Cardiotoxicity in Newly Diagnosed Acute Myeloid Leukemia Patients

Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy that necessitates immediate risk assessment and therapeutic intervention.

Acute myeloid leukemia (AML) is a rapidly progressing myeloid neoplasm characterized by the clonal expansion of immature myeloid-derived cells, known as blasts, in the peripheral blood and bone marrow. This expansion results in ineffective erythropoiesis and megakaryopoiesis, clinically manifesting as relatively rapid bone marrow failure compared to chronic and indolent leukemias. This leads to inadequate production of red blood cells and platelets.

Although the administration of multiagent induction chemotherapy can induce complete remission, allogeneic stem cell transplantation is the only established curative therapy. Despite advancements in therapeutic approaches, prognosis remains suboptimal, especially among the older populations.

Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Unfortunately, anthracyclines are considered the principal culprit drugs behind chemotherapy-induced cardiotoxicity. Anthracycline-induced cardiotoxicity (AIC) is classified into acute and chronic based on the time of onset, with chronic cardiotoxicity potentially occurring within a year or several years after the completion of anthracycline treatment. The cardiotoxicity is almost exclusively chronic, and only a small proportion is acute and typically reversible upon discontinuation of anthracycline treatment.

In contrast, Venetoclax, a B-cell leukemia/lymphoma-2 inhibitor, is a promising novel drug that is currently used with hypomethylating agents (HMAs) like Azacitidine or Decitabine in older patients with acute myeloid leukemia (AML). These patients are known to have a high burden of cardiovascular (CV) risk factors and comorbidities.

The toxicity profile of Venetoclax includes neutropenia, gastrointestinal issues, and diarrhea, while there is growing concern regarding its potential cardiotoxicity in patients undergoing treatment for Acute Myeloid Leukemia. High doses or prolonged use of Venetoclax may lead to serious cardiac complications, such as myocardial infarction, new-onset atrial fibrillation, and even sudden cardiac death.

Traditionally, cardiotoxicity monitoring is conducted via serial measurements of Left Ventricular Ejection Fraction (LVEF) through standard echocardiography. However, LVEF is an insensitive and late indicator; a drop in LVEF occurs only after a significant loss of myocardial reserve has already taken place, often rendering the damage irreversible.Speckle Tracking Echocardiography (STE) is an advanced, non-invasive imaging modality that quantifies myocardial deformation by tracking acoustic markers (speckles) frame-by-frame. It measures Global Longitudinal Strain (GLS), which can detect subclinical cardiotoxicity (early micro-vascular and myofibrillar dysfunction) long before any detectable decline in conventional LVEF manifests.