Rationale for setting up a cardio-oncology unit: our experience at Mayo Clinic
© Barros-Gomes et al. 2016
Received: 22 December 2015
Accepted: 6 April 2016
Published: 19 April 2016
The diagnosis and management of cardiovascular complications have become a clinical concern for oncologists, cardiologists, surgeons, interventional radiologists, radiation therapy physicians, internists, nurses, pharmacists, administrators, and all the stakeholders involved in the care of cancer patients. Anticancer therapies have extended the lives of patients with cancer, but for some this benefit is attenuated by adverse cardiovascular effects.
This review article aims to provide an overview of the rationale of setting up a cardio-oncology unit and reflect on our own experience establishing this service, and conclude with some fundamental aspects of consideration for evaluation and management of patients with cancer and cardiovascular diseases.
Cardiotoxicity can lead to congestive heart failure and cardiac death. In fact, chemotherapy-related cardiac dysfunction may carry one of the worst prognoses of all types of cardiomyopathies, and has a profound impact on morbidity and mortality in oncology patients. Other complex clinical situations involve cancer patients who might benefit from a highly curative drug in terms of cancer survival but face limitations of its administration because of concomitant cardiovascular diseases. Indeed, the balance between the benefits and risks of the cancer therapy regimen in the context of the cardiovascular status of the individual patient can sometimes be extraordinarily challenging. A subspecialty with a multidisciplinary integrative approach between oncologists, hematologists, cardiologists, among others has thus emerged to address these issues, termed cardio-oncology. Cardio-oncology addresses the spectrum of prevention, detection, monitoring and treatment of cancer patients with cardiovascular diseases, or at risk for cardiotoxicity, in a multidisciplinary manner. In this field, cardiologists assist oncologists and hematologists with cardiovascular recommendations. This can be mediated through e-consultations or face-to-face evaluations.
Cardio-oncology is a subspecialty that assists in the overall care of cancer patients with and without cardiovascular disease in an interdisciplinary fashion. We believe that this partnership of sharing responsibilities and experiences among health-care team members can potentially decrease cancer therapeutics-related cardiovascular complications and improve clinical outcomes.
KeywordsCardio-oncology Cardiotoxicity Cardiovascular risk factors Multidisciplinary Cardio-oncology program Electronic medical records
Population growth and ageing as well as improvements in early diagnosis and anticancer therapies has led to a projected nearly 19 million cancer survivors in the United States alone by the year 2024 [1–3]. As successful anticancer therapies are developed, the benefit comes with an increased number of cardiovascular complications [4–6]. In the past decades, the risk of congestive heart failure (CHF) with high cumulative dose of anthracyclines was found to be from 3 to 26 % [6–11]. With improved knowledge and reduction of the total anthracycline-dose, this cardiotoxicity risk of anthracyclines has been reduced to nearly 2-3 % over a time period that extends at least 5 years , but with the increased incidence and survival rates of cancer patients in an aging population that is at greater risk for complications with chemotherapy, the number of patients with cardiac complications remains high [1, 3, 5, 13, 14]. Although it has been extremely difficult to know the incidence and prevalence of chemotherapy-induced cardiotoxicity (due to limitations on the definition, the lack of reportable data regarding cardiotoxicity, and the presence of selection bias in recruiting special populations, etc) , this has also been outlined in a cohort of patients referred for endomyocardial biopsy that chemotherapy-induced cardiomyopathy carries one of the worst prognoses of all types of cardiomyopathies . Additionally, there are other chemotherapeutic- and radiotherapeutic-related cardiovascular complications besides overt cardiac dysfunction that can negatively impact the overall outcome of cancer patients, including hypertension, ischemia, and arrhythmias [5, 17–19].
