Atrial Septal Defect (ASD) is the most common form of congenital heart disease (CHD) found in adults. The slow progression of the disease is the unique characteristic of ASD so it remains undiagnosed until young adulthood [1]. In the COngenital HeARt Disease in Adult and Pulmonary Hypertension (COHARD-PH) registry, secundum ASD constitutes the majority population in this hospital-based registry (73.4% of all population). The majority of patients (66.9%) in COHARD-PH suffered from pulmonary arterial hypertension (PAH) [2]. PAH may commonly develop in uncorrected ASD due to chronic volume overload to the pulmonary circulation. It can also cause pulmonary vascular remodeling and lead to irreversible pulmonary vascular disease, the most feared complication of uncorrected left-to-right shunt [3].

According to the European Society of Echocardiography (ESC) guideline on Pulmonary Hypertension 2015, pulmonary hypertension (PH) is diagnosed if the mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest in right heart catheterization (RHC). Pulmonary artery hypertension (PAH) is diagnosed if the pulmonary artery wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) >3 Woods Unit (WU) without other causes of precapillary PH [4]. In the recent ESC guideline on PH, the lower limit of mPAP is lowered to >20 mmHg and PVR > 2 WU [5,6]. Echocardiography has not been studied in predicting PH based on the new criteria of mPAP >20 mmHg instead of ≥25 mmHg and PVR > 2 WU rather than >3 WU.

PVR is an important variable in the diagnosis of precapillary PH. PVR is significant in determining the diagnosis, management, and prognosis of adult congenital heart disease (ACHD) patients. PVR is crucial in the diagnosis of PH in the ACHD population, in order to differentiate group 2 PH associated with left heart disease from other groups. RHC remains the gold standard in the calculation of PVR in ACHD [5,7]. Nevertheless, in developing countries, the availability of cardiac catheterization laboratories is limited. Besides, echocardiography is widely available, easy to perform, and less costly. Doppler echocardiography using Abbas’ Formula has been known to be strongly correlated with invasively measured PVR. However, PVR using Abbas’ Formula has a mean difference of 2.07 WU and wide standard deviation in ASD with PVR < 3 WU. The sensitivity and specificity of the Abbas method in PVR > 3 WU are 100% and 31.5%, respectively [2,7,8].

PVR is an important parameter to obtain because it determines the need for PAH-specific drugs in ASD-associated PAH. The American Society of Echocardiography (ASE) recommendation suggests the use of the Abbas formula for assessing echocardiographic PVR. Non-invasive estimation of PVR should not be used to replace invasively measured PVR [9]. However, not all centers have the invasive modality. In addition, echocardiography is widely available and easier to perform in a bedside setting. We aimed to investigate whether echocardiographic PVR could help screen patients with high PVR who need PAH-targeted therapy in uncorrected secundum ASD.

Due to the new definition of PAH according to the 2022 ESC guideline on PH, we aimed to assess the reliability of echocardiographic PVR to diagnose PAH based on the recent guideline in uncorrected ostium secundum ASD and to help screen for the high PVR group.

PVR can serve as a dependable alternative for pulmonary vascular disease in individuals with CHD at a specific stage. The key factors influencing vascular resistance are transitional and muscular arterioles, which have smooth muscle cells in their walls and allow the vasoreactivity required to regulate pulmonary blood flow. Ohm’s law is applied hydraulically to calculate the PVR [11]. PVR=mPAP−LAPQp=PCWPQp

Although PVR by RHC is the gold standard, PVR can be assessed noninvasively by Doppler echocardiography. Invasive PVR is measured by ∆p and Qp. In echocardiography, ∆p is substituted by tricuspid regurgitation velocity (TRV), whereas Qp is quantified using TVI_RVOT. As peak TRV increases, systolic pulmonary arterial pressure (SPAP) increases. It is widely acknowledged that, in the absence of a large pulmonary systolic gradient, the right ventricular (RV) systolic pressure measured from Doppler peak TRV corresponded well with invasive pulmonary arterial systolic pressure (PASP). Furthermore, it was previously understood that a non-invasive Doppler-derived metric that took into consideration the area of the aortic valve and the velocity time integral (VTI) of the aortic root had a significant association with cardiac output measured by catheterization [10,11]. Analysis of Qp is crucial for PVR estimation because increased PVR and hyperkinetic PAH both have the potential to raise PASP. TVI_RVOT serves as a replacement for Qp. A conformational shift in TVI_RVOT, which causes mid-systolic notching and early deceleration of pulmonary flow and results in a reduced right ventricular ejection time, reflects an increase in PVR. TVI_RVOT declines while PVR rises. In numerous research, TRV/TVI_RVOT has been verified as an estimation of PVR_cath [12]. However, Doppler echocardiography as a non-invasive measurement has drawbacks due to the limitation of acoustic windows especially in evaluating pulmonary circulation, and is operator-dependent [11].

