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CardioNerds Co-Founder Dr. Daniel Ambinder, Episode Chair Dr. Dinu Balanescu, and FIT Lead Dr. Natalie Tapaskar discuss advanced heart failure in CardioOncology with expert Dr. Richard Cheng. Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig.

In this episode, we discuss the spectrum of advanced heart failure in patients with a history of cancer. We dissect cancer therapy-related cardiac dysfunction (CTRCD) cases and the imaging and biomarker tools available for risk stratification and disease monitoring. We delve into the data on the use of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT) in these patients. We discuss the risk of prior radiation and chemotherapy during cardiac surgery. Finally, we learn about the post-transplant risk of rejection, recurrent malignancy, and de-novo malignancies, as well as treatment strategies we can employ for these patients.

This episode is supported by a grant from Pfizer Inc.

This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan. 

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Pearls and Quotes – Advanced Heart Failure in CardioOncology

1. Use the HFA-ICOS risk tool to understand the baseline risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Key factors are type of cancer therapy, baseline CV risk factors, and age.
2. A relative change in global longitudinal strain of more than 15% from baseline is a marker of early cardiac dysfunction and predicts the subsequent risk for systolic dysfunction in patients undergoing cardiotoxic chemotherapy.
3. Statins may be useful in prevention of cardiovascular dysfunction in patients receiving anthracycline chemotherapy. There is limited data on the 4 pillars of GDMT in prevention of CTRCD, but should be started early once CRTCD is suspected or diagnosed!
4. Mediastinal radiation causes adhesions and scarring which increase the risk of bleeding during cardiac surgery, lead to longer operative times, and can lead to RV failure and poor wound healing.
5. Patients with a pre-transplant history of malignancy have a higher risk of mortality due to post-transplant malignancy. And patients with active cancer should not be considered for heart transplant. Post-transplant malignancy risk can be mitigated by utilizing an mTOR based, CNI free immunosuppression regimen.

Show notes – Advanced Heart Failure in CardioOncology

How do cardio-oncology and advanced heart failure intersect?

• There are 3 basic populations of patients to consider:
  • Patients with advanced heart failure who develop cancer.
  • Patients with pre-existing chemotherapy and radiation exposure for cancer treatment who later develop advanced heart failure
  • Heart transplant recipients who, in the long term are at very high risk of developing cancer
  • Cardio-oncologists must consider risk assessment and mitigation, long-term prognosis, and treatment strategies for each of these unique populations.

How can we assess the risk of developing cardiovascular disease during cancer treatment (CTRCD)?

• There are many proposed risk tools. However, the majority are not well-validated.
  • One of the most used tools is the HFA-ICOS risk tool.¹
    • You can select the planned cancer therapy for the patient (anthracyclines, HER-2, VEGF, RAF/MEK inhibitors, Kinase inhibitors, multiple myeloma therapies) and then calculate their risk of developing CV disease during cancer treatment based on baseline variables:
      • 1) previous history of CV disease,
      • 2) biomarkers – troponin and NT-proBNP
      • 3)age,
      • 4) CV risk factors -HTN, DM, CKD,
      • 5) previous cardio-toxic treatments,
      • 6) lifestyle risk factors- smoking, obesity
    • The risk tool will then give you a ranking of very high, high, medium, or low risks.

How should we use imaging to evaluate cardiac dysfunction in patients undergoing cancer treatments?

• Echo with global longitudinal strainA relative change in global longitudinal strain of more than 15% from baseline is a marker of early cardiac dysfunction and predicts the subsequent risk for systolic dysfunction.Data are mixed on the benefit of intervening on drops in GLS without a concomitant drop in LVEF. Current vendor software has improved the consistency in GLS measurements across vendors, which used to be quite problematic.
  • Echo LVEF
    • Some centers prefer to use 3D LVEF to track patients over time.
    • For asymptomatic high-risk patients, we should obtain echocardiograms at 1, 3, and 5 years post-cancer therapies and then every 5 years thereafter.
    • But surveillance should occur on a case-by-case basis.
  • CPET
    • Can be used to risk stratify patients with lung or colon cancer before starting cancer treatment.
    • You can trend peak VO2 over time after cancer treatments.
    • However, this is generally a data-sparse zone!

Can we use serum biomarkers such as troponin or NT-proBNP in monitoring for the development of CTRCD?

• Elevations in BNP during cancer treatment are associated with subsequent cardiovascular disease.
  • Elevations in troponin and myeloperoxidase in breast cancer patients receiving anthracyclines can predict the risk of cardiotoxicity.
  • Novel biomarkers – data-free zone
    • CRP is a marker of inflammation and may be helpful in patients undergoing radiation therapy.
    • Immunoglobulins- baseline elevated IgE levels have a lower risk for cardiotoxicity.
    • Cell-free DNA – may be the future?

What is the role of cardiovascular medications and devices in preventing and treating CTRCD?

• Prevention:
  • Statins – The STOP-CA trial showed that use of atorvastatin 40 mg/day in patients with lymphoma receiving anthracycline chemotherapy reduced the incidence of cardiac systolic dysfunction compared to placebo.²
  • SGLT2i – limited retrospective data in patients with diabetes and anthracycline chemotherapy. May have lower rates of cardiac events on SGLT2i.
  • Currently there is not enough data to recommend routine use of SGLT2i, ARNI, and BB for cardioprotection before cancer therapies.
  • Treatment:
    •  Treat these patients similarly to other heart failure patients. The four pillars of GDMT work! Early recognition is critical to confer better long-term outcomes.
    • CRT-D: MADIT-CHIC³ showed that CRT therapy improved LVEF at 6 months in patients with chemotherapy-induced cardiomyopathy.
      • Only consider ICD if life expectancy is >1 year.
      • There is a risk of device reset for radiation directly over the device. ICDs are more sensitive to ionizing radiation, leading to inappropriate shocks.
      • Can consider moving the device to a non-radiation field.

What do we need to consider when patients with a history of cancer are being evaluated for heart transplant and left ventricular assist device (LVAD)?

• Heart transplant
  • Patients with chemo-induced cardiomyopathy have no differences in post-transplant outcomes compared to patients with other causes of cardiomyopathy.
  • Patients with a pre-transplant history of malignancy have a higher risk of mortality due to post-transplant malignancy, particularly in those with a history of hematologic malignancy.
  • Patients with active cancer should not be considered for heart transplant.
  • The duration and interval of waiting after active cancer before a heart transplant depends on the type and stage of cancer.
  • LVAD
    • Patients with chemotherapy-induced cardiomyopathy have similar outcomes and rates of post-LVAD RV dysfunction as patients with other etiologies of cardiomyopathy.
    • Limited data on performing LVAD in patients with active cancer.

What risk does prior mediastinal radiation pose to cardiac surgery?

• Mediastinal radiation
  • Increases adhesions and scarring, increasing the risk of bleeding during cardiac surgery. Longer operative times may also increase the risk of RV failure.
  • There can also be atrophy of sternal muscles, which can lead to poor wound healing

What do the post-heart transplant rejection and malignancy profiles look like for patients with a history of chemotherapy-induced cardiomyopathy?

• Patients with prior chemotherapy have depressed immunosurveillance from their innate immune system and, thus, may have a lower risk of rejection. But there