Therefore, early recognition of cancer therapy-related toxicity has become a clinical concern for hematologists, oncologists, and cardiologists [12, 20, 21]. A subspecialty that includes an integrative multidisciplinary approach to this issue has established, termed cardio-oncology [22–24]. The origins of the discipline date back late in 1960s, when cardiac dysfunction resulting from anthracyclines was first recognized as an important side effect. The field since then has arisen in few centers, and in the past years has rapidly evolved and become more a formal subspecialty with smaller units emerging within major centers. The scope of cardio-oncology includes not only the prevention, detection, monitoring and treatment of cardiovascular toxicity related to cancer therapy but also to assist in the overall care of cancer patients from cancer diagnosis into survivorship. The goal is to provide optimal care for patients with cancer and cardiovascular disease. A brief discussion of the cardiotoxicity disease spectrum is provided in the first part of this review article. We will then provide an overview about the rationale of setting up a cardio-oncology service line and our initial experience of establishing a collaborative cardio-oncology program within our practice will be presented, emphasizing important points of consideration in the cardiovascular evaluation before, during, and at completion of anticancer treatment.
There are different cardiovascular manifestations related to chemotherapy. There are agents that primarily affect cardiac function (eg, doxorubicin [anthracycline], cyclophosphamide [alkylating agent], and trastuzumab [tyrosine kinase inhibitor]). In addition, there are agents that indirectly contribute to cardiac decompensation by altering preload (imatinib [VEGFi] through fluid retention), afterload (bevacizumab [VEGFi] through hypertension), and heart rate (ifosfamide [alkylating agent] through arrhythmias) and agents that cause cerebrovascular disease (5- cisplatin [alkylating agents - platinum], 5-fluorouracil [antimetabolites]) [19–25]. There is also radiotherapy that has an all-inclusive involvement of the heart (myocardium, pericardium, valves and coronary arteries)  and can affect extra cardiac structures such as the great vessels where accelerated atherosclerosis can occur . However, a reduction in left ventricular ejection fraction (LVEF) and subsequent development of CHF has drawn most of the attention among physicians. Cardiac function impairment as a consequence of cancer therapy was first recognized in the 1960s , may be reversible or irreversible, and can occur acutely (at the time or within 1 week) or chronic with early (<1 year) and late onset (>1 year) after completion of chemotherapy [29, 30]. Importantly, chemotherapeutic agents are implicated in the development of myocardial ischemia, hypertension, hypertensive heart disease, or a combination, which may lead to left ventricular dysfunction [31, 32].
An operational classification model has been introduced distinguishing two types of cardiotoxicity . Type I causes a direct irreversible damage to the cardiomyocyte, mainly in a dose-dependent manner [34, 35], as observed with anthracyclines . Conversely, a type II cardiotoxicity pattern entails cardiac dysfunction with less prominent structural injury or irreversible cell damage since electron microscopy has shown structural changes in the animal model with trastuzumab [36, 37]. Type II cardiotoxicity does not exhibit dose dependency, is usually transient and carries a better prognosis .
Rationale for a multidisciplinary approach
Cardiovascular complications from cancer therapy have become a leading cause of morbidity and mortality in cancer survivors [7, 38]. Anticancer therapies have extended the lives of patients with cancer, but for some at the cost of adverse cardiovascular events [6, 12]. Increasing age, underlying heart disease and other comorbidities are contributing factors. Moreover, a variety of cardiovascular scenarios can occur in this population. For patients with an advanced metastatic tumor, the development of heart failure compromises their quality of life and palliative care. In contrast, for patients with a high likelihood of cure, chemotherapy-induced heart failure significantly impacts their long-term outcome . Additionally, we are often confronted with challenging decisions on drug therapies beforehand based on the curative benefit on the one hand and cardiotoxicity risk on the other hand in patients with significant cardiovascular risk factors. These challenges have advocated the compelling need for the multidisciplinary integrative approach of cardio-oncology [22, 39–41]. Cardio-oncology aims not only to detect and manage cardiotoxicity but also to assist in the overall care of cancer patients with and without heart disease in an interdisciplinary manner that ranges from the initial assessment of cardiovascular diseases and cardiotoxic risks to survivorship and long-term follow-up.
