Building a Cardio-Onco-Hematology Program

Abstract

Purpose of Review

This review aims to outline the general principles of how to build a cardio-onco-hematology clinic, acknowledging that there are diverse practices ranging from private community settings to academic hospitals and each practice environment has to build its own program.

Recent Findings

The refinement of regimens and introduction of molecularly directed therapies have substantially increased survival rates for patients with cancer. In fact, a number of previous imminently fatal malignant disease processes have been turned into chronic diseases, such that patients now live with certain incurable cancers as they do, for instance, with rheumatoid arthritis. Improved cure rates and longer survivals have raised side effects of cancer treatments to a completely new level of significance. Cardiovascular toxicities are of particular concern given their impact on morbidity and mortality. In most extreme cases, patients might be cured from cancer but remain debilitated or die prematurely because of cardiovascular disease. Furthermore, not an insignificant proportion of cancer patients start cancer therapy with cardiovascular risk factors and diseases at baseline. With the aging of the population, this “joint venture” is only expected to increase with important implications for the management of cancer patients.

Summary

Given the need for familiarity with both, cancer and cardiovascular diseases and their ever-evolving start-of-the-art therapy and interaction potential, specialized efforts have been invoked, which may collectively be termed “onco-cardiology,” “cardio-oncology,” or “cardio-onco-hematology.” Herein, we provide recommendations for the creation and optimization of any such programmatic efforts.

Introduction

In the past, cardiology and oncology/hematology have existed as two very different and separate entities. Now, with longer cancer survival times, expanding cancer therapeutics, and treatment of increasingly older patient populations, standard care models that do not facilitate cross-disciplinary coordination of care are not adequate anymore to account for the increasing complexity of care [1, 2]. The interplay of cancer therapies with cardiovascular risk factors and diseases are of particular significance in this context, based on the fact that the cardiovascular aspects are common and with high impact on morbidity and mortality [3-5]. In isolation, the oncologist/hematologist is less likely to focus on the risks, signs, and symptoms of cardiovascular disease (CVD); this may not only delay appropriate work-up and management of cardiovascular conditions, but may lead to continuation of cancer therapy beyond the point of cardiac safety. Vice versa, the cardiologist, without an understanding of the cancer disease processes, therapies, and prognoses, may provide suboptimal recommendations that cause more harm than good to patients, e.g., premature discontinuation or suboptimal modification of lifesaving cancer therapies.

Based on the outlined imperative, multidisciplinary care teams (MDTs) have been convened for patients with cancer in recent years [6•]. Despite such efforts, a systematic review concluded that comorbidities are often not adequately presented and addressed in MDTs, leading to more conservative treatment decisions [7]. With proper knowledge, however, it is expected that even patients with comorbidities can receive optimal cancer treatments [7]. A cohort study including more than 60,000 patients in Denmark showed that an increasing number of comorbidities translated into a higher cancer-related death rate, presumably due to suboptimal receipt of oncologic treatment [8]. Furthermore, it was noted that improvement in breast cancer outcomes over time was noted only in patients without comorbidities, but not in those with comorbidities. Data from the US SEER registry show that elderly women with early stage breast cancer were four and five times more likely to die from comorbidities than from breast cancer 5 and 10 years from cancer diagnosis [9]. The most common cause of death was heart disease, and this, by itself, accounted for more deaths than breast cancer. Heart disease also has been noted as being one of the leading causes of morbidity and mortality after chemo- and radiation therapy for Hodgkin’s lymphoma [10]. This has been attributed to the cardiovascular toxicities related to cancer therapies, which can play a significant role in the induction and/or acceleration of CVDs [3, 4, 11, 12].

