5 Cardio-Oncology Gile

Lecture 5 Feb 27, 2018

©AllinaHealthSystem

CARDIO-ONCOLOGY:A COLLABORATIVE APPROACH TO CARE AND THE

PREVENTION OF CARDIOTOXICITY

LAURA GILE, BSN, RN, RNFA

February 27th, 2018

OBJECTIVES

1. Define Cardiotoxicity

2. Identify ways to reduce cardiotoxicity in cancer patients receiving cancer therapies.



CARDIO-ONCOLOGY BACKGROUND

Advances in cancer treatment have improved the long-term survival of cancer patients but have also lead to

life-threatening cardiac side effects

Bloom et al, 2016, Curigliano et al., 2016, Hermann et al, 2014

Risk of CVD death in cancer survivors is higher than the actual risk of tumor recurrence

• 7-fold higher mortality than general population – 15 fold increased risk of developing

heart failure – 10 fold increased risk ischemia

• Higher incidence of hypertension, dyslipidemia, acute coronary syndromes, CVA.

Mulrooney et al, 2009

There is significant increase in incidence of cardiac events in adult survivors of childhood and adolescent cancers



CARDIO-ONCOLOGY BACKGROUND

• Cardiovascular disease the second leading cause of morbidity and mortality among cancer survivors

• Patients who develop heart failure because of chemotherapy have a 3.5 – fold increased mortality risk compared to idiopathic cardiomyopathy

• Leads to disruption or discontinuation of life-saving cancer therapy

Bloom et al, 2016, Curigliano et al., 2016, Hermann et al, 2014

What is Cardiotoxicity?



CARDIOTOXICITY

• LV dysfunction

• Heart Failure

• Hypertension

• CAD

• Valvular Disease

• Peripheral Vascular Disease

• Vasospastic/thromboembolic ischemia

• Arrhythmias

• Conduction damage

• Pulmonary Hypertension

• Pericardial Complications

Curigliano et al., 2016, Cardinale & Cipolla, 2016, Ewer & Yeh, 2006, Luis Zamorano, et al., 2016 & Plana et al., 2014

CARDIOTOXICITY Damage to heart can be irreversible Type I or reversible Type II

Dependent On:

• Type of treatment prescribed • Duration • Dose• Underlying comorbidities • Additional Clinical Risk Factors

Chemotherapy Agents Known to Cause Cardiotoxicity:

• Anthracyclines• Alkylating Agents• Antimetabolites• Antimicrotubule Agents• Anti‐HER‐2 Monoclonal Antibodies• Tyrosine Kinase Inhibitors• Proteasome Inhibitors

Curigliano et al., 2016, Cardinale & Cipolla, 2016, Ewer & Yeh, 2006, Luis Zamorano, et al., 2016 & Plana et al., 2014



An overview of the cardiovascular side effects of chemotherapy and radiation.

Carrie G. Lenneman, and Douglas B. Sawyer Circ Res. 2016;118:1008-1020

Copyright © American Heart Association, Inc. All rights reserved.

CARDIO-ONCOLGY BACKGROUND

• Oncologist is generally responsible for cardiotoxicity monitoring during treatment

• Monitor for signs or symptoms heart failure or decline in ejection fraction

• Often manage cardiotoxic effects themselves or refer patients to cardiology for treatment

Cardinale & Cipolla, 2016, Luis Zamorano, et al, 2016 & Plana et al., 2014



CARDIO-ONCOLGY BACKGROUNDSurveillance system based on heart failure symptoms

and LVEF alone are not enough to protect cancer patients from irreversible heart damage

• A new approach to patient management and disease prevention encourages a multidisciplinary Cardio-Oncology team be used to detect and prevent cardiotoxicity long before LVEF drops or symptomatic heart failure is detected

Cardinale & Cipolla, 2016, Luis Zamorano, et al, 2016 & Plana et al., 2014

CARDIO-ONCOLOGY BACKGROUNDCardio-Oncology is a new subspecialty of cardiology that

promotes collaborative efforts between cardiology and oncology providers to prevent and manage the cardiotoxic effects of cancer

therapy and increase survivability of cancer patients

Barros‐Gomes, et al, 2016, Hermann et al, 2014, Sulpher, et al, 2015



What can we do?

CARDIO-ONCOLOGY: Creating a partnership



CARDIO-ONCOLOGY: AIM

To improve patient outcomes by developing a strong collaboration between cardiology and oncology providers

Help patients become cancer survivors

Through early detection & prevention!

