What are the vascular complications of acromegaly?

Vascular Complications of Acromegaly

Acromegaly causes a hyperkinetic syndrome with increased cardiac output and reduced vascular resistance, progressing through distinct stages of cardiac dysfunction that can ultimately lead to heart failure and death if left untreated. 1

Cardiac and Vascular Manifestations

Acromegalic Cardiomyopathy

The hallmark vascular complication is acromegalic cardiomyopathy, characterized by:

• Biventricular concentric hypertrophy due to increased cardiac myocyte width from parallel apposition of new sarcomeres 1
• Interstitial fibrosis, increased extracellular collagen deposition, myofibrillar derangement, and areas of monocyte necrosis with lymphomononuclear infiltration 1
• Left ventricular hypertrophy occurs in more than two-thirds of patients at diagnosis, with higher prevalence in patients >50 years of age 1, 2

Three-Stage Progression

The American Heart Association describes a natural progression through three distinct stages 1:

1. Early/Hyperkinetic Stage (young patients, short disease duration):

   • Biventricular cardiac hypertrophy with increased contractility
   • Increased systolic output and cardiac output
   • Reduced vascular resistance 1

2. Intermediate Stage:

   • More significant hypertrophy
   • Diastolic filling abnormalities at rest
   • Impaired cardiac performance during exercise 1

3. End Stage (late, untreated disease):

   • Impaired systolic and diastolic performance
   • Low cardiac output
   • Overt heart failure
   • May be indistinguishable from idiopathic dilated cardiomyopathy 1

Cardiac Rhythm and Conduction Abnormalities

Life-threatening ventricular arrhythmias are an established manifestation of acromegaly and contribute to sudden cardiac death. 1

• Up to 50% of acromegalic patients have complex ventricular arrhythmias on 24-hour Holter monitoring, with approximately two-thirds being repetitive 1
• Strong correlation exists between ventricular arrhythmias and left ventricular mass and disease duration (but not hormone levels) 1
• Sinus bradycardia occurs in 5.5% of patients, with bradycardia in 2.8% 3
• In patients with baseline heart rates ≥60 bpm, 23% develop heart rates <60 bpm during treatment 3

Valvular Heart Disease

Valvular heart disease is a specific complication of acromegaly and represents one of the most common causes of death in these patients. 4

Hypertension

• Hypertension is one of the most frequent cardiovascular complications 5, 6
• Occurs in 5.5% of patients in cardiac studies 3
• Aggravates the underlying acromegalic cardiomyopathy 2

Atherosclerotic and Thrombotic Complications

• Atherosclerosis and coronary artery disease develop in acromegalic patients 6, 7
• Cerebrovascular disease is a significant cause of mortality 4

Clinical Management Implications

Diagnostic Recommendations

The American Heart Association recommends testing for acromegaly in patients with dilated cardiomyopathy who have other signs and symptoms of the disorder. 1

• Serum GH and IGF-1 levels should be monitored as markers of disease activity and treatment effectiveness 3
• Cardiac assessment should include evaluation for left ventricular hypertrophy, diastolic dysfunction, and arrhythmias 1

Treatment Impact

Appropriate therapy of the primary GH excess disorder should be performed in all patients with coexisting cardiomyopathy. 1

• Normalization of GH and IGF-1 levels decreases mortality rates and improves cardiovascular outcomes 4
• Surgical management of the pituitary tumor can lead to regression of cardiac changes, especially in younger patients 1, 4
• Somatostatin analogs (octreotide and lanreotide) reduce left ventricular hypertrophy and improve ventricular arrhythmia profiles 1, 4
• Cardiac changes are more reversible in young patients with short disease duration compared to those with longer disease duration 2

Important Caveats

• Aging and long duration of exposure to elevated GH and IGF-1 levels are important determinants of cardiac abnormalities 1
• Coexistence of other cardiovascular risk factors (diabetes mellitus, hypertension) aggravates acromegalic cardiomyopathy 2, 6
• In late stages, it can be difficult to differentiate dilated cardiomyopathy secondary to acromegaly from idiopathic dilated cardiomyopathy 1
• Heart failure is the most common cause of death in patients with acromegaly 4