Importantly, the burden of pre-existing CVD in cancer patients may not be trivial and, likely, is considerably underestimated. One single-center cross-sectional assessment concluded that as many as 17–43% of patients with cancer may have one some form of CVD at baseline, including a history of heart failure in 4–12% of patients [13]. The prevalence of CVD varies considerably by type of cancer, with the highest rates among patients with lung cancer (43%) and the lowest rates in patients with breast cancer (17%). In agreement with these numbers, 10–20% of cancer survivors self-reported that they had heart disease before cancer treatment, and 20–40% reported that they later developed cardiac side effects from cancer therapy that affected their lifestyle [14]. Only 40% recalled having been counseled on cardiovascular side effects of cancer therapy and, of those who were counseled, 30–40% still had questions. Only 24–27% of patients were offered screening for cardiovascular toxicities during cancer therapy, and only 5–10% had heard about a cardio-oncology program.

Cardio-oncology programs have become increasingly popular to address the increasing needs and demands as outlined above [15•, 16, 17••]. While no study has yet shown their benefit in quantitative or even sound qualitative measures, MDT approaches in other patient populations have resulted in clinically meaningful care advances [6•]. Herein, we will discuss the steps to the build of a cardio-oncology program. While “cardio-oncology” has been the most common terminology, we prefer the term “cardio-onco-hematology” (COH) moving forward to account for the fact that often, patients with both solid as well as hematological malignancies are seen in these programs. Only very few places may have separate clinics, for instance, for patients with amyloid and for those with various solid tumors. In keeping with a previous outline [17], there are three successive milestones on the road to a successful COH program as reviewed in detail in the following (Fig. 1).

Fig. 1.

Illustration of the three milestones to a COH program

Milestone #1: Cardio-Onco-Hematology Program Vision

It might be perceived as trivial, but clear leadership and a clear vision is the first and most important step to the development of a successful program. While the wish or passion to pursue such efforts is a key ingredient, it is also critical that concrete data and feasible objectives are established early. A valid starting point is by reviewing current needs and demands of cancer patients with regard to cardiovascular tests and CVDs. Defining and prioritizing these will form the agenda and deliverables, in terms of outcome and impact assessments.

It is important to engage in cross-disciplinary discussions from the very beginning. COH programs often develop as cardiologists are noticing increasing referrals from oncologists and hematologists for tests or consultations. The perspectives of both groups, cardiology and oncology/hematology, however, should be considered when projecting what a COH program is to look like in a given environment. The COH structure should take into account the referral population as well as the practice environment (Fig. 2). For instance, will the clinic population be composed of breast cancer patients during or after anthracyclines or HER-2-directed therapies or patients with genitourinary cancers who are on VEGF inhibitors or patients with colorectal cancer who have chest pain during 5-FU-based therapy? Alternatively, will a large referral population consist of patients with multiple myeloma or amyloidosis? The specific gaps in the cardiovascular care of cancer patients at an institution should be prioritized in discussions with hematology-oncology leadership as part of the cardio-oncology program building process, specifically to accomplish improvement in areas the cancer group deems to be important.

Fig. 2.

Illustration of the interplay of the three disciplines for the patient population in the COH program defining the scope of the practice

A next step then is to model the shape of a COH clinic that will meet the existing and evolving demands of the practice and practice structure (Table 1). Is this a community care setting or a hospital setting? Is the practice weighed towards oncology/hematology or towards cardiology? What resources, including space and nursing support, are available? Depending on the answers to these questions, it can be decided if the COH program will be based in cardiology or in oncology/hematology, or jointly held, and where the best geographic location for it will be (Fig. 3). For instance, the program could be run jointly in the heart center by cardiologists within the cancer center, or it could be run by cardiologists in shared private offices.

Table 1.