The multidisciplinary role becomes even more important as cardiotoxicities are identified at earlier stages of cancer treatment than they used to be. However, while much progress has been made in early detection and management of toxicities, there has been less progress in the understanding of short- and long-term outcomes of cancer therapies and intervention efforts. The cardiologist needs to know the goal of the oncology treatment, whether this treatment is curative or palliative, and the potential anticipated benefit of anticancer therapy to further assist the oncologist/hematologist . Mutual understanding and the communication between the cardiologist and oncologist/hematologist needs is paramount for risk stratification and decisions on the therapeutic window for any given therapy. Indeed, there is a critical balance between potential benefits and risks of different chemotherapeutic regimens and the need of the patients.
Setting up the cardio-oncology practice
Mayo Clinic has established a Cardio-oncology Clinic to improve the overall acute and long-term outcome of cancer patients. This subspecialty was initially created: 1) to facilitate the diagnosis, monitoring and therapy of cancer treatment related cardiovascular complications; 2) to evaluate baseline cardiovascular risks prior to cancer treatment and implement strategies for risk reduction of developing cardiovascular complications; and 3) to assist the patient with cardiovascular care through long-term follow up. The multidisciplinary team consists of cardiologists with additional expertise in prevention, heart failure, vascular disease, and cardiovascular imaging. It also encompasses oncologists, hematologists, internists, nurses, pharmacists, and all others involved in the care of cancer patients. As previously mentioned, the interdisciplinary communication and coordination is crucial to the operational functionality of the cardio-oncology practice.
At our institution, the cardio-oncology practice was initially established through the internal electronic referral management system (“e-consults”). E-consultations are electronic-based consultations where the specialist the “e-consultant” answers questions and provides advice about patient care. The referring provider generates a question to the consulting specialist with the appropriate clinical material and the e-consultant specialist answers it through the electronic medical record. There is no patient verbal contact, only medical assistance through the patient medical records [43–45]. These electronic-based consultations are provided by a cardiologist of the cardio-oncology team in response to specific questions. These types of consultations emerged as a mechanism to provide efficient clinical care in a timely manner. In cardio-oncology, for instance, this method enables cardiologists to further assist oncologists and hematologists to assess risk factors and manage existing cardiovascular diseases. The implementation of e-consultation is only feasible in the presence of an electronic medical record (EMR), which is another crucial element that avoids the fragmentation of data between patients and providers . The EMR system provides a continuum of communication and clarification of information, wherein physicians have easy access to patient’s charts, laboratories, and procedures (ie, ECG, echocardiogram, etc). This integration between two systems (e-consult and EMR) delivers a high-quality coordinated care that potentially avoids the time and wait of a visit between the patient and specialist.
Setting up a cardio-oncology clinic
Define practice and logistic
Recognize gaps and priorities in cardio-oncology
Joint meetings with cardiologists, oncologists, hematologists, nurses and nurse practitioners, pharmacists, nutritionists, rehabilitation services, palliative care, and social services
Discuss criteria for referral consultations, standards of pre-orders of tests (biomarkers and strain), location and timing of a full clinic, integration of services, education and training of staffs
Implement a coordinated service
Exchange patient information with the counterparts, allow a flexible scheduling system to accommodate a multidisciplinary team, ensure an updated medications list (cardiac and oncologic regimens)
Health staff education
Teaching material on cardio-oncology, updates, educational seminars, symposium and conferences
Provide awareness of the cardio-oncology program
Patient booklet, educational website, seminars, symposium, and community events
Standardization of care
Create algorithms, cardio-oncology group meetings, joint educational sessions with oncology, hematology and cardiology
Conduct lab-based experimental studies, apply for funding and awards, registry expansion (clinical data and bio bank), and create clinical and laboratory facilities with new techniques (biomarkers and strain)
Every other month meetings with updates and outcomes
Establish targets and goals
The Clinic has slowly expanded to avoid miscommunication in the coordination of patient care, since this is a multidisciplinary team and all efforts have been focused on avoiding errors due to a lack of adequate communication among team-members. This is accomplished by an integrated electronic medical record that ensures that all the clinical impressions, reports and plans are available to all the care team.
