Management of pulmonary arteriovenous malformations involves additional factors aside from the diameter of feeding arteries: a 3-year case-case retrospective analysis

In this retrospective observational study, we reviewed the radiographic reports of 838,447 patients who presented to our hospital from January 2018 to December 2020. The review group consists of five radiologists with experience in radiodiagnosis and embolisation. Firstly, two radiologists with over 7 years of experience (X.M., L.L.L.) carried out the reports review process, and all the reports regarding PAVMs and pulmonary vascular abnormalities were included for further review. Then three radiologists with over 15 years of experience (D.Y., B.J., S.J.) performed the imaging review. PAVMs were confirmed by multi-slice spiral computed tomography (MSCT) (slice thickness, 1 mm; slice gap, 1 mm) or multi-slice spiral CT angiography (CTA) (slice thickness, 0.625 mm; slice gap, 0.625 mm). All detected PAVMs were classified as the simple type or the complex type based on the MSCT or CTA findings as described in previous studies [2, 18, 19]. The complex type included the following two subtypes: the diffuse subtype (involvement of a large part of the parenchyma) and the telangiectatic subtype (multiple microscopic vascular networks) [20, 21]. All enrolled patients were divided into different groups according to the number of PAVMs, and all detected PAVMs were grouped based on their location in the lung. The largest diameter of the feeding artery and the largest diameter of the sac of each PAVM was recorded based on the MSCT or CTA findings.

The clinical data, respiratory symptoms, central nervous system symptoms, and treatment regimens of all enrolled patients were obtained from the medical records and telephone follow-ups. The clinical diagnosis of HHT was confirmed according to the Curaçao criteria: (1) spontaneous epistaxis; (2) multiple telangiectasias of the body surface; (3) visceral lesions in the gastrointestinal mucosa, liver, or brain; and (4) first-degree relatives with HHT. Patients who met two criteria had a possible clinical diagnosis of HHT, and those who met three criteria had a definite diagnosis of HHT [8, 22]. Among patients who underwent embolisation, CTA was performed in the first month after embolisation, and MSCT scans were regularly performed if there was no evidence of PAVM recurrence as shown by MSCT.

We performed a questionnaire-based investigation in four tertiary university hospitals. This investigation involved the pathogenesis, related complications, and treatment strategy of PAVMs. The results were obtained from 121 doctors in the departments of respiration, thoracic surgery, radiology, oncology, intervention, and emergency in 4 different tertiary university hospitals.

All results are expressed as mean ± standard deviation or frequency (percentage). The statistical analysis was performed using SPSS version 19.0 (IBM Corp., Armonk, NY, USA). A P-value of < 0.05 was considered statistically significant.

Valid results of blood gas analyses (exclusion criteria: blood samples obtained during oxygen therapy or massive haemoptysis) were obtained from 64 enrolled patients, and hierarchical multiple regression analysis was used to determine the relationship of multiple factors (collective characteristics of PAVMs, age, sex, and other lung diseases) with the oxygen pressure. Simple linear regression and variable correlation scatter plots were used to analyse the correlation between the diameter of the feeding artery and oxygen pressure. Paired-sample t-tests were applied to compare the results of the blood gas analysis before and after treatment of PAVMs in 24 enrolled patients.

The severity of central nervous system symptoms was classified on a scale of 1 to 4 (level 1, none; level 2, headache or dizziness; level 3, transient ischaemic attack [TIA]; and level 4, stroke or brain abscess). Ordered multivariable logistic regression analysis was performed to analyse the relationship between multiple factors (collective characteristics of PAVMs, age, and sex) and central nervous system symptoms in all enrolled patients. Differences of the largest diameter of the feeding artery in different levels were compared with One-way ANOVA analysis.

Among 838,447 patients, 207 patients were enrolled in the present study, and the detection rate of PAVMs was 0.025%. The baseline characteristics of all enrolled patients are shown in Table 1. In total, 77.78% of the enrolled patients were female. The patients’ mean age was 53 ± 14.2 years (range 14–87 years). A clinical diagnosis of definite or possible HHT was made in 37.7% of patients (78/207), and 73.1% of these 78 patients were female. Eight patients with HHT had bilateral diffuse multiple PAVMs (n > 10), including multiple telangiectatic lesions, simple lesions, and complex lesions. One hundred twenty-eight patients chose to undergo regular follow-up. Endovascular embolisation was performed in 76 patients, and 4 patients chose video-assisted thoracoscopic surgery. One patient diagnosed with a diffuse PAVM received embolisation because of intermittent haemoptysis. Massive haemoptysis recurred 2 days after embolisation, and the patient then underwent video-assisted thoracoscopic surgery.

Table 2 shows the patients’ clinical manifestations. Seventy-one (34.3%) of 207 patients were asymptomatic. Ninety-nine (47.8%) enrolled patients exhibited dyspnoea on exertion. Forty-three patients (20.8%) exhibited serious central nervous system manifestations (TIA, stroke, or brain abscess), and their mean age was 45.58 ± 15.23 years (range 14–83 years; median 47 years).

