Multimodality profiling of pulmonary hypertension in a group of South African patients with congenital heart disease

Abstract

INTRODUCTION Pulmonary hypertension (PH) associated with congenital heart disease (CHD) is a serious condition that can cause significant disability and death. Around 80% of the global disease burden occurs in low- and middle-income countries, where PH is strongly associated with CHD. Unoperated but potentially operable patients face a high risk of developing PH. In sub-Saharan Africa, patients often present late, which contributes to high mortality rates. Imaging is fundamental for determining the causes and severity of PH, particularly in evaluating both right and left cardiac function, which are key predictors of morbidity and mortality. To our knowledge, limited data exist on the evaluation of imaging modalities in patients with secondary PH due to left-to-right shunts, particularly in South Africa, where data on functional impairment in children are scarce. This study describes the clinical and imaging characteristics of PH resulting from congenital heart lesions with a left-to-right shunt in a group of South African patients. METHODS The study was conducted at Dr George Mukhari Hospital, Gauteng, South Africa, using a prospective observational design to investigate PH resulting from CHD. Demographic and anthropometric data were collected. A 12-lead electrocardiogram (ECG) was conducted using a Nihon Kohden Cardiofax ECG apparatus. A detailed echocardiographic study was performed using GE Medical Vivid E9 ultrasound equipment with an M5SC phased array transducer. A 6-minute walk test was performed according to American Thoracic Society guidelines. Patients were referred for cardiac catheterisation if the screening echocardiogram right ventricular systolic pressure was ≥ 25 mmHg. Cardiac magnetic resonance imaging was performed on all patients at rest using a 1.5 T Magnetom Symphony Siemens system. Nuclear ventriculography was conducted with an Intevo scanner, Siemens Medical Solution, and Syngo MI application software, using a Technetium-99m labelled diethylenetriamine pentaacetate injection at rest. Standard statistical software was used for data analysis. RESULTS Most patients (73%) were aged 6–17 years, with a median age of 9.98 years. The most common congenital abnormality associated with PH was simple ventricular septal defect (41%). The pulmonary valve annulus was dilated in all patients (z-score 4.23). Prolonged right ventricular (RV) myocardial performance index (MPI), reduced tricuspid annular velocity, decreased tricuspid annular plane systolic excursion (TAPSE), and impaired calculated RV free wall strain confirmed RV dysfunction in all patients. The right heart was dilated, likely resulting in tricuspid regurgitation and a dilated tricuspid valve annulus with a median z-score of 2.44. The median six-minute walking distance was diminished in all patients. The combination of RV systolic pressure > 50 mmHg plus pulmonary annulus z-score > 3 to predict pulmonary vascular resistance > 3 Wood unit.m² had a sensitivity of 82.4% but a low specificity of 14.3%. RV end-diastolic indexed volumes were at least double the normal reference ranges in most patients (median 240:165–268 mL/m²) on cardiac magnetic resonance imaging (CMRI). Interestingly, CMRI showed that 70% of male patients had normal RV systolic function, compared to only 45% of female patients (p < 0.05). Echocardiographic markers of RV function correlated poorly with CMRI RV ejection fraction. Echocardiography and isotopes left ventricular (LV) ejection fraction correlated strongly with CMRI LV ejection fraction (r = 0.90). CONCLUSION Patients in South Africa with simple, potentially operable lesions suffer from severe PH. These patients exhibited significant right-sided dilation, particularly in the pulmonary arteries, which could be an early warning sign of PH. Additionally, all patients demonstrated substantial functional impairment and right heart dysfunction. Both echocardiography and CMRI consistently revealed right heart dilation in patients with PH associated with left-to-right shunts. Right heart dimensions measured by transthoracic echocardiography and CMRI showed a strong correlation. This study’s echocardiographic markers of RV function aligned well with clinical functional assessments. However, these echocardiographic markers exhibited poor correlation with RV ejection fraction measured by CMRI. Furthermore, a subset of patients presented with reduced LV ejection fraction.