Our goals for this current year are to establish Cardio-Oncology group meetings every other month and standardization of care (Mayo algorithms); expansion of care (increasing referral and patient volume as well as further integration into survivorship and rehabilitation); joint educational sessions with oncology, hematology and radiation therapy, applications for institutional, extramural, and industry grants; initiation of new lab-based experimental studies; continuation of ongoing experimental collaborations; continuation of two cardiovascular prospective awards; registry expansion (clinical data, bio bank) with research nurse support; and a Mayo Clinic Cardio-Oncology Symposium. We hope that we and other new cardio-oncology programs may bring improvements in clinical outcomes and may contribute to health and well-being in patients with cancer.
Baseline and monitoring evaluation of oncology patients
From a clinical practice standpoint, prediction of the risk of cardiotoxicity has a very high priority as it allows for better allocation and individualization of therapy. A formal recommendation has been recently proposed from the ASE Expert Consensus Group , wherein cancer therapeutics-related cardiac dysfunction (CTRCD) is defined as a decrease in LVEF of > 10 percentage points, to a value < 53 %. Mayo Clinic established a standardized approach based on this consensus and our own experience.
Risk assessment and monitoring associated with left ventricular dysfunction
Patient-related risk factors
Medication-related risk factor a
1 point for each risk factor present
High (risk score 4): Anthracyclines, Trastuzumab, Ifosfamide, Cyclophosphamide, Clofarabine
Age (bimodal distribution): <15 or > 65 years
Atherosclerosis (coronary artery disease, cerebrovascular disease, peripheral artery disease)
Preexisting heart disease or heart failure
Prior radiation therapy to the chest
Intermediate (risk score 2): Docetaxel, Pertuzumab, Sunitinib, Sorafenib
Low (risk score 1): Bevacizumab, Imatinib, Lapatinib, Dasatinib
Rare (risk score 0): Etoposide, Rituximab, Thalidomide
Cardiotoxicity Risk Score (CRS)
Medication-related risk score + number of patient-related risk factors = CRS > 6: very high; CRS 5-6: high; CRS 3-4: intermediate; CRS 1-2: low; CRS 0: very low
Mayo Clinic monitoring recommendations
Very high risk: Echocardiogram with GLS before every (other) cycle, end, 3-6 months and 1 year. Optional ECG, cTn with echocardiogram during chemotherapy
High risk: Echocardiogram with GLS every 3 cycles, end, 3-6 months and 1 year after treatment. Optional ECG, cTn with echocardiogram during chemotherapy
Intermediate risk: Echocardiogram with GLS, mid-term, end and 3-6 after treatment. Optional ECG, cTn mid-term of chemotherapy
Low risk: Optional echocardiogram with GLS and/or ECG. cTn at the end of treatment
Very low risk: None
Also, cardiac biomarkers have been shown to have incremental value in the detection of CTRCD [54–60]. cTn in particular was able to predict CTRCD in a very early phase of treatment [57, 58]. Cardinale et al. demonstrated that patients without cTn elevation after chemotherapy completion have a good prognosis whereas persistence of positive values for 1 month is associated with a higher incidence of cardiovascular events (87 %) . In particular, cTn can be used to identify lower risk patients (higher negative predictive value). However, its predictive value is not superior and possibly not additive to that obtained with strain imaging (ie, GLS by 2D-STE) [55, 62].
Although much progress has been made, we believe we do not know the best method of monitoring these patients, how long they should be monitored, or the ways that these new techniques (strain imaging and biomarkers) will impact on survivorship. Anticancer therapies have brought hope and cure and extended the lives of patients with cancer, but for some these remarkable advances are attenuated by adverse cardiovascular effects. Mutual understanding and open discussions between team members in order to share expertise and responsibilities are required to achieve the best outcome for the patient.
