What is the impact of Hereditary Hemorrhagic Telangiectasia (HHT) on cardiac function?

Impact of HHT on Cardiac Function

HHT causes high-output cardiac failure (HOCF) through massive intrahepatic arteriovenous shunting, creating a hyperdynamic circulatory state that leads to volume overload, ventricular remodeling, and ultimately heart failure with symptoms of exertional dyspnea, ascites, and edema. 1, 2

Pathophysiology of Cardiac Dysfunction

The cardiac impact of HHT stems from hepatic vascular malformations that create three distinct types of intrahepatic shunting 1:

• Hepatic artery to hepatic vein shunts bypass the normal hepatic circulation, dumping high-flow arterial blood directly into the venous system 1
• Hepatic artery to portal vein shunts increase portal pressures while simultaneously increasing cardiac preload 1
• Portal vein to hepatic vein shunts further compound the hemodynamic burden 1

Up to 78% of HHT patients develop hepatic AVMs, though only 8% become symptomatic—but when they do, the morbidity and mortality are substantial 2, 3. The massive left-to-right extracardiac shunting forces the heart into a hyperdynamic state with markedly elevated cardiac output (often >9.6 L/min) 4, 3, 5.

Clinical Manifestations

The hyperdynamic circulatory state manifests as:

• Exertional dyspnea and orthopnea from volume overload and pulmonary congestion 1, 2
• Peripheral edema and ascites from elevated right-sided pressures and hepatic congestion 1, 2
• Atrial fibrillation and other arrhythmias from atrial stretch and remodeling 2
• Progressive right heart failure if pulmonary hypertension develops secondary to chronic high flow 3

The continued peripheral tissue hypoxemia paradoxically persists despite the high cardiac output because the shunted blood bypasses normal tissue perfusion 3.

Secondary Cardiac Complications

Pulmonary hypertension develops through two distinct mechanisms in HHT:

• Post-capillary pulmonary hypertension occurs when pulmonary vessels cannot adequately dilate to accommodate the high flow from hepatic AVMs 3
• Pre-capillary pulmonary arterial hypertension results directly from HHT-related mutations in ENG and ACVRL1 genes causing congestive arteriopathy 3

Both forms, if untreated or refractory, progress to right heart failure 3.

Diagnostic Approach

Doppler ultrasonography is the first-line imaging modality to detect hepatic AVMs and grade liver involvement—it is sufficiently accurate, non-invasive, and allows risk stratification 2.

Critical diagnostic caveat: Never perform liver biopsy in proven or suspected HHT due to catastrophic hemorrhage risk from the high prevalence of liver vascular malformations 2, 6, 7.

Cardiac catheterization may reveal elevated pulmonary artery pressures (e.g., 37/13 mmHg) and markedly elevated cardiac output, confirming the high-output state 4.

Management Algorithm

Intensive medical therapy is first-line treatment and should be implemented simultaneously 2:

• Aggressively correct anemia with IV iron replacement and RBC transfusions to reduce the compensatory high-output state 2
• Salt restriction and loop diuretics to reduce preload and volume overload 2
• Beta-blockers to reduce heart rate and cardiac output 2
• ACE inhibitors or carvedilol to prevent cardiac remodeling 2
• Digoxin for rate control if atrial fibrillation develops 2
• Antiarrhythmic agents and cardioversion/radiofrequency catheter ablation as clinically indicated 2

Reserve invasive interventions only for patients failing medical management after 6-12 months 2. Transcatheter embolization of hepatic AVMs can reduce shunting and has been used successfully with concurrent cardiac output monitoring 8, 9.

Orthotopic liver transplantation is the only definitive curative option for intractable HOCF failing medical therapy, with post-operative mortality of 7-10% but long-term survival of 82-92% 2.

Anticoagulation Considerations

Bleeding in HHT is not an absolute contraindication for anticoagulation when there is a clear indication such as atrial fibrillation, mechanical valve, or venous thromboembolism 2, 7.

Prefer heparin agents or vitamin K antagonists over direct oral anticoagulants (DOACs), as DOACs may be less well tolerated due to increased bleeding risk 2. Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation wherever possible 7. Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation 7.

Screening for Concurrent AVMs

All HHT patients with cardiac issues require comprehensive screening for pulmonary AVMs, cerebral AVMs, and gastrointestinal telangiectasias, as these can complicate cardiac management and contribute to the overall hemodynamic burden 2.