Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association
Authors, Journal, Affiliations, Type, DOI
- Authors: Daniel Addison MD (Chair), Tomas G. Neilan MD MPH (Vice Chair), Ana Barac MD PhD, Marielle Scherrer-Crosbie MD PhD, Tochi M. Okwuosa DO, Juan C. Plana MD, Kerryn W. Reding PhD MPH, Viviany R. Taqueti MD MPH, Eric H. Yang MD, Vlad G. Zaha MD PhD; on behalf of the AHA Council on Cardiovascular Radiology and Intervention; Cardio-Oncology Committee of the Council on Clinical Cardiology and Council on Genomic and Precision Medicine; and Council on Cardiovascular and Stroke Nursing
- Journal: Circulation
- Affiliations: The Ohio State University (Addison), Massachusetts General Hospital (Neilan), Inova Schar Heart and Vascular (Barac), University of Pennsylvania (Scherrer-Crosbie), Rush University Medical Center (Okwuosa), Baylor College of Medicine (Plana), University of Washington (Reding), Brigham and Women's Hospital (Taqueti), UCLA (Yang), UT Southwestern Medical Center (Zaha)
- Type: AHA Scientific Statement
- DOI: 10.1161/CIR.0000000000001174
- Published: October 17, 2023; Circulation 2023;148:1271–1286
Overview
This AHA Scientific Statement defines best practices for multimodality cardiovascular imaging in patients with cancer receiving therapy, covering echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography (CCT), SPECT, and PET. The document argues that the traditional focus on LVEF alone is insufficient — newer markers such as global longitudinal strain (GLS), T1/T2 mapping, and multiparametric CMR are needed to detect subclinical cardiotoxicity across the spectrum of modern anticancer therapies including immunotherapy, HER2-targeted agents, BTK inhibitors, and CAR-T. Evidence-based tables map optimal imaging modalities by cancer therapy type (Table 1) and by clinical cardiac presentation (Table 2), and a clinical algorithm integrates multimodal imaging across the pre-, during-, and post-treatment continuum.
Keywords
AHA Scientific Statements, amyloidosis, cardiac magnetic resonance imaging, cardio-oncology, echocardiography, immunotherapy
Key Takeaways
Current Definitions of Cardiotoxicity
Cancer Therapy–Related Cardiac Dysfunction (CTRCD)
- CTRCD includes symptomatic heart failure and asymptomatic LVEF decline; most commonly defined as an absolute decrease >10 percentage points to LVEF <53%.
- More recently, GLS decline and elevation of cardiac biomarkers have also been incorporated into asymptomatic CTRCD diagnosis.
- The IC-OS harmonisation framework provides standardised definitions across cardiology and oncology.
Myocarditis
- Immune checkpoint inhibitor (ICI) myocarditis results from overactivation of T lymphocytes with inflammatory response.
- Clinical diagnosis requires significant troponin elevation + 1 major criterion (CMR evidence of myocarditis) OR 2 minor criteria (clinical syndrome, ventricular arrhythmia, LV dysfunction decline, overlap syndrome, or suggestive CMR).
- Histopathological diagnosis requires inflammatory cell infiltrate with myocyte loss.
Arrhythmias
- Defined as any significant arrhythmia during or within 6 months after anticancer treatment.
- AF, ventricular arrhythmias, and other arrhythmias are increasingly recognised toxicities.
Vascular Toxicities
- Heterogeneous pathophysiology: atherosclerosis, vasospasm, thrombosis, stroke (radiotherapy, 5-FU, ICI).
Hypertension
- Elevated BP >130/80 mmHg; on-target side effect of BTK inhibitors and VEGF pathway inhibitors.
Evidence of Imaging Parameters as Markers of Cardiotoxicity
- Imaging markers provide a way to detect toxicity before irreversible organ damage, allowing continued safe cancer treatment.
- Key parameters: LVEF, GLS (peak systolic), T1/T2 mapping — objective, reproducible, widely available.
- T1/T2 elevation after ICI therapy predicted future or recurrent MACE in 136 patients.
- Reduced GLS predicted heart failure in anthracycline- and HER2-treated patients.
- Increased left atrial volume and ventricular fibrosis predicted future AF in ibrutinib-treated patients.
- Markers can be applied before, during, and after treatment for early identification of late effects.
Use and Role of Echocardiography in Cardio-Oncology
- First-line imaging modality for cardiac function in cardio-oncology.
- 3D acquisition preferred for LVEF; GLS and RV function should also be obtained at baseline.
- Baseline LVEF is a powerful predictor of subsequent HF; patients at the lower limits of normal are also at risk.
- Anthracyclines: generally not prescribed if LVEF <30%; used cautiously (with intensive surveillance) if LVEF 30–50%.
- Repeat echocardiography at ≥250 mg/m² doxorubicin equivalent in higher-risk patients.
