Chemotherapy-related cardiotoxicity: Bridging the gap between evidence and practice

Abstract

Chemotherapy-related cardiac dysfunction (CTRCD) remains a major barrier to optimal cancer survivorship, threatening quality of life and long-term outcomes. Contemporary guidelines emphasize early detection through multimodal strategies, including echocardiographic global longitudinal strain (GLS) and cardiac biomarkers, but their real-world uptake is inconsistent. In this issue, Méndez-Toro et al present a retrospective cohort from Colombia that highlights this gap, reporting a CTRCD incidence of 8.8% in high-risk oncology patients. Although the authors observed clear declines in left ventricular ejection fraction and GLS among affected patients, less than 40% underwent end-of-treatment echocardiography and only one-quarter had biomarker surveillance. The study underscores three critical lessons: Multimodal monitoring is under-utilized, reported incidence likely underestimates the true burden, and low- and middle-income countries face unique challenges in implementing structured cardio-oncology programs. These findings demand a shift from sporadic monitoring to pragmatic, risk-adapted protocols that can translate early detection into meaningful cardioprotection.

Key Words: Cardio-oncology; Chemotherapy-related cardiac dysfunction; Global longitudinal strain; Biomarkers; Echocardiography; Cancer survivorship; Low- and middle-income countries; Multimodal monitoring

Core Tip: This study shows that chemotherapy-related cardiotoxicity is underestimated when multimodal surveillance is inconsistently applied. Cardio-oncology must now move beyond sporadic imaging and biomarkers toward structured, risk-adapted protocols, particularly in low- and middle-income countries where there is a high incidence of global cancer care.

INTRODUCTION

The growing population of cancer survivors reflects remarkable advances in oncology but also brings new challenges for long-term care[1]. Cardiotoxicity, particularly chemotherapy-related cardiac dysfunction (CTRCD), has emerged as one of the most consequential late effects of cancer therapy[2]. Anthracyclines, HER2-targeted agents, and immune checkpoint inhibitors are well-established drivers of cardiac injury, with effects ranging from silent subclinical changes to overt heart failure[3]. The highest risk of cardiotoxicity occurs with anthracyclines (e.g., doxorubicin), which cause dose-dependent, often irreversible left ventricular dysfunction, and with HER2-targeted agents such as trastuzumab, which can induce reversible heart failure, particularly when combined with anthracyclines. Fluoropyrimidines (capecitabine), cyclophosphamide, and vascular endothelial growth factor inhibitors (e.g., bevacizumab, sunitinib) may provoke ischemic or hypertensive injury, while thoracic radiation increases long-term coronary and valvular risk, especially in breast cancer and lymphoma survivors[4]. Reported incidence has been as high as 44%, depending on how closely they were monitored[5]. Early detection is vital, as data from prospective cohorts show that delays of more than six months in identifying CTRCD markedly reduce the chance of functional recovery[6]. Guidelines from the European Society of Cardiology and American Society of Echocardiography now recommend a multimodal strategy that includes echocardiography with global longitudinal strain (GLS) and serial cardiac biomarkers, in addition to conventional left ventricular ejection fraction (LVEF)[7]. These tools can identify myocardial injury earlier and more reliably than LVEF alone, offering an opportunity for cardioprotective intervention before irreversible dysfunction occurs. Yet, translation of these recommendations into practice has been inconsistent, especially outside specialized cardio-oncology programs[8]. Méndez-Toro et al[9] present an important contribution from Colombia that examines how CTRCD surveillance is currently conducted in a real-world middle-income setting.

Their findings show that GLS and biomarker testing are used too little, the rate of heart damage seems low, and many hospitals face challenges following guidelines in settings with limited resources. These results raise important questions about how to improve cardio-oncology care worldwide.