CARDIO-ONCOLOGY: GOALS

• Promote increased survival of cancer patients• Create a multidisciplinary “Cardio-Oncology” clinic• Develop a cardiotoxicity risk assessment tool • Identify and develop cardiac monitoring and management strategies• Create comprehensive individualized treatment plans



CARDIOTOXICITY PREVENTION: RISK ASSESSMENT

Evidence suggests clinical assessment of cardiac risk before cancer therapy would support cardiotoxicity prevention, treatment

planning, and surveillance of cardiac function before, during, and after treatment

• Understand individual risk • Encourage collaboration between providers • Develop future protocols• Assist in determining dose and duration of treatment, frequency of cardiac monitoring• Inform clinicians when to initiate cardio-protective treatments • Supports patient-centered care

Currently there are proposed operational models but no formal clinical guidelines

Ezaz, Long, Gross, & Chen, 2014, Hermann et al, 2014Shelburne, et al, 2014, & Sulpher, et al, 2015b

Who are “High Risk” for cardiotoxicity?Traditional cardiovascular risk factors

– History of heart failure (LVEF <55%)– Older age (>60) or post-menopausal– Previous coronary disease– Obese, BMI>35– Diabetes– Hypertension– Smoking

Clinical Risk Factors– Prior anthracycline or radiation therapy– Current cancer therapy that demonstrates a >3% incidence of cardiotoxicity at

normal dose ranges (i.e. Doxorubicin, daunorubicin, trastuzumab etc.)

Curigliano et al., 2016, Cardinale & Cipolla, 2016 & Ewer & Yeh, 2006



CARDIOTOXICITY PREVENTION: RISK ASSESSMENT

Focus on disease prevention through screening

• Developed a Cardiotoxicity Risk Assessment Tool that stratifies risk based on cancer treatment, clinical, and cardiac risk factors

• Cardiotoxicity Risk Scores : 0-2 low risk3-4 intermediate risk5 or greater high risk



EARLY DETECTION: Strain Imaging“The rate at which deformation (positive or negative strain) occurs”

• Echocardiographic imaging using speckle doppler to track changes in multiple axis to allow for more accurate measurement of LV function.

• Takes out intra-observer variability

• Can detect earlier changes in the myocardium

Citro et al, 2008

EARLY DETECTION: Strain Imaging

Citro et al, 2008



EARLY DETECTION: Strain imaging

• Normal values are -20% +/- 2%

• Strain <-17% is significant

The less negative the number = BAD = there is less movement in the myocardium and more damage there is

PREVENTION: MANTICORE Trial

• Trastuzumab - About 20% of patients treated with trastuzumabexperience left-ventricular dysfunction, and about 1%–5% develop heart failure.

• Three arm 1:1:1 studied placebo vs BB (bisoprolol) vs ACEi (perindopril) in patients receiving trastuzumab-based chemotherapy for 24 months

• 94 patients. Low risk population – age 50, normal LVEF

Pituskin et al, 2017



PREVENTION: MANTICORE Results• Perindopril and bisoprolol were well tolerated in patients with

HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy–related declines in LVEF;

• Decline in LVEF (via cMRI) 5% with placebo, 3% with ACEi, 1% BB.

• LV Dysfunction noted in 20% in placebo, 3% ACEi or BB

Trastuzumab therapy was interrupted in 30% placebo and only 10% ACEi & BB groups.

Pituskin et al, 2017

PREVENTION: PRADA Trial• The goal of the trial was to evaluate treatment with a beta-blocker

and/or angiotensin-receptor blocker (ARB) among patients with breast cancer undergoing anthracycline chemotherapy.

• Women with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and/or radiation were randomized by 2X2 factorial design to metoprolol succinate (target

dose 100 mg daily) versus placebo, and to candesartan (target dose 32 mg daily)

versus placebo. The duration of the study medication ranged from 10-61 weeks.

Gulati et al, 2016



PREVENTION: PRADA Results

In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function

Gulati et al, 2016

What’s the process?



Cardiotoxicity Risk Assessment Workflow

Oncology Consult For New Diagnosis or Recurrence of

Cancer

Oncology Provider Conducts Cardiotoxicity Risk Assessment

During Consult

Oncology Provider Monitors & Manages Patient for Adverse

Cardiac Events

Place Order for Cardio‐Oncology (Cardiology) Consult & ECHO

w/ Strain

MNO Schedulers Schedule Cardiology Consult & ECHO w/ Strain after Oncology Consult

Score > 5

Cardiology Manages & Monitors Patient for Adverse Cardiac

Events

Cardiology Collaborates Oncology to Optimize

Treatment

Continue to Monitor & Manage

Adverse Cardiac Event

YES

YES

NO

NO

ECHO before

survivorship visit

Cardiology Consult

within 1‐2 weeks

EF < 50%, GLS < ‐17%,

CP, S/S of HF

DISCUSSION

Implemented cardiotoxicity risk assessment tool on May 1st 2017

• Implementation of the cardiotoxicity risk assessment tool has led to a 194% increase in referrals over 7 months.

• Has led to more awareness of cardiotoxicity and improved collaboration and communication among oncology and cardiology providers

• Both organizations demonstrate a high satisfaction with the implementation process and strongly support the development of cardiotoxicity prevention measures



DISCUSSIONMoving Forward…

• Plan to evaluate sensitivity and specificity of cardiotoxicity risk assessment tool at one year

• Continue to evaluate and make changes to workflow and communication processes

• Based on preliminary results considering additional cohort and retrospective studies associated with risk factors

https://www.pinterest.com/pin/143622675597081662/



Thank you!

