Can multiple myeloma cause cardiac symptoms in older adults with pre-existing cardiovascular conditions, such as hypertension or diabetes, and elevated Beta-2 microglobulin and abnormal free light chain levels?

Can Multiple Myeloma Cause Cardiac Symptoms?

Yes, multiple myeloma can directly cause cardiac symptoms through disease-related mechanisms including cardiac amyloidosis, anemia-induced cardiomyopathy, and hyperviscosity syndrome, with these complications occurring independently of treatment effects. 1, 2

Disease-Related Cardiac Complications

Multiple myeloma itself produces cardiac symptoms through several direct pathophysiologic mechanisms:

Cardiac Amyloidosis

• Up to 15% of patients with multiple myeloma develop systemic amyloidosis, with cardiac involvement determining prognosis. 2
• Cardiac amyloidosis causes restrictive cardiomyopathy and heart failure as the primary disease manifestation. 1
• This occurs when abnormal light chains deposit in cardiac tissue, leading to progressive myocardial dysfunction. 1

Anemia and Hyperviscosity

• Multiple myeloma commonly causes severe anemia, which directly precipitates heart failure and cardiac decompensation. 1
• Hyperviscosity from elevated paraprotein levels impairs cardiac perfusion and function. 1
• These mechanisms are particularly problematic in older adults with pre-existing cardiovascular conditions. 2

High-Risk Patient Populations

Older adults with pre-existing cardiovascular conditions (hypertension, diabetes) face substantially elevated risk for cardiac complications from multiple myeloma. 2

Age-Related Vulnerability

• Multiple myeloma predominantly affects elderly patients with median age at diagnosis of 70 years. 1
• Many patients already have established cardiovascular disease or multiple risk factors at diagnosis. 2
• Advanced age independently increases susceptibility to both disease-related and treatment-related cardiac toxicity. 3

Pre-existing Cardiovascular Disease

• Patients with hypertension, diabetes, or established coronary artery disease experience exacerbated cardiac symptoms. 4
• Renal impairment from myeloma (common with elevated Beta-2 microglobulin) further compounds cardiovascular risk. 4, 2
• The combination of myeloma-related renal dysfunction and pre-existing hypertension creates a particularly high-risk scenario. 4

Clinical Manifestations

Cardiac symptoms from multiple myeloma present as:

• Heart failure symptoms including dyspnea, elevated venous pressure, lung crackles, and pedal edema. 4
• Arrhythmias including atrial fibrillation and other conduction abnormalities. 4, 5
• Ischemic symptoms from hyperviscosity or amyloid infiltration. 1
• Exercise intolerance from anemia-induced reduced cardiac output. 1

Important Clinical Pitfall

A critical error is attributing all cardiac symptoms in myeloma patients solely to treatment effects while missing underlying disease-related cardiac involvement, particularly cardiac amyloidosis. 2 Elevated free light chains and abnormal free light chain ratios should prompt specific evaluation for cardiac amyloidosis with:

• Echocardiography looking for characteristic features (increased wall thickness, granular sparkling appearance, restrictive physiology). 4
• Cardiac biomarkers (troponin, NT-proBNP) which are elevated in cardiac amyloidosis. 3
• Cardiac MRI or nuclear imaging when amyloidosis is suspected. 4

Baseline Cardiac Assessment

All multiple myeloma patients require comprehensive baseline cardiovascular evaluation before treatment initiation, particularly those with elevated Beta-2 microglobulin or abnormal free light chains. 4, 2

Essential baseline workup includes:

• 12-lead ECG to detect left ventricular hypertrophy, prior infarction, or conduction abnormalities. 4
• Echocardiography with LVEF measurement to establish baseline cardiac function and detect structural abnormalities. 4, 2
• Blood pressure monitoring (home or ambulatory) to identify uncontrolled hypertension. 4
• Assessment of cardiovascular risk factors including diabetes control, lipid levels, and renal function. 4

Treatment-Related Considerations

While the question focuses on disease-related cardiac symptoms, it's important to note that treatment compounds cardiovascular risk:

• Cardiovascular events affect up to 7.5% of individuals with multiple myeloma overall. 2
• Proteasome inhibitors (particularly carfilzomib) cause hypertension, heart failure, and ischemic events at rates of 18.1% (all grades) and 8.2% (grade ≥3). 4, 3
• Immunomodulatory drugs increase thrombotic risk requiring prophylaxis. 2, 6

The presence of pre-existing cardiovascular conditions, elevated Beta-2 microglobulin, and abnormal free light chains identifies patients requiring cardiology co-management from diagnosis. 2 This multidisciplinary approach allows early detection and treatment of cardiac complications, whether disease-related or treatment-induced, improving overall survival outcomes. 2