[HKU Medical Grand Rounds] Clinical outcomes of high-risk cardiac-pregnancy cases in a university hospital in Hong Kong

Case 1

Madam A was diagnosed with rheumatoid arthritis at the age of 31 years and had since been taking tocilizumab, sulphasalazine, hydroxychloroquine and prednisolone.  She also had secundum atrial septal defect with pulmonary hypertension. Surgical closure was performed at the age of 22 years at Grantham Hospital, but there was no resolution of her pulmonary hypertension.  Subsequent reassessment by right heart catheterization confirmed persistent pulmonary arterial hypertension with a mean pulmonary arterial pressure of 38 mm Hg and a pulmonary vascular resistance (PVR) of approximately 6 Wood units. Vasoreactivity testing was negative. CT scan of thorax and ventilation-perfusion (VQ) scan found no evidence of chronic pulmonary thromboembolism or interstitial lung disease. Madam A could cover 600 metres in a 6-minute walk test (6MWT). She was categorized as functional class II under the WHO’s pulmonary hypertension functional classification. A trial of sildenafil was given for 6 months, with no significant improvement in functional status or echocardiographic parameters.  She was unable to afford other medications for pulmonary arterial hypertension. 

Madam A became pregnant at 38 years of age.  She carried a class IV risk under the modified WHO classification of maternal cardiovascular risk, for which pregnancy was contraindicated. Termination of pregnancy was repeatedly suggested, but the couple opted to continue with the pregnancy.

Management

Madam A was given low molecular weight heparin for prophylaxis of pulmonary embolism. Regular assessment and echocardiography were provided by the cardiac team every 2–4 weeks, in addition to obstetrics and rheumatology follow-up. Tocilizumab was stopped due to pregnancy.

At 13 weeks of gestation, she was diagnosed with gestational diabetes and was managed with diet control.  At 28 weeks of gestation, ultrasound found her foetus to be small for gestational age.

At 33 weeks of gestation, she noted hypertension with systolic blood pressure (BP) up to 190 mm Hg on home BP monitoring. The elevated BP was associated with persistent chest pain, which had no radiation and was not pleuritic. She was urgently admitted to our hospital.  Electrocardiogram showed absence of acute ischaemic changes. New-onset proteinuria with a spot urine protein-to-creatinine ratio of 397 mg/mmol was found. Liver function was deranged with alanine transaminase level of 223 U/L and aspartate transaminase level of 492 U/L. Her antenatal hepatitis B surface antigen was negative.

A clinical diagnosis of pre-eclampsia was made, and emergency lower segment Caesarean section under general anaesthesia was promptly arranged.  Right femoral arterial sheath and venous sheath were inserted before the operation for possible use of extracorporeal membrane oxygenation machine in case of cardio-pulmonary collapse.  The operation was largely uneventful despite a transient hypotensive episode, which was managed by an inotropic agent. Anticoagulant therapy was continued for 1 week postoperatively to prevent pulmonary embolism. The neonate was a baby girl with a low birth weight of 1.234 kg.  She was discharged from hospital after a prolonged stay of 2 months in the Neonatal Intensive Care and High Dependency Care Unit.

Madam A had no deterioration in functional status or echocardiographic parameters after the successful pregnancy.  Her latest right ventricular systolic pressure was 55 mm Hg at 1 year postpartum.  Intrauterine contraception device was later inserted.

Case 2

Madam B had had hypertension since early adolescence. Apart from being obese with a Body Mass Index of 34 kg/m² and fatty liver disease, extensive investigations were unrevealing. Her family history was unremarkable.  She was then lost to follow-up. 

At 24 years of age, madam B was referred back to our hospital for a high-risk pregnancy situation during her first trimester.  Her initial antenatal examination performed in China showed sinus tachycardia and left ventricular hypertrophic changes on electrocardiography. Follow-up echocardiography found a reduced left ventricular ejection fraction of 32 percent by M-mode.  Clinically, Madam B was asymptomatic with New York Heart Association (NYHA) class I functional status.

In view of impaired left ventricular function secondary to long-standing untreated hypertensive cardiomyopathy, termination of pregnancy was discussed, but Madam B opted to continue with pregnancy despite an imminent chance of further deterioration.