Two hundred thirty-six PAVMs were detected in 199 patients, excluding 8 patients with bilateral diffuse multiple PAVMs (n > 10). Of the 236 lesions, 209 (88.6%) were located in the peripheral pulmonary area. The simple type was the most common type among these 236 PAVMs (88.6%). Two diffuse PAVMs were detected in two patients, and all six telangiectatic PAVMs were detected in a single patient with HHT (Fig. 1). The mean largest diameter of the feeding artery and mean largest diameter of the sac was 4.13 ± 1.92 mm and 10.31 ± 7.48 mm, respectively (Table 3).

Most of the enrolled patients visited the department of respiration (40.5%) or thoracic surgery (21.3%) (Fig. 2A). One hundred eleven patients (53.6%) were first diagnosed with PAVMs during a health check-up. The chief complaint in 44 patients (21.3%) was various degrees of dyspnoea at their first visit, and the main causes of hospital visits were different respiratory manifestations (44.9%, 93/207) (Fig. 2B).

The results of the hierarchical multiple regression analysis of the relationship between multiple factors and hypoxaemia are shown in Table 4. The largest diameter of the feeding artery, type and number of PAVMs, and other lung diseases were closely associated with hypoxaemia (P < 0.001, P < 0.001, P = 0.037, and P = 0.03, respectively; R² = 0.65). In the final multivariable model, the diameter of the feeding artery had the strongest correlation with hypoxaemia (R² = 0.43). The diameter of the feeding artery had a significant linear correlation with the oxygen pressure prior to any treatments (P < 0.0001) (Fig. 2C). According to the linear correlative model and the scatter plot graph, the oxygen pressure was < 80 mmHg when the diameter of the feeding artery was > 4.1 mm. The results of the blood gas analysis before and after embolisation were available in 24 patients and showed significant differences (before, 69.08 ± 13.14 mmHg; after, 96.98 ± 25.89 mmHg; P < 0.0001).

Type of PAVMs: 1 for simple type, 2 for complex type, 3 for diffuse type, 4 for mixed types. Other lung diseases: bronchiectasis was present in two patients, lobectomy in two, chronic bronchitis in four, pulmonary fibrosis in one, pneumonectasis in two, tuberculosis in one, and pulmonary arterial hypertension in two. PAVMs, pulmonary arteriovenous malformations.

The results of the ordered multivariable logistic regression analysis showed no association of the largest diameter of the feeding artery and sac of the PAVMs, the type and number of PAVMs, sex, and age with the severity of central nervous system manifestations (P = 0.8, P = 0.42, P = 0.99, P = 0.35, P = 0.17, and P = 0.68, respectively). These results are shown in Table 5. There were no significant differences in the largest diameter of the feeding artery among patients with different levels of central nervous system symptoms (P = 0.44) (Fig. 2D). The range of the largest diameter of the feeding artery was similar among all levels (lF value = 0.11, P = 0.95) (Fig. 2E).

Among 81 patients who received treatment, only 1 patient with a diffuse PAVM developed a relapse 2 days after embolisation and underwent video-assisted thoracoscopic surgery. No PAVMs recurred in the other 80 patients during follow-up. Before embolisation, 46 patients had dyspnoea on exertion, and this symptom was greatly relieved in all 46 patients after embolisation (mean age 50 ± 15.55 years; range 16–76 years). In five patients who underwent thoracoscopic surgery, dyspnoea on exertion persisted because of lung lobe resection. Before embolisation, 17 patients had serious central nervous system manifestations (TIA in 12, stroke in 4, and a brain abscess in 1), and none of these patients developed relapse of symptoms during follow-up (median age 49 years; range 31–64 years).

Fifty-nine doctors (48.76%) were unfamiliar with PAVMs and rarely encountered patients with PAVMs. A total of 95.04% of doctors (115/121) knew that most PAVMs are congenital, but 60.37% of doctors (73/121) did not link PAVMs to HHT in clinical practice. Ninety-eight doctors (80.99%) believed that PAVMs do not induce serious manifestations. Most doctors (up to 86.68%) realised the correlation between respiratory symptoms and PAVMs, but only up to 28.93% of doctors (35/121) knew that PAVMs induce central nervous system manifestations. Thirty-eight doctors (31.4%) did not fully understand all the serious complications of PAVMs (Fig. 2F). The doctors were divided on the treatment of PAVMs, and 50.41% of doctors believed that PAVMs do not require medical attention. One hundred eleven doctors (91.74%) considered that embolisation is the best alternative for treatment of PAVMs if necessary, but 64.46% of doctors (78/121) were unaware that the presence of feeding arteries of ≥ 3 mm in diameter is the proper indication for embolisation.