What is the management approach for a patient with a pulmonary arteriovenous malformation (AVM), particularly with a history of hereditary hemorrhagic telangiectasia (HHT)?

Management of Pulmonary Arteriovenous Malformations

Immediate Screening and Diagnosis

All patients with suspected or confirmed pulmonary AVMs must undergo transthoracic contrast echocardiography as the initial screening test, followed by chest CT with IV contrast to define the number, size, and location of PAVMs for treatment planning. 1, 2

• Contrast echocardiography demonstrates 98-99% sensitivity for detecting intrapulmonary shunts and should be performed first 2
• CT chest with IV contrast provides definitive anatomic detail including feeding artery diameter, which determines treatment eligibility 2
• Measure arterial oxygen saturation (SaO2) both supine and upright, as orthodeoxia occurs in 65-83% of cases due to lower lobe predominance 3
• Obtain PaO2 measurements in room air and while breathing 100% oxygen, as the 100% oxygen test shows 100% sensitivity for identifying treatable PAVMs 4

Evaluation for Hereditary Hemorrhagic Telangiectasia

Because 70-90% of pulmonary AVMs occur with HHT, systematically evaluate all PAVM patients using the Curaçao criteria and consider genetic testing. 2, 3

Apply Curaçao Diagnostic Criteria 2, 5:

• Spontaneous and recurrent epistaxis (present in >90% of HHT adults)
• Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose)
• Visceral AVMs (pulmonary, hepatic, cerebral, gastrointestinal, spinal)
• First-degree relative with HHT diagnosed by these criteria

A definite diagnosis requires 3 of 4 criteria; possible diagnosis requires 2 of 4 criteria 2, 5

Genetic Testing Strategy 2, 5:

• Order simultaneous sequencing and deletion/duplication analysis of ENG, ACVRL1, and SMAD4 genes, which identifies causative mutations in 97% of clinically definite HHT cases 2, 5
• Prioritize genetic testing for asymptomatic family members of known HHT patients to enable presymptomatic screening and prevention 2, 5
• Include SMAD4 testing in all panels, as 1-2% of HHT patients have SMAD4 mutations causing combined HHT-juvenile polyposis syndrome requiring intensive gastrointestinal surveillance 2, 5

Comprehensive Organ Screening for HHT Patients

All patients with confirmed or suspected HHT require systematic screening for asymptomatic but life-threatening AVMs in multiple organ systems. 2, 5

Mandatory Screening Protocol 2, 5:

• Brain MRI to detect cerebral vascular malformations, as nearly one in five HHT patients develop stroke or cerebral abscess 2, 5
• Contrast echocardiography or chest CT for pulmonary AVMs, which can be treated presymptomatically to prevent neurologic complications 2, 5
• Doppler ultrasonography as first-line imaging for liver involvement, assessing hepatic artery diameter (>6 mm abnormal), peak flow velocity (>80 cm/sec abnormal), and resistivity index (<0.55 abnormal) 2, 5
• Never perform liver biopsy in any patient with proven or suspected HHT due to catastrophic hemorrhage risk from vascular malformations 2, 5

Treatment Indications and Technique

Perform percutaneous transcatheter embolization for all PAVMs with feeding arteries ≥3 mm diameter to prevent paradoxical embolic stroke, transient ischemic attack, and brain abscess. 1, 3

Evidence for Treatment Threshold 1, 3:

• PAVMs create direct pulmonary artery-to-vein connections allowing paradoxical emboli to bypass pulmonary capillary filtration, causing stroke or TIA in 3.2-55% of untreated patients 2, 3
• Brain abscesses occur in 0-25% of untreated cases when bacterial emboli bypass pulmonary filtration 2, 3
• The 3 mm feeding artery diameter threshold represents the standard treatment indication based on embolic risk 1, 3
• Some experts recommend treating any PAVM detected by CT regardless of feeding artery size due to paradoxical embolism risk 3

Embolization Technique 1, 3, 6:

• Deploy coils or plugs in the feeding artery as close to the arteriovenous communication as possible 3
• Embolization demonstrates low complication rates and effectively prevents neurologic complications 3, 6
• Expect improvement in dyspnea in 80% of patients following successful embolization 6
• Anticipate better PaO2 improvement when PAVMs involve segmental rather than subsegmental arteries 6

