Subjects
This registry, COngenital HeARt Diseases in adult and Pulmonary Hypertension (COHARD-PH) registry, is a single-center, observational, and prospective registry which enrolls adult patients with CHD and CHD-related PH. The adult patients presented in Dr. Sardjito Hospital, Jogjakarta, Indonesia with suspected CHD and CHD-related PH were undergone a series of examinations to confirm the CHD and CHD-related PH diagnosis. The subjects are enrolled consecutively from outpatients’ clinics and inpatients wards. , and echo-lab. The enrollment and follow-up have been performed from July 2012 until currently. This study was evaluated the patients of COHARD-PH registry from July 2012 until July 2018 2019. This registry enrolls adult patients with age ≥ 18 years old.
Procedures
Patients are interviewed, undergo physical examination, electrocardiography (ECG) examination, and chest x-ray examination. The suspected CHD patients are proceed for transthoracic echocardiography (TTE) as the initial examination to confirm the diagnosis of CHD. By TTE, the probability of PH is also assessed based on current guideline.4 The bubble test is performed in selected cases if the TTE examination is dubious regarding septal defects/shunts. Transoesofageal echocardiography (TOE) is performed in patients with confirmed ASD and VSD by TTE examination. The TTE and TOE examination were conducted with G.E Vivid 7 (G.E Healthcare, U.S.A), G.E Vivid S6 (G.E Healthcare, U.S.A) or Phillips HD 15 (Philips N.V, The Netherland). The image acquisitions are conducted by three experience sonographers. The validation and confirmation of TTE and TOE examinations are performed by cardiologist consultants in our center dedicated to the registry. The image acquisition, validation and confirmation are in accordance with E.A.E and A.S.E guidelines. The 6 minute walking test to measure the distant of walking is performed for baseline of the registry.
Patients with simple defects such as ASD, VSD, PDA, AVSD, patent foramen ovale (PFO), and AP window are included in this study. The combined defects and other defect types were categorized as multiple defects. Patients with high probability of PH by TTE without confirmed CHD were excluded from the COHARD-PH registry (they included in other PH registry). Complex CHD were excluded from the registry. The signs of Eisenmenger syndrome (desaturasion and bidirectional shunt from TTE) is noted and later confirmed by RHC.
Right heart catheterisation (RHC) is subsequently performed in all patients after being confirmed as CHD by TTE and TOE and enrolled for the registry. The RHC is performed by cardiologist consultants using standard procedures in non-sedated patients. The purpose of RHC is to measure hemodynamics, diagnose pulmonary artery hypertension (PAH) and decide the closure procedure for septal defects/shunts. The cardiac output is determined by indirect Fick method, as per hospital protocol. The flow ratio is calculated with the formula: pulmonary blood flow (Qp)/systemic blood flow (Qs)= (aorta saturation - mixed vein (MV) saturation)/(pulmonary vein (PV) saturation-pulmonary artery (PA) saturation). A MV saturation is calculated from: ((3 x superior vena cava saturation) + inferior vena cava saturation)/4. The pulmonary vascular resistance index (PVRi) is derived from the formula: (mPAP – mean left atrial pressure (mLAP) (or mPAWP)/Qp. A Qp is calculated from the formula: O2 consumption (ml/min)/(1.36x10xhemoglobin level x ((PV saturation-PA saturation)/100). The PAH diagnosis is established when mPAP ≥25 mmHg, PVR >3 WU and PAWP ≤15 mmHg.4 The diagnosis of Eisenmenger syndrome is established hemodynamically when Qp/Qs <1 and PVRi >8 WU.m2.4 The vasoreactivity test is performed in selected patients (discretion by cardiologist consultants). The vasoreactivity result is assessed based on current guideline (reduced in PVR > 20% and final PVRi < 6 WU.m2). The correctability of shunt is defined as patients with suitable anatomy of defects (surgery and/or device), Qp:Qs >2 and PVRi < 6 WU.m2. Figure 1 shows the flowchart of COHARD-PH registry enrollment from July 2012 until July 2019.
The blood sample is collected from each patient by venipuncture in peripheral veins and during RHC. The blood sample is centrifuged and stored in -80º for further analysis. The hemoglobin and haematocrit levels are measured from routine hemocytometer. The NTproBNP measurement is performed using a electrochemiluminescence immunoassay (ElecsysProBNP II) and performed in Cobas e immunoassay analyzer (Roche Diagnostics, Germany).
Data Collection
The research assistants dedicated to the registry collect and compile the data and subsequently input the data to the electronic case report form of the COHARD-PH registry database. The baseline characteristics of patients are collected, comprising demographic data and clinical data. The ECG and chest X-ray results are documented. The TTE and TOE data are collected, comprising the type of CHD, dimension of right atrium (RA) and right ventricle (RV), left ventricle ejection fraction, tricuspid valvular regurgitation gradient (TVRG), tricuspid annular plane systolic excursion (TAPSE) and estimated mPAP. The 6 minute walking distance is collected. The laboratory data are also compiled. The RHC data were collected, comprising mPAP, PCWP, mRAP, PVRi, mLAP, flow ratio, Qp:Qs and oxygen saturations.
The signed informed consents were acquired for each patient to be included in the registry. The ethics committee of Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada and Dr. Sardjito Hospital had approved the registry protocol.
Statistics Analysis
We performed the descriptive analysis of the data. The continuous data was presented in mean and standard deviation (SD) or median and interquartile range (IQR) depended on normality data distribution after tested with the Shapiro Wilk or Kolmogorov Smirnov test. The categorical data was presented in percentage. The comparison between two groups was conducted with Student T test and Chi-square test according to the type of data. The comparison among groups was conducted with one-way ANOVA test. A p <0.05 was deemed statistics significance.