Introduction
Cancer and cardiovascular disease are the leading causes of morbidity and mortality in Canada and the United States [
1,
2]. With early detection and improvements in cancer treatment, an increasing number of individuals are surviving a cancer diagnosis [
3]. By 2020 it is estimated there will be over 18 million cancer survivors in the United States alone [
4]. Cancer treatments, however, can have a deleterious impact on the cardiovascular system, including: myocardial dysfunction, systemic hypertension, QT prolongation, arrhythmias, thromboembolic events, pericardial and valvular heart disease [
5]. In the years after curative breast cancer treatment, post-menopausal women have a greater risk of dying of cardiovascular disease than recurrence of their cancer—in part due to baseline risk factors that may be potentiated by cancer treatment related cardiac dysfunction (CTRCD) [
6].
Cardio-oncology is an emerging speciality focused on the cardiovascular care of cancer patients and cancer survivors. The scope of cardio-oncology includes pre-cancer treatment optimization, diagnosis, and management of cardiac complications of cancer treatment during and following completion of cancer treatment. A number of position statements and guidelines in cardio-oncology have been published by international organizations including: the American Society of Clinical Oncology (ASCO), European Society of Cardiology (ESC), and the Canadian Cardiovascular Society (CCS) to provide guidance on the detection and management of CTRCD [
7‐
9]. While these efforts should be applauded, there is no data examining the uptake of these guidelines in clinical practice. Education of health care providers (HCPs), specifically, cardiologists, oncologists, general internists, primary care providers, or nurse practitioners, has been facilitated by organizations such as the Canadian Cardiac Oncology Network (CCON) and the International Cardio-Oncology Society (ICOS) through conferences and continuing medical education events; however the impact of these educational initiatives is not clear [
10,
11]. The lack of formal training programs in cardio-oncology has limited the knowledge uptake in this field [
12].
The objective of this international cardio-oncology survey was to gain a better understanding of the current knowledge of HCPs tasked with caring for cancer patients with CTRCD. We specifically targeted cardiologists and oncologists from sites within and outside of North America. Information from this study will inform cardio-oncologists and cardio-oncology training programs of existing knowledge gaps and help to direct future educational and research efforts.
Discussion
Despite the emergence of cardio-oncology programs globally, the consequences of CTRCD remain incompletely understood by many cardiologists, oncologists, and primary care providers in the community. Previous studies have explored the knowledge of HCPs in cardio-oncology; however, they were limited in scope [
16‐
18]. Barac et al. conducted a nationwide survey in the United States limited to cardiologists, while Jovenaux et al. conducted a cross-sectional survey of oncologists from across France [
17,
18]. Our group previously conducted a survey of cardiologists and oncologists in 2015, however, the majority of participants were from North America [
16].
For this study, we conducted an international survey to determine the current perception, practices, and knowledge of CTRCD among HCPs globally. While the majority of cancer care is delivered in the community, respondents were largely from academic institutions [
19]. This likely reflects the novelty of cardio-oncology as a sub-speciality, as well as the limited number of HCPs with expertise in this area. Future directions should include the education and training of HCPs in the community, as well as improvement in patient access to cardio-oncology services through use of modern technologies such as tele-medicine and tele-health [
19].
The clinical value of cardio-oncology clinics was perceived differently between HCPs. Cardiologists felt strongly that access to cardio-oncology clinics would improve prognosis for cancer patients; oncologists were less convinced. These findings are similar to a previous survey of U.S. based cardiologists [
18]. While there has been growth of cardio-oncology clinics globally, information on whether cardio-oncology clinics ‘really’ improve care is lacking. Research to define qualitative (e.g patient satisfaction) and quantitative measures (e.g completion of cancer therapy; prevention of heart failure) for cardio-oncology clinics is needed to determine the short and long term benefits) of this multidisciplinary approach.
