Pulmonary hypertension in pregnancy: two sides to a coin

CASE 1

Clinical presentation

Mrs S, a previously healthy 33-year-old Malay woman (G4P3), was newly diagnosed with severe pulmonary artery hypertension (PAH) during the second trimester of pregnancy. She subsequently underwent therapeutic termination of pregnancy due to critical right-sided heart failure.

Mrs S presented with a spontaneous monochorionic, diamniotic twin pregnancy at 16 weeks and 0 days of gestation, with three prior healthy pregnancies. Her pertinent medical history included macroprolactinoma with hypopituitarism, hypothyroidism, gestational thrombocytopenia and gastritis. She was routinely reviewed in an obstetric clinic at a local tertiary academic hospital and was electively admitted to the obstetric inpatient service due to a 2-month history of progressively worsening exertional dyspnoea, lower limb swelling, nausea and palpitations. On clinical examination, there was a loud pulmonary component of the second heart sound, a soft systolic murmur, reduced air entry at the lung bases and mild pitting oedema in the lower limbs. What does the electrocardiogram (ECG) in Figure 1 show?

Figure 1.

Case 1: ECG on initial admission.

ECG interpretation

Initial admission ECG [Figure 1] shows sinus rhythm (heart rate 99 beats/min), right axis deviation, right ventricular hypertrophy, and widespread anterior and inferior ST-segment depression with T-wave inversions.

Further investigations

Laboratory biomarkers showed high-sensitivity troponin I (hs-cTnI) levels of 50.8–54.6 ng/L, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level of 268 pg/mL. Chest radiograph revealed a prominent pulmonary artery and pruning of the peripheral vessels. A formal transthoracic echocardiogram (TTE) [Figure 2] indicated severe pulmonary hypertension (PH) with a pulmonary artery systolic pressure (PASP) of 105 mmHg, short right ventricular outflow tract acceleration time of 70 ms with mid-systolic notching, tricuspid annular plane systolic excursion/PASP ratio of 0.16, and an estimated mean pulmonary artery pressure (mPAP) of 47.5 mmHg using Mahan’s equation. The left ventricular ejection fraction (LVEF) was 50%. Computed tomography pulmonary angiogram (CT-PA) showed no evidence of pulmonary embolism but revealed dilated pulmonary arteries, dilated right heart chambers with reversal of the right ventricle to left ventricle ratio, a thickened right ventricular wall, increased right ventricular trabeculations, and reflux into the inferior vena cava and hepatic veins. A right heart catheterisation (RHC) performed in the coronary care unit revealed a mPAP of 66 mHg, pulmonary capillary wedge pressure (PCWP) of 15 mmHg, peripheral vascular resistance (PVR) of 9.98 Wood units (WU), pulmonary artery pulsatility index of 7.75 and cardiac power output of 0.98. Antenatal scans confirmed the presence of both twins, with findings of cystic hygroma, skin oedema and fetal ascites. The autoimmune panel results were negative.

Figure 2.

Case 1: Transthoracic echocardiogram images show (a) features of severe pulmonary hypertension with right ventricular pressure overload, right ventricle to left ventricle ratio > 1 and a D-shaped septum and (b) dilated right heart chambers (right atrium and ventricle).

Clinical course

The results of the abovementioned tests were consistent with a diagnosis of high-risk idiopathic PAH, a form of pre-capillary PH. The patient was admitted to the high-dependency unit for closer monitoring of her haemodynamic and respiratory status. A multidisciplinary consensus was reached among PH specialists, cardiac intensivists, anaesthesiologists, advanced heart failure specialists and maternal-fetal medicine obstetricians. The recommended course of action for therapeutic termination of pregnancy (TOP) was discussed with the patient, and a shared decision was made in light of the high maternal mortality risk from right heart failure and potential teratogenic effects of essential cardiac medications.

She was promptly started on triple PH specific therapy, including sildenafil, iloprost and ambrisentan. She underwent medical TOP uneventfully, with extracorporeal membrane oxygenation (ECMO) on standby, and was administered dostinex to suppress lactation. Following the procedure, she was transferred from the coronary care unit to the general ward and discharged in stable condition a few days later. A year after discharge, she was found to be well on review in the outpatient clinic and classified as functional class II PAH.[1]

CASE 2

Clinical presentation

Mrs C was a 30-year-old Chinese woman (G1P1 ) who had pulmonary venous hypertension (PVH), which was synonymous with post-capillary PH, secondary to anthracycline-induced dilated cardiomyopathy. She developed acute decompensated heart failure and subsequently underwent an emergency caesarean section at 28 weeks of gestation.

