The Application of Point of Care Ultrasound to Screen for Pulmonary Hypertension: A Narrative Review

Abstract Background: Pulmonary Hypertension (PH) is a condition with several cardiopulmonary etiologies that has the potential of progressing to right heart failure without proper intervention. After a history, physical exam, and investigations, cases of suspected PH typically undergo imaging via a transthoracic echocardiogram (TTE). This is a resource-intensive procedure that is less accessible in remote communities. However, point of care ultrasound (POCUS), a portable ultrasound administered at the bedside, has potential to aid in the diagnostic process of PH. Methods: The MEDLINE, Embase, and CENTRAL databases were searched to screen the intersection of POCUS and PH. Studies involved adult patients, and only English articles were accepted. Reviews, case reports, unfinished research, and conference abstracts were excluded. Our aim was to identify primary studies that correlated POCUS scan results and additional clinical findings related to PH. Results: Nine studies were included after our search. In these studies, POCUS was effective in identifying dilatation of inferior vena cava (IVC); internal jugular vein (IJV); and hepatic, portal, and intrarenal veins in patients with PH. The presence of pericardial effusion, pleural effusion, or b-lines on POCUS are also associated with PH. Conclusions: This review suggests important potential for the use of POCUS in the initial screening of PH. IVC and basic cardiopulmonary POCUS exams are key for PH screening in patients with dyspnea. Right-heart dilatation can be visualized, and peripheral veins may be scanned based on clinical suspicion. POCUS offers screening as an extension of a physical exam, with direct visualization of cardiac morphology. However, more studies are required to develop a statistically validated POCUS exam for PH diagnosis. More studies should also be conducted at the primary-care level to evaluate the value of screening using POCUS for PH in less-differentiated patients.


Introduction
Pulmonary hypertension (PH) is a severe condition arising from increased pulmonary vascular resistance with complications including right heart (RH) failure and hypoxia [1].Pulmonary Arterial Hypertension (PAH), also known as primary PH, has no other cardiopulmonary etiology, and its 3-year mortality can be as high as 21% [2].Therefore, early screening and detection is an important component of PH management.
There are five types of PH, labeled groups 1-5 by the World Health Organization (WHO) [3,4] as follows: PAH, PH due to left heart disease, PH due to hypoxia and lung disease, chronic thromboembolic pulmonary hypertension (CTEPH), and PH with unclear or multifactorial mechanisms, respectively.Group 2 PH comprises 68% of PH cases, as reported by Brown et al. [5].Group 5 is the second most common, making up 15%.Group 3 forms 9% and Groups 1 and 4 account for 3% and 2%, respectively [4,5].Within PAH, there are several subtypes which include idiopathic, heritable conditions associated with PAH such as connective tissue diseases, human immunodeficiency virus infection, portal hypertension, congenital heart disease, schistosomiasis, PAH associated with drugs and toxins, PAH with features of venous/capillary involvement, and persistent PH of the newborn.Though relatively rare, PH is increasing in incidence around the world and becoming a greater healthcare burden [4,6].indicated.After an electrocardiogram and bloodwork, the next step in the workup is typically a trans-thoracic echocardiogram (TTE) [8,9].Access to echocardiography can pose a barrier to rapid early diagnosis, depending on resource availability such as requiring specialized personnel and equipment [10][11][12].Furthermore, echocardiography may be less accessible in some remote communities since these facilities are typically situated in urban centers [13].
However, with the advent of point of care ultrasound (POCUS), ultrasound scans are now employed at the bedside.Images may be obtained quickly and cheaply, allowing for efficient examination and extension of the physical examination that may point to etiologies such as PH contributing to patient symptoms.
Currently, PH is often missed, especially in younger patients using existing bedside approaches to history and physical examination [5].Even in secondary PH, there is still the risk of RH failure in addition to the primary disease.The increased efficiency of a cardiopulmonary POCUS exam could motivate a broader differential diagnosis that includes PH.Relevant cardiovascular images that apply to PH are shown in Figure 1.This article reviews the potential for POCUS to aid in the diagnostic process of PH and discuss its implications.

Methods
We conducted a literature review using the MEDLINE, Embase, and CENTRAL databases, capturing the intersection of POCUS and PH using these terms, their synonyms, and relevant subject headings.The full search criteria are shown in the Supplementary Material.Only English studies involving adult patients were included.Conference abstracts, reviews, unfinished research, and case studies were excluded.After title and abstracts were screened, included articles underwent full -text screening.Data from relevant articles were extracted.One reviewer [D.K.] performed the entire screening and extraction.

