department of Obstetrics, University Hospital of Wales, Cardiff
6
3.
Department of Cardiology, University Hospital of Wales, Cardiff
8
4.
Correspondence to Dr. S. Churchill, Department of Anaesthetics, University Hospital of
9
Wales, Cardiff
7
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
E-mail address: [email protected]
36
ABSTRACT
37
Heterotopic heart transplants were introduced in 1974. The technique allows the patient’s native
38
heart to be preserved in situ, alongside the transplanted heterotopic donor heart.1 We present the
39
case of a nulliparous women who underwent heterotopic heart transplant in infancy, and subsequent
40
explantation of the donor heart eleven years later, when her native heart function recovered.
41
In adulthood the patient attended pre-pregnancy counselling and was awaiting cardiac magnetic
42
resonance imaging when she presented pregnant at 6 weeks-of-gestation. She attended the joint
43
cardiac obstetric and anaesthetic clinic, where she was reviewed monthly and had bi-monthly
44
echocardiograms. At 35 weeks-of-gestation she was admitted to hospital with preeclampsia. After
45
blood pressure control and steroid administration, a category 3 caesarean delivery under spinal
46
anaesthesia was performed. To our knowledge this is the first case report describing pregnancy in a
47
patient with a removed heterotopic heart transplant.
48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70
Keywords: pregnancy, heterotopic heart transplant, preeclampsia, removal of donor heart.
71
Introduction
72
Cardiac transplantation usually involves removal of the diseased native heart and replacement with
73
a donor heart (orthotopic transplantation). In heterotopic transplantation, the diseased native heart is
74
retained in situ, and the donor heart is ‘piggybacked’ alongside it (Fig. 1). Heterotopic heart
75
transplantation is an unusual technique whereby the donor heart functions alongside the native
76
heart, essentially as a ventricular assist device. It was originally introduced to improve safety in the
77
event of acute rejection occurring following orthotopic heart transplantation. With the advent of
78
improved immunosuppressive regimens using cyclosporin, this advantage has been lost and
79
orthotopic heart transplantation is now the technique of choice in most cases. Heterotopic heart
80
transplants are reserved for highly-selected cases, such as an alternative to heart-lung
81
transplantation in patients with severe pulmonary hypertension or in the case of severe donor
82
recipient size mismatch.2,3
83 84
Case report
85
The patient had developed dilated cardiomyopathy in infancy, which led to heart failure that
86
required heterotopic cardiac transplantation at two years of age. The transplant functioned well, but
87
the immunosuppression induced post-transplant lymphoproliferative disease, which relapsed despite
88
treatment with several cycles of chemotherapy. Her native cardiac function recovered over the
89
following years to a point that allowed removal of the heterotopic heart 11 years later. The
90
lymphoproliferative disease resolved once immunosuppression had ceased and her native heart was
91
maintaining adequate function.4
92
She remained under annual review in the congenital cardiac clinic. In adulthood, the patient sought
93
pre-pregnancy counselling and underwent exercise testing, which was sub-optimal because of its
94
limitation by chest tightness. The anaerobic threshold was not reached and she achieved a
95
maximum rate of oxygen consumption (VO2) peak of 29.8 mL/kg/min. Cardiac magnetic resonance
96
imaging (MRI) was requested but had not yet been performed when she presented with a pregnancy
97
at 6 weeks-of-gestation.
98
She was referred to the joint cardiac-obstetric-anaesthetic clinic and was reviewed at 12 weeks-of-
99
gestation. She was asymptomatic from a cardiac perspective (American Heart Association (AHA)
100
functional status 1), took no regular cardiovascular medication and had a normal body mass index
101
of 23 kg/m2. Transthoracic echocardiogram (TTE) showed good overall left ventricular function,
102
with some reduction of radial and longitudinal function of the right ventricle. Electrocardiogram
103
showed sinus tachycardia of 100 beats/min and a partial right bundle-branch block.
104
She gave a history of longstanding wheeze and shortness of breath, with morning expectoration and
105
recurrent chest infections. Her general practitioner had diagnosed asthma and prescribed salbutamol
106
inhalers. She was referred to a respiratory physician during the forced expiratory pregnancy.