MULTIMODAL MONITORING: UNDER-RECOGNIZED AND UNDER-UTILIZED

The foundation of effective cardio-oncology lies in detecting cardiotoxicity prior to progression of symptomatic heart failure[10]. Historically, surveillance has relied on LVEF, but this measure is relatively insensitive, often declining only after substantial myocardial injury has occurred[11]. In contrast, GLS and biomarkers such as troponin and NT-proBNP can reveal early, subclinical dysfunction[12]. A relative GLS reduction of ≥ 15% predicts later CTRCD with high sensitivity, and troponin elevation has been consistently associated with both ventricular dysfunction and adverse outcomes in cancer survivors[13]. In clinical monitoring, biomarker thresholds provide objective indicators of early cardiac injury. A rise in high-sensitivity cardiac troponin I or T (hs-cTnI/T) above the 99^th-percentile upper reference limit-commonly > 14 ng/L for hs-cTnT or > 34 ng/L (men) and > 16 ng/L (women) for hs-cTnI-suggests myocardial injury and should prompt closer evaluation. Similarly, NT-proBNP levels > 125 pg/mL at baseline or a > 2-fold increase during therapy are associated with developing ventricular dysfunction. Incorporating these markers alongside imaging improves detection of subclinical chemotherapy-related cardiac damage and enables earlier intervention[14,15]. Reflecting this evidence, international guidelines recommend incorporating GLS and biomarkers into baseline and follow-up assessments for high-risk patients[16]. In the Colombian study, however, the use of these modalities was limited. Less than 40% of patients had an end-of-treatment echocardiogram, and only 15.8% had GLS calculated. Biomarker surveillance was even rarer: Troponin was checked in just 20.1% of patients before chemotherapy and in 15.3% during treatment, while NT-proBNP was used in fewer than 10%. Despite this, where GLS and biomarkers were applied, they revealed clinically significant deterioration. Patients who developed CTRCD had GLS worsen from -18.4% to -14.2% and LVEF fall from 62% to 46%. These findings confirm that multimodal monitoring is not only feasible but also valuable, even if inconsistently applied. The challenge, therefore, is not whether these tools work, but how to implement them systematically in real-world practice.

INTERPRETING INCIDENCE: WHAT WE SEE DEPENDS ON HOW WE LOOK

The authors reported an overall CTRCD incidence of 8.8%. At first glance, this number seems low, especially for patients receiving high-risk chemotherapy, such as anthracyclines or anthracycline–antimetabolite combinations. However, the reported rate depends greatly on how closely patients are monitored. Prospective studies that use regular imaging and biomarker testing-like the CARDIOTOX registry-have shown cardiotoxicity rates of about 30%-40%[17]. Similarly, trials with required GLS and biomarker monitoring detect subclinical dysfunction in nearly one-third of patients[18]. The dissimilarity with the Colombian data is stark, and it reflects the adage that “we find what we look for”. This inconsistency underscores a critical point: Low incidence in the context of sparse monitoring is not reassuring. Rather, it highlights how infrequent testing can mask the true burden of disease. Importantly, the authors did observe significant functional decline in those classified as having CTRCD, but without comprehensive surveillance, many early cases likely went undetected. For clinicians and policymakers, the lesson is clear - incidence rates are only as reliable as the surveillance strategy behind them. The goal should not be to generate lower numbers but to capture subclinical disease when intervention remains effective.

The Colombian study also has some important limitations. Because it was a single-center, retrospective analysis, the results may not reflect all patient groups and could be affected by selection bias. Many patients did not have regular follow-up or complete testing, which may have led to missing cases of heart damage. The timing and technique of echocardiograms and biomarker tests were not standardized, making the findings harder to compare with larger prospective studies like the CARDIOTOX registry. Finally, the study did not fully adjust for other factors such as chemotherapy dose or coexisting illnesses. These limitations suggest that the true rate of chemotherapy-related heart dysfunction may be higher and highlight the need for larger, well-structured studies in similar settings.

IMPLICATIONS FOR LOW- AND MIDDLE-INCOME COUNTRIES: TOWARD MINIMAL VIABLE PATHWAYS

Perhaps the most important contribution of this study is its honest portrayal of practice in a middle-income setting. Cardio-oncology guidelines are often written from the viewpoint of tertiary centers in high-income countries, where GLS-capable echocardiography and serial biomarker assays are routine[8]. For much of the world, these resources are scarce or inconsistently available[19]. The Colombian experience highlights this gap and challenges the field to consider what “good” cardio-oncology looks like in constrained systems. The solution may lie in designing minimal viable pathways that balance feasibility with impact. A practical framework for low- and middle-income countries (LMICs) cardio-oncology programs should follow a clear, stepwise structure that balances feasibility and clinical yield. Table 1 outlines a simplified “minimal viable pathway” designed for settings with limited imaging capacity but access to basic laboratory assays. This model emphasizes early baseline evaluation, risk-adapted surveillance, and actionable intervention thresholds that can be implemented even in resource-constrained hospitals. This structured approach creates a low-cost, risk-adapted pathway that can be scaled across public institutions. It relies primarily on troponin testing and targeted echocardiography rather than universal GLS use, making it both feasible and evidence-aligned for LMIC healthcare systems.

