cardiology grand rounds · 1/26/2015 cardiovascular grand rounds 26‐jan‐2015 minneapolis heart...

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C A R D I O L O G Y G R A N D R O U N D S Presentation: The Emerging Science and Clinical Practice of Cardio

Oncology Speaker: Amin F. Rahmatullah, MD

Director, Cardiac CT Program; Director, Heart Failure Program Metropolitan Heart and Vascular Institute, Mercy and Unity Heart Center

Date: Monday, January 26, 2015, 7:00 – 8:00 AM

Location: ANW Education Building, Watson Room

OBJECTIVES At the completion of this activity, the participants should be able to: 1. Appreciate the cardiotoxic potential of some newer chemotherapeutic agents to treat common

malignancies. 2. Screen and detect early signs of cardiotoxicity of these chemotherapeutic agents 3. Describe intervention to prevent and halt progression of cardiotoxicity of these chemotherapeutic agents

ACCREDITATION Physicians: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Allina Health and Minneapolis Heart Institute Foundation. Allina Health is accredited by the ACCME to provide continuing medical education for physicians.

Allina Health designates this live activity for a maximum of 1.0 AMA PRA Category 1 CreditTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Nurses: This activity has been designed to meet the Minnesota Board of Nursing continuing education requirements for 1.2 hours of credit. However, the nurse is responsible for determining whether this activity meets the requirements for acceptable continuing education.

Others: Individuals representing other professional disciplines may submit course materials to their respective professional associations for 1.0 hours of continuing education credit.

DISCLOSURE STATEMENTS Speaker(s): Dr. Rahmatullah has declared that he does not have a conflict of interest in making this presentation.

Planning Committee: Dr. Michael Miedema and Eva Zewdie have declared that they do not have any conflicts of interest associated with the planning of this activity. Dr. Robert Schwartz declared the following relationships ‐ stockholder: Cardiomind, Interface Biologics, Aritech, DSI/Transoma, InstyMeds, Intervalve, Medtronic, Osprey Medical, Stout Medical, Tricardia LLC, CoAptus Inc, Augustine Biomedical; scientific advisory board: Abbott Laboratories, Boston Scientific, MEDRAD Inc, Thomas, McNerney & Partners, Cardiomind, Interface Biologics; options: BackBeat Medical, BioHeart, CHF Solutions; speakers bureau: Vital Images; consultant: Edwards LifeSciences.

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Cardiovascular Grand Rounds 26‐Jan‐2015Minneapolis Heart Institute® at Abbott Northwestern Hospital Page 1

INTRODUCING CARDIO ONCOLOGYTHE EMERGING SCIENCE

AND CLINICAL PRACTICE OF

CARDIO ONCOLGY

AMIN RAHMATULLAH, MD DIRECTOR, HEART FAILURE

METROPOLITAN HEART AND VASCULAR INSTITUTE

BREAST CANCER SURVIVAL

•Breast cancer survival improved by 20% in last 30 yrs

•5 yr survival is now 98% for early stage disease

•In 2012 there are > 3 million breast cancer survivor in the US alone

•Partly attributed to effective treatment strategies through collaboration amongst breast surgeons, medical and radiation oncologists.

•Other factors include effective tumor and cancer cell‐specific adjuvant therapies.

•Neoangiogenesis directed therapies.

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CANCER “SURVIVORSHIP:

•New Theme in cancer care •CV toxicity may interfere with the completion of treatment that has made the survivorship possible

•Cardiac issues may arise years after the completion of the cancer treatment, where subclinical myocardial damage may be exacerbated by stress, hypertension, CAD, alcohol etc

•Time to address the Cancer “survivorship” is at the time of cancer diagnosis and before treatment rather than after completion of therapy

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CARDIOTOXICITY

• RECOGNIZED IN 1960’S, ANTHRACYCLINES STILL CONTINUE TO BE USED IN CANCER THERAPY

• THE RED DEVIL

ANTHRACYCLINE TOXICITY

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“

”

Cardiac Toxicity

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Type I and II chemo related cardiac dysfunction

ACUTE , SUBACUTE AND CHRONIC CARDIOTOXICITY

• ACUTE and SUBACUTE

– QT prolongation

– Ventricular and supraventricular arrhythmias

– Pericarditis / myocarditis

– Acute coronary Syndrome

• CHRONIC

– Less than a year

– > 1 year

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DEFINITION OF CARDIOTOXICITY

• A decrease in LVEF > 10% to a value less than 53%

• Confirm by repeat cardiac imaging in 2‐3 weeks

• Reversible : within 5% of baseline

• Partially reversible: improved by >10% but still >5% below the baseline

• Irreversible : Improved by <10% from the nadir, yet > 5% below the baseline

Cardiac Toxicity

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Even in early stage breast cancer, cardiac disease does matter…

• Patients with early stage breast cancer are 4x more likely to die of non-cancer conditions (up to 45 % are cardiac in nature)

Hanrahan, et al. JCO 25: 4952-4960, 2007

Hundley, 2012

Cardiac Toxicity

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Cardiac Toxicity

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CV TOXICITY DETECTION, PREVENTION AND TREATMENT

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ECHO EVALUATION IS SUSPECTED CARDIOTOXICITY

•LV EF is widely used to monitor cardiac systolic function

•EF quantification by Simpson’s biplane technique.

