Introduction

Cardio-oncology is the care of patients with cancer with cardiovascular disease, overt or occult, already established or acquired during treatment. It also involves the prevention, early recognition, and mitigation of the effects of modern cancer treatment on the cardiovascular system.

The mortality rate among patients with cancer has decreased dramatically over the last 20-30 years. However, the toxicity of conventional cancer treatment (both chemotherapy and radiotherapy) is greater than previously appreciated and is a leading cause of morbidity and mortality in survivors.¹ New "targeted therapies" are being developed at a rapid pace, many of which have recognised or unrecognised cardiovascular toxicities.

Although cardio-oncology is often regarded as synonymous with treating the cardiovascular toxicity of cancer therapies, it is important to remember that there are other interactions between cancer and heart disease with many common risk factors and disease pathways at the cellular and molecular levels.² The cardiac toxicities of cancer treatment include heart failure, cardiac ischaemia, arrhythmias, pericarditis, valve disease, and fibrosis of the pericardium and myocardium.³

Cardio-oncology services have been established in the United States and in parts of Europe, but they are still a relatively new concept in the United Kingdom and many other countries. Nevertheless, a perceived clinical need is driving several hospitals to develop formal cardio-oncology services, such as at the Barts Heart Centre, St Bartholomew's Hospital London, and University College London Hospital, and this is also reflected in several recent cardio-oncology guidelines.⁴

In this article, we explain the clinical requirement for cardio-oncology services and reflect on our experiences in setting these up at Barts Heart Centre and at University College London Hospital.

Why Do We Need Cardio-Oncology Services?

The rapid increase in the number of available anti-cancer agents, many of which have potential cardiac side effects, is increasing treatment complexity in this group of patients.⁵ A larger number of patients is surviving or even living with cancer, often receiving a series of therapies over many years that aim to maintain remission rather than achieve cure. Additionally, with an ageing population, many patients with cancer have several co-existing cardiovascular risk factors or cardiac diseases at the time of initiation of cancer therapy. Cardiovascular disease is now very often one of the principal determinants of morbidity and mortality in many patients with cancer, and thus cardiovascular screening before and during therapy is essential to decrease cardiovascular complications.⁶ Such patients need rapid access to cardiovascular investigations and assessment, and they need to be seen by cardiologists with special experience and interest in the management of cardiac conditions in patients with cancer. Having a dedicated cardio-oncology service not only provides this, but also facilitates direct communication between oncologists and cardiologists about shared patients. A cardio-oncology service can also facilitate the nuanced management of these patients in the context of the cardiology subspecialties like coronary stenting in a patient on chemotherapy and with a low platelet count. There is now emerging evidence that the presence of a dedicated cardio-oncology service within a cancer centre will improve rates of screening for cardiotoxicity within patients with cancer and hence should affect outcome in the future.⁷

Who Needs to Be Involved?

Different stakeholders need to be considered when setting up a new service; cardio-oncology is no different (Figure 1).

Figure 1: The Many Stakeholders in a Cardio-Oncology Service

The biggest challenge in setting up a successful cardio-oncology service is bringing members of all these groups together in an effective manner. The lack of formalised cardio-oncology services at other hospitals allied with the novel nature of the specialty can lead to a lack of awareness of the need for the service. It can be problematic to convince managers and key opinion leaders in the hospital of the utility of the service, especially due to the relative paucity of real-world outcome data related to cardio-oncology services. However, a cardio-oncology service enables optimal cardiac care for patients with cancer, and resources that are currently used to provide this care in an inefficient and haphazard way can be streamlined into efficient use in the cardio-oncology service. The ultimate aim would be to prevent cardiotoxicity in these patients and prevent their associated costs.

Who Needs to Know?

Publicising the value of a new cardio-oncology service is very important, and it must be done marketed to both cardiologists and oncologists. A multitude of presentations may need to be given at both oncology and cardiology meetings. In addition, the wider hospital community should be made aware of the existence of and work done by the new service. Allied healthcare staff involved in the care of these patients (for example, specialised pharmacists, clinical nurse specialists, and cardiac physiologists) should also understand the remit of the new service. Face-to-face contact with all potential users is a useful way to garner support at service inception, and hospital social media services should also be utilized to spread the word.

It is also important to publicize the service in the primary care centres associated with the hospital. Letters from the cardio-oncology service would be sent to patients' oncologists as well as their primary care physicians. Spreading awareness of the new service amongst primary care would be helpful in this context and could help provide referrals to the service for cancer survivors who may have cardiac symptoms (and who are not being followed up with in "late effects" clinics).

What Does the Service Comprise?

A full cardio-oncology service needs a number of components for both inpatient care as well as the provision of outpatient services (Table 1).

Table 1: Key Members of a Cardio-Oncology Service

Component	Function
Cardiologists trained in cardio-oncology	Cardiologists trained in cardio-oncology are required. The number of cardiologists should be sufficient to run an inpatient rota for the review of cardio-oncology inpatients. Ideally, the cardiologists in the cardio-oncology service should have a mixed background with subspecialty interests including heart failure, imaging, electrophysiology, and intervention.
Other cardiologists	Although not formal members of the cardio-oncology service, close cooperation is required with cardiology subspecialty colleagues (e.g., the head of echocardiography to develop cardio-oncology echocardiography protocols and to facilitate echocardiography provision in a one-stop clinic).
Oncologists	Interested oncologists should be part of the cardio-oncology team. Although not yet in place in the United Kingdom, the aim for the future should be cardio-oncology training open to both cardiology and oncology trainees.
Specialist nurses	Specialist nurses are invaluable in acting as a bridge between cardiologists and oncologists/specialist oncology nurses. They can help ensure that appropriate tests are booked and results are given promptly to the referring oncologists.
Research nurses	Research nurses can play a vital role in a new specialty such as cardio-oncology by managing a database of patients seen by the service and their outcomes. They can also help coordinate research projects in cardio-oncology and help in the consent-taking process.
Cardiac physiologists	Echocardiography is a key investigative modality in cardio-oncology. Cardiac physiologists performing cardio-oncology echocardiograms should be trained in 3-dimensional acquisition and in assessing global longitudinal strain. Cardiac physiologists may even run physiologist-led ejection fraction/global longitudinal strain clinics
Secretarial support	This is vital to ensure smooth booking of patients into clinic at short notice and rapid turnaround of clinic letters, which is especially important in the context of cancer care.
Manager	A manager, especially one experienced in cardiology and cancer care, can be very valuable in facilitating the various requirements for setting up a service, like organizing and keeping minutes of meetings, obtaining clinic space, allocating secretarial support, financial planning, and business case writing.

How to Run a Cardio-Oncology Clinic

For a clinic to run efficiently and effectively, a multitude of factors need to be considered:

• Time is of the essence, both from a cancer-prognosis view-point and in case life-saving/prolonging treatment is being temporarily withheld pending cardiology review. Patients should ideally be seen within a week.
• Projected patient numbers (likely to increase exponentially) to decide on number of clinics required in a week.
• Number of clinic rooms required per clinic (consultant, fellow, nurse, etc.).
• Possibility of being a one-stop clinic (i.e., offer echocardiography/cardiac magnetic resonance [CMR] imaging the same day).
• Timing of patients' appointment so that tests (electrocardiography, echocardiogram, CMR, etc.) can be done beforehand.
• Intended ratio of new patients to follow-up patients.
• Location of the clinic (i.e., consideration of a multidisciplinary clinic with oncologists).
• Ability to coordinate timings of clinic with cancer clinics (even if not physically adjacent to each other).
• Availability of phlebotomists (e.g., for Troponin and N-terminal pro-B-type natriuretic peptide measurements).
• Secretarial support to get clinic letters out quickly.

It is likely that patient numbers will be small at the beginning of the service, but numbers should be expected to increase rapidly, and this should be factored into any projections regarding doctors required in clinic, echocardiogram slots for the clinic, and the like. Flexibility is key in setting up any new service, and there needs to be a willingness to adapt quickly to meet new challenges. In addition, consideration needs to be given to the possibility of having nurse-run clinics for stable patients or even physiologist-run clinics for those patients in whom only echocardiographic monitoring is being carried out. An outline of the clinic set-up at Barts Heart Centre is shown in Table 2.

Table 2: Cardio-Oncology Clinic Set-up at Barts Heart Centre

Electrocardiography	On arrival at clinic by cardiac technician
Echocardiography	Before clinic (on same day) by small group of specially trained cardiac physiologists
Doctors	Consultants and cardio-oncology Fellow
Oncology Involvement	Oncology clinics running next door allow easy interaction and facilitate quick update of progress
Specialist Nurse Involvement	Facilitates smooth running of the clinic
Additional Services	CMR imaging, cardiopulmonary exercise test available on the day on an ad-hoc basis

What About Inpatients?

A comprehensive cardio-oncology service should provide timely advice for inpatients as required. The range of potential referral indications is wide and may include assessment of new pericardial effusions, heart failure, rhythm abnormalities, or coronary events during inpatient chemotherapy. Occasionally advice can also be sought regarding management of patients with implantable cardiac devices (pacemakers and defibrillators) receiving thoracic radiotherapy. To enable same or next day review, a requisite quorum of doctors is needed in the service. A dedicated email account may be set up to receive referrals monitored by the Cardio-Oncology specialist nurse or could come via the on-call junior cardiology staff. Close liaison between the cardio-oncology service and other cardiology colleagues is essential if specialised investigations (e.g., advanced imaging) or interventions (e.g., pericardial fluid drainage) are required.

The Role of Multidisciplinary Team Meetings

We have found that multidisciplinary team meetings are an invaluable way to achieve buy-in of a new cardio-oncology service from oncologists. They allow an interactive platform through which cardiologists can be educated about cancer care and oncologists can better understand the rationale behind the management of cardiac issues in patients with cancer. In addition, they provide an excellent opportunity to discuss cases seen in clinic to develop a local consensus for the management of patients. Face-to-face discussion on complex patients is especially beneficial in cardio-oncology given the relative lack of experience of cardiologists with state-of-the art oncology and vice-versa. The presence of cardio-oncology and oncology specialist nurses as well as specialised oncology pharmacists in multidisciplinary teams is very helpful because their input allows a variety of viewpoints to be taken into consideration.

Protocols

There are a few cardio-oncology guidelines currently published,^4,8-14 and more are currently being written. It is useful to have departmental protocols allied to these guidelines to guide local cardio-oncology practice. Such protocols can include the following:

• Cardiovascular risk assessment to determine those patients who need cardio-oncology review; consider using established risk scoring systems and modifying accordingly
• Cardiovascular monitoring of patients on cardiotoxic therapy
  • Anthracyclines
  • Trastuzumab
  • Tyrosine kinase inhibitors
  • Vascular endothelial growth factor inhibitors
• Coronary intervention in patients with cancer
• Arrhythmias and pacing in patients with cancer
• Echocardiography in the monitoring of patients on cardiotoxic cancer therapy
• New oral anticoagulants in patients with cancer

Should Data Be Collected?

A very important component of any new service is being able to audit practice to determine if patient outcomes are changing for the better. This is especially required in a new service because there is a need to demonstrate need and clinical effectiveness. Collecting data on patients seen by the service creates an invaluable resource to better understand this new patient cohort and the role of interventions in it. A research nurse or specialist cardio-oncology nurse is invaluable in this regard. In addition to audit for service and clinical governance purposes, cardio-oncology is an area ripe for research because it is a developing specialty. Numerous research areas can be considered, ranging from determining the benefit gained with early cardioprotection (e.g., with betablockers and angiotensin-converting enzyme inhibitors) in patients seen in the cardio-oncology clinic to assessing the effectiveness of cardiac resynchronization therapy in appropriate patients with cardiotoxicity. Because cardio-oncology is a growing field, collaboration with other centres is beneficial and will allow multi-centre trials to run to increase the evidence base in cardio-oncology. We would also advocate involvement from cardiology in clinical trials of new cancer treatments with potential cardiotoxic side effects to ensure that adverse events are detected and treated early.

Continuing Professional Development and Training in Cardio-Oncology

Cardio-oncology conferences play a key role in meeting continuing professional development requirements. Multidisciplinary team meetings also play a role in continuing professional education. It is also important to educate others in the hospital about the service and about new developments in the field. Training junior doctors is an important part of any specialty; fellowships in cardio-oncology both within training and potentially post-certification allow specialization in cardio-oncology.^15,16 We hope that fellowships would attract applicants from both cardiology and oncology training programmes, and a formal curriculum and syllabus will need to be formulated to cater to these.

Communication Skills

The pivotal role of communication when setting up a new service cannot be over-stressed. Clear communication and elucidation of service goals with all stakeholders will help to clarify the purpose of the service to all and allow the service to grow and fulfil its potential. Buy-in from different stakeholders is key and requires a lot of time and effort. Good communication skills, unsurprisingly, significantly aid this process and will play a large role in determining whether the service is successful.

Conclusion

Cardio-oncology is a developing specialty. Rapid, coordinated specialised care for the cardiac needs of patients with cancer will likely improve the care we give these patients. Further experience and research is required to determine if cardio-oncology services can improve patient outcomes and improve efficiency.

Acknowledgments

The author would like to acknowledge the instrumental role played by the members of the cardio-oncology services at Barts Heart Centre (Drs. Charlotte Manisty, Mark Westwood, Simon Woldman, and Tom Crake and Specialist Nurse Ms. Meredith Maxwell) and University College London Hospital (Drs. Malcolm Walker and Robin Chung).

References

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Keywords: Cardiotoxicity, Cardiovascular Diseases, Physicians, Primary Care, Risk Factors, Pharmacists, Nurse Clinicians, Inpatients, Platelet Count, Ambulatory Care, Heart Failure, Pericardium, Arrhythmias, Cardiac, Myocardium, Pericarditis, Primary Health Care, Referral and Consultation

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