Management

Initial cardiac management targeted her hypertension and heart failure.  Madam B was thus given methyldopa, metoprolol and digoxin.  The dose of metoprolol was titrated to 25 mg twice daily, with a target heart rate of 60 bpm.  Her left ventricular ejection fraction gradually improved to 60 percent by M-mode on echocardiography towards the end of her second trimester. However, she was also found to have gestational diabetes requiring the use of insulin.

Intrauterine growth restriction of her foetus was noted on ultrasound since 33 weeks of gestation.  The dose of metoprolol was maintained for optimal BP and heart failure control.  Proteinuria was absent all along. At a multidisciplinary meeting, it was concurred that timed delivery by induction of labour at 38 weeks of gestation would be performed. However, madam B subsequently underwent emergency lower segment Caesarean section due to failed induction. Her baby boy, with a birth weight of 2.21 kg, was delivered uneventfully. Her antihypertensive regimen was switched to amlodipine 10 mg daily and metoprolol succinate 25 mg daily after delivery.

Discussion

Maternal cardiac disease is present in 0.6–1 percent of pregnancies.^2,3  The majority of lesions in Asian countries are acquired valvular lesions,^4,5 whereas in European countries congenital heart diseases are predominant.^6,7  The overall maternal mortality rate in pregnant ladies with cardiac diseases was reported to be 0.4 percent in the largest prospective registry to date.⁸  Cardiac diseases represent the main cause of maternal death and are associated with a maternal mortality rate of 2.31–8.2 per 100,000 pregnancies in developed countries.^1,9,10

Various scoring systems, such as the CARPREG risk score and ZAHARA risk score,^11,12 have been developed to assess the risk of pregnancy associated with different maternal cardiac diseases. In 2011, the European Society of Cardiology recommended in their guidelines that estimation of maternal risk be performed with the modified WHO risk classification,¹³ which classifies patients into four different classes based on the type and grading of cardiac disease as well as the patients’ functional status.  The associated risk increases from Class I, where there is a very low risk of maternal morbidity or mortality, to Class IV, where the risk is extremely high such that pregnancy is contraindicated and termination of pregnancy should be considered.  The modified WHO classification has been validated by different groups, and is shown in some studies to be more accurate than the CARPREG and ZAHARA risk scores.^8,14,15  The two cases reported in this article are both categorized as Class IV risk, with a predicted 50.3 percent risk of cardiac events.⁸

Neonatal complications and mortality were reported in 20–28 percent and 1–4 percent of pregnancies associated with maternal cardiac diseases, respectively.¹³ The most common neonatal complications, namely premature birth and low birth weight,¹¹ unfortunately occurred in our two cases reported here.  Known predictors of neonatal events include mechanical valve prosthesis, use of oral anticoagulants during pregnancy, multiple gestation, smoking during pregnancy, maternal left heart obstruction, baseline NYHA class II or above, and cyanosis.¹³

As exemplified by the aforementioned cases, management of ladies with high-risk cardiac-pregnancy scenarios is challenging owing to significant maternal and neonatal complications.  In such cases, counselling with the couple involved also plays a crucial role. Cardiologists with special interest in managing high-risk pregnancies should take a leading role in explaining the actual and foreseeable risks and to offer the couple clinical management choices, including pregnancy termination and other available medical options if termination is not sought after. 

In our clinical experience, not every couple will choose termination of pregnancy even when the chance of maternal and foetal mortality is as high as 50 percent.  In situations where continuation of pregnancy is chosen, the couple’s wish should be highly respected, and a multidisciplinary team is needed to take immediate action to provide all-rounded care for the pregnant lady. Early team discussion on delivery and emergency treatment plans is needed. Clearly summarizing team consensus and setting alerts on the hospital computer system facilitate successful management of high-risk pregnancy situations.  Cardiologists involved should clinically assess and echocardiographically monitor the pregnant lady at appropriate intervals according to her clinical status, and be vigilant to even the subtlest changes. Besides, the choice of cardiac medications is often restricted in such cases due to potential foetal side effects.  Attending obstetricians and paediatricians should be duly informed of the use of such medications, so as to provide corresponding levels of surveillance and preparation upon delivery.  Fortunately, it is to date still a rarity to have interventional cardiac procedures performed on pregnant ladies in our hospital. 

Conclusion

Managing pregnant ladies with high-risk cardiac diseases is challenging. It requires the concerted effort of a multidisciplinary team to provide the highest level of attention and all-rounded care to both the mother and foetus, so as to safeguard their well-being and ensure a successful pregnancy outcome.