•Echo can help with RV function and pressures ( dasatinib) .

•Echo allows careful and reproducible assessment of valve structure and function.

•Echo role in pericardial diseases.

•Cheap and widely available

•Changes in EF are load dependant.

Limitations of Echocardiography

• 3D echo superior to 2D echo due to less affected by acquisition differences , reproducible and automated calculation of EF and lower temporal variability for longitudinal follow up of chemo patients.

• Poor echo windows.

• Lower reproducibility and high variation when contrast is used.

• Not sensitive enough to detect subtle EF changes and wma

• LV EF at completion of therapy or a change during therapy was NOT a predictor of later cardiotoxicity.

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Strain Imaging

Cleveland Clinic

LV Strain and Strain Rate Imaging

• Measurement of deformation indices are the earliest changes in cardiac toxicity.

• Global longitudinal strain ( GLS) is the optical parameter of deformation for early detection of subclinical LV dysfunction.

• More than 10% reduction of GLS predicts a later occurrence of toxicity with a sensitivity and specificity of 78% and 79% respectively. Negative predictive value of 93%

• Vendor and software specific

• Reproducibility not studied.

• Heavily dependant on quality of 2D images.

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Other Imaging modalities.

• MUGA used historically . Reproducible , widely available and correlates well with CMR and 3D echo .

• Radiation exposure

• No RV, LV volumes, valves or pericardial information

• No prediction of future LV dysfunction risks.

• CMR, excellent LV volume, mass and EF assessment.

• CMR likely will be used when the LV function is at the threshold of chemo discontinuation

• CMR demonstrates an inverse relationship between LV mass and anthracycline dose

• Lack of LGE

• Expensive and not widely available. Patient limitations.

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Sub clinical LV dysfunction using Biomarkers

• hsTnI is a very sensitive marker of subclinical myocardial damage.

• Persistent increase associated with increased severity of cardio toxicity compared to transient increase.

• Negative predictive value of 99% helps ruling out high risk patients.

• TnI elevation, absolute and relative ( delta change) provides both a qualitative and quantitative risk assessment..

• BNP elevation suggests elevated filling pressure and to date have not shown any evidence of predicting subclinical LV dysfunction.

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Elevated values according to MD Anderson:

Trop >0.05BNP >125Strain < 19%

Elevated values according to MD Anderson:

Trop >0.05BNP >125Strain < 19%

Markers and Images

Markers and Images

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Management of Cardiac Toxicity.

• There are currently NO published guidelines for management of cardiac toxicity.

• Primordial prevention –– ACEI and/or beta blocker

– Statins

– Dexrazoxane

• Primary Prevention– Based on early reduction in GLS and/or biomarkers

• Secondary Prevention – Response rate decreased with increasing time delay .

• Treatment of overt heart failure

Cardinale, 2012

Treatment

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Cardinale, 2012

Treatment

Treatment

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Carvedilol appears protective during adriamycinbased chemotherapy

Kalay et al. JACC. Dec 2006. 48:2258-62Data expressed as mean values.

Integrated Approach.

• Cooperation between cardiologist and oncologist is absolutely necessary

• Ideal to perform baseline assessment on every patient scheduled to receive potentially cardiotoxic drug.

• If not all, then definitely , patients> 65 yrs, CV disease, type I or a combination of Type I and II chemo agents

• Baseline echo, with GLS and trop I

• If baseline EF is <50%, abnormal GLS or abnormal baseline trop – cardiology must be consulted .

• If above is negative , follow up at completion of treatment and at 6 months ????

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Future Directions

• Need to establish a comprehensive and universal definition of cancer treatment related cardiac toxicity

• Establish the importance of short and long term consequence of abnormal imaging, biomarkers and EF with short and long term clinical events

• Determine the relative efficacy/ cost / safety of primordial and primary prevention.

• Evaluate CV interventions in patients receiving conventional and/or novel adjuvant therapies.

• Balance cancer and CV outcomes –avoiding compromising the anti‐cancer therapy while minimizing cardiac side effects.

Starting ACE‐I for Troponin I positive patients

Algorithms

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THANK YOU

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CARDIOTOXICITY

CARDIOTOXICITY

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