The WHO classification of pulmonary hypertension: A case-based imaging compendium

Abstract

Pulmonary hypertension (PH) is defined as a resting mean pulmonary artery pressure greater than 25 mmHg. The World Health Organization (WHO) classifies PH into five categories. The WHO nomenclature assumes shared histology and pathophysiology within categories and implies category-specific treatment. Imaging of the heart and pulmonary vasculature is critical to assigning a patient's PH syndrome to the correct WHO category and is also important in predicting outcomes. Imaging studies often reveal that the etiology of PH in a patient reflects contributions from several categories. Overlap between Categories 2 and 3 (left heart disease and lung disease) is particularly common, reflecting shared risk factors. Correct classification of PH patients requires the combination of standard imaging (chest roentgenograms, ventilation-perfusion scans, echocardiography, and the 12-lead electrocardiogram) and advanced imaging (computed tomography, cardiac magnetic resonance imaging, and positron emission tomography). Despite the value of imaging, cardiac catheterization remains the gold standard for quantification of hemodynamics and is required before initiation of PH-specific therapy. These cases illustrate the use of imaging in classifying patients into WHO PH Categories 1-5.

Keywords: CREST; Eisenmenger's syndrome; late gadolinium enhancement; pulmonary artery acceleration time; pulmonary capillary hemangiomatosis; pulmonary veno-occlusive disease; right ventricular hypertrophy.

Figure 1

Images obtained in a 43-year-old female with idiopathic PAH. (A) S1Q3T3 pattern noted consistent with right ventricle strain. T-wave inversion on anterior leads and ST depression is also suggestive of RVH with strain (note early R wave predominance in V1-V2 consistent with RVH). (B) Chest X-ray showing enlarged pulmonary artery and pruning of the distal pulmonary vasculature. (C) Lateral chest X-ray showing filling of the retrosternal space by an enlarged RV. (D) Parasternal long axis echocardiography view showing dilated RV. (E) Parasternal short axis echocardiography view showing flatted interventricular septum (thin white arrow), severely dilated RV and pericardial effusion (thick white arrow). (F) Tricuspid regurgitation velocity (represented by *) is proportional to right ventricular systolic pressure and estimated by Bernoulli's equation. (G) Measurement of PAAT (time from onset of flow to peak velocity) (thin white arrow). Note the notching of the PA Doppler envelope, suggestive of pulmonary vascular hypertension (thick white arrow). (H) “Moth eaten” appearance of ventilation/ perfusion scan in idiopathic PAH with patchy perfusion defects, in this case predominantly in the left lower lobe. (I, J) Histopathology from a different patient with Category 1 PAH showing medial hypertrophy and intimal fibrosis of small (<200 μm) PAs

Figure 2

(A) Cardiac MRI image showing late gadolinium enhancement in the RV insertion site (thick white arrow). (B, C) Cardiac MRI showing dilated right ventricle.

Figure 3

Calcified PAs in a patient with atrial septal defect (ASD) and Eisenmenger's physiology. (A) ECG shows first-degree AV block, right bundle branch block. (B, C) Chest X-ray showing enlarged and calcified pulmonary artery. (D, E) Axial CT scan below the carina demonstrates calcification of the left and right pulmonary arteries. (F) Apical four-chamber echocardiography view showing ASD. (G) Color-flow Doppler echocardiogram showing flow through the ASD with right-to-left shunt that caused her paradoxical embolic stroke.

Figure 4

Congenital heart disease patient (ASD) with out-of-hospital sudden cardiac death. (A) ECG showing severe RVH. (B) Severe RV hypertrophy and dilatation. (C, D) Ostium secundum atrial septal defect.

Figure 5

Patient with ASD and left main coronary artery compression. (A) ECG showing right atrial enlargement and severe RVH. (B) Chest X-ray showing severely enlarged PA. (C) Lateral chest X-ray showing filling of the retrosternal space. (D, E) Coronary angiogram showing compression of left main coronary artery (small caliber of left main, white arrow). (F) Transverse section at level of bifurcation of pulmonary artery showing proximity of left pulmonary artery (LPA) to the left main coronary artery and compression (white arrow). RPA: Right pulmonary artery; Ao: Aorta. (G) Sagittal views left main coronary artery (white arrow) compressed by pulmonary artery (PA).

Figure 6

Category 1 PH diagnosed postmortem as secondary to pulmonary capillary hemangiomatosis (PCH). (A) ECG shows mild left ventricular hypertrophy and right atrial enlargement. (B, C) Chest X-ray shows PA enlargement and cephalization with Kerly B lines. (D) Gross dissection of the heart shows thickened and dilated right ventricle. (E) Pulmonary capillary hemangiomatosis, seen as increased numbers of pulmonary capillaries swollen with large numbers of red blood cells, sharply demarcated from normal-appearing lung parenchyma (H and E, ×100). (F) Muscularization of a small-caliber arteriole. Surrounding alveolar septal capillaries with changes of pulmonary capillary hemangiomatosis (H and E, ×200).

Figure 7

Category 1 PH due to a second case of pulmonary capillary hemangiomatosis. (A) ECG showing sinus tachycardia and right atrial enlargement. (B) Chest X-ray on presentation with cardiomegaly and clear lung fields. (C) Chest X-ray after initiation of sildenafil showing pulmonary edema. (D) Ventilation-perfusion scan showing accentuation of basilar perfusion images. (E) Gross dissection of the heart shows thickened and dilated RV. (F) Patchy areas of pulmonary capillary proliferations engorged with red blood. (G) Concentric intimal fibrosis and medial hypertrophy of pulmonary arteries and arterioles.