Practice-based cardio-onco-hematology (COH) programs

	Low volume COH program	Medium volume COH program	Large volume COH program	Cancer center
Practice environment	Private community Smaller-sized hospitals	Medium-sized hospitals	Larger-sized hospitals	Specialized high volume center
Patient volume	< 5 per week	5–10 per week	> 10 per week	> > 10 per week
COH providers	Single COH specialists	Few COH specialists	Team of COH specialists	Focused COH specialists
Cardiology practice	General consultant cardiologists	Consultant cardiologists with specialties	Specialized care in cardiology	General and COH specialized cardiologists
Oncology/hematology practice	General and focused oncologist/hematologist	General and specialty oncology/hematology	Specialized care in oncology/hematology	Highly specialized care in oncology/hematology
Outpatient	+	+	+	+
Inpatient	−/+	+	+	+
On-call availability	−/+	(+)	+	+
Advanced cardiac tests available	Upon referral	Routinely	All the time	Variable
Heart transplantation	−	−	+	−
Training program	−	−	+	+
Research collaborations	±	±	+	+
Challenges	Educational experience	In-between stage	Organization and harmonization	Overspecialization

Fig. 3.

Outline of the three principle COH programs with corresponding pros and cons

For community physicians or private community group practices, the question often is whether a specific service line is needed, or whether these patients should be referred to larger centers. Referral and care might be complicated by geographic distances. A certain volume per week is generally required to make it worthwhile to establish a COH practice. A focus group of patients in the clinic may be informative, regarding whether or not a COH clinic would be used. If patient demand is not high, an alternative to an in-person clinic would be assigned times in the week, during which oncologists and cardiologists would both be available to set aside time to communicate by tele- or videoconference. Virtual visits would also be a possibility if demand is high but space or geography is an obstacle. If in-person visits are to occur, planning the number and timing of slots should take into account what wait times are acceptable, what tests are needed, and how the existing clinic workflow will be affected.

At hospitals, cardiologists and oncologists/hematologists often work more closely together already. However, smaller hospitals usually have less equipment and capacity, and cardiology providers are unlikely to be able to focus primarily on cardio-oncology. At larger hospitals, there is a great degree of differentiation and specialization [18•], potentially allowing for dedicated COH providers. This being said, the physical location of the COH clinic can be more controversial in larger institutions because cardiology and oncology may not be “under one roof.” Also, geographic spread can hinder communication, and with greater extents of specialization, providers may become more focused and isolated. Successful COH clinics in this setting often begin with one oncology/hematology service line (e.g., breast medical oncologists) and a small group of interested and dedicated cardiologists. These do not need to be of the same specialized group, e.g., all heart failure specialists. In fact, it can be advantageous to have a broad spectrum of providers. Defining the initial and goal volume of the clinic and how the required number of visits will be accommodated for is important. Other decisions that should be made are in regard to the question whether this will be strictly an outpatient or also inpatient practice and if curbside and on-call options will be made available. Furthermore, it would be advisable to determine and guarantee access, feasibility, and projected volume of timely imaging and other diagnostic tests and procedures needed for and as a consequence of this practice. This is an important aspect for the operation and the finances overall.

Thus, the extent of the COH service line/program should be outlined as clearly as possible, so that at initiation and throughout the life of the COH clinic, the vision for the scope and shape of the program can be summarized (and updated as needed be) as follows: The COH clinic will see … (type of patients) by … (cardiologists-oncologists-hematologists) in the …. (heart/cancer center, clinic, hospital). The appointment types might include virtual consultations as well as in-person, outpatient, and inpatient visits. Curbside and on-call options will be/will not be made available. It is projected that, based on current demand, number of patients will be seen in the COH clinic every month.

Milestone #2: Institutional Support and Organization

Defining the vision, i.e., accomplishing the first milestone, as precisely as possible will lay the best possible basis for negotiations with the practice leadership. If there is an executive decision that a COH program is worth pursuing, it will be critical to detail the expected scope of practice, providing as much data as needed for cost projections as well. Stakeholders from administration (private practice executive members) and cardiology and oncology/hematology medical practice sections should participate in this process. At hospitals, buy-in and support from division and department chairs is vital.

Allied health staff will also need to be centrally involved, including secretaries in private community offices and operation managers, staff coordinators, appointment coordinators, desk attendants, and equivalent or alternative individuals across different practice types. Ordering systems must be programmed, appointment requests have to be directed to the correct location, desk attendants need instruction on the new type of clinic, and provider schedules have to be arranged accordingly. Depending on the complexity of the practice, it may take months for these arrangements to be complete.