Results
We found nine studies that correlate POCUS findings with PH-related clinical features.The PRISMA diagram is displayed in Figure 2. The results are summarized in Table 1.
Avriel et al. [15] studied the effect of POCUS in a PAH clinic.36 patients were randomized 1:1 to either receive an additional POCUS assessment or not.The number of changes to patients' management was recorded.Cardiac, pulmonary, and IVC POCUS exams were performed.There were 48 management changes in the POCUS group and 18 in the control group (p<0.001).
Torres-Arrese et al. [16] used POCUS to scan acute heart failure patients' lungs and their hepatic, portal, intrarenal, and femoral veins, both on admission and discharge.The congestion values of the hepatic, portal, and intrarenal veins were used to calculate a Venous Excess Ultrasound Score (VExUS), estimating the congestion in the venous system [17].In paired analysis for patients' results on admission and discharge, the researchers found that the score significantly correlated with the EVEREST score, a validated clinical scoring for congestion [18], with a correlation of 0.532 (p=0.004).The VExUS also correlated with a decrease in NT-proBNP, with a correlation of −0.411 (p = 0.024).
Dayioglu et al. [19] employed POCUS to measure the following cardiopulmonary parameters, comparing them to conventional ultrasound: fractionated area change; IVC collapsibility/distensibility; LV/RV end-diastolic and IVC diameter; LV/RV diastolic and systolic centricity index; right atrium area; pulmonary artery diameter.None of these parameters were significantly different from conventional handheld ultrasound.Overall, POCUS was 68% accurate for detecting PH with 88% negative predictive value.
Elzeneini et al. [21] compared POCUS RAP, estimated from the IVC scan, to that determined by RHC.They found a correlation of 0.80, P<.001, and that POCUS was 76-92% accurate overall.
Chopra et al. [22] found that in PH patients, pericardial effusion was 89% predictive of systemic venous hypertension (RAP > 10mg at rest), while pleural effusion had only a 67% positive predictive value for pulmonary venous hypertension (pulmonary artery wedge pressure > 15mmHg).Both effusions were found using POCUS.
Parikh et al. [23] used POCUS to measure the internal jugular vein (IJV) in patients undergoing RHC for PH.The following were measured: IJV diameter at rest, during respiratory variation, and during manual compression.The collapsibility indices were calculated during respiration and during manual compression.The measured RAP correlated significantly with the IJV diameter (r=0.26,p=0.029).Furthermore, the compression collapsibility index correlated significantly with mRAP (r=-0.43,p=0.0002), pulmonary artery occlusion pressure also obtained from an RHC (r=-0.35,p<0.0027), and BNP levels (r=-0.31,p=0.015).
Simon et al. [24] studied patients undergoing RHC, but not necessarily for suspected PH.The right IJV crosssectional area (CSA) with and without the Valsalva maneuver was measured using POCUS.Patients were grouped as normal and elevated mRAPs.The Valsalva maneuver increased IJV CSA by a median of 35% (IQR 19%-79%) in normal mRAP patients, and 5% in high mRAP patients (IQR 3%-14%).They reported that a >17% increase in right IJV CSA with Valsalva can predict elevated RAP with a sensitivity and specificity of 90% and 74%, respectively.

