What is the risk of cardiomyopathy in patients with acromegaly and how is it managed?

Acromegaly and Cardiomyopathy Risk

Acromegalic cardiomyopathy is the leading cause of death in acromegaly patients, with cardiovascular disease accounting for 60% of mortality, and left ventricular hypertrophy occurring in more than two-thirds of patients at diagnosis. 1, 2

Risk Stratification and Natural History

The risk of cardiomyopathy in acromegaly follows a predictable three-stage progression that directly correlates with disease duration and age 1, 2:

Stage 1: Early/Hyperkinetic Phase

• Biventricular concentric hypertrophy with increased contractility and cardiac output 1
• Typically seen in younger patients with short disease duration 1
• Characterized by high heart rate and increased systolic output 1

Stage 2: Intermediate Phase

• More significant hypertrophy with diastolic filling abnormalities at rest 1
• Impaired cardiac performance during exercise 1
• This stage represents the transition to clinically significant dysfunction 1

Stage 3: End-Stage Disease

• Impaired systolic and diastolic performance with low cardiac output and overt heart failure 1
• At this late stage, differentiation from idiopathic dilated cardiomyopathy becomes difficult 1
• May be irreversible even with successful treatment 3

Key Risk Factors

Age over 50 years and prolonged exposure to elevated GH/IGF-1 levels are the most important determinants of cardiac abnormalities 1, 2:

• Left ventricular hypertrophy prevalence is significantly higher in patients >50 years 1, 2
• Disease duration directly correlates with severity of cardiac involvement 4
• Up to 50% of acromegalic patients have complex ventricular arrhythmias on 24-hour Holter monitoring, with strong correlation to left ventricular mass and disease duration 2

Pathophysiology

The cardiac damage results from multiple mechanisms 1:

• Myocyte hypertrophy from parallel apposition of new sarcomeres causing increased cardiac myocyte width 1
• Interstitial fibrosis and increased extracellular collagen deposition 1
• Myofibrillar derangement with areas of monocyte necrosis and lymphomononuclear infiltration 1
• Coexisting hypertension and diabetes significantly worsen the cardiomyopathy 5, 4

Management Algorithm

Diagnostic Approach

Testing for acromegaly is indicated in any patient with dilated cardiomyopathy who has other signs and symptoms of the disorder 1:

• Measure serum GH and IGF-1 levels using specific and sensitive assays 6
• Perform cardiac assessment including echocardiography for left ventricular hypertrophy and diastolic dysfunction 2
• Obtain 24-hour Holter monitoring to evaluate for ventricular arrhythmias 2
• Assess for valve abnormalities 7

Treatment Strategy

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

1. Transsphenoidal surgery is the primary treatment when an experienced surgeon is available 1, 7

   • Most cost-effective and potentially curative 1, 7
   • Can lead to regression of cardiac changes, especially in younger patients with shorter disease duration 2, 4

2. Medical therapy for persistent disease or non-surgical candidates 1:

   • Somatostatin receptor ligands (SRLs) as first-line medical treatment 1
   • Reduce left ventricular hypertrophy and improve ventricular arrhythmia profiles 2
   • May negatively affect glucose metabolism, though usually with marginal clinical relevance 1

3. Pegvisomant for inadequate response to SRLs 1:

   • Normalizes IGF-1 levels in most patients at appropriate doses 1
   • Usually has beneficial effects on glucose metabolism 1
   • Can be combined with SRLs for partial responders 1

Treatment Goals and Monitoring

Normalization of GH and IGF-1 levels decreases mortality rates and improves cardiovascular outcomes 1, 2:

• Successful control induces decreased left ventricular mass and improved diastolic function 4, 7
• Effects on systolic function are more variable, particularly in advanced disease 4
• Monitor cardiac function serially with echocardiography 5, 8
• Manage coexisting hypertension and diabetes aggressively as they worsen cardiomyopathy 1, 5

Critical Pitfalls

Early diagnosis and prompt treatment are essential because cardiac changes in younger patients with short disease duration are more reversible than in those with longer disease duration 4:

• Late-stage cardiomyopathy may be irreversible even after successful pituitary surgery, as demonstrated by case reports of young patients dying from cardiac failure despite normalized GH levels 3
• The insidious progression commonly results in delayed diagnosis when cardiac damage is already advanced 7
• Radiation therapy should be used cautiously due to reports of increased mortality and morbidity 1