Leukemia, a cancer originating in the blood-forming tissues of the bone marrow, is often viewed primarily as a blood disorder. However, the disease and its subsequent treatment exert profound systemic effects, frequently impacting the cardiovascular system. This complex interplay between cancer and heart function led to the emergence of cardio-oncology, a specialized field focusing on managing these risks. Understanding how this cancer and its therapies strain the heart is important for improving long-term patient outcomes.
Direct Hematological and Cellular Consequences
The cancer creates systemic changes in the blood that directly challenge the heart’s function. A common complication is anemia, which occurs when the rapid proliferation of abnormal white blood cells crowds out healthy red blood cell production in the bone marrow. Reduced red blood cell count decreases the blood’s capacity to deliver oxygen, prompting the heart to compensate.
The heart responds by increasing its output, pumping a greater volume of blood faster to meet the body’s oxygen demand. This sustained, high-volume workload can lead to high-output cardiac failure, where the heart works excessively hard but still fails to meet tissue needs. Additionally, the massive number of white blood cells in some acute leukemias can physically thicken the blood, a state called hyperviscosity. This sluggish flow strains the heart and increases the risk of microvascular obstruction.
In rare instances, leukemic cells can physically infiltrate the structure of the heart. These malignant cells may invade the myocardium (heart muscle) or the pericardium (the sac surrounding the heart). Infiltration of the pericardium can lead to inflammation and the accumulation of fluid, known as pericardial effusion. This cellular invasion can directly impair the heart’s function and electrical signaling.
Cardiotoxicity Caused by Leukemia Treatments
Many effective therapies designed to eliminate cancer carry a risk of damaging heart tissue, known as cardiotoxicity. Anthracyclines, a long-standing class of chemotherapy agents including doxorubicin, damage heart muscle cells. The mechanism involves generating reactive oxygen species (free radicals), which cause oxidative stress and irreversible damage to mitochondria within the cells. This damage can manifest as acute toxicity during treatment or as chronic, progressive heart dysfunction years later.
Newer, more targeted therapies have revolutionized leukemia treatment but carry cardiovascular risks. Tyrosine Kinase Inhibitors (TKIs), used for chronic myeloid leukemia, are linked to hypertension and vascular damage. Some TKIs cause QTc prolongation, a delay in the heart’s electrical recovery phase, increasing the risk for serious arrhythmias. Bruton’s Tyrosine Kinase (BTK) inhibitors, used for chronic lymphocytic leukemia, are associated with an increased risk of atrial fibrillation.
Radiation therapy directed at the chest, often used before stem cell transplantation, can cause delayed cardiotoxicity. The ionizing radiation damages endothelial cells lining the blood vessels, triggering inflammation and accelerating atherosclerosis. This process, which can occur decades after treatment, leads to the hardening and narrowing of the coronary arteries. Radiation exposure also causes fibrosis, or scarring, of the heart valves and the pericardium, resulting in valvular disease and restrictive heart conditions.
Resulting Cardiovascular Conditions
The direct effects of cancer and treatment damage often result in several clinical outcomes. Heart failure is the most common serious complication, presenting either as a high-output state from chronic anemia or a low-output state from chemotherapy damage to the left ventricle. Treatment-related heart failure is characterized by a weakened heart muscle that cannot pump sufficient blood. This condition is often irreversible once symptomatic.
Arrhythmias, or irregular heartbeats, are a significant concern arising from distinct causes. Specific chemotherapy agents, such as arsenic trioxide, and targeted inhibitors can disrupt the heart’s electrical system by prolonging the QTc interval. This electrical instability can lead to a life-threatening rhythm called torsade de pointes. Systemic inflammation and electrolyte imbalances common during intensive treatment can also precipitate various atrial and ventricular arrhythmias.
Pericardial disease involves the tissues surrounding the heart, often presenting as pericardial effusion, where fluid accumulates between the pericardium layers. This accumulation can be caused by leukemic cell infiltration or as a side effect of chemotherapy drugs. If the fluid accumulates rapidly, it can compress the heart, leading to cardiac tamponade. Inflammation and scarring from radiation and chemotherapy can also cause chronic pericarditis, restricting heart movement.
Monitoring and Protecting Cardiovascular Health
To mitigate these complex cardiovascular risks, cardio-oncology has established specialized protocols for monitoring and managing patients. The process begins with a comprehensive baseline assessment before initiating any cardiotoxic therapy. This initial screening involves a detailed cardiovascular risk assessment and non-invasive imaging, such as an echocardiogram, to measure the heart’s pumping function, specifically the left ventricular ejection fraction (LVEF).
During active treatment, patients receiving high-risk drugs undergo regular surveillance to detect early damage before they become symptomatic. Periodic echocardiograms track changes in LVEF and heart strain, a sensitive measure of early muscle dysfunction. Clinicians also monitor cardiac biomarkers, such as troponin, which are proteins released when heart muscle cells are injured. An increase in troponin can signal subclinical cardiotoxicity before changes appear on imaging.
For patients at the highest risk, such as those receiving high-dose anthracyclines, cardioprotective agents like dexrazoxane may be administered. Dexrazoxane works by reducing the formation of toxic free radicals that cause mitochondrial damage in heart cells. After therapy completion, patients who received cardiotoxic treatments require lifelong, individualized follow-up care, as cardiac dysfunction can emerge years later. This long-term surveillance ensures that late-onset heart problems, such as valvular disease from prior radiation, are identified and managed promptly.