Hyperthyroid heart disease in pregnancy: Retrospective analysis of a case series and review of the literature

Table 1 Clinical characteristics of six pregnant patients with hyperthyroid heart disease

Demographic	Vital signs at admission	Cardiac evaluation at admission	Complications and aggravating factors	NYHA
26 yr G5P1+3 (31 + 4 wk)	T 36.5 °C, HR 153 bpm, BP 141/78 mmHg, R 32 breaths/min, SpO2 85%; Vaginal examination revealed blood-stained mucus and a dilated cervix of 1 cm	Echocardiography: Enlarged left atrium and ventricle (LA 31 mm, LV 46 mm); EF 25%. Thoracic ultrasound: Bilateral pleural effusion, left 3.5 cm right 3.0 cm	Scarred uterus, stillbirth	IV
24 yr G2P0+1 (35 + 1 wk)	T 36.6 °C, HR 110 bpm, BP 168/98 mmHg, R 30 breaths/min, SpO2 89%	Echocardiography: Enlarged left atrium and ventricle (LA 44 mm, LV 58 mm); moderate mitral regurgitation (Vmax 4.0 m/S); EF 53%. Chest radiography: Cardiomegaly and mild bilateral pleural effusion; patchy consolidation in low lobes of lung of both sides; Cardiothoracic ratio 0.61	Preeclampsia, pulmonary infection, anaemia	IV
30 yr G2P1 (34 + 4 wk)	T 37.4 °C, HR 130 bpm, BP126/80 mmHg, R 35 breaths/min, SpO2 94%	Echocardiography: Enlarged left atrium and ventricle (LA 39 mm, LV 51 mm); grossly mitral regurgitation (Vmax 5.3 m/S); EF 50%. Chest radiography: Cardiomegaly and mild bilateral pleural effusion; cardiothoracic ratio 0.59. Thoracic ultrasound: Bilateral pleural effusion, left 0.8 cm right 2.9 cm	Anaemia, pulmonary infection	IV
29 yr G3P1+1 (30 + 4w)	T 38.3 °C, HR 130 bpm, BP 138/80 mmHg, R 40 breaths/min, SpO2 88%	Echocardiography: Enlarged left atrium (LA 40 mm); moderate mitral regurgitation (Vmax 5.6m/S); EF 62%	Chorioamnionitis?	III
24 G4P1+2 (38 + 6 wk)	T 36.3 °C, HR 100 bpm, BP 113/70 mmHg, R 25 breaths/min, SpO2 95%	Echocardiography: Normal, EF 59%. 24 hours dynamic electrocardiogram: normal	Scarred uterus, pulmonary infection	III
27 yr G1P0 (38 + 6 wk)	T 36.5 °C, HR 80 bpm, BP 102/60 mmHg, R 25 breaths/min, SpO2 97%	Echocardiography: Enlarged left atrium and ventricle (LA 39 mm, LV 62 mm); EF 37%. 24-hour dynamic electrocardiogram: Premature ventricular contractions	Pulmonary infection	III

BP: Blood pressure; EF: Ejection fraction; HR: Heart rate; LA: Left atrium; LV: Left ventricle; LVEF: Left ventricular ejection fraction; NYHA: New York Heart Association; R: Respiratory rate; SpO₂: Oxygen saturation while breathing air; T: Temperature.