107
Spirometry showed a forced expiratory volume in one second (FEV1) of 59% predicted and a
108
forced vital capacity of 70% predicted, with a ratio of 72% suggestive of a mild airflow obstruction
109
without significant reversibility. She was commenced on a fluticasone and salmeterol inhaler.
110
Respiratory symptoms remained stable during pregnancy. A high-resolution computerized
111
tomography scan was requested for after delivery.
112
She had monthly follow-up in the joint clinic, with TTE performed bi-monthly throughout her
113
pregnancy (Table 1). Longitudinal function of the left ventricle was assessed by serial tissue
114
Doppler imaging measurements of the basal lateral wall, recording peak systolic velocity. Right
115
ventricular longitudinal assessment was assessed by measuring tricuspid annular plane systolic
116
excursion (TAPSE).
117
Proteinuria had been identified early in pregnancy and blood results at booking showed a urea of 5
118
mmol/L and creatinine of 60 µmol/L, these being attributed to pre-existing renal disease. At 25
119
weeks-of-gestation the protein/creatinine ratio was elevated at 219 mg/mmol (expressed as mg of
120
protein:mmol creatinine; the normal value <30 mg/mmol). At 35 weeks-of-gestation she was
121
admitted to hospital with a blood pressure of 160/100 mmHg. Hydralazine (5 mg IV) was
122
administered to stabilise her blood pressure and regular nifedipine (10 mg) was commenced. Blood
123
test results at this time showed urea 6.9 mmol/L, creatinine 70 mol/L, haemoglobin 126 g/L and
124
platelet count 246 x109/L. This reflected mild renal impairment but no hepatic or haematological
125
evidence of severe preeclampsia. She received betamethasone for fetal lung maturation. A TTE
126
showed that the left ventricular (LV) ejection fraction had fallen from over 55% to 45%, with
127
reduction in radial and longitudinal right ventricular (RV) function (Fig. 2). The protein-to-
128
creatinine ratio increased to 445 mg/mmol and her renal function deteriorated (urea 8.1 mmol/L,
129
creatinine 95 µmol/L). Although she remained clinically well, the decision was made at 35+6
130
weeks-of-gestation to proceed with a planned caesarean delivery, in view of evolving preeclampsia
131
and the potential for maternal deterioration.
132
The anaesthetic plan was for combined spinal-epidural anaesthesia and invasive arterial blood
133
pressure monitoring. There was to be a low threshold for mechanical uterotonic treatment due to
134
relative contraindications to ergometrine (hypertension) and 15-methyl-prostaglandin F2a (asthma).
135
Uterine tone was to be aided with 5 IU oxytocin as a fractionated, slow IV bolus and a further 40 IU
136
by infusion over four hours, and cautious fluid administration due to the impaired ventricular
137
function and preeclampsia.
138
The patient was severely needle phobic and reported a history of difficulty with IV access. Insertion
139
of the arterial cannula proved difficult and was abandoned at her request. Non-invasive blood
140
pressure was measured every 2.5 minutes. Large bore peripheral intravenous access was
141
established. Epidural catheter insertion also proved difficult and was abandoned after several
142
attempts in favour of single-shot spinal anaesthesia, which was achieved using 2.0 mL hyperbaric
143
bupivacaine 0.5% plus 20 µg intrathecal fentanyl and 100 µg intrathecal morphine. Haemodynamic
144
stability was maintained throughout surgery with an infusion of phenylephrine and a healthy infant
145
was delivered. Prominent vasculature over the lower uterine segment resulted in bleeding to a
146
measured blood loss 1.4 L, which was controlled surgically. She showed no signs of hypovolaemia
147
despite her blood loss and 200 mL IV Hartmann’s solution was infused intraoperatively. Uterine
148
tone was good both intraoperatively and postoperatively and mechanical uterotonics were not
149
required.
150
Postoperatively her blood pressure normalised and antihypertensive therapy was no longer required.
