R4. Yoo, Jung-sun Rodrigo Cartin-Ceba, MD ; Karen L. Swanson, DO, FCCP ; and Michael J. Krowka, MD, FCCP CHEST. (2013) September Vol. 144 Pulmonary Arteriovenous Malformations

Introduction - Low-resistance, high-flow abnormal vascular structures that most often connect a pulmonary artery to a pulmonary vein intrapulmonary right to left shunt. -Degree of right-to-left shunt  clinical finding : hypoxemia, dyspnea, and cyanosis - Complication : paradoxical systemic embolization (stroke, brain abscess) Pulmonary arteriovenous malformations (PAVMs) (=Pulmonary arteriovenous fistula)

Introduction - PAVMs usually are hereditary with most associated with hereditary hemorrhagic telangiectasia (HHT) - Hereditary PAVMs tend to increase in size over time (second and third decades of life.) - PAVMs do not exhibit a malignant potential

Epidemiology - PAVMs : rare (two to three per 100,000) - Male-to-female ratio : 1:1.5 to % to 95% occurring in patients with HHT(hereditary hemorrhagic telangiectasia) - Most are diagnosed in the first 3 decades of life.

Pathophysiology - Single, multiple / unilateral, bilateral / simple, complex - Solitary(single) PAVMs : lower lobe (Lt>Rt) - Multiple PAVMs : lower lobe (Bilateral : 8% to 20%)

Pathophysiology - Simple PAVMs : receive blood through a single artery - Complex PAVMs : receive blood through two or more arteries

Pathophysiology Pulmonary a. (rare : bronchial & intercostal a.) Large single sac or a plexiform mass of dilated vascular channels or consist of dilated and tortuous communications between artery and vein. Pulmonary v. (inferior vena cava and the left atrium) - Fragile, rupture and bleed (as the PAVM size increases) : hemoptysis or hemothorax. - Diffuse PAVMs : severe hypoxemia, challenging to treat.

Pathophysiology Right-to-left shunt 1. Hypoxemia - Blood flows directly from the pulmonary a. to the Pulmonary v. (shunt) -No effective gas exchange -Degree of shunt α severity of hypoxemia -Severe symptom : shunt exceeds 20% of the Cardiac output 2. Paradoxical emboli - Pulmonary capillary bed : remove small thrombi and bacteria - In PAVM, bypassing Pulmonary capillary bed - Transient ischemic attack, stroke, brain abscess

Etiology Hereditary Hemorrhagic Telangiectasia (HHT) -heterogenous, autosomal dominant vascular disorder -recurrent epistaxis, mucocutaneous telangiectasia, visceral involvement - Diagnosis : Curaçao criteria (at least three) (1) epistaxis (spontaneous, recurrent) (2) telangiectases (multiple at characteristic sites) (3) Visceral lesions, including, but not limited to, GI telangiectasia (with or without bleeding), pulmonary, hepatic, cerebral, and spinal arteriovenous malformations (4) family history of a first-degree relative with HHT

Etiology -Genetic Considerations and Biology 1. Gene mutation Hereditary Hemorrhagic Telangiectasia (HHT)

Etiology

Hepatopulmonary Syndrome - There is no association with the type or severity of liver dz. - Resolve after liver transplantation (Mechanisms are as yet unknown.) - Clinical triad (1)Portal hypertension with or without cirrhosis, (2) Hypoxemia : PaO2 of <70 mmHg or alveolar-arterial O2 gradient 20 mmHg while breathing room air (3) intrapulmonary vascular dilatations

Etiology Bidirectional Cavopulmonary Shunt -Surgical procedure establishing anastomoses between the vena cava and the pulmonary arteries - PAVM developed in 13 a median of 4 years after the procedure

Clinical Manifestations & Complications - Clinical feature : not uniform - Sign and symptom : hypoxemia, orthodeoxia, platypnea, worsening of V/Q mismatch (when upright) : classic traid ; dyspnea, cyanosis, clubbing

Clinical Manifestations & Complications - The most feared complications : rupture leading to Hemoptysis or hemothorax. - Less common complication : catamenial hemoptysis, congestive heart failure as a result of high output from large extrapulmonary arteriovenous malformations (primarily intrahepatic), and polycythemia secondary to chronic hypoxemia

Diagnostic Testing

Contrast Echocardiography -Visualize delayed appearance of microbubbles in the left side of the heart after three to four cardiac cycles. -Safe screening. -Sensitivity 100%, specificity ranging from 67% to 91%.