Table 2 Clinical course of six pregnant patients with hyperthyroid heart disease

Patient	Clinical course
1	No antenatal care. Previous history: Diagnosed with Graves’s disease at age 12 and treated with antithyroid treatment till 16. Lower extremity edema for 3 mo, and palpitations and heat intolerance for 3 wk. No fetal movement for 1 day, and regular uterine contraction for 12 h. Altered level of consciousness after admission, oxygen was immediately administered via a facemask, recovered to consciousness. Artificial rupture of membranes and Willett-Martel scalp flap forceps were used to deliver the fetus. Transferred to ICU after delivery. 5 times of acute heart failure attacks in 3 d after delivery. Except for normal approach, CRRT and NIPPV were applied. Blood plasma and albumin were given. After reaching a stable situation, she was discharged at day 7 at patients’ request. Follow-up: Conservative treatment in local hospital for a month after delivery. I131 treatment one year after delivery, recovered well. Normal thyroid function at follow-up
2	Irregular antenatal care in local hospital. Previous history: Diagnosed with Graves’s disease at 14, irregular treatment with ATD therapy 2 yr before, stopped treatment during pregnancy. Cough with phlegm for 10 d, and generalized edema, dyspnea, and palpitations for 3 d. Treatments included PTU, propranolol, and antibiotics. Magnesium sulfate was used for pree-clampsia, and blood transfusion was applied for anaemia. Onset of labour at her 35 + 5 wk. Presented with symptoms and signs of heart failure during the second stage of labour, digoxin injection, furosemide, and oxygen mask were administered immediately to arrest heart failure, and continuous intra-venous pumping of nitroglycerin was used to control high blood pressure. Gave birth vaginally with the assistance of vacuum to a female baby weigh-ing 2010 g, Apgar 7-8-9. Admitted to NICU. Discharged at day 9. Follow-up: Chest radiography revealed small patchy consolidation in low lobes of right lung two days after delivery. Chest radiography returned to normal 6 wk after delivery, but thyroid function test still showed high levels of T3 and T4. Used ATDs regularly and had thyroid function test every half year. Normal thyroid function and stopped ATD treatment 5 yr after delivery
3	Irregular antenatal care in local hospital. Never been diagnosed as hyperthyroidism. Previous history: Accepted blood transfusion 1 mo before in local hospital. Generalized edema for 1 month, and cough, orthopnea, and dyspnea for 4 d. Treatments included PTU, propranolol, antibiotics, furose-mide, magnesium, and dexamethasone. Gave birth vaginally at her 36 wk to a female baby weighing 2080 g, Apgar 9-10-10. Discharged at day 12. Follow-up: Chest radiography returned to normal 6 wk after delivery. Used ATDs for one year after delivery, then thyroid function test returned to normal
4	Regular antenatal care in local hospital. Diagnosed with Graves’s disease at local hospital at 14 wk. PTU was applied after diagnosis. Previous history: Treated with PTU, propranolol, magnesium sulfate, and antibiotics at local hospital for a week. Lower extremity edema for 1 mo, and anxiety and palpitations for 2 wk. Enlargement of left atrium and atrial fibrillation was found in local hospital without appropriate treatment. Increased vaginal discharge and suspected premature rupture of membrane for 1 wk, and dyspnea and orthopnea for 2 d. Treatments included increased dose of PTU, propranolol, more potent antibiotics, frusemide, and magnesium sulfate. Regular monitoring included blood white cell count, C-reactive protein, procalcitonin, and vaginal secretion culture. Gave birth vaginally to a male baby at her 33 + 2 wk weighing 2220 g, Apgar 10-10-10. Admitted to NICU. Discharged at day 20. Follow-up: Chest radiography returned to normal 6 wk after delivery. Used ATDs and had thyroid function test regularly, and used MMI 5 mg per day
5	Regular antenatal care. Previous history: Diagnosed with Graves’s disease for loss of weight and exophthalmos 2 mo before pregnancy, then regularly treated with ATDs. Cough with phlegm, dyspnea, and palpitations at 34 wk. Enlarged left atrium was found. Hospitalization treatments included antibiotics, PTU, propranolol, and magnesium sulfate for 10 d. Cough and moderate palpitations for 2 d. Treatments included MMI and antibiotics. A female baby weighing 3360 g was delivered by caesarean section at her 39 + 4 wk, Apgar 10-10-10. Discharged at day 8. Lost to follow-up
6	Regular antenatal care at local hospital. Previous history: Diagnosed with Graves’s disease at age 22, RAI therapy at 24, and continuous treatment with ATD. Moderate palpitations for 3 mo, cough and heart intolerance for 3 d, and rupture of membrane for 6 h. Treatment included PTU. A female baby weighing 3860 g was delivered by caesarean section at her 39 wk, Apgar 10-10-10. Discharged at day 6. Follow-up: Echocardiography showed only enlarged left ventricle and normal EF six days after delivery. Normal chest radiography and normal thyroid function 6 wk after delivery

ATD: Anti-thyroid drug; CRRT: Continuous renal replacement therapy; EF: Ejection fraction; ICU: Intensive care unit; PTU: Propylthiouracil; MMI: Methimazole; NICU: Neonatal intensive care unit; NIPPV: Non-invasive positive pressure ventilation therapy; RAI: Radioiodine therapy.

Table 3 Thyroid function tests in patients with prolonged pregnancy after control of hyperthyroid heart disease

	Initial	1 wk	2 wk		Reference range
Patient 3			Before delivery
TSH (mIU/L)	< 0.003	0.003	0.006		0.55-4.78
Total T3 (nmol/L)	7.67	2.83	2.54		0.92-3.7
Total T4 (nmol/L)	> 387	> 387	295.1		58.1-173
Free T3 (pmol/L)	16.7	6.31	4.53		3.5-6.5
Free T4 (pmol/L)	61.91	42.75	35.43		11.5-22.7
TGAb (IU/mL)	> 500	> 500	> 500		< 60
TPOAb (IU/mL)	> 1300	> 1300	> 1300		< 60
	Initial	1 wk	2 wk	3 wk
Patient 4				Before delivery
TSH (mIU/L)	0.008	0.008	0.01	0.006	0.55-4.78
Total T3 (nmol/L)	4.01	1.95	1.60	1.72	0.92-3.7
Total T4 (nmol/L)	194	122.80	76.7	69.4	58.1-173
Free T3 (pmol/L)	9.15	4.97	4.03	3.57	3.5-6.5
Free T4 (pmol/L)	23.79	13.79	8.58	7.75	11.5-22.7
TGAb (IU/mL)	> 500	> 500	> 500	> 500	< 60
TPOAb (IU/mL)	> 1300	> 1300	> 1300	> 1300	< 60

T3: Triiodothyronine; T4: Thyroxine; TGAb: Thyroglobulin antibody; TPOAb: Thyroid peroxidase antibodies; TSH: Thyroid-stimulant hormone.