151
She remained haemodynamically stable and was discharged home four days postoperatively, having
152
had cardiology follow-up arranged. Three months after discharge she remained asymptomatic
153
(AHA status 1) but her cardiac function had not recovered to the pre-pregnancy baseline. An
154
echocardiogram at six-months postpartum showed an increased LV diastolic diameter (5 cm), an
155
LV ejection fraction of 49% and mildly impaired RV function (Fig. 2).
156 157
Discussion
158
Compared to orthotopic transplantation, heterotopic heart transplantation, which retains the native
159
heart in situ, may have significant long-term benefits, as recovery of the diseased myocardium at
160
some point in the future remains a possibility. Since explantation, this patient had led a relatively
161
normal life, with good cardiac function, resolution of her lymphoproliferative disease, and no
162
requirement for immunosuppression. To our knowledge this is the first case report describing
163
pregnancy in a patient with an explanted heterotopic heart transplant, after recovery of the native
164
heart.
165
In contrast to patients after removed heterotopic cardiac transplant, pregnancy in women with
166
orthotopic cardiac transplantation is well documented and established, and there are several case
167
series describing maternal and fetal outcomes.5,6 These patients constitute a high-risk group, with
168
specific management challenges.
169
The risk of developing preeclampsia and deteriorating renal function is increased in patients with
170
cardiac transplantation, as is the risk of preterm delivery. The mean gestational age at delivery has
171
been reported as 34 to 35 weeks.5,6 During pregnancy medications with known teratogenicity must
172
be stopped and replaced. It is crucial that adequate immunosuppression is maintained to prevent
173
graft rejection. This can be challenging in the face of altered drug distribution and clearance
174
associated with evolving pregnancy. Maternal death may occur after delivery: in two case series, 4
175
of 22; and 2 of 17 patients respectively, died postnatally.5,6 In these series deaths were due to
176
postpartum haemorrhage (n=1), complications related to atheromatous coronary disease (n=1) and
177
complications related to graft rejection, thought to be related to poor compliance with
178
immunosuppressant medication (n=4).
179
Risk-stratification of pregnancy in a patient with such an unusual cardiac history is difficult due to
180
the lack of a precedent. In this patient, although her heart appeared to function well before
181
pregnancy, its response to the additional cardiovascular demands of pregnancy was unpredictable,
182
given her past history of fulminant heart failure. High-risk cardiac patients should attend for formal
183
pre-pregnancy counselling. This will allow thorough assessment of baseline status, optimisation of
184
management, preparation for pregnancy, and discussion of the potential risks to the mother and her
185
fetus.7,8 Cardiac MRI may assist in this regard and had been requested, but the patient became
186
pregnant before it had been performed.
187
The pregnancy was regarded as high-risk and joint cardiac and obstetric monitoring was instituted
188
early. This facilitated communication between specialists and the formulation of multidisciplinary
189
care plans. It is a model that has been recommended to optimise patient care.9
190
Although her principal pathology was cardiac, our patient had other medical conditions.
191
Cardiopulmonary exercise testing pre-pregnancy was limited by breathlessness and she gave a
192
history of recurrent chest infections, morning expectoration and shortness of breath, which were
193
attributed to poorly-controlled asthma. Lung function tests suggested obstructive airway disease
194
more consistent with bronchiectasis and further investigation was planned postpartum. Chronic lung
195
disease may have been a consequence of the cardiac transplant, immunosuppression and
196
chemotherapy. Despite explantation of the heterotopic heart, her good reported AHA status and
197
cardiac function on TTE, her medical morbidity status was complex and was further complicated by
198
severe needle phobia and challenging venous access.