In this process, key questions to address are the following: which patients are eligible? What is the triage mechanism? What are acceptable wait times? What are the provider roles and responsibilities? A simple and efficient mode to address these questions is to meet the patient in their continuum of cancer care (Fig. 4). Is this a pre-chemotherapy, pre-radiation therapy, or pre-surgery visit with the outlined goals of defining risk and mitigating risk? Is this an on-therapy visit with the outlined goal of extending care from a pre-therapy visit or for treating newly developing cardiovascular complications? Or is this a post-therapy/survivorship visit with the goal of prevention and optimization of overall care. Patients with any of the outlined issues should, ideally, be eligible for a COH clinic.

Fig. 4.

Outline of the cancer treatment continuum and related different cardiovascular disease aspects and goals of COH consultations

With regard to the triage mechanism, it is a general question whether any of the above goals can be accomplished by a virtual consultation/call or whether they require a face-to-face consultation. As a general rule, if major treatment decisions are to be made, personal appointments are preferred. The same is true if the referring provider or the patient prefers a full appointment. Otherwise, very specific and confined questions can often be addressed without a formal visit. The cardiology care provider may also be able to guide the oncologist/hematologist with recommendations for drug dosages or tests to order over the phone. Availability of a triage provider might help directing these questions and regulating volume in the clinic.

Regarding patient wait times for an appointment, metrics might be different in a COH clinic than in some other clinics (Table 2). An urgent referral might ideally result in a same day appointment, as the patient needs to be started on therapy as soon as possible. The same is true for acute complications. Any COH program must have mechanisms in place to provide enough flexibility to accommodate for these cases. Ideally seen as direct consultations, some very urgent cases might also be accommodated for by virtual consultations or telemedicine. Some practices might default to cover only these very imminent needs as a starting point for a COH clinic. However, such practice is not likely to provide enough volume to develop expertise. The next step then could be to reserve a COH spot every day for any possible COH patient (rather than ad hoc emergency case). Such slots can be made available for other patients if not taken by a cancer patient within a defined time interval, providing an administratively attractive model. These humble beginnings furthermore provide a very gentle way to grow, and as more and more extra patients are seen, this model provides the visit numbers needed to justify having several slots in a row, i.e., a half-day or full-day clinic. These then provide much more structure and allow for other activities, such as teaching. Given the needs of cancer patients, a single clinic day may not be enough and one needs to be prepared to integrate flexibility of one slot a day and on-demand extra patient programs.

Table 2.

Outline of wait times for cardio-onco-hematology appointment

Wait time	Clinical scenario	Location
Emergent (immediate)	Acute coronary syndrome, flash pulmonary edema, cardiogenic shock, complete heart block, ventricular tachycardia, hypertensive emergency or initiation of cancer therapy with acutely recognized risk or any of the above outlined presentations	Hospital, ED, rarely outpatient
Urgent (same day)	Initiation of next day cancer therapy in a high CV risk patient Development of CV complications on cancer therapy with less acuity, e.g., hypertensive urgency, atrial fibrillation with RVR Newly diagnosed malignancy with need for urgent treatment Logistic reasons	Outpatient, hospital, ED
Semiurgent (within a few days)	Planned cancer therapy in a high CV risk patient Development of CV complications on cancer therapy with less acuity Uncontrolled, progressive CV conditions irrespective of therapy Newly diagnosed malignancy with need for timely therapy	Outpatient
Routine (within a few weeks)	Survivorship visits Post-hospitalization visits Routine follow-up visits	Outpatient

For inpatient services, not every group will be able to provide staffing and may not need to do so. Providers in the outpatient COH clinic may be able to cover questions as they arise, in conjunction with a general inpatient cardiology consultation team. However, it needs to be clearly expressed that if a COH program is present, it should be utilized as a resource also for inpatients. Divisions and departments should be aware of the presence of the COH program and should consult with providers of this specific service line to address consultation aspects that relate to COH issues. If the program is large enough, one person could be assigned to be on call for such questions in addition to any triage questions and e-consultation requests.

