What are the cardiac contraindications to starting chemotherapy?

Cardiac Contraindications to Starting Chemotherapy

There are no absolute cardiac contraindications to chemotherapy, but severe left ventricular dysfunction (LVEF <40%), decompensated heart failure, recent myocardial infarction, unstable angina, and uncontrolled arrhythmias represent high-risk conditions requiring stabilization, alternative regimens, or dose modification before initiating cardiotoxic agents. 1, 2

Risk Stratification Before Chemotherapy Initiation

Mandatory Pre-Treatment Cardiac Assessment

All patients require comprehensive cardiovascular evaluation before starting potentially cardiotoxic chemotherapy, including assessment of cardiac structure, performance, and hemodynamics 1. This evaluation must include:

• Clinical assessment of cardiovascular risk factors and comorbidities - age, hypertension, diabetes, coronary artery disease, prior cardiovascular disease 1, 3
• Baseline ECG to screen for cardiomyopathy, conduction disturbances, and QT interval abnormalities before anthracycline, paclitaxel, or tyrosine kinase inhibitor therapy 1
• Baseline echocardiogram with LVEF measurement for all patients receiving anthracyclines (especially with CV risk factors, age >60 years, previous CVD, or prior mediastinal irradiation) and all patients receiving trastuzumab 1

High-Risk Cardiac Conditions Requiring Intervention

LVEF <54% is identified as a risk factor for development of heart failure in patients undergoing trastuzumab therapy 1, and represents a threshold requiring careful consideration:

• LVEF <40%: Chemotherapy should be stopped or not initiated, alternative treatments discussed, and heart failure therapy initiated 2
• LVEF 40-50%: Requires reassessment after 3 weeks, holding chemotherapy if confirmed, and consideration of therapy for left ventricular dysfunction 2
• Symptomatic heart failure: All patients with symptomatic LVD and LVEF <40% should be treated with ACE inhibitor plus beta-blocker before considering cardiotoxic chemotherapy 2, 4

Agent-Specific Contraindications and Precautions

5-Fluorouracil (5-FU) presents unique risks:

• Prior coronary vasospasm: 5-FU should generally be avoided in favor of alternative regimens whenever oncologically feasible, as these patients face substantially elevated risk for recurrent and potentially life-threatening cardiac events 5
• Recent acute coronary syndrome or unstable angina: Requires stabilization and ischemic workup before 5-FU administration 5
• History of cardiovascular disease: Substantially increases risk of 5-FU-induced coronary vasospasm and ischemia 1, 5, 6

Anthracyclines (doxorubicin, epirubicin) carry dose-dependent cardiotoxicity risk:

• Prior anthracycline exposure approaching cumulative dose limits (doxorubicin 500-550 mg/m² associated with 4-36% cardiotoxicity incidence) 1, 6
• Combination with trastuzumab: Increases heart failure risk to 27% compared to 2-7% with trastuzumab alone 6
• Prior mediastinal radiation: Accelerates drug-related coronary damage and increases cardiotoxicity risk 1, 6

Trastuzumab requires specific LVEF thresholds:

• LVEF <54% represents increased risk for heart failure development 1
• Previous anthracycline treatment mandates baseline echocardiogram in all patients 1

Clinical Decision Algorithm

Step 1: Identify Unstable Cardiac Conditions (Require Stabilization First)

• Decompensated heart failure
• Acute coronary syndrome or unstable angina
• Uncontrolled arrhythmias
• Recent myocardial infarction

Step 2: Measure Baseline LVEF

• LVEF ≥54%: Proceed with chemotherapy and standard monitoring 1
• LVEF 40-53%: Consider alternative regimens, cardioprotective strategies (ACE inhibitors, beta-blockers, dexrazoxane), or less cardiotoxic agents (liposomal doxorubicin) 1, 2, 4
• LVEF <40%: Defer cardiotoxic chemotherapy, initiate heart failure therapy, discuss alternative oncologic treatments 2

Step 3: Agent-Specific Risk Assessment

• For 5-FU: Screen for prior coronary vasospasm, recent ACS, or significant CAD - consider alternative regimens if present 5, 6
• For anthracyclines: Calculate cumulative dose exposure, assess for prior radiation, consider liposomal formulations in high-risk patients 1, 6
• For trastuzumab: Mandatory if prior anthracycline exposure or LVEF <54% 1, 6

Step 4: Implement Cardioprotective Strategies When Proceeding

Prophylactic interventions reduce cardiac events significantly (RR=0.31,95% CI: 0.25-0.39) 4:

• Dexrazoxane for anthracyclines (RR=0.35) 4
• Beta-blockers (RR=0.31) 4
• ACE inhibitors or angiotensin antagonists (RR=0.11) 4, 7
• Statins (RR=0.31) 4

Critical Pitfalls to Avoid

• Do not assume normal coronary angiography excludes 5-FU cardiotoxicity - endothelial injury and small vessel thrombosis may be undetectable by angiography 5
• Do not underestimate silent ischemia - detected in 6-7% of patients with stress testing, more prevalent than symptomatic cases 5, 6
• Do not rely solely on LVEF - it is not a sensitive parameter for detecting early myocardial dysfunction; Doppler-derived diastolic indexes represent earlier signs of LV dysfunction 1, 7
• Do not ignore the temporal pattern - cardiac events with 5-FU typically occur within 2-5 days of initiation, requiring vigilant early monitoring 6
• Do not overlook modifiable risk factors - hypertension, diabetes, and coronary artery disease should be optimized before treatment when possible 3

Monitoring During Treatment

Serial cardiac function monitoring is essential 2:

• Baseline, 3,6, and 9 months during treatment
• 12 and 18 months after initiation
• Cardiac biomarkers (troponin I, BNP) measured at baseline and periodically to identify at-risk patients 2, 8
• Frequent vital signs monitoring during infusion, particularly with 5-FU or paclitaxel 1

Early intervention is critical - treatment initiated within 2 months from end of chemotherapy has higher likelihood of complete LVEF recovery 2.