199 200
It is well recognized that pregnancy in patients after cardiac transplantation is associated with an
201
increased risk of developing preeclampsia.10 Despite removal of the donor heart, it is likely that this
202
risk remained elevated. This patient was noted to have proteinuria early in the pregnancy, attributed
203
to her complex medical history, which included relapsing lymphoproliferative disease and multiple
204
cycles of chemotherapy. She also carried the morbidity burden of a previous cardiac transplant and
205
it is unknown whether risk reduces to that of the baseline population after explantation. Low-dose
206
aspirin started early in pregnancy may reduce the likelihood of developing preeclampsia in those at
207
high risk and administration is recommended by the National Institute of Health and Care
208
Excellence (NICE) for patients recognized to be at increased risk of developing the condition.11,12
209
Whether aspirin warrants consideration in patients with the risk factor of cardiac transplantation is
210
of interest, particularly as patients with vulnerable myocardium are at high risk of sustaining
211
morbidity as a result of preeclampsia. Studies exploring this area would be useful.
212
Although an appropriately managed vaginal delivery may be preferable to maintain cardiac
213
stability, the patient had made it clear throughout the antenatal period that she wished for a
214
caesarean delivery.13 The plan for delivery was to administer combined spinal-epidural anaesthesia,
215
with low-dose spinal and an epidural top-up, and with continuous blood pressure monitoring. This
216
was not possible and blood pressure was measured intermittently due to maternal request. The
217
epidural catheter component could not be achieved, so single-shot spinal anaesthesia was
218
administered, with careful maternal positioning to minimize aortocaval compression. It is of note
219
that ‘plan A’ may not be feasible, but it remains important that the principles of management are
220
maintained. Continuous spinal anaesthesia may have been an appropriate alternative choice,
221
however this technique is not in use at our institution.
222
We aimed to avoid fluid overload whilst maintaining venous return and ventricular filling. Fluid
223
was infused judiciously, as discrete small boluses with review, to avoid a hypervolaemic state.
224
Although there is a risk of oxytocin causing vasodilation and hypotension, the patient experienced
225
no cardiovascular compromise from a carefully fractionated, slow IV bolus of 5 units of oxytocin,
226
followed by an infusion. Ergometrine and 15-methyl-prostaglandin F2a were relatively
227
contraindicated and, as bleeding was rapidly controlled surgically, were not required.
228
Although she remained well, the fact that TTE performed three months after delivery did not show
229
recovery of LV function to pre-pregnancy levels is a reminder that pregnancy can have long term
230
deleterious effects on the vulnerable myocardium. At her first postpartum appointment the
231
importance of reliable contraception was discussed. She was strongly advised to undergo detailed
232
pre-pregnancy assessment and counselling before considering further pregnancy.
233
In conclusion, this case illustrates that high-risk cardiac patients should be referred for pre-
234
pregnancy counselling. Referral to a specialized high-risk joint cardiac, obstetric and anaesthetic
235
clinic should occur at an early stage in the pregnancy. Transthoracic echocardiography is a useful
236
and sensitive monitor of cardiac function in this setting. Women becoming pregnant after an
237
explanted heterotopic heart transplant may remain within the cardiac transplantation cohort in terms
238
of risks of developing preeclampsia and renal dysfunction. There should be a low threshold for
239
delivery of patients presenting with pre-existing cardiac disease and superimposed preeclampsia,
240
particularly after 34 weeks’ gestation.
241 242 243 244
245
References
246 247
1. Newcomb AE, Esmore DS, Rosenfeldt FL, Richardson M, Marasco SF. Heterotopic heart
248
transplantation: an expanding role in the twenty-first century? Ann Thorac Surg 2004;78:1345-50
249 250
2. Kadner A, Chen RH, Adams DH. Heterotopic heart transplantation: experimental development
251
and clinical experience. Eur J Cardiothoracic Surg 2000;17:474-81.
252 253
3. Jahanyar J, Koerner MM, Ghodsizad A, Loebe M, Noon GP. Heterotopic heart transplantation:
254
The United States experience. Heart Surg Forum 2014;17:E132-40.
255 256
4. Tsang V, Yacoub M, Sridharan S, et al. Late donor cardiectomy after paediatric heterotopic
257
cardiac transplantation. Lancet 2009;374:L387-92.
258 259
5. Bhagra CJ, Bhagra SK, Donado A, Butt T, Forrest L, MacGowan GA, Parry G. Pregnancy in
260
cardiac transplant recipients. Clin Transplant 2016;30:1059-65.