Cardiologists were more likely than oncologists to recommend early referral of cancer patients to a cardio-oncology clinic. Studies have shown that patients with one or more cardiovascular risk factors are more likely to experience a cardiac event when exposed to cancer therapy [
20,
21]. Anthracyclines, a cornerstone of cancer treatment, are associated with increased risk of irreversible cardiotoxicity, and ultimately, cardiomyopathy [
22]. However, Cardinale et al. demonstrated that if anthracycline induced cardiotoxicity is detected early (< 6 months from insult), medical intervention can reverse cardiac damage; thereby, supporting early detection and management of high risk patients [
23]. Early referral to a cardio-oncology clinic may also improve implementation of primary prevention strategies to reduce the risk of cardiotoxicity. Primary prevention strategies for individuals at highest risk of CTRCD are currently being explored. In breast cancer patients, there is emerging evidence for prescribing beta-blockers or angiotensin converting enzyme (ACE) inhibitors upfront in patients receiving chemotherapy and/or trastuzumab for prevention of CTRCD [
24‐
26].
Our study indicated that compared to oncologists, cardiologists were more accepting of a higher risk of cardiotoxicity, especially in the setting of advanced disease. This likely reflects the expertise of the cardiologists who completed this survey. Oncologists, even in the academic setting, may feel less comfortable with this approach, perhaps due to a less comprehensive understanding of potential treatment options available to mitigate cardiotoxicity in these patients. In addition, CTRCD remains a largely unfamiliar topic among many oncologists who practice in the community. This places cancer patients at risk of permanent discontinuation of life saving or sustaining cancer therapy. Education of oncologists, cardiologists, and allied health care providers on the impact of CTRCD and strategies to mitigate and treat CTRCD should be supported by institutions.
There is limited information on the utilization of cardio-oncology guidelines in clinical practice—an area our survey attempted to address. Responses to our two clinical cases suggest that HCPs were selecting evidence-based answers more frequently than in previous studies [
16]. In the first case, almost half of respondents selected the evidence-based answer to discontinue trastuzumab in a patient with an LVEF < 50%, repeat an echocardiogram (ECHO), and continue therapy at full dose if the LVEF normalized [
15,
27]. This is an improvement from a previous survey, where only 21% of oncologists resumed trastuzumab in an asymptomatic patient with a LVEF of 40–50% [
16]. Familiarity with the literature highlighting the reversibility of trastuzumab-associated cardiotoxicity; use of biomarkers to predict cardiotoxicity in patients receiving cancer therapy; and increased comfort among cardiologists in managing cardiotoxicity, likely account for these changing results in our survey [
28‐
30]. The second case described the most common manifestation of 5-FU cardiotoxicity: angina [
31‐
33]. More oncologists decided to switch therapy to raltitrexed rather than re-challenge with 5-FU. In this case, oncologists’ preference to switch to raltitrexed is supported by current guidelines, although centers with expertise in cardio-oncology are now re-challenging patients with 5-FU using strict protocols [
9,
34,
35].
This study was not without limitations. We had a lower than expected number of responses, receiving only 160 responses despite reaching out to major cardiology and oncology associations. For future studies, personalized contact rather than open distribution of the survey link may improve response rates. We were also not able to assess regional differences due to limited responses per country. There was a component of sampling bias, where opinions reflected in this survey were primarily those of attending physicians working at academic centres. The opinions of physicians who practice in the community may suggest different values (e.g. risk tolerance for cardiotoxicity, when specialists should be involved in a cancer patient’s care) and uptake of guidelines in cardio-oncology. It is conceivable that the survey had higher uptake by specialists who were interested and experienced in the field of cardio-oncology; HCP’s were less likely to participate if they did not have confidence in their knowledge of this field. These limitations should inform clinicians on the importance of ongoing educational campaigns and updated guidelines to assist in clinical decision making.
Conclusion
Cancer and Cardiovascular disease are the leading causes of morbidity and mortality in developed countries. The complexity of caring for cancer patients who develop CTRCD or patients with pre-existing cardiovascular disease who develop cancer will continue to increase. Cardio-oncology has emerged as a new field to address the needs of these patients; however, it remains an unknown entity for many HCPs and patients. There is a need to educate HCPs and cancer patients on the impact of cancer therapy on cardiovascular health. Our survey results, although limited due to the small number of respondents, still identified knowledge gaps and differing opinions in this field. Several societies, including the International Cardio-Oncology Society (ICOS), the Canadian Cardiac Oncology Network (CCON) and the British Cardio-Oncology Society (BCOS) have emerged to foster the clinical care, education, and research in this field. Future studies should address knowledge gaps among community HCPs who are tasked with providing the majority of cancer care in North America and globally.
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