Discussion
POCUS is an inexpensive, fast, and accessible tool that is increasingly prevalent in outpatient settings.POCUS examinations have the potential to be used as a screening tool for PH.The POCUS exams used to screen for PH are: parasternal long axis (PLAX), parasternal short axis (PSAX), apical (A4C), and subcostal 4-chamber (S4C), subcostal for the IVC  Table 1.Results of the review.Five primary studies evaluating point of care ultrasound (POCUS) were found relevant to pulmonary hypertension (PH).The number of patients (n), patient population, and clinical findings are also summarized.
and estimating RAP, and B-mode pulmonary views of each lobe.These techniques are derived from ultrasound guidelines and are standard across included studies [25][26][27].The full cardiopulmonary POCUS exam and veins encompassing the IVC and peripheral veins are all reasonable in the screening of PH, as outlined below.
The IVC diameter and collapsibility arising from the subcostal view has been the most used and validated estimate of the RAP among the studies, and it should be the preferred method for PH on POCUS.
The cardiac exam uses standard visualizations PLAX, PSAX, A4C, and S4C.The goal is to identify pericardial effusion, RH dilatation, tricuspid regurgitation, and rule out other cardiac etiologies such as left heart or valvular diseases.RH dilatation was not thoroughly investigated in the studies included, as it arises later in the disease process of PH [28,29].Meanwhile, tricuspid regurgitation is a complication of RH dilatation and can also be viewed on POCUS [30,31].
The pulmonary exam employs B-mode investigating each lobe, and visualizes the presence of b-lines and pleural effusion.These are associated with PH based on our results.In addition, the pulmonary exam scans for signs of pulmonary decompensation while ruling out other pulmonary causes of the presentation.
The IJV may be useful to obtain RAP.However, the IVC has been more thoroughly studied in the studies we reviewed.Other peripheral veins such as the hepatic, portal, and intrarenal veins are also effective proxies for the RAP.However, they are distal to the IVC and should only be examined under exceptional circumstances or with complaints such as peripheral swelling.
A summary of the POCUS exam for PH screening is outlined in Table 2.The screening role of POCUS in the diagnostic algorithm of PH is outlined in Figure 3. Select abnormal POCUS findings are pictured in Figure 4.
There are several limitations of this study.First, while RHC is the gold-standard for the diagnosis of PH, it is utilized less due to its invasiveness.Therefore, other   Therefore, the goal for the future is to produce a fast and clinically validated screening exam utilizing current standards.This screening exam would be intended for patients in the primary care setting who present with dyspnea and other PH-related symptoms, and would ultimately serve as an extension of the physical exam.To that end, more studies are required in this field, to determine exact measurements, their cutoffs for severity, and their relative weights of consideration.These studies should be replicated to allow for the creation of more statistically robust POCUS exams for PH.
In addition, more studies should be conducted in a primary care setting.None of the studies reviewed focus on undifferentiated patients presenting with dyspnea and how POCUS can help screen them for PH.These studies would be more similar to their proposed use in the context of PH.While the studies that were reviewed illustrated the ability for POCUS to estimate severity in cohorts of PH patients, undifferentiated patients at an earlier stage of disease may present with less discernible findings.Other presentations and differential diagnoses in a primary care setting may also add complexity to the protocols outlined in these studies.
Nonetheless, POCUS should still be used today to help screen for PH where indicated.Even though the absence of positive findings on POCUS cannot rule out PH, the presence of findings can further the probability of PH and the acute risk to the patient.This information can be used to triage limited space and resources in the echocardiography lab, and to communicate the urgency of such a procedure.This information would still be of great importance in rural and remote communities, where transportation to an echocardiography lab may be less accessible.

Conclusion
POCUS can supplement the physical exam during the screening for PH.Compared to echocardiography, POCUS is also more accessible in outpatient and rural/ remote areas.We find that POCUS for PH should primarily involve the IVC.A cardiac and pulmonary exam are also indicated to look for RH dilatation, pleural and pericardial effusions, b-lines, and other cardiopulmonary comorbidities.Other peripheral veins such as the IJV, hepatic, portal, and intrarenal veins may be assessed if clinical suspicion is present for peripheral vascular decompensation.Basic cardiopulmonary POCUS techniques are standard across studies we reviewed, but a standardized and validated POCUS exam for PH still needs to be developed.To that end, more studies are required in both PH and primary care populations.The use of POCUS to screen for PH is still in its infancy, and this article provides a foundation on which future research can build.Nevertheless, POCUS can still serve an important role in triaging, maximizing limited echocardiographic resources, and more accurately estimating a patient's urgency in rural and remote areas.

Figure 1 .
Figure 1.Images of normal cardiac and subcostal views obtainable using a point of care ultrasound (POCUS) examination.The following heart and abdominal structures are labeled: Right and left ventricles (RV, LV), tricuspid and mitral valves (TV, MV), right and left atria (RA, LA), inferior vena cava (IVC), liver, and hepatic vein (HV).

Figure 2 .
Figure 2. The PRISMA diagram of the resulting literature search.Nine studies were included in this review.

Figure 3 .
Figure 3.The proposed addition of point of care ultrasound (POCUS) to the initial screening for pulmonary hypertension (PH).Echocardiography, a ventilation/perfusion (V/Q) scan, and a gold-standard right-heart catheterization (RHC) are still required to progress in the diagnosis as needed should the PH probability be high.CTEPH = Chronic thromboembolic pulmonary hypertension.

Figure 4 .
Figure 4. Abnormal point of care ultrasound (POCUS) scans of patients with PH.A) Inferior Vena Cava (IVC) Dilatation.B) Right Ventricle (RV) Dilatation.C) Severe Tricuspid Regurgitation.D) Dilated RV in the parasternal short axis.The D-shaped septum is indicative of RV pressure overload.E) Pericardial effusion.

Table 2 .
Summary of POCUS exam for PH screening, illustrating techniques used and the exam's objectives.clinical findings indicative of PH such as lab values and clinical scores were also used.This makes it is difficult to isolate the effect of the PH itself in a patient complicated by other cardiopulmonary disease unless the focus was only on patients with PAH.Another limitation was the heterogeneity and overall low number of studies in this field.The studies are unable to be amalgamated due to differences in patient population, group of PH, experimental design, regions investigated by POCUS, and outcomes examined.