Diagnostic Testing CCT scan - Further evaluation of patients with a high suspicion of PAVM. - Small, multiple lesions and thrombosed lesions - Contrast, three dimensional reconstruction added : identifying structures

Diagnostic Testing Pulmonary Angiography - Therapeutic purposes after a diagnosis has been established - Gold standard for inconclusive cases. - Performed on all portions of the lungs.

Diagnostic Test MRI (contrast enhanced magnetic resonance angiography, CE-MRA) Advantage - Noninvasive methods - Provide precise information on the number, location, and complexity of PAVMs - Without concern about radiation exposure, and avoiding potentially nephrotoxic contrast, inherent complications of catheter angiography

Diagnostic Test MRI (contrast enhanced magnetic resonance angiography, CE-MRA) Disadventage - Expense - Potential side effects of gadolinium-based contrast in patients with renal disease -Time of the procedure. -Limited availability in some centers. -Specialized nature of the test

Diagnostic Test Quantitative Right-to-Left Shunt Assessment. 1.The 100% oxygen method. - breathing 100% oxygen for 15 to 20 min (to allow full washout of nitrogen from the alveoli) - subsequent arterial blood gas measurement of PO2 and oxygen saturation.

Diagnostic Test Quantitative Right-to-Left Shunt Assessment. 2. Radionuclide perfusion scanning - Tc-labeled macroaggregated albumin -particles pass through the lung, and shunt fraction can be calculated by radionuclide scanning over brain, kidneys, or both -Disadvantage : expensive, requiring radiation, not Uniformly available at many facilities.

Treatment and Management Percutaneous Transcatheter Embolization -Gold standard -Regardless of symptom, feeding artery of ≥ 3 mm in detected by CCT scan -Prevention of neurologic complications ( stroke and cerebral abscess from paradoxical embolism, improvement in exercise tolerance, reduction in migraine prevalence and prevention of lung hemorrhage) -Less invasive and easy to repeat -Collateralization and revascularization over time

Treatment and Management Percutaneous Transcatheter Embolization -Target : supplying artery immediately preceding the PAVM -Important to achieve as distal an embolization as possible in the feeding artery to avoid occluding branches to normal adjacent lung.

Treatment and Management Percutaneous Transcatheter Embolization - A variety of materials (by the size and complexity of the vessels) : balloons, coils( Magnetic resonance-compatible steel or platinum), vascular plugs (AVPs) : Feeding artery diameters of 3 to 9 : balloons or coils : Feeding artery diameters >8mm : coils alone, overinflated balloon impacted within a nest of coils, Vascular plugs

Treatment and Management Percutaneous Transcatheter Embolization -Complication : Device-associated complications, (downstream migration of the device) : Recanalization and collateralization ranging of 5% to 19%.

Treatment and Management Surgery -Rarely necessary -Emergency procedure to control bleeding and when loss of lung is justified -The goal : lung conservation -Lung transplantation : severe diffuse disease with severe hypoxemia and failure of TCE

Other Management Issues, Follow-up, and Pregnancy Management, F/U -Recurrence of PAVM occurs after 15% of embolizations -TTCE : not useful after embolization -CCT scan : performed 6 to 12 months after embolization and then every 3 to 5 years -For patients with untreated PAVM (because of size or suspected microscopic PAVMs) : case by case, but a period of 3 to 5 years -Recurrence of PAVMs : treated by repeat TCE. -Procedures with a risk of bacteremia : Antibiotic prophylaxis, all patients, To avoid SCUBA diving.

Other Management Issues, Follow-up, and Pregnancy Pregnancy -PAVMs often increase in size and number. -Majority of patients : normal pregnancy -Small proportion of women experienced life-threatening Complications (PAVM bleed, stroke, myocardial infarction, and pulmonary embolism) -1% of pregnancies : maternal and fetal death, all deaths -Treatment : TCE in the third trimester

Conclusion -PAVMs : abnormal vascular structures that most often connect a pulmonary artery to a pulmonary Vein (intrapulmonary right-to-left shunt). -Complication : stroke, brain abscess, hypoxemia. -Cause : idiopathic or genetic (eg, HHT m/c) -Secondary conditions : HPS and BCPS. -Screening test for PAVM : TTCE (contrast echo) -Establishing the presence of PAVM : CCT scan. -Treatment : Embolization with the use of TCE. -Lifelong follow-up : Collateralization and recanalization -Procedures with a risk of bacteremia : Antibiotic prophylaxis, all patients.