Figure 8

Category 2 PH after mitral valve repair. (A) Normal sinus rhythm with lateral T wave flattening. (B) Chest X-ray showing splaying of carina and left atrial enlargement. (C) Lateral chest X-ray showing mitral ring in place and RV enlargement. (D) Representative long axis echocardiography view showing RV enlargement, left ventricular hypertrophy (RVDd: Right ventricular diastolic diameter; LVDd: Left ventricular diastolic diameter; IVS: Interventricular septum). (E) Parasternal short axis echocardiography view showing septal flattening. (F) Color flow Doppler showing severe TR. (G) TR velocity and waveform. (H) Turbulence across the prosthetic mitral valve. (I) CW Doppler flow across mitral valve showing normal gradient for size (dashed tracing) and short half-time (dashed line) suggesting normally functioning mitral valve repair. Pressure half-time of >180 ms may be abnormal. (J) Pulmonary artery pressure tracing and pulmonary capillary wedge pressure tracing showing pulmonary hypertension and normal pulmonary wedge (PW) pressure.

Figure 9

Category 2 PH secondary to restrictive physiology. (A) ECG showing diffuse T wave inversion. (B) Chest X-ray with right-sided pleural effusion on presentation. (C) Chest X-ray after pleurocentesis left-sided heart enlargement is apparent. (D) Apical 4-chamber echocardiography view showing thickening of the lateral LV wall (black arrow). (E) CT scan showing fibrotic lung disease with right pleural effusion and left ventricle wall mass (white arrow). (F) Cardiac MRI showing right-sided pleural effusion and LV wall mass secondary to growth from non-Hodgkins lymphoma in thorax (white arrow). (G) Still-frame left ventriculogram showing restriction of filling due to extrinsic compression. (H) Simultaneous right and left heart catheterization showing equalization of diastolic filling pressures at ~28 mmHg. PVR in this study was normal (1.9 Wood Units), indicating that the PH was not due to pulmonary vascular disease.

Figure 10

(A) ECG showing left ventricular hypertrophy. (B, C) Chest X-ray showing cardiomegaly. (D) T2 Star Cardiac MRI short axis images demonstrating reduced T2 star time <10 ms suggesting significant iron overload and no signal from dark liver (white arrow). (E) CT transverse section of abdomen showing hepatomegaly. (F) T2 Star MRI of the liver showing total darkness consistent with iron overload (white arrow). (G) Simultaneous right and left heart catheterization showing near-equalization of diastolic filling pressures at ~20 mmHg.

Figure 11

Images obtained in 35-year-old male with cor pulmonale. (A) S1Q3T3 pattern noted consistent with right ventricle strain. RVH is evident from the prominent R wave in the early precordial leads. Evidence of pulmonary disease, with failure of R wave transition and presence of Rs in V4. (B, C) PA and lateral chest X-ray with severe 4-chamber cardiomegaly with pulmonary vascular redistribution and visible obesity. (D, E) Normal VQ scan, performed anteriorly due to excess obesity. (F-H) CT showing moderate to severe cardiomegaly with normal lung parenchyma, mild dependent hypoventilatory changes and abdominal obesity. (I) PA pressure measurements decrease over the course of first 5 days of hospitalization while receiving CPAP and intensive diuresis (red line: Systolic PAP, green line: Diastolic PAP).

Figure 12

WHO Group 4 – chronic thromboembolic pulmonary hypertension. (A) Twelve-lead electrocardiogram showing S1Q3T3 suggestive of right ventricular strain, and right axis deviation. (B, C) Chest X-ray: Massively enlarged central pulmonary arteries. (D-E) Ventilation perfusion scan revealing perfusion defect in left lower lobe (F-H) Computed tomographic pulmonary angiogram demonstrating massively dilated main pulmonary artery, eccentric mural thrombus in the right main pulmonary artery and its proximal branches (dashed white arrow).

Figure 13

WHO Group 5 – Pulmonary hypertension with unclear or multifactorial etiologies. (A) ECG showing left ventricular hypertrophy. (B, C) Chest X-ray, PA and lateral with no edema or cardiomegaly. (D) Computerized tomographic scan of the chest showing a 4.9 × 2.9 cm calcified mediastinal mass compressing the right main pulmonary artery (white arrow). (E) A filling defect from a thrombus in the right main pulmonary artery (dashed white arrow). (F) CT scan showing oligemia of the entire right lung. (G, H) VQ scan showing a complete absence of perfusion to the entire right lung (white arrow).

Figure 14

Category 5 PH. (A) ECG showed non-specific TW flattening. (B, C) Chest X-ray showed left-sided pleural effusion. (D, E) CT scan showed extensive confluent mediastinal and bihilar lymphadenopathy, compressing both pulmonary arteries, right more so than left. The tumor was also seen around the pericardium. Left-sided pleural effusion is visualized. (F) Right ventricular outflow tract echocardiogram color flow view showing turbulence distal to the pulmonic valve. (G) Pulsed wave Doppler across stenosis showing flow acceleration, with flow of 2 m/s (compared with normal of 1 m/s).