Once the aforementioned steps are taken and everything is in place, the COH program and its scope can be and should be announced publically. All possible referring providers including local cardiologists should be informed so that they can redirect patients with cancer to the new service line if they are accidentally referred to general or other subspecialty cardiology clinics. Various media tools are acceptable for general announcements (e.g., e-mail, websites, paper flyers). It is also recommended to announce the new program at division and department meetings and multidisciplinary grand rounds. The most effective mode of communication, however, is the personal route in direct contact with other care providers. The personal aspects of a working relationship are not to be disregarded; in fact, they are the most important, and the most successful COH clinics started based on personal interactions and collaborations between one cardiologist and one oncologist/hematologist.

Milestone #3: Implementation and Operation

As the second milestone is reached and the program starts, the infrastructure will be naturally tested, and major issues may declare themselves. The first 10–20 patients should be followed closely, to assess for gaps in the scheduling and triage procedure and for lapses in communication. A patient and provider survey can also provide important feedback at this early time point.

Optimal care models may include algorithms that help hematology-oncology providers with the ordering of tests prior to a patient’s visit in the COH clinic. Pre-order sets may vary by the type of reason for the COH clinic visit. For example, patients to be seen for potential cardiotoxicity will need an echocardiogram, and those referred for potential vascular toxicity may have vasoreactivity and ankle-brachial index studies, while those with palpitations may undergo a 24-h or 48-h Holter monitoring prior to the appointment. Another important pre-visit requirement is timely communication from the hematology-oncology team to the COH team regarding the details of the patient’s cancer therapy (past, planned, and ongoing). Likewise, it is important that the COH providers provide clear recommendations to both the patient and the referring provider and that the COH providers document these in the medical record. Sometimes, it can be beneficial to call the referring provider while the patient is in the room, e.g., for shared decision-making. This can be particularly valuable if CVD issues may warrant changes to the cancer treatment plan. This allows the preferences and wishes of the patient to be immediately integrated into a joint agreement between all involved parties [19, 20].

Indeed, a COH clinic thrives on optimal coordination of care centered on the individual needs of the patient. In fact, one might state that one of the most important aspects and primary reason for creating a COH clinic is to offer an integrated multidisciplinary approach to care otherwise not available [21]. This refers primarily to the interaction of the medical disciplines involved. However, the MDT may be much larger and may include a pharmacist, a nurse, and a physician assistant, at times even a nutritionist, and an exercise physiologist/therapist. This certainly depends on the location of the practice and the resources available.

It is also recommended that each cardio-oncology clinic schedules regular “tumor board-type” sessions to discuss difficult cases. All MDT members involved in the care of these patients should be engaged, reflecting on the concrete medical aspects as well as the broader context of quality of life and the patient’s preferences and goals of care. These sessions can be extended and cases discussed here could be presented at all staff multidisciplinary meetings to learn and reach consensus for institutional practices. These could be formalized as algorithms directed by or modified from expert consensus statements and guidelines published by several societies in recent times. Standardization of clinical processes and care is very important, especially for larger COH practices [19]. One would like to make sure that COH providers espouse a generally similar approach for the management of COH patient scenarios.

Other opportunities for engagement, interaction, and discussion across disciplines are grand rounds and joint conferences. Especially at teaching centers, an Onc-CV or Hem-CV journal club can provide a key opportunity to train students, residents, and fellows across disciplines. Unaccredited 1-year training programs in cardio-oncology have been launched at certain institutions, and a general outline of suggestions for level 1, level 2, and level 3 training is provided in Table 3. Moving forward, it will be important to define the requirements to function as a cardio-oncologist, including standards and qualifying tests. In this context, it should also be encouraged that COH faculty and trainees should make efforts to attend national/local COH-related conferences for personal and group education, improvement of institutional programs, collaboration (networks) across institutions, and involvement in registry/research efforts.