Table 1 Suggested stepwise cardiotoxicity surveillance pathway for low- and middle-income countries settings.

Phase	Key actions	Recommended tools	Frequency/timing	Intervention triggers
(1) Baseline assessment (pre-chemotherapy)	Assess cardiac history, risk factors. Perform baseline ECG, echocardiography (LVEF ± GLS if available), and troponin	2D echocardiogram (GLS optional); high-sensitivity troponin	Once before treatment	LVEF < 50% or elevated troponin → consider cardiology referral, optimization before therapy
(2) Surveillance during therapy (high-risk regimens)	Repeat troponin testing at mid-cycle and end-of-cycle. Echocardiogram only if troponin rises or symptoms develop	Troponin (hs-TnI or TnT); focused echo if abnormal	Mid-therapy and end-therapy	Troponin rise > 20% from baseline or new symptoms → initiate cardioprotective therapy, repeat echo
(3) End-of-treatment evaluation	Reassess LVEF and troponin. Document change in GLS if available	Echo ± GLS; troponin	Within 2-4 weeks after therapy	GLS decline ≥ 15% or LVEF drop ≥ 10% → start ACEi/BB therapy, closer follow-up
(4) Post-treatment follow-up	Annual troponin or echo for patients with prior abnormalities or cumulative anthracycline > 250 mg/m²	Troponin; limited echo	Every 12 months	Any new troponin elevation or LVEF decline → reinitiate monitoring or therapy

LVEF: Left ventricular ejection fraction; 2D: 2-dimension; GLS: Global longitudinal strain; ACEi: Angiotensin converting enzyme inhibitor; BB: Beta blockers; hs-TnI/TnT: High-sensitivity cardiac troponin I or T.

Cost and feasibility are major barriers to widespread GLS monitoring, especially in low- and middle-income countries. GLS requires advanced echocardiography software, experienced operators, and consistent image quality - factors that increase both cost and complexity[7,10]. Many centers, particularly public hospitals, lack access to such technology or trained personnel, making routine imaging impractical. In contrast, high-sensitivity troponin assays are inexpensive, widely available, and easily repeated during chemotherapy cycles. Several studies have shown that even modest troponin rises during treatment can predict later cardiac dysfunction with reasonable accuracy[20]. A simplified troponin-based surveillance approach-for example, baseline testing followed by checks at mid- and end-therapy-could therefore serve as a feasible and cost-effective alternative in resource-limited systems. Integrating such strategies into “minimal viable pathways” would extend cardioprotection to a broader patient population while maintaining affordability and practicality.

FUTURE DIRECTIONS

The Colombian study is a strong reminder that the challenges in cardio-oncology are not only about understanding disease mechanisms but also about putting knowledge into practice. Moving forward, three key priorities stand out. First, research should focus not only on detecting heart injury but also on showing that early findings lead to action-such as earlier use of heart-protective drugs, safer chemotherapy delivery, and better survival. Randomized trials that link monitoring results to outcomes are urgently needed. Second, follow-up strategies should be based on patient risk and treatment type. Drugs like anthracyclines, HER2-targeted agents, and immune checkpoint inhibitors damage the heart in different ways, so a single approach will not work for all. Finally, equity must be central to global cardio-oncology. Building simple, affordable care pathways for low- and middle-income countries-using basic biomarker tests and clear thresholds for action-will help extend the benefits of modern cardio-oncology to more patients worldwide.

CONCLUSION

CTRCD remains a formidable challenge to cancer survivorship. The Colombian cohort underscores three enduring lessons: Multimodal monitoring is under-utilized, reported incidence underestimates true burden, and pragmatic strategies are needed to deliver cardio-oncology in resource-limited settings. The time has come to move beyond sporadic surveillance toward structured, risk-adapted, and globally scalable protocols. Only then can early detection translate into meaningful cardioprotection and improved outcomes for patients living with and beyond cancer.