Mrs C had a significant medical history of childhood acute myeloid leukaemia, which was in remission following anthracycline chemotherapy with daunorubicin. She was on regular follow-up, with her cardiac function stabilised at an LVEF of 50% prior to spontaneous conception. Medications contraindicated in pregnancy, such as Entresto, were discontinued, and she remained on a low dose of furosemide. Her antenatal course was complicated by heart failure, initially requiring admission at 8 weeks of gestation, during which metoprolol was added to her treatment regimen. However, her symptoms worsened, leading to readmission at 22 weeks of gestation with a 3-day history of worsening dyspnoea, unaccompanied by chest pain or lower limb swelling. Clinical evaluation indicated low-output left heart failure. What does the ECG in Figure 3 show?

Figure 3.

Case 2: ECG on readmission.

ECG interpretation

Initial ECG [Figure 3] at readmission shows Goldberger’s triad, which was characterised by the following findings: SV2 + RV5 ≥ 3.5 mV, total QRS amplitude in individual limb leads ≤ 0.8 mV and R/S ratio < 1 in lead V4.

Further investigations

Laboratory biomarkers revealed a hs-cTnI level of 27.7 ng/L, NT-ProBNP level of 1837 pg/mL and a haemoglobin level of 13.6 g/dL. Transthoracic echocardiogram [Figure 4] showed newly reduced LVEF of 36%, multiple regional wall motion abnormalities, eccentric left ventricular hypertrophy and severe functional mitral regurgitation (MR). Further, moderate PH, severe right ventricular systolic dysfunction and moderate tricuspid regurgitation (TR) were observed. A right heart catheterisation revealed decompensated cardiac function with low cardiac output, increased left ventricular filling pressures and normal pulmonary venous resistance [Figure 4]. A CT-PA confirmed the presence of an acute left lower segmental pulmonary embolus with evidence of right heart strain. Therapeutic clexane was initiated for treatment.

Figure 4.

Case 2: Transthoracic echocardiogram images in the (a) parasternal short axis (PSAX) view and (b) apical 4-chamber (A4C) view show severe mitral regurgitation.

Clinical course

The patient received multidisciplinary care with close inpatient monitoring and was initially planned for a caesarean delivery at 28 weeks of gestation. However, her condition deteriorated, with worsening haemodynamics, decompensated metabolic acidosis, hyperlactaemia and respiratory compensation. This prompted a joint consensus for an emergency caesarean delivery under general anaesthesia. Milrinone and noradrenaline support were initiated, and pre-emptive ECMO lines were placed. Intravenous magnesium sulfate was administered for fetal neuroprotection prior to delivery. Following an uneventful procedure, she was closely monitored in the coronary cardiac unit. Over the following 2 weeks, she developed acute kidney injury secondary to cardiorenal syndrome and was initiated on continuous renal replacement therapy. Despite dual inotropic support, her recovery trajectory remained poor, and she eventually required ECMO. On postpartum day 18, she was transferred to another tertiary institution for continued care and evaluation for an emergent heart transplant. She subsequently received biventricular assist devices for circulatory support. Her recovery was complicated by multiple complications, including intracranial haemorrhage, cardiac tamponade requiring pericardiocentesis, prolonged ventilator dependence, recurrent episodes of sepsis and severe deconditioning. After 4 months of intensive rehabilitative care, she was eventually discharged home.[1]

DISCUSSION

Pulmonary hypertension refers to a group of conditions defined haemodynamically by an mPAP ≥ 20 mmHg.[2] Further classification of PH into the five World Health Organization (WHO) groups is based on underlying aetiology, haemodynamic characteristics, namely PVR and PCWP, and available therapeutic options.[2] In this article, Case 1 and Case 2 depict WHO Group 1 PH and Group 2 PH, respectively. Although both involve PH with eventual right heart decompensation, there are noteworthy differences in their ECG findings, warranting a comparative discussion.

Pre-capillary or WHO Group 1 PH (such as PAH diagnosed in Case 1) is haemodynamically denoted by mPAP > 20 mmHg, PVR > 2 WU and PCWP ≤ 15 mmHg.[2] The pathophysiology of pre-capillary PH is characterised by progressive pulmonary arteriolar remodelling and obliterative pulmonary vascular proliferation. Due to high mPAP and PVR, patients with PAH can present with right ventricular pressure overload, as evidenced by specific ECG findings. P pulmonale (p wave height > 1.5 mm in V1/2 or > 2.5 mm in II, III, aVF), suggestive of right atrial dilatation, may be observed along with right axis deviation (> +90 degrees), right bundle branch block (RSR’ pattern in V1–V3, wide slurred S wave in V5–V6, QRS duration > 120 ms), McGinn–White sign or S1Q3T3 (prominent S wave in lead I, Q wave and T wave inversion in lead III or S1Q2T3), suggestive of right ventricular strain in the context of pressure or volume overload. These ECG findings may include ST depressions or T wave inversions in either the inferior or right precordial leads in V1–V4 and right ventricular hypertrophy (either a dominant R wave in V1 > 7 mm tall or R/S ratio > 1, a dominant S wave in V5 or V6 that is > 7 mm deep or R/S ratio < 1).[3,4,5]

