Patients with cancer carry cardiovascular risk before treatment, and treatment adds to it.

Cancer treatment is only one source of cardiovascular risk

Cardio-oncology is the cardiovascular management of patients with cancer.

Cancer and cardiovascular disease are usually taught as separate problems. They share many modifiable risk factors, including smoking, obesity and diabetes, and chronic inflammation contributes to the pathogenesis of both [1, 2]. In 20,305 adults from two community-based cohorts followed for a median of 15 years, estimated 10-year atherosclerotic cardiovascular disease risk was associated with incident cancer (HR 1.16 per 5% increment in risk, 95% CI 1.14–1.17) [3]. A patient referred to a cardio-oncology clinic has often been accumulating cardiovascular risk for years before seeing an oncologist.

Treatment then adds to that risk, and more patients now live long enough for it to matter. In the United States, five-year relative survival for all cancers combined rose from 49% for diagnoses in the mid-1970s to 70% for diagnoses in 2015–2021 [4]. Survivors carry their baseline risk, plus whatever the treatment added, for years and often decades after the cancer is gone. The two sources also interact: preexisting cardiac risk factors strongly influence subsequent treatment-related cardiotoxicity [1].

In long-term survivors, cardiovascular death can overtake cancer death

With long enough follow-up after a cancer diagnosis, cardiovascular disease becomes a competing cause of death.

Among 3.2 million patients diagnosed with cancer in the United States Surveillance, Epidemiology, and End Results program between 1973 and 2012, 38.0% died of cancer and 11.3% of cardiovascular disease [5]. In 104,028 survivors of 9 common cancers in linked English health records, the predicted cardiovascular mortality rate overtook the mortality rate from the primary cancer 12.7 years (95% CI 11.6–21.6) after a breast cancer diagnosis at age 60 to 79. In survivors diagnosed at 80 or older, it did so for all 9 cancers [6].

These registry data do not show that treatment caused those deaths. They capture cause of death but little about treatment exposure, and part of that burden would have arisen without any cancer therapy. Separating treatment-attributable risk from preexisting risk requires studies that measure both, which is one reason this program runs alongside the lab's work on inflammation.

Cancer therapies injure the heart in three unrelated ways

Cancer therapies injure the heart through largely unrelated mechanisms and on different timescales. No single test or surveillance schedule detects them all.

Immune checkpoint inhibitors block the PD-1, PD-L1 or CTLA-4 pathways that restrain T cells, and the released T cells can infiltrate the myocardium. The resulting myocarditis affects about 1% of treated patients [7], has the highest reported fatality of any immune-related adverse event [8], and presents early, at a median of 30 days after the first dose [9].

Anthracyclines are directly toxic to cardiomyocytes, and the injury is cumulative, so risk can be estimated from the total dose before treatment begins. Among 2,625 patients under prospective surveillance with serial ejection fraction measurement, 9% developed cardiotoxicity (a fall of more than 10 percentage points, to below 50%), 98% of cases occurred within the first year, and cumulative doxorubicin dose was independently associated with risk (HR 1.09 per 50 mg/m², 95% CI 1.04–1.15) [10]. Therapy directed at human epidermal growth factor receptor 2 (HER2) injures differently again: the dysfunction is not dose-dependent and is usually reversible once the drug is withheld.

Cellular therapies produce the third pattern, in which cardiac injury follows cytokine release syndrome rather than dose. In a registry of 137 adults treated with chimeric antigen receptor (CAR) T-cells, all 17 cardiovascular events (12%) occurred in patients with grade 2 or higher cytokine release syndrome, at a median of 21 days [11]. Heart function falls within days of infusion and recovers in most of those affected [12].

Each is therefore a separate research problem. Checkpoint inhibitor myocarditis is rare, early and hard to predict, and calls for surveillance with a sensitive assay. Anthracycline cardiotoxicity is dose-dependent, so risk stratification has to happen before the first dose. After chimeric antigen receptor (CAR) T-cell therapy, cardiac injury tracks cytokine release syndrome and has to be monitored through the acute illness. Little that is built for one transfers to the others.

Cardiology should prepare patients for treatment, not rule them out

Rather than ruling on who may be treated, a cardio-oncologist optimizes the patient's cardiovascular health before treatment, protects it during treatment, and monitors it after the oncologist has finished.

Hematopoietic stem cell transplantation cures diseases that nothing else will, and it is among the most physiologically demanding treatments in medicine. The cardiologist's task is to assess cardiovascular reserve, treat what can be treated first, and bring the patient to the point where the transplant can go ahead. Too often the assessment stops at a single number instead. In a 2022 survey answered by 26 transplant centers in the United Kingdom, 81% of adult centers used an ejection fraction cutoff to exclude patients. The cutoff ranged from 50% to 30%, with no justification given for the difference [13].

No guideline sets that number. The 2024 American Heart Association statement on this question, which this lab led, holds that refusing transplantation for cardiovascular reasons should be reserved for the occasional patient with severe untreatable disease or a life expectancy under a year [14]. A known risk is a reason to manage it rather than to withhold treatment. Identifying the patients at highest risk lets their physicians monitor them closely, treat early, and carry them through.

Risk persists for decades; the evidence on surveillance is thin

Cardiovascular risk persists for decades after treatment, and the evidence on how to monitor it remains thin.

Radiation gives the clearest picture, because the dose to the heart can be estimated in grays. In a population-based case-control study of 2,168 women treated with radiotherapy for breast cancer, the rate of major coronary events rose linearly by 7.4% per gray of mean heart dose (95% CI 2.9–14.5), with no apparent threshold. The increase began within 5 years and continued into the third decade [15].

How to manage that risk is far less settled than the risk itself. Guidelines recommend surveillance and state that the recommendation rests on expert consensus. For asymptomatic survivors at increased risk, the American Society of Clinical Oncology suggests an echocardiogram 6 to 12 months after treatment and makes no recommendation on how often or for how long to monitor after that [16]. No trial has shown that scheduled surveillance improves outcomes.

Circulating biomarkers would be most useful in long-term survivors, yet the evidence for them is weakest there. Measurement during treatment has an evidence base; measurement in a survivor a decade later mostly does not. The American Heart Association scientific statement on biomarkers in cancer survivors, which this lab helped write, treats those two uses separately [17]. What a given level means in a survivor, whose baseline differs from that of a typical cardiology patient, remains unclear.

Cardio-oncology is a young field, and training has not caught up

Besides running studies, building a field means deciding what the practice should be and training the people who will carry it out.

Cardio-oncology's professional society was founded in 2009, the European Society of Cardiology issued its first guideline for it in 2022 [18], and there is still no board certification in the field. Much of what a cardio-oncologist should do has had to be written down for the first time by the people doing it.

A 2014 survey found a dedicated cardio-oncology service at 27% of centers. In a 2017–2018 survey of cardiology fellowship programs, 51% of respondents were at institutions with such a service, but only 9 programs offered training specific to the field [19]. That gap between the patients who need this care and the clinicians trained to provide it is the field's bottleneck, and closing it required a training curriculum written from scratch [20].

For this lab that has meant chairing the American Heart Association statement on cardiovascular care through stem cell transplantation [14] and serving as vice chair of its statement on biomarkers in cancer survivors [17]. The lab has also made the case for the training pathway itself [19]. Consensus documents of this kind report no new data; they translate published evidence into recommendations for practice.