Neglected intrapulmonary arteriovenous anastomoses: A comparative study of pulmonary right-to-left shunts in patients with patent foramen ovale

Abstract

Objective: Pulmonary right-to-left shunt (P-RLS) and patent foramen ovale right-to-left shunt (PFO-RLS) often appear in combination, and there are often differences and connections between them. Intrapulmonary arteriovenous anastomoses (IPAVAs), as part of P-RLS, are often overlooked because there are no technologies to detect and identify them. This study aimed to further clarify the incidence and characteristics of P-RLS with the help of contrast transesophageal echocardiography (c-TEE) and contrast transthoracic echocardiography (c-TTE), providing a reference for clinically relevant research and patent foramen ovale (PFO) management disposal decisions.

Methods: We retrospectively investigated 414 subjects who came to our hospital for c-TEE from October 2021 to July 2022, and all subjects completed c-TTE simultaneously. 7 Patients who were newly diagnosed with an atrial septal defect were excluded. Eventually, 407 patients were included in this study. Among them, 157 patients with PFO (58 patients were treated with PFO closure subsequently) and 250 patients without PFO confirmed by c-TEE were finally enrolled. In the process, we observed and analysed the presence of P-RLS.

Results: A total of 407 patients were included in the final analysis and divided into PFO group (N = 157) and non-PFO group (N = 250) according to the results of c-TEE. Whether at rest or after Valsalva maneuver, the incidence of P-RLS was significantly higher under c-TEE than under c-TTE in the two groups (P < 0.001). For both c-TTE and c-TEE, the incidence of P-RLS was slightly higher after Valsalva maneuver than at rest, but the difference was not significant (c-TTE: rest vs. Valsalva maneuver, P = 0.214; c-TEE: rest vs. Valsalva maneuver, P = 0.076). The Valsalva maneuver increased the incidence of P-RLS in the group without PFO, which was more significant in c-TEE (c-TTE: rest vs. Valsalva maneuver, P = 0.591; c-TEE: rest vs. Valsalva maneuver, P = 0.008). In both groups, the P-RLS semiquantitative grading was statistical significance under different states and examinations (P < 0.001).

Conclusion: The vast majority of P-RLS are grade 1-2 and are derived from physiological IPAVAs. Even so, attention should be given to the differentiation between P-RLS and PFO-RLS. c-TEE is an effective method to detect P-RLS; however, the recruitments of c-TEE and Valsalva maneuver to P-RLS should be noted.

Keywords: intrapulmonary arteriovenous anastomoses; patent foramen ovale; pulmonary right-to-left shunt; saline contrast echocardiography; transesophageal echocardiography; transthoracic echocardiography.

Figure 1

Biplane images of PFO-RLS and P-RLS under c-TEE. (A) PFO-RLS: microbubbles were observed to squeeze through the PFO. (B) P-RLS: microbubbles were observed to originate from the right superior pulmonary veins. PFO-RLS, patent foramen ovale right-to-left shunt; P-RLS, pulmonary right-to-left shunt; c-TEE, contrast transesophageal echocardiography; LA, left atrium; RA, right atrium; RUPV, right upper pulmonary vein.

Figure 2

Flow chart of patient enrollment. c-TTE, contrast transthoracic echocardiography; c-TEE, contrast transesophageal echocardiography; ASD, atrial septal defect; PFO, patent foramen ovale; PFO-RLS, patent foramen ovale right-to-left shunt; P-RLS, pulmonary right-to-left shunt of patients after PFO closure; P-RLS, pulmonary right-to-left under c-TEE and after Valsalva maneuver.

Figure 3

Representative echocardiograms of P-RLS grading under c-TTE (grade 0–3). (A) grade 0: negative in LV, (B) grade 1:1–30 bubbles in LV, (C) grade 2:31–100 bubbles in LV, (D) and grade 3:>100 bubbles in LV. P-RLS, pulmonary right-to-left shunt; c-TTE, contrast transthoracic echocardiography; LA, left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle.

Figure 4

Distribution of stroke in different grades of P-RLS between PFO and non-PFO groups. P-RLS, pulmonary right-to-left shunt under c-TEE and after Valsalva maneuver; PFO, patent foramen ovale.

Figure 5

Sankey diagram of P-RLS semi-quantitative gradings between PFO and non-PFO groups. This diagram shows the trend of P-RLS grades under c-TTE and c-TEE and before and after Valsalva maneuver. RLS, right-to-left shunt; c-TTE-REST, under contrast transthoracic echocardiography and at rest; c-TTE-VM, under contrast transthoracic echocardiography and after Valsalva maneuver; c-TEE-REST, under contrast transesophageal echocardiography and at rest; c-TEE-VM, under contrast transesophageal echocardiography and after Valsalva maneuver; PFO, patent foramen ovale.

Figure 6

Comparison of two P-RLS quantitative classifications in PFO group (A); comparison of two P-RLS quantitative classifications in non-PFO group (B). P-RLS, pulmonary right-to-left shunt under c-TEE and after Valsalva maneuver; PFO, patent foramen ovale. Classification 1: grade 0 = no bubbles, grade 1 = 1–10 bubbles, grade 2 = 11–30 bubbles, and grade 3 > 30 bubbles (or left atrial opacity) were detected; Classification 2: grade 0 = no bubbles, grade 1 = 1–30 bubbles, grade 2 = 31–100 bubbles, and grade 3 > 100 bubbles (or left atrial opacity) were detected, respectively.