- GLS threshold: GLS <16% (absolute) or >15% relative decline from baseline, even with LVEF ≥53% → closer surveillance + possible cardioprotection.
- SUCCOUR trial: strain-guided vs. LVEF-guided therapy did not show clinical end-point advantage, but limitations noted (2D LVEF endpoint only; strain most useful for low-normal LVEF).
- ICI patients: Routine echocardiography not required; indicated if HF symptoms or myocarditis suspected.
- CAR-T: LVEF most often decreased during HF episodes; role not fully elucidated.
Use and Role of CMR in Cardio-Oncology
- Reference standard for cardiac chamber volumes, myocardial mass, and contractile function.
- Second-line after echocardiography — reserved for difficult sonographic windows, borderline/abnormal LVEF, or complex differentials.
- CMR strain (LV + LA deformation) useful in HFpEF and for subclinical cardiotoxicity detection.
- Multiparametric T1/T2 mapping: diagnostic and prognostic value for cardiotoxicity; native T1 and ECV capture fibrotic change in preclinical models.
- Principal indications: Confounding disease presentations (suspected myocarditis, HF of unclear origin, scar burden in uncertain cardiotoxicity, ventricular arrhythmias).
- CMR can differentiate toxic vs. ischaemic vs. inflammatory cardiomyopathy — potentially replacing multiple sequential studies.
- CMR pericardial assessment: mitral/tricuspid inflow variation, interventricular dependence, pericardial thickness, edema, and fibrosis.
- Machine learning integration may lower costs, enable rapid protocols, and enhance early mechanistic diagnosis.
Use and Role of CCT in Cardio-Oncology
- Standard test for ASCVD, cardiac masses, and pericardial imaging.
- For cancer patients at high bleeding risk, CCTA provides noninvasive alternative to invasive coronary angiography.
- Coronary artery calcium (CAC) scoring re-stratifies ASCVD risk in intermediate-risk cancer survivors; statins are underused in incidentally identified CAC.
- CAC can be derived from existing oncological CT imaging already used for cancer staging.
- For significant valvular disease: CCTA standard of care for structural intervention pre-planning (TAVR, TMVR).
- Fluoropyrimidines and ICI can mimic ACS; CCTA has extremely high negative predictive value as noninvasive alternative in cancer patients with bleeding risk or haematologic derangements.
- CCT provides LVEF assessment with ECG-triggered acquisition when other modalities are suboptimal.
Use and Role of Cardiac Nuclear Imaging in Cardio-Oncology
- MUGA scan: Third-line only — reserve when CMR, CCTA, and quality echocardiography are unavailable.
- SPECT/PET myocardial perfusion: Established role for ischaemia risk stratification; PET increasingly accessible with improved quantitative flow capability.
- ¹²³I-MIBG SPECT: Detects anthracycline cardiotoxicity before severe damage.
- FDG-PET: Most widely used tracer for tumour metabolic imaging; also used for myocardial viability and cardiac inflammation (sarcoidosis-like protocols). FDG-PET cardiac activity did not differentiate ICI myocarditis outcomes.
- Novel PET tracers: ⁶⁸Ga-DOTATOC and ⁶⁸Ga-FAPI show promise (uptake strongly associated with histological disease in small series).
- 99mTc-PYP SPECT: Greatly accelerated diagnosis and treatment initiation in suspected cardiac transthyretin amyloidosis.
- CAR-T: Degree of cytokine release syndrome correlated with FDG-PET–derived tumour burden.
Table 1 Summary — Imaging by Cancer Therapy Type
| Therapy | Echo | CMR | CCT | Nuclear | Best Practice |
|---|---|---|---|---|---|
| Anthracyclines | +++ | ++ | − | − | Baseline echo/CMR if ≥1 risk factor; consider repeat during treatment; post-Rx every 2–5 years |
| HER2-targeted | +++ | ++ | − | − | As anthracyclines |
| ICI | +++ | +++ | ++ | ++ | Baseline if ≥1 risk factor; repeat if suspected cardiotoxicity |
| CAR-T | +++ | ++ | + | − | Baseline if ≥1 risk factor; post-Rx echo/CMR within 12 months |
| BTK inhibitors | +++ | ++ | − | − | Baseline if ≥1 risk factor; post-Rx if suspected toxicity |
| VEGF | ++ | + | + | + | Baseline if ≥1 risk factor; post-Rx if suspected toxicity |
| Stem cell transplantation | +++ | + | + | + | Baseline; post-Rx for suspected toxicity; CCT/nuclear/CMR/PET if suspected ACS |
| Radiation | +++ | + | ++ | ++ | Baseline; post-Rx for suspected toxicity; CCT/nuclear/CMR/PET if suspected ACS |
| Fluoropyrimidines | ++ | + | ++ | + | CCT/nuclear/CMR/PET if suspected ACS |
| Proteasome inhibitors | ++ | ++ | − | − | Post-Rx if suspected toxicity |
Table 2 Summary — Imaging by Cardiac Presentation
| Clinical Presentation | Echo | CMR | CCT | SPECT | PET |
|---|---|---|---|---|---|
| Heart failure | +++ | ++ | + | ++ | + |
| ACS | +++ | ++ | +++ | +++ | +++ |
| Atrial fibrillation/SVT | +++ | + | + | − | − |
| Ventricular arrhythmia | +++ | +++ | + | − | − |
| Myocarditis | +++ | +++ | + | − | + |
| Pericarditis | +++ | ++ | + | − | − |
| Cardiac amyloidosis | +++ | +++ | − | +++ (99mTc-PYP) | − |
| Cardiac mass | +++ | +++ | ++ | − | + |
Paediatric Cancer Populations
-
50% of children with cancer receive cardiotoxic therapies; cardiotoxicity is a key long-term outcome limitation.
