Cardiotoxicity

Cardiotoxicity is injury to the heart caused by drugs or other chemicals, including impaired contractile function, arrhythmias, and structural damage to heart muscle. It has become especially prominent in cancer therapy, where effective treatments such as anthracyclines and some targeted agents can damage the heart.

Definition

Cardiotoxicity is functional or structural injury to the heart — affecting contractility, rhythm, or myocardial integrity — caused by exposure to a drug or other chemical agent.

Scope

This topic covers the main forms of drug-induced cardiac injury — contractile dysfunction, arrhythmia, and ischemia — their mechanisms, the distinction between irreversible and potentially reversible injury, and the role of cardiac monitoring in cardio-oncology. It is a reference and educational entry, not clinical guidance.

Core questions

• What forms can drug-induced cardiac injury take?
• By what mechanisms do anthracyclines and targeted cancer therapies damage the heart?
• Which cardiotoxic injuries are reversible and which are not?
• How is the heart monitored when cardiotoxic drugs are used?

Key concepts

• Cancer therapy-related cardiac dysfunction
• Anthracycline-induced cardiomyopathy
• Type I (irreversible) vs type II (reversible) injury
• QT prolongation and arrhythmia
• Oxidative and mitochondrial myocardial injury
• Cardio-oncology monitoring

Mechanisms

Drugs injure the heart by several routes. Anthracycline chemotherapy is the classic dose-dependent cardiotoxin, causing cumulative, often irreversible myocardial injury attributed to oxidative stress, mitochondrial damage, and topoisomerase-II-beta-mediated effects in cardiomyocytes. Some targeted agents impair signalling pathways that the heart depends on, producing dysfunction that may be reversible if treatment is modified. Other drugs are cardiotoxic chiefly through electrophysiological effects, such as prolonging the QT interval and predisposing to arrhythmia. A common distinction contrasts type I injury, characterised by structural damage and irreversibility, with type II injury, characterised by functional and potentially reversible dysfunction (Henriksen, 2017; Moslehi, 2016).

Clinical relevance

Cardiotoxicity is a major reason that cardiac function is assessed before and during certain cancer treatments and is the organising concern of the field of cardio-oncology. Recognising and monitoring for cardiac injury allows the benefits of effective therapies to be weighed against cardiac risk. This entry describes how cardiotoxicity is understood and monitored at a conceptual level; it is not a source of treatment thresholds or instructions for individual patients.

Epidemiology

A range of cancer therapies carry cardiovascular risk, and a European position paper catalogued the cardiotoxic potential of chemotherapy, targeted agents, and radiotherapy and set out a framework for surveillance, reflecting the growing population of patients exposed to potentially cardiotoxic treatment (Zamorano et al., 2016; Moslehi, 2016).

History

Recognition of anthracycline cardiomyopathy in the 1970s established drug-induced heart injury as a dose-limiting toxicity of cancer therapy. The later expansion of targeted and immune-based cancer treatments broadened the spectrum of cardiotoxicity and helped give rise to cardio-oncology as a defined field (Henriksen, 2017; Zamorano et al., 2016).

Debates

How reversible is cancer therapy-related cardiac dysfunction?

Whether and when drug-induced cardiac dysfunction can recover — and how strictly type I and type II injury can be separated — affects decisions about continuing or modifying therapy, and the boundaries between reversible and irreversible injury remain debated.

Key figures

• Javid Moslehi
• Peter Henriksen
• Jose Luis Zamorano

Seminal works

• henriksen-2017
• zamorano-2016

Frequently asked questions

Which drugs are most associated with cardiotoxicity?

Anthracycline chemotherapy is the classic example of dose-dependent cardiac injury, and several targeted cancer therapies can also impair cardiac function; separately, some drugs are cardiotoxic mainly by prolonging the QT interval and provoking arrhythmias.

Is drug-induced heart injury always permanent?

Not necessarily. A common distinction separates irreversible structural injury, typified by anthracyclines, from potentially reversible functional dysfunction seen with some other agents, though the boundary is not always clear-cut.