What is the recommended management for patients with Hereditary Hemorrhagic Telangiectasia (HHT) and cardiac issues?

Management of Hereditary Hemorrhagic Telangiectasia (HHT) and Cardiac Issues

Patients with HHT and cardiac complications should receive intensive medical therapy as first-line treatment, including correction of anemia, salt restriction, diuretics, beta-blockers, ACE inhibitors, digoxin, and antiarrhythmic agents, with invasive interventions reserved only for those failing medical management after 6-12 months. 1

Understanding Cardiac Complications in HHT

The primary cardiac issue in HHT is high-output cardiac failure (HOCF), which occurs in symptomatic patients with hepatic arteriovenous malformations (AVMs) creating massive intrahepatic shunting. 1 This hyperdynamic circulatory state results from direct artery-to-vein connections bypassing capillaries, forcing the heart to pump excessive volumes. 1

• Only 8% of HHT patients with liver involvement become symptomatic, but when they do, the clinical significance is substantial with associated morbidity and mortality. 1
• Hepatic AVMs are more common and symptomatic in females. 2
• Atrial fibrillation may develop secondary to cardiac remodeling from chronic volume overload. 1

Initial Diagnostic Evaluation

Perform Doppler ultrasonography as first-line imaging for all HHT patients to detect hepatic AVMs, as this is sufficiently accurate, non-invasive, and allows grading of liver involvement (grades 0-4 based on hepatic artery diameter, peak flow velocity, resistivity index, and peripheral hypervascularization). 1

• Never perform liver biopsy in any patient with proven or suspected HHT due to catastrophic hemorrhage risk from the high prevalence (32-74%) of liver vascular malformations. 1
• Obtain echocardiography at baseline and during follow-up for patients with severe (grade 3-4) liver AVMs to monitor hemodynamic impact. 1
• Perform right heart catheterization in patients being evaluated for liver transplantation to exclude severe pulmonary hypertension (transplant may be allowed if pulmonary vascular resistance <240 dynes·sec·cm⁻⁵). 1

Medical Management Algorithm

First-Line Intensive Medical Therapy (63% complete response, 21% partial response) 1

Implement the following simultaneously for HOCF:

• Correct anemia aggressively with IV iron replacement (oral iron often inadequate) and RBC transfusions if hemodynamically unstable or unable to maintain adequate hemoglobin despite frequent iron infusions. 1
• Salt restriction and loop diuretics to reduce preload and volume overload. 1
• Beta-blockers to reduce heart rate and cardiac output, and potentially prevent gastrointestinal bleeding from varices or telangiectasias. 1
• ACE inhibitors or carvedilol to prevent cardiac remodeling in patients with severe grade 4 liver AVMs at high risk of poor outcome. 1
• Digoxin for rate control if atrial fibrillation develops. 1
• Antiarrhythmic agents and cardioversion/radiofrequency catheter ablation as clinically indicated for arrhythmias. 1

Portal Hypertension Complications

If portal hypertension develops (ascites, variceal bleeding), treat as recommended for cirrhotic patients with beta-blockers for primary prophylaxis and endoscopic band ligation for acute variceal hemorrhage. 1

• Avoid transjugular intrahepatic portosystemic shunt (TIPS) as it increases shunting and worsens the hyperdynamic circulatory state. 1

Cholangitis Management

Treat bile duct ischemia-related cholangitis with antibiotics (biliary stenting has no role), though this complication carries a poor prognosis. 1

Anticoagulation in HHT Patients with Cardiac Issues

Bleeding in HHT is not an absolute contraindication for anticoagulation or antiplatelet therapy when there is a clear indication (e.g., atrial fibrillation, mechanical valve, venous thromboembolism). 1

Anticoagulation Strategy:

• Prefer heparin agents or vitamin K antagonists over direct oral anticoagulants (DOACs), as DOACs may be less well tolerated due to increased bleeding risk. 1, 3
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation wherever possible to minimize bleeding risk. 1, 3
• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation or are too high-risk. 1, 3
• If anticoagulation is poorly tolerated, pursue hemostatic treatments (systemic bevacizumab or local therapies) or anticoagulation modification. 1

Second-Line Therapy: Bevacizumab

For patients with HOCF and severe liver AVMs failing medical therapy, bevacizumab (an angiogenesis inhibitor) reduces cardiac index with complete response in 12% and partial response in 70%. 1

Critical Caveats for Bevacizumab:

• Unpredictable efficacy and non-negligible toxicity. 1
• Revascularization occurs following drug withdrawal, requiring ongoing maintenance therapy. 1
• Problems with wound and anastomosis healing, which could be critical in patients requiring emergency liver transplantation. 1
• Bevacizumab should be considered carefully, weighing these risks against potential benefits. 1

Invasive Interventions (Only After Medical Failure)

Judge response to intensive medical therapy within 6-12 months before considering invasive options. 1

Transarterial Embolization

• Use with extreme caution as a palliative, temporizing procedure only in severely symptomatic patients not amenable to transplant. 1
• Significant morbidity with 10% fatal complications reported. 1
• Main indication is HOCF refractory to medical therapy. 1
• Cholangiopathy is a contraindication to transarterial embolization. 1

Orthotopic Liver Transplantation (OLT)

OLT is the only definitive curative option, indicated for: 1

• Intractable HOCF failing medical therapy
• Ischemic biliary necrosis (urgent indication)
• Complicated portal hypertension

Post-operative mortality is 7-10%, with long-term survival of 82-92%. 1

Screening for Other Vascular Malformations

All HHT patients with cardiac issues require comprehensive screening for other AVMs that could complicate management:

• Pulmonary AVMs: Screen with contrast echocardiography or chest CT; treat with percutaneous transcatheter embolization regardless of feeding artery size due to paradoxical embolism risk (stroke, cerebral abscess). 3, 4, 5
• Cerebral AVMs: Screen with brain MRI. 3, 2
• Gastrointestinal telangiectasias: Evaluate with upper endoscopy if anemia is disproportionate to epistaxis severity. 2

Patients with pulmonary RLS at baseline require rescreening every 5 years, while those without pulmonary RLS can extend rescreening to 10 years. 6

Critical Pitfalls to Avoid

• Never perform liver biopsy in HHT patients—this cannot be overstated given the catastrophic hemorrhage risk. 1
• Do not rush to invasive therapies—the majority (84%) of patients respond to intensive medical management. 1
• Do not place TIPS for portal hypertension as it worsens cardiac output. 1
• Do not withhold indicated anticoagulation simply because the patient has HHT—individualize bleeding risk and consider alternatives like left atrial appendage closure. 1, 3
• Ensure all treatment decisions are made in consultation with an HHT specialized center for standardized, expert management. 1, 5