A subspecialty with a multi-disciplinary integrative approach has emerged termed cardio-oncology. Cardio-oncology has the scope of diagnosing, preventing and treating patients with cancer and cardiovascular diseases. The discipline assists in the overall care of cancer patients from cancer diagnosis into survivorship. In this field, cardiologists assist oncologists and hematologists to further assess risk factors and manage existing or developing cardiovascular diseases. This partnership of shared responsibilities among multi-disciplinary professionals is a key element in improving the quality of care for cancer patients. This can be mediated through e-consultations or face-to-face evaluations and reported in an electronic medical record for better communication with all stakeholders involved in the care of the cancer patient. It is anticipated that this multidisciplinary approach will have an impact in decreasing cancer therapeutics-related cardiac dysfunction and improve patient outcomes.
two-dimensional speckle-tracking echocardiography
brain natriuretic peptide
congestive heart failure
serum cardiac troponin
cancer therapeutics-related cardiac dysfunction
electronic referral management system
electronic medical records
global longitudinal strain
left ventricular ejection fraction
vascular endothelial growth factor inhibitor
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- DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71. doi:10.3322/caac.21235.View ArticlePubMedGoogle Scholar
- Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.View ArticlePubMedGoogle Scholar
- Yancik R. Population aging and cancer: a cross-national concern. Cancer J. 2005;11(6):437–41.View ArticlePubMedGoogle Scholar
- Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213–20.View ArticlePubMedGoogle Scholar
- Yeh ETH, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–47.View ArticlePubMedGoogle Scholar
- Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991;266(12):1672–7.View ArticlePubMedGoogle Scholar
- Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99(5):365–75.View ArticlePubMedGoogle Scholar
- Jensen BV. Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer. Semin Oncol. 2006;33(3 Suppl 8):S15–21.View ArticlePubMedGoogle Scholar
- Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;324(12):808–15.View ArticlePubMedGoogle Scholar
- Limat S, Demesmay K, Voillat L, Bernard Y, Deconinck E, Brion A, et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2003;14(2):277–81.View ArticlePubMedGoogle Scholar
- Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.View ArticlePubMedGoogle Scholar
- Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2011;13(1):1–10. doi:10.1093/eurjhf/hfq213.View ArticlePubMedGoogle Scholar
- Holford TR, Cronin KA, Mariotto AB, Feuer EJ. Chapter 4: Changing patterns in breast cancer incidence trends. J Natl Cancer Inst Monogr. 2006;36:19–25.View ArticlePubMedGoogle Scholar
- Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer Statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.View ArticlePubMedGoogle Scholar
- Lenihan DJ, Oliva S, Chow EJ, Cardinale D. Cardiac toxicity in cancer survivors. Cancer. 2013;119 Suppl 11:2131–42. doi:10.1002/cncr.28061.View ArticlePubMedGoogle Scholar
- Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077–84.View ArticlePubMedGoogle Scholar
- Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol. 2015;12(9):547–58.View ArticlePubMedGoogle Scholar
- Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109(25):3122–31.View ArticlePubMedGoogle Scholar
- Kim KW, Shinagare AB, Krajewski KM, Pyo J, Tirumani SH, Jagannathan JP, et al. Fluid retention associated with imatinib treatment in patients with gastrointestinal stromal tumor: quantitative radiologic assessment and implications for management. Korean J Radiol. 2015;16(2):304–13. doi:10.3348/kjr.2015.16.2.304.View ArticlePubMedPubMed CentralGoogle Scholar
- Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27(9):911–39.View ArticlePubMedGoogle Scholar
- Herrmann J, Lerman A, Sandhu NP, Villarraga HR, Mulvagh SL, Kohli M. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. 2014;89(9):1287–306.View ArticlePubMedPubMed CentralGoogle Scholar
- Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102(1):14–25.View ArticlePubMedPubMed CentralGoogle Scholar
- Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, et al. Cardio-oncology: a new medical issue. Ecancermedicalscience. 2008;2:126. doi:10.3332/ecancer.2008.126. PMID: 22275992.PubMedPubMed CentralGoogle Scholar
- Herrmann J, Lerman A. An update on cardio-oncology. Trends Cardiovasc Med. 2014;24(7):285–95.View ArticlePubMedPubMed CentralGoogle Scholar
- Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail. 2013;1(1):72–8. doi:10.1016/j.jchf.2012.09.001.View ArticlePubMedGoogle Scholar
- Du XL, Xia R, Liu CC, Cormier JN, Xing Y, Hardy D, et al. Cardiac toxicity associated with anthracycline-containing chemotherapy in older women with breast cancer. Cancer. 2009;115(22):5296–308. doi:10.1002/cncr.24621.View ArticlePubMedGoogle Scholar
- Lancellotti P, Nkomo VT, Badano LP, Bergler-Klein J, Bogaert J, Davin L, et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2013;14(8):721–40. doi:10.1093/ehjci/jet123.View ArticlePubMedGoogle Scholar
- Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967;20(3):333–53.View ArticlePubMedGoogle Scholar
- Ferrans VJ. Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat Rep. 1978;62(6):955–61. PMID: 352510.PubMedGoogle Scholar
- Shan K, Lincoff AM, Young JB. Anthracycline-Induced Cardiotoxicity. Ann Intern Med. 1996;125(1):47–58.View ArticlePubMedGoogle Scholar
- Choueiri TK, Mayer EL, Je Y, Rosenberg JE, Nguyen PL, Azzi GR, et al. Congestive heart failure risk in patients with breast cancer treated with Bevacizumab. J Clin Oncol. 2011;29(6):632–8.View ArticlePubMedGoogle Scholar
- Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla J-P, Weaver C, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352(22):2302–13.View ArticlePubMedGoogle Scholar
- Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23(13):2900–2.View ArticlePubMedGoogle Scholar
- Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep. 1978;62(6):865–72. PMID: 667860.PubMedGoogle Scholar
- Mackay B, Ewer MS, Carrasco CH, Benjamin RS. Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct Pathol. 1994;18(1-2):203–11.View ArticlePubMedGoogle Scholar
- Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, et al. Cancer treatment–related cardiotoxicity: current state of knowledge and future research priorities. J Natl Cancer Inst. 2014;10:106(9).Google Scholar
- Kertmen N, Aksoy S, Uner A, Sargon M, Ozkayar O, Keskin O, et al. Which sequence best protects the heart against trastuzumab and anthracycline toxicity? An electron microscopy study in rats. Anticancer Res. 2015;35(2):857–64.PubMedGoogle Scholar
- Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23(34):8597–605.View ArticlePubMedGoogle Scholar
- van Heeckeren WJ, Bhakta S, Ortiz J, Duerk J, Cooney MM, Dowlati A, et al. Promise of new vascular-disrupting agents balanced with cardiac toxicity: is it time for oncologists to get to know their cardiologists? J Clin Oncol. 2006;24(10):1485–8.View ArticlePubMedGoogle Scholar
- Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol. 2010;7(10):564–75.View ArticlePubMedGoogle Scholar
- Fleissig A, Jenkins V, Catt S, Fallowfield L. Multidisciplinary teams in cancer care: are they effective in the UK? Lancet Oncol. 2006;7(11):935–43.View ArticlePubMedGoogle Scholar
- Cohen DJ, Davis M, Balasubramanian BA, Gunn R, Hall J, DeGruy FV, et al. Integrating behavioral health and primary care: consulting, coordinating and collaborating among professionals. J Am Board Fam Med. 2015;28 Suppl 1:S21–31. doi:10.3122/jabfm.2015.S1.150042.View ArticlePubMedGoogle Scholar
- Wootton R, Harno K, Fau-Reponen J, Reponen J. Organizational aspects of e-referrals. J Telemed Telecare. 2003;9 Suppl 2:S76–9.View ArticlePubMedGoogle Scholar
- Chittle MD, Rao SK, Jaff MR, Patel VI, Gallen KM, Avadhani R, et al. Asynchronous vascular consultation via electronic methods: a feasibility pilot. Vasc Med. 2015;20(6):551–6.View ArticlePubMedGoogle Scholar
- Pecina JL, North F. Early e-consultation face-to-face conversions. J Telemed Telecare. 2015.
