Cardiac Disease in Paget's Disease of Bone
Cardiac complications in Paget's disease are clinically significant but uncommon, occurring primarily in patients with extensive skeletal involvement (>15% of skeleton), where increased blood flow through pagetic bone can lead to increased cardiac output and, rarely, high-output heart failure. 1
Cardiovascular Manifestations
The Endocrine Society Clinical Practice Guideline (2014) formally recognizes several cardiovascular complications of Paget's disease 1:
Primary Cardiac Complications:
- Congestive heart failure (rare, occurs with widespread active disease)
- Increased cardiac output (compensatory response to decreased peripheral vascular resistance)
- Aortic stenosis (more common than age-matched controls)
- Generalized atherosclerosis
- Endocardial calcification
Pathophysiologic Mechanism
The cardiac involvement stems from the hypervascularity of pagetic bone, which creates multiple arteriovenous shunts. This leads to:
- Decreased peripheral vascular resistance - particularly evident in patients with >15% skeletal involvement 2
- Increased stroke volume to maintain blood pressure 2
- Compensatory increase in cardiac output 1
Research demonstrates that peripheral vascular resistance correlates inversely with disease activity (measured by urinary hydroxyproline) and is influenced by both disease extent and patient age 2.
Clinical Significance by Disease Extent
The extent of skeletal involvement is the critical determinant:
- <15% skeletal involvement: No significant cardiac abnormalities compared to controls 3
- >15% skeletal involvement:
- Cardiomegaly present
- Left ventricular hypertrophy
- Increased left ventricular mass and diastolic dimension
- Signs of depressed myocardial contractility 3
Contemporary Evidence on Cardiovascular Risk
Recent data from the CARTaGENE cohort (2026) reveals Paget's disease independently increases the risk of major adverse cardiovascular events (MACE) with a hazard ratio of 2.06 (95% CI 1.06-4.04) for 5-component MACE, even after propensity-score matching 4. Notably, this increased risk was not mediated by arterial stiffness, suggesting alternative mechanisms beyond the traditional high-output state explanation.
Clinical Reality vs. Historical Teaching
Important caveat: While high-output heart failure is the classic teaching, the guideline explicitly states that "heart failure is unusual" even with widespread active disease 1. When heart failure does occur, it represents a high-output state where the heart itself is normal but overwhelmed by decreased systemic vascular resistance 5.
Clinical Implications for Management
When to Suspect Cardiac Involvement:
- Extensive skeletal disease (>15% of skeleton)
- Elevated disease activity markers (alkaline phosphatase, urinary hydroxyproline)
- Symptoms of heart failure in absence of other cardiac disease
- Increased warmth over multiple affected bones (indicating high blood flow)
Treatment Considerations:
Critical pitfall: Traditional vasodilator therapy for heart failure may worsen high-output cardiac failure by further decreasing peripheral vascular resistance 5. The primary treatment should target the underlying Paget's disease with bisphosphonates, particularly zoledronate, which can normalize bone turnover and reduce the hypermetabolic state driving cardiac stress 1.
Monitoring:
Patients with extensive Paget's disease warrant cardiovascular assessment including:
- Baseline echocardiography if >15% skeletal involvement
- Monitoring for symptoms of heart failure
- Assessment of disease activity with alkaline phosphatase
- Consideration of cardiovascular risk factor modification given the independently increased MACE risk 4
The cardiovascular significance of Paget's disease has evolved from purely a high-output phenomenon to recognition of broader cardiovascular risk, making cardiac surveillance and aggressive treatment of active disease with bisphosphonates clinically important for patients with extensive skeletal involvement.