261 262
6. D’Souza R, Soete E, Silversides CK, et al. Pregnancy outcomes following cardiac
263
transplantation. J Obstet Gynaecol Can 2017 Nov 15. pii: S1701-2163(17)30416-4. doi:
264
10.1016/j.jogc.2017.08.030.
265 266
7. Ruys T, Cornette J, Roos Hesselink JW. Pregnancy and delivery in cardiac disease. J Cardiol
267
2013;61:107–12.
268 269
8. Canobbio MM, Warnes CA, Aboulhosn J, et al. Management of pregnancy in patients with
270
complex congenital heart disease: A scientific statement for healthcare professionals from the
271
American Heart Association. Circulation 2017;135:e50-e87.
272 273
9. Knight M, Nair M, Tuffnell D, et al (eds). on behalf of MBRRACE-UK. Saving lives, improving
274
mothers’ care - surveillance of maternal deaths in the UK 2012-14 and lessons learned to inform
275
maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity
276
2009-14. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2016. Available at:
277
https://www.npeu.ox.ac.uk. Accessed March 21, 2017.
278
279
10. Abdalla M, Mancini D. Management of pregnancy in the post cardiac transplant patient. Semin
280
Perinatol 2014;38:318-25.
281 282
11. Moore GS, Allshouse AA, Post AL, Galan HL, Heybourne KD. Early Initiation of low-dose
283
aspirin for reduction in preeclampsia risk in high risk women: a secondary analysis of the MFMU
284
High-Risk Aspirin Study. J Perinatol 2015;35:328-31.
285 286
12. National Institute of Health and Care Excellence (NICE) Guidance, Hypertension in pregnancy:
287
diagnosis and management. Clinical guideline [CG107]. https://www.nice.org.uk>guidance.
288 289 290
Accessed March 21, 2018.
291
delivery in patients with adult congenital heart disease? Interact Cardiovasc Thorac Surg
292
2013;17:144-150.
293 294
13. Asfour V, Murphy M, Attia R. Is vaginal delivery or caesarian section the safer mode of
Heterotopic heart transplant anatomy SVC
KEY LVd Left ventricle, donor PAd Pulmonary artery, donor Ad Aortic root, donor
SVC RV AA PA RV
PA
Ad
Superior vena cava Right ventricle Aortic arch Pulmonary artery Right ventricle
PAd
RA LVd
295 296
AA
RV
Gestation
LV ejection
LV end-diastolic RV
RV end-
fraction (%)
diameter (cm)
TAPSE
diastolic
(mm)
diameter (cm)
Pre-pregnancy
55
4.7
10
19 weeks
> 55
4.6
20
35 + 6/7 weeks
45
4.9
13
3 mth post-
45
4.9
16
3.1
3.9
partum 297
Fig. 2: Transthoracic echocardiography performed throughout pregnancy
298 299
TAPSE: Tricuspid Annular Plane Systolic Excursion (normal range 15 – 20 mm). LV: Left
300
ventricular. RV: Right ventricular
301 302
GESTATION
303
LV ejection
LV end diastolic RV
RV end
fraction (%)
diameter (cm)
TAPSE
diastolic
(mm)
diameter (cm)
Pre-pregnancy
55
4.7
10
19 weeks
> 55
4.6
20
35+6 weeks
45
4.9
13
3/12 post-partum 45
4.9
16
3.1
3.9
Figure 2: transthoracic echocardiography performed throughout pregnancy
304 305
KEY:
306
TAPSE, Tricuspid Annular Plane Systolic Excursion, normal range 15 – 20 mm
307
LV Left ventricular
308
RV Right ventricular
309 310
311
Highlights
312 313 314
This patient received heterotopic cardiac transplantation in childhood
315 316
Native cardiac function recovered allowing explantation of the donor heart
317 318
This report describes pregnancy after removal of a heterotopic heart transplant
319 320
Pregnancy after explantation of a heterotopic heart transplant is high-risk
321 322 323 324
Care should be within a joint high-risk cardiac, obstetric, anaesthetic environment