- Chen AH, Kushel MB, Grumbach K, Yee HF. A safety-net system gains efficiencies through ‘eReferrals’ to specialists. Health Aff (Millwood). 2010;29(5):969–71.View ArticleGoogle Scholar
- Barac A, Murtagh G, Carver JR, Chen MH, Freeman AM, Herrmann J, et al. Cardiovascular health of patients with cancer and cancer survivors: a roadmap to the next level. J Am Coll Cardiol. 2015;65(25):2739–46.View ArticlePubMedGoogle Scholar
- Okwuosa TM, Akhter N, Williams KA, DeCara JM. Building a cardio-oncology program in a small- to medium-sized, nonprimary cancer center, academic hospital in the USA: challenges and pitfalls. Future Cardiol. 2015;11(4):413–20.View ArticlePubMedGoogle Scholar
- Lotrionte M, Biondi-Zoccai G, Abbate A, Lanzetta G, D’Ascenzo F, Malavasi V, et al. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity. Am J Cardiol. 2013;112(12):1980–4.View ArticlePubMedGoogle Scholar
- Villarraga HR, Herrmann J, Nkomo VT. Cardio-oncology: role of echocardiography. Prog Cardiovasc Dis. 2014;57(1):10–8.View ArticlePubMedGoogle Scholar
- Xu Y, Herrmann J, Pellikka PA, Ansell SM, Cha SS, Villarraga HR. Early Changes in 2D-Speckle-Tracking Echocardiography May Predict a Decrease in Left Ventricular Ejection Fraction in Lymphoma Patients Undergoing Anthracycline Chemotherapy: A Pilot Study. J Clin Exp Oncol. 2015. doi:10.4172/2324-9110.1000134.
- Sandhu N, Spoon J, Herrmann J, Pellikka PA, Villarraga HR. Two Dimensional Speckle Tracking Echocardiography Predicts Preclinical Cardiotoxicity in Breast Cancer Patients. J Am Coll Cardiol. [Abstract] 2014;63. doi: 10.1016/S0735-1097(14)60829-9
- Nhola LF, Abdelmoneim SS, Hermann J, Bordun KA, Premecz S, Cheung D, et al. Is there a change in myocardial mechanical function in patients on vascular endothelial grow factor axis inhibitor therapy for genitourinary and gastrointestinal cancer? J Am Soc Echocardiogr. 2015;28(6):B41–2. doi:10.1016/S0894-7317(15)00343-0.Google Scholar
- Thavendiranathan P, Poulin F, Lim K-D, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol. 2014;63(25 Pt A):2751–68.View ArticlePubMedGoogle Scholar
- Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5(5):596–603.View ArticlePubMedPubMed CentralGoogle Scholar
- Bordun K-A, Premecz S, DaSilva M, Mandal S, Goyal V, Glavinovic T, et al. The utility of cardiac biomarkers and echocardiography for the early detection of Bevacizumab and Sunitinib mediated cardiotoxicity. Am J Physiol Heart Circ Physiol. 2015;309(4):H692–701. doi:0.1152/ajpheart.00172.2015. PMID: 26092985.View ArticlePubMedGoogle Scholar
- Cardinale D, Sandri MT, Martinoni A, Tricca LabTech A, Civelli M, Lamantia G, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36(2):517–22.View ArticlePubMedGoogle Scholar
- Cardinale D, Sandri MT, Martinoni A, Borghini E, Civelli M, Lamantia G, et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol. 2002;13(5):710–5.View ArticlePubMedGoogle Scholar
- Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57(22):2263–70. doi:10.1016/j.jacc.2010.11.063.View ArticlePubMedGoogle Scholar
- Ky B, Putt M, Sawaya H, French B, Januzzi JL, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63(8):809–16.View ArticlePubMedPubMed CentralGoogle Scholar
- Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109(22):2749–54.View ArticlePubMedGoogle Scholar
- Kang Y, Xu X, Cheng L, Li L, Sun M, Chen H, et al. Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy. Eur J Heart Fail. 2014;16(3):300–8.View ArticlePubMedGoogle Scholar