Essentials of cardio-oncology

Baseline cardiovascular risk stratification assessment

Baseline clinical assessment for cardiovascular risk factors, history of antecedent CVD and cardiotoxic therapies, physical examination, electrocardiogram and laboratory analysis are mandatory (Fig 2). Although echocardiography is the preferred baseline imaging modality, cardiac magnetic resonance (CMR) and cardiac computed tomography (CT) might also be required.

• Download figure
• Open in new tab
• Download powerpoint

Fig 2.

Cardio-oncology patient clinical trajectory. The patient at the centre is followed up by the multidisciplinary team after diagnosis and during cancer therapy. There has been a paradigm shift in cancer as a chronic disease, because some cancers have sequelae even when they are considered cured. Pretreatment cardiovascular assessment, detection and management of CVT and surveillance of survivors at higher risk for cardiovascular disease (CVD) are key roles of a cardio-oncologist. CAD = coronary artery disease; ECG = electrocardiogram.

Several risk stratification tools have been designed to grade patients into low, moderate, high or very high risk of CVT before starting treatment.⁴ Some guidelines have incorporated the Heart Failure Association/International Cardio-Oncology Society risk assessment tool.⁵ In clinical practice, even though these calculators can be useful, it is vital that clinicians adopt a systematic approach avoiding the tendency to delay oncological treatment, because therapy for cancer is time sensitive and any delay can adversely affect outcomes.

A personalised cardiac surveillance and prevention strategy, based on baseline CVT risk, type and stage of cancer and proposed oncological therapy, is formulated at first review with a cardio-oncologist. Prevention strategies include measures to optimise lifestyle choices and mitigate traditional cardiovascular risk factors. In those with high or very high risk of CVT, guideline-directed cardioprotective heart failure (HF) therapy or dexrazoxane/liposomal anthracyclines, for those treated with anthracyclines, should be considered.

Diagnosis and monitoring of CVT

Regular clinical evaluation and physical examination are recommended during cancer treatment to detect early symptoms and signs of CVT. Electrocardiograms are required in patients at risk of cardiac arrhythmias or QTc prolongation according to specific drug protocols. Cardiac serum biomarkers, such as natriuretic peptides and cardiac troponin, can be helpful to detect and monitor CVT or to attribute a cardiac cause to unspecified symptoms, such as shortness of breath.

Echocardiography can detect deterioration of LV function by measurement of ejection fraction with conventional techniques or more refined ones, such as 3D echocardiography. Assessment of global longitudinal strain, a marker of early LV subclinical dysfunction, provides additional information.⁴ CMR in patients with poor image quality or when the echocardiogram is not diagnostic can detect both functional and structural changes assessing cardiac function, cardiac invasion and ischaemia. CMR is particularly helpful for the tissue characterisation of cardiac masses and the diagnosis of myocarditis. However, CMR is limited by its availability and cost.⁶

Cardiac CT can be used to assess the coronary arteries to exclude acute coronary syndromes and assess cardiac masses. In some cases, invasive coronary angiography might be required to directly visualise the coronary arteries. Nuclear imaging can also have a role in specific situations, such as cardiac amyloidosis and interrogation of metabolic activity of suspicious cardiac masses.

Cancer treatment-related cardiac dysfunction

The cancer treatment-related cardiac dysfunction (CTRCD) that typically occurs with anthracycline and HER-2 inhibitors might present clinically or be detected in asymptomatic patients during surveillance. Temporary interruption of treatment is recommended in patients who develop moderate to severe CTRCD and rechallenge can be considered, using cardioprotective strategies with close monitoring.⁷ Cardioprotective strategies include minimising the drug dose and, in the case of anthracycline, switching to liposomal anthracycline preparations or pretreatment with dexrazoxane before each further cycle. Guideline-directed HF therapy is recommended in patients who develop symptomatic CVT or moderate to severe CTRCD. The use of an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) or angiotensin receptor–neprilysin inhibitor (ARNI), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium–glucose co-transporter 2 inhibitor (SGLT2i) is recommended, with uptitration to target doses as tolerated. Notably, most clinical trials in HF excluded patients with cancer, reflecting the use of these agents in an extrapolated manner. Frequent cardiac surveillance with imaging and serum biomarkers is recommended in all patients with CTRCD.

Myocarditis

Myocarditis is a rare but severe complication of ICI, characterised by severe cardiovascular symptoms, a new increase in troponin and electrocardiographic abnormalities (atrioventricular or ventricular conduction disorders, bradycardia and tachyarrhythmias). Interruption of ICI is recommended and treatment with high-dose methylprednisolone should be promptly initiated in patients who are haemodynamically unstable, while awaiting further confirmatory testing with echocardiogram and CMR.

Acute coronary syndrome

Diagnosis of acute coronary syndrome (ACS) is based on the same principles as in patients without cancer, including symptoms, an early 12-lead electrocardiogram, and serial measurements of troponin. Cancer treatment should be temporarily interrupted, and an individualised action plan, considering the severity of ACS, the cancer status and prognosis, is prudent. Some agents, such as fluoropyrimidines, can induce coronary vasospasm and myocardial ischaemia at rest several days later after their administration.

Arrhythmias

Chemotherapy, radiotherapy, cancer surgery, cancer itself (invasion), related electrolyte disturbances or pre-existing substrates can increase the risk of arrhythmias. Atrial fibrillation is the most prevalent arrhythmia and the risk–benefit ratio of long-term anticoagulation in patients with cancer is a major concern. It is important to realise that the CHA₂DS₂-VASC score is not validated specifically in cardio-oncology patients. Cancer therapy-induced ventricular arrhythmias are rare and are related to a prolongation of QTc leading to the development of torsade de pointes. Immediate withdrawal of any QT prolongation drug, correction of electrolyte abnormalities and close electrocardiographic monitoring are essential.

Arterial hypertension

Arterial hypertension in patients with cancer can be caused by their oncological treatments, non-cancer drugs and other factors, including stress, pain, renal impairment or metabolic factors.⁸ Given their well-established cardioprotective effects, ACEi or ARB are first-line therapies in this context.

Radiation induced-coronary artery, valve and pericardial disease

Many years after radiation therapy, damage can be detected in the coronary arteries, cardiac valves and the pericardium, especially if the cardiac chambers are in the field of therapy. Dose modulation and adequate chest shielding should be used.

Cardiac masses and infiltration

Both CMR and CT can help differentiate between tumour and thrombus in the cardiac chambers. With its ability to identify metabolic activity, positron emission tomography (PET) can help identify primary and secondary tumours.