- Emphasise minimisation of radiation and contrast exposure.
- Paediatric echo should include segmental approach and extracardiac anatomical relationships.
- CMR: useful for cardiac inflammation and fibrosis + congenital/tumour anatomy; prospective data show CMR-biomarker correlation after anthracycline in children.
- CCTA/PET: fast acquisition protocols to minimise radiation.
Disparities in Cardio-Oncology Imaging
- Black patients with breast cancer have higher cardiotoxicity rates and incomplete HER2-targeted therapy vs. White patients (OR 4.61 [95% CI 1.70–13.07]).
- Black individuals and women had 3-fold increase in ICI-related cardiac events (retrospective data).
- Black race/ethnicity associated with higher cardiotoxicity prevalence in childhood cancer survivors (RR 1.68).
- Medicare claims data: decreased transthoracic echocardiography use in Black women vs. other racial groups (RR 0.92).
- Underdiagnosis and access barriers are contributing factors; dedicated cardio-oncology referral with serial imaging may mitigate disparities.
- More prospective studies in diverse populations and inclusion of underrepresented groups in oncology trials are needed.
Integrated Clinical Practice and Evidence Gaps
- Major shift from LVEF-only surveillance to integrated multimodal imaging throughout the cancer care continuum.
- LVEF alone is not sensitive enough to predict HF or detect ICI myocarditis or targeted therapy arrhythmias.
- GLS, T1/T2 mapping, and blood biomarkers add to cardiotoxicity definitions.
- Key unmet need: Oral TKIs presenting with subclinical metabolic and vascular effects lack adequate imaging biomarkers.
- Education gap: imaging in breast cancer patients at highest cardiotoxicity risk is often not performed.
- Future studies should test imaging-based strategies (echo vs. CMR) with hard clinical endpoints.
Limitations of the Document
- Most supporting studies derived from anthracycline and HER2-targeted therapy populations — evidence for newer therapies (ICI, CAR-T, BTK inhibitors) is largely small-scale and observational.
- Lacks formal RCT evidence comparing specific imaging strategies with clinical endpoints (e.g., SUCCOUR used 2D LVEF endpoint, not clinical HF).
- Rapid growth of novel cancer therapeutics means some guidance may be outdated quickly.
- Racial and sex-based disparities data are sparse and largely retrospective; cardio-oncology imaging trials have not systematically enrolled diverse populations.
- Evidence levels for many recommendations are low (small studies, retrospective designs, limited generalisability).
Key Concepts Mentioned
- concepts/Cancer-Therapy-Related-CV-Toxicity — CTRCD definitions; imaging monitoring thresholds per therapy
- concepts/Cardio-Oncology — integrated imaging framework across the cancer care continuum
- concepts/Late-Gadolinium-Enhancement — CMR fibrosis/scar in ICI myocarditis and cardiotoxicity
- concepts/Cardiac-Amyloidosis-Imaging — 99mTc-PYP SPECT for ATTR; CMR patterns
- concepts/HFA-ICOS-Risk-Stratification — baseline risk stratification informing imaging intensity
Key Entities Mentioned
- entities/Atrial-Fibrillation — arrhythmia toxicity; ibrutinib-associated AF; imaging predictors
- entities/Heart-Failure — CTRCD endpoint; LV function monitoring
- entities/ATTR-Amyloidosis — 99mTc-PYP nuclear imaging in cancer patients
Wiki Pages Updated
- wiki/sources/imaging-cardio-oncology-aha-2024.md (created)
- wiki/sourceindex.md (updated)
- wiki/wikiindex.md (updated)
- wiki/concepts/Cancer-Therapy-Related-CV-Toxicity.md (updated)
- wiki/concepts/Cardio-Oncology.md (updated)
- wiki/concepts/Cardiac-Amyloidosis-Imaging.md (updated)