12.3 Cardiovascular Effects

TCO IV.A.3 tests cardiovascular acute, chronic, and late effects of pediatric cancer therapy. It is not the emergency chapter for arrhythmias, tamponade resuscitation, or acute chest syndrome. Those full playbooks live later. Here the CPHON nurse tracks cumulative anthracycline dose, reads the echocardiogram schedule, teaches heart-failure signs that look like feeding problems, and knows when tretinoin, arsenic trioxide, dinutuximab, or chimeric antigen receptor T-cell (CAR-T) therapy has turned the lungs and blood pressure into a leak.

A 6-year-old after doxorubicin who sweats through every bottle, a teenager with Hodgkin lymphoma who had mediastinal radiation plus an anthracycline, and a child with acute promyelocytic leukemia (APL) who gains two kilograms and desaturates on tretinoin are the same domain at different clocks.

Anthracyclines, echoes, and chest radiation

Doxorubicin, daunorubicin, idarubicin, and the related agent mitoxantrone injure myocytes in a cumulative, doxorubicin-equivalent dose. Acute arrhythmias or pericarditis can occur, but the signature injury is dilated cardiomyopathy that may appear during therapy or years later. Young age at exposure, female sex in some series, and chest radiation add risk. Do not memorize a single milligram-per-square-meter cutoff as ONCC fact; pediatric protocol caps differ. Your job is to record the running total on the treatment summary, protect protocol echocardiographic surveillance (shortening fraction or ejection fraction as the center reports), and not skip the echo because the child "looks well" or because therapy has ended.

Dexrazoxane appears as a cardioprotectant on some pediatric protocols. Afterload reduction—often an angiotensin-converting-enzyme (ACE) inhibitor such as enalapril, or another agent cardiology chooses—is given as ordered when function falls or as prevention on selected pathways. Do not start or stop these medicines from a website. Chest radiation (Hodgkin mediastinal fields, left-chest or TBI exposure) adds valvular, coronary, and restrictive risk across the survivor's life. Combined anthracycline-plus-radiation survivors need lifelong cardiology, not a one-time "normal echo after last cycle."

Pediatric heart-failure signs—not adult ankle edema

Children in congestive heart failure (CHF) rarely present like older adults with pitting pretibial edema as the first sentence. Teach families and chart:

• Infants: poor feeding, prolonged feeding, diaphoresis with feeds, tachypnea, failure to gain weight.
• Toddlers and school-age children: unexplained tachycardia, tachypnea, fatigue, abdominal pain or nausea, and hepatomegaly from hepatic congestion.
• A gallop, increased work of breathing, and poor perfusion are later bedside signs.

A 6-year-old whose liver edge is down, whose resting heart rate is well above baseline, and who has stopped finishing meals after a high anthracycline block is a cardiac patient until the echo says otherwise. Peripheral edema can appear, but waiting for adult-style ankle swelling misses the child.

Activity restrictions after anthracycline follow cardiology, not the physical-education teacher and not a blanket lifetime ban invented on the unit. Some children with recovered function still have isometric or competitive-sport limits; others are cleared with surveillance. Document the cardiology letter. A school tournament is not the place to discover a falling shortening fraction.

High-dose cyclophosphamide, differentiation syndrome, and cytokine leak

High-dose cyclophosphamide in HSCT conditioning can cause acute hemorrhagic myocarditis and pericarditis. Watch tachycardia, chest pain, a new rub, increasing heart size, and tamponade clues (muffled sounds, hypotension, pulsus paradoxus). That is a signpost to urgent evaluation—not a chapter-length tamponade algorithm here.

Tretinoin (all-trans retinoic acid, ATRA) and arsenic trioxide used for APL can trigger differentiation syndrome: fever, weight gain, edema, hypotension, pulmonary infiltrates, and pleural or pericardial effusions in the first days to weeks. Hold tretinoin and arsenic per protocol, give dexamethasone as the pathway orders, and support oxygen and blood pressure. This is a cardiopulmonary leak, not "just fluids from the IV." Extra arsenic to "clear blasts faster" is the wrong instinct when the child is drowning in capillary leak.

Dinutuximab (anti-GD2 immunotherapy for high-risk neuroblastoma) causes capillary leak, hypotension, hypoxia, and severe pain (opioid infusions are expected). CAR-T therapy causes cytokine-release syndrome (CRS) that can look like the same leak plus fever; the dedicated CRS emergency section owns titration of tocilizumab and intensive-care transfer. In this chapter, recognize weight up, blood pressure down, lungs wet as immunotherapy leak, stop or hold per protocol, and do not attribute it to ordinary anthracycline cardiomyopathy on day 2 of dinutuximab.

Hypertension, QTc, and what you signpost

Hypertension is common on corticosteroids and on calcineurin inhibitors (tacrolimus, cyclosporine) after transplant. Use a correctly sized cuff, trend readings, and give antihypertensives as ordered. Pain and anxiety raise blood pressure too, but do not ignore a sustained high reading because the child is "just on steroids." Severe hypertension plus visual change, seizure, or headache signposts PRES—an emergency-chapter problem.

QTc prolongation is a classic arsenic trioxide watch and also occurs with some antiemetics (notably intravenous ondansetron in higher-risk settings) and other QT-active medicines. Keep potassium and magnesium replete, obtain protocol electrocardiograms, and hold the offending infusion when the team sets a QTc threshold. Torsades and unstable arrhythmias are signposted to the arrhythmia emergency section; this chapter is the monitoring and electrolyte work that keeps the child off that path.

The CPHON product is a family that can describe poor feeding, a fast heart rate, and a big liver as reasons to call, a treatment summary that actually lists doxorubicin-equivalents and chest-radiation fields, an echo that was not skipped, and a nurse who holds tretinoin or dinutuximab when the leak starts rather than waiting for adult ankle edema.