Critical Complications Requiring Urgent Awareness

Recognize that untreated PAVMs pose life-threatening risks including stroke (3.2-55%), brain abscess (0-25%), and pregnancy-related hemorrhage (1 in 100 women). 1, 2, 3

Neurologic Complications 2, 3, 7:

• Cerebral abscess occurs at median age 33 years (range 11-66 years), often as the presenting manifestation before PAVM or HHT diagnosis 7
• Ischemic cerebral events occur at median age 53.5 years (range 2-72 years) 7
• In 54% of cerebral abscess cases, both PAVM and HHT diagnoses are made at the time of the abscess presentation 7
• Neurologic events occur more frequently (62.5%) in patients with diffuse subsegmental PAVM involvement compared to segmental involvement (35%) 6

Hemorrhagic Complications 1, 3:

• Massive hemoptysis and hemothorax are rare (0-2%) but represent life-threatening emergencies 3
• Pregnancy dramatically increases hemorrhage risk due to hormonal and hemodynamic changes, affecting 1 in 100 women with PAVMs 1, 2
• Four patients in one series experienced hemothorax, including one during pregnancy 7

Post-Embolization Surveillance

Perform follow-up imaging at 6 months and annually thereafter to detect reperfusion of embolized PAVMs or enlargement of non-embolized lesions. 1, 6

• Ischemic or infectious complications occur in approximately 10% of patients due to reperfusion of embolized PAVMs or enlargement of non-embolized PAVMs 6
• Complete treatment success on CT scanning occurs in 59% of cases, with partial success in 38% 6
• Continue annual surveillance indefinitely, as new PAVMs can develop over time in HHT patients 1

Management of HHT-Related Bleeding

For patients with confirmed HHT and recurrent epistaxis or gastrointestinal bleeding, implement stepwise escalation starting with nasal moisturization, advancing to oral tranexamic acid, then local ablative therapies, and reserving systemic bevacizumab for refractory cases. 5

Stepwise Treatment Algorithm 5:

• First-line: Air humidification and topical saline solution or gels to prevent mucosal cracking 5
• Second-line: Oral tranexamic acid (starting 500 mg twice daily, increasing to 1000 mg four times daily or 1500 mg three times daily), which reduces epistaxis duration by 17.3% and composite endpoints by 54% 5
• Third-line: Local ablative therapies for persistent bleeding despite medical management 5
• Fourth-line: Systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses, then maintenance every 1-3 months) for severe refractory bleeding, producing 50% reduction in epistaxis severity score and mean hemoglobin improvement of 3.2 g/dL 5

Iron Replacement 5:

• Screen all HHT adults for iron deficiency and anemia regardless of symptoms 5
• Start oral iron (35-65 mg elemental iron daily), reassessing at 1 month for adequate response (hemoglobin rise ≥1.0 g/dL) 5
• Switch to intravenous iron for inadequate absorption, intolerance, or severe anemia 5
• Normalize ferritin and transferrin saturation, not just hemoglobin, as iron deficiency without anemia still causes fatigue 5

Special Considerations for SMAD4 Mutation Carriers

Patients with SMAD4 mutations require combined HHT and juvenile polyposis management, including upper GI surveillance every 1-3 years starting at age 18 years due to 73% prevalence of gastric polyposis and exclusive occurrence of gastric cancers in SMAD4 carriers. 5

• All gastric cancers in one cohort occurred exclusively in SMAD4 pathogenic variant carriers, necessitating intensive surveillance 5
• SMAD4 carriers may lack overt HHT symptoms but remain at risk of asymptomatic life-threatening AVMs 5
• Manage all SMAD4 patients in conjunction with a specialist HHT center experienced in both HHT and juvenile polyposis complications 5

Non-HHT Pulmonary AVMs

In the 10-30% of PAVM patients without HHT, investigate potential acquired causes including previous thoracic surgery (23.4%), congenital heart disease (19.5%), chest trauma (10.4%), Glenn shunts, or Fontan circulation. 2, 8

• Non-HHT PAVMs occur more commonly in females (59.7%), are predominantly simple and single (75.3% and 89.6% respectively), and have lower lobe predominance (66.7%) 8
• Neurologic complications still occur in 19.5% of non-HHT PAVM patients, mandating the same treatment approach as HHT-related PAVMs 8
• Most non-HHT PAVMs are idiopathic (61%), but clinicians should maintain awareness of PAVM development risk in patients with chest trauma, congenital heart disease, lung infection/abscess, and thoracic surgery history 8