Post-capillary or WHO Group 2 is most commonly associated with left-sided heart disease (such as underlying anthracycline cardiomyopathy exacerbated by pregnancy in Case 2). Clinically, it is often synonymous with PVH and can result from systolic or diastolic heart failure, or any left-sided valvular disease affecting the aortic or mitral valves.[2] The pathophysiology of post-capillary PH is characterised by the chronic backward transmission of increased left heart filling pressure, leading to pulmonary venous congestion and subsequent pulmonary vascular remodelling. Post-capillary PH is haemodynamically denoted by mPAP > 20 mmHg, PVR ≤ 2 WU and PCWP > 15 mmHg.[2] Pulmonary venous hypertension can present with a range of ECG patterns, from atrioventricular conduction disorders to tachyarrhythmias.[6] One of the prognostically significant findings is low QRS voltage, defined as QRS height < 5 mm in all limb leads and < 10 mm in all precordial leads.[6,7] Other commonly encountered ECG changes include those indicative of left ventricular dysfunction, such as left axis deviation (axis between –30 to + 90 degrees), repolarisation abnormalities with T wave inversions (T wave inversion ≥ 0.1 mV in ≥ 2 contiguous leads in the absence of bundle branch block, particularly in the anterolateral or inferior leads), pathological Q waves (Q wave duration ≥ 40 ms, depth > 3 mm, amplitude ≥ 25% of the R wave) and left ventricular hypertrophy (LVH). Left ventricular hypertrophy can be assessed using Sokolov–Lyon voltage criteria, which defines LVH as a V1 S wave depth + V5–6 R wave height > 35 mm, along with non-voltage criteria such as an R wave peak time > 50 ms in V5 or V6, or ST depression and T wave inversion in the left sided leads. Alternatively, Cornell criteria describe LVH as a VL R wave height + V3 S wave depth > 28 mm in males or > 20 mm in females.[8] Goldberger has previously described a pathognomonic triad of features of SV1 or SV2 + RV5 or RV6 of > 3.5 mV, total QRS amplitude in each limb lead of 0.8 mV and R/S ratio of < 1 in lead V4. This triad has a positive predictive value of > 90% and specificity of > 90% for detecting severe left ventricular systolic dysfunction, as demonstrated in Case 2.[9]

In conclusion, the haemodynamic sequelae of pre- and post-capillary PH during pregnancy are associated with a range of right and left ventricular overload features, respectively, which can be observed on surface ECG. These ECG findings should be interpreted in conjunction with other diagnostic tools, such as those obtained from a TTE and RHC, to guide subsequent classification, therapeutic decisions and prognosis. Knowledge of these unique ECG features and their early identification may prompt timely referral and evaluation of PH in obstetric patients.

Conflicts of interest

Choolani M and Poh KK are members of the SMJ Editorial Board and were thus not involved in the peer review and publication decisions of this article.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 21 April 2025

Question: Answer True or False
1. The following are associated with pulmonary arterial hypertension:
(a) P-pulmonale.
(b) Right ventricular hypertrophy.
(c) McGinn–White sign.
(d) ST depression in leads V4-6.
2. Regarding P-pulmonale:
(a) It is defined by the presence of bifid P waves.
(b) It is caused by elevated right atrial pressures.
(c) It is characterised by P wave height >1.5 mm in V1/2.
(d) It is characterised by P wave height >2.5 mm in II, III, aVF.
3. Regarding pulmonary venous hypertension:
(a) It is the most common cause of pulmonary hypertension worldwide.
(b) It can occur in patients with both preserved and reduced ejection fraction.
(c) It can present with conduction disturbances on electrocardiogram (ECG).
(d) Low QRS voltage ECG subtype has prognostic significance in patients.
4. These ECG features are associated with pulmonary venous hypertension:
(a) Pathological Q waves.
(b) Generalised T wave inversions over multiple coronary territories.
(c) Left axis deviation.
(d) Left ventricular hypertrophy.
5. Regarding the Goldberger triad:
(a) There is good R wave progression with R/S ratio>1 in lead V4.
(b) There are low limb lead voltages.
(c) It is >90% specific for the diagnosis of left ventricular dysfunction.
(d) It is >70% sensitive for the diagnosis of left ventricular dysfunction.

Funding Statement

Nil.