REFERENCES• Barros-Gomes, S., Herrmann, J., Mulvagh, S.L., Lerman, A., Lin, G., & Villarraga, H.R., (2016). Rationale for setting up a cardio-

oncology unit: our experience at mayo clinic. Cardio-Oncology, 16(733). doi: 10.1186/s40959-016-0014-2• Bloom, M. W., Hamo, C. E., Cardinale, D., Ky, B., Nohria, A., Baer, L., & ... Butler, J. (2016). Cancer Therapy-Related Cardiac Dysfunction

and Heart Failure: Part 1: Definitions, Pathophysiology, Risk Factors, and Imaging. Circulation. Heart Failure, 9(1), e002661. doi:10.1161/CIRCHEARTFAILURE.115.002661

• Cardinale, D. & Cipolla, C.M. (2016). Chemotherapy-induced cardiotoxicity: importance of early detection. Expert Review of Cardiovascular Therapy. Retrieved from http://dx.doi.org/10.1080/14779072.2016.1239528

• Citro, R., Bossone, E., Kuersten, B., Gregorio, G., & Salustri, A. (2008). Tissue Doppler and strain imaging: anything left in the echo-lab?. Cardiovascular Ultrasound, 654. doi:10.1186/1476-7120-6-54

• Curigliano, G., Cardinale, D., Dent, S., Criscitiello, C., Aseyev, O., Lenihan, D., & Cipolla, C.M. (2016). Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA: A Cancer Journal for Clinicians, 66(4), 309-325. doi:10.3322/caac.21341

• Ewer, M.S. & Yeh, E. (2006) Cancer and the Heart. Hamilton, Ontario: BC Decker Inc.• Gulati, G., Heck, S. L., Geisler, J., Fagerland, M. W., Hoffmann, P., Gravdehaug, B., . . . Omland, T. (2016). EFFECT OF CANDESARTAN

AND METOPROLOL ON SUBCLINICAL MYOCARDIAL INJURY DURING ANTHRACYCLINE THERAPY: DATA FROM THE PREVENTION OF CARDIAC DYSFUNCTION DURING ADJUVANT BREAST CANCER THERAPY (PRADA) STUDY. Journal of the American College of Cardiology, 67(13), 1530. http://dx.doi.org.mtrproxy.mnpals.net/10.1016/S0735-1097(16)31531-5

• Hermann, J., Lerman, A., Sandhu, N.P., Villarraga, H.R., Mulvagh, S.L. & Kohli, M. (2014). Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Foundation for Medical Education and Research Clinical Proceedings. 89(9). (p. 1287-1306). dMeuth, C.L. & Lech, T.K. (2016) Drug list. In Yeh, E.T.H. MD Anderson Practices in Cardio-Oncology. Department of Cardiology, The University of Texas MD Anderson Cancer Center.oi.org/10.1016/j.mayocp.2014.05.013



REFERENCES• Luis Zamorano, J., Lancellotti, P., Rodriguez Muñoz, D., Aboyans, V., Asteggiano, R., Galderisi, M., & ... Suter, T. M. (2017). 2016 ESC

Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Journal Of Heart Failure. Supplements, 19(1), 9-42. doi:10.1002/ejhf.654

• Mulrooney, D. A., Yeazel, M. W., Kawashima, T., Mertens, A. C., Mitby, P., Stovall, M., & ... Leisenring, W. M. (2009). Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Studycohort. BMJ (Clinical Research Ed.), 339b4606. doi:10.1136/bmj.b4606

• Plana, J.C., Galderisi, M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, & … Lancellotti P. (2014). 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. European Heart Journal of Cardiovascular Imaging 15(10). (p. 1063-93). doi: 10.1093/ehjci/jeu192.

• Pituskin, E., Mackey, J. R., Koshman, S., Jassal, D., Pitz, M., Haykowsky, M. J., & ... Paterson, D. I. (2017). Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity. Journal Of Clinical Oncology: Official Journal Of The American Society Of Clinical Oncology, 35(8), 870-877. doi:10.1200/JCO.2016.68.7830

• Shelburne, N., Adhikari, B., Brell, J., Davis, M., Desvigne-Nickens, P., Freedman, A., &… Remick, S. C. (2014). Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. Journal of The National Cancer Institute, 106(9), doi:10.1093/jnci/dju232

• Sulpher, J., Mathur, S., Graham, N., Crawley, F., Turek, M., Johnson, C., & ... Dent, S. (2015). Clinical experience of patients referred to a multidisciplinary cardiac oncology clinic: an observational study. Journal of Oncology, 20151-5. doi:10.1155/2015/671232

CONTACT INFORMATION

Laura Gile BSN, RN, RNFAEmail: [email protected]

[email protected]

Work phone: 763-236-9500

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5 Cardio-Oncology Gile