According to the underlying lesion, a variety of processes contribute to the gradual vascular remodeling that causes PAH in CHD. A common cause of this is a significant left-to-right shunt defect in CHD, resulting in elevated shear stress, endothelial dysfunction, proliferation, and gradual alteration of the pulmonary vessels, all contributing to the onset of PAH [13].

Pulmonary vascular disease is the most unwanted complication in ASD and other shunt lesions. Our study reported a surprisingly higher percentage. The bulk of patients belong to the high PVR group in our study (63.4%). A systematic review conducted in 2018 reported the prevalence of PAH before ASD closure varies from approximately 30%–70% [14]. PAH CHD associated with left-to-right shunt exhibits significant variation in outcome, depending on the severity and reversibility of vascular remodeling [15]. Although there seem to be more factors, the hemodynamic impact of increased pulmonary blood flow is the most widely known predisposing factor for developing PAH in ASD. Large ASD patients may experience long lifespans free of PAH. In middle age, some people experience arrhythmias or right heart failure without any indication of PAH. On the other hand, a tiny percentage of individuals with mild to moderate ASD, sometimes at a young age and without obvious risk factors, present with PAH. When and why specific patients gain PAH in ASD remains unanswered, despite findings indicating a potential genetic susceptibility [16].

In our study, PVR_echo was significantly correlated with PVR_cath. However, there is a wide limit of agreement between both methods. Using the new high PVR definition, the sensitivity of PVR_echo slightly increases, but the sensitivity, NPV, and accuracy decrease. Abbas et al.’s simplified technique showed reduced accuracy while analyzing different causes of PH in a study [10]. PVR should be evaluated based on cardiac output, pulmonary artery mean pressure (PAMP), and pulmonary capillary wedge pressure (PCWP) instead of using Abbas’s formula. By substituting the ratio of the RVOT VTI to the peak velocity of TR for PA pressure and cardiac output. This method disregards the filling pressure on either the right or left heart [11,17,18]. Doppler method has inherent limitations linked to the echocardiography window and correct ultrasound beam alignment. For accurate measurement of TVI_RVOT, the ultrasonic beam must be properly aligned. Accurate TVI_RVOT measurements in patients with PH can occasionally be challenging due to anatomical differences in the right heart components, which carries a risk of introducing large inaccuracies in RV stroke volume estimation [18]. Furthermore, as the RHC and echocardiography measurements were not carried out at the same time, the results may be compromised by the inaccuracy of the separate hemodynamic measurements.

In low PVR situations, many studies found a strong association between Doppler-derived measures and invasive PVR. There is no concrete proof of the use of these Doppler surrogates in high PVR situations, despite the ROC curves showing good cut-off values for PVR. Abbas et al. demonstrated that 44 patients with high PVR, who had a pulmonary catheter in place, had a good correlation between their TRV/TVI_RVOT ratio and postulated that these patients had higher TRV correlations when squared [10]. Abbas et al. concluded from their study that squaring the TRV in line with Bernoulli’s principle would lead to a robust correlation. However, only the ratio of the TRV and TVI_RVOT is used in the non-invasive calculation of PVR [19]. As PVR rises, the TRV rises and TVI_RVOT falls, while still preserving the linear correlation with PVR [12]. Most of the studies showed a good correlation between both methods. A study by Bech-Hensen et al. showed that PVR calculated using Abbas’ Formula showed a larger limit of agreement compared with PVR_Doppler which was calculated using the stroke volume formula [17]. Studies that compare PVR_echo and PVR_cath showed varying results. However, previous studies used diverse populations, and there have been no studies examining the population of uncorrected secundum ASD.

Due to its wide limit of agreement, PVR_echo cannot accurately calculate PVR values but can classify ASD patients into high PVR groups (>2 WU). Therefore, we proposed a new PVR_echo cut-off value that could identify patients in the high PVR group. We proposed a cut-off value of PVR_echo to determine high PVR. The cut-off value of PVR_echo for high PVR is 1.62 WU, with a good discriminatory power. Given this finding, we hope that this new cut-off value can guide clinicians in starting anti-PAH therapy in ASD patients even though no catheterization has been performed. PAH-specific therapy could improve the hemodynamics and quality of life [15].

We conclude that PVR_echo is reliable in predicting high PVR in uncorrected secundum ASD. PVR measured by echocardiography according to Abbas’ Formula had a significant correlation with its gold standard. However, there is a wide range of agreement between the two methods. We suggested using an PVR_echo cut-off value of 1.62 WU to identify individuals in the high PVR group.