Table 3.

Mayo Clinic Proposal for levels 1–3 training in cardio-onco-hematology

Level	Elements
Level 1 training: exposure and basic overview: basic core curriculum	•Context: general residency and fellowship training program (“rotation”) •Goal: to gain basic exposure and understanding of cardio-oncology •Eligible: residents and fellows in internal medicine, cardiology, and oncology/hematology •Format: combination of core didactic lectures, exposure to key review articles •Exposure: clinical inpatient and outpatient patient care •Duration: minimum of 2 weeks and a maximum of 4 weeks
Level 2 training: advanced clinical experience and knowledge	•Context: general fellowship training program •Goal: to broaden the exposure and understanding in the area of cardio-oncology and to contribute, start and/or complete a research project •Eligible: fellows in internal medicine, cardiology, and oncology/hematology •Format: extension of level 1, assumption is prior level 1 experience; if not, the first month of the rotation would mirror level 1 •Exposure: clinical inpatient and outpatient patient care including time in diagnostic testing •Duration: minimum of 2 months
Start and/or complete a clinical research project leading to a publication
Level 3 training: cardio-onco-hematology fellowship	•Context: advanced, unaccredited fellowship program •Goal: to gain proficiency in this discipline for a cardio-oncology program •Eligible: fellows in cardiology, and oncology/hematology •Format: same as level 1 and 2, but for a longer duration, which allows for a path to “independence,” enhancing basic primary fellowship skills, dedicated blocks in cardiology, oncology, hematology, bone marrow transplantation, and radiation oncology, opportunity for exposure and training in areas relevant to cardio-oncology, and academic and educational contributions •Exposure: clinical inpatient and outpatient patient care including involvement in treatment and diagnostic testing •Duration: 12 months
Complete a clinical research project leading to a publication

Given that there are many unknowns in the field of COH, research activities are of key importance. Many patients in oncology/hematology are already enrolled in clinical trials. Without overburdening the individual or the system, COH programs should try to participate in registries and in clinical trials. Some will also be able to conduct their own research projects, and a few will be involved in a broader scope of investigation from basic science to being leaders of national and/or international clinical trials.

Patient education is another important aspect of COH clinics. Patients should have the opportunity to learn more about their disease processes and risk factors that are common to both cancer and CVD and how these two disease entities and their treatments affect each other. Teaching materials, such as booklets, fact sheets, and educational websites, should be made available. Practices can also consider offering individual and/or group educational sessions as well as community events.

Finally, reflecting on quality and outcomes will allow for refinement and improvement of COH programs (Fig. 2). Programs can learn from each other and new programs can benefit from the experience of older programs regarding how to overcome barriers and troubleshoot problems in establishing a COH program. Routine collection of outcome measures will also help inform standardization and accreditation of these practices. Even once established, COH programs will need to remain adaptable, striving to continuously provide best possible practice. Ongoing feedback from the referring providers and recipients of the COH service line, informal (e.g., personal communication) or formal (e.g., regular meetings), is an essential element in this regard. It is to foster the cross-disciplinary relationship and sustainability of practice, determine and improve upon gaps in care, and identify areas for collaboration on academic level. Defining specific outcome and quality metrics, as encouraged early on, might also help to define and refine the COH practice for the best possible service to the patient. With this then, one has come full cycle to meet the goals and objectives of a COH program and can testify that vision was turned into reality (Fig. 1).

Conclusion

Cardiovascular diseases in oncology and hematology patients can significantly impact outcomes. The discipline of COH is growing, and COH clinics are becoming more popular. Herein, we provided recommendations regarding helpful approaches for the creation and optimization of COH programs. There is no “one size fits all,” and every COH program must determine how to meet the unique goals and objectives of the patients and providers who will use it. Failures and successes should be tracked, and quality improvement measures should be implemented as COH clinics are entering a new era in their goal of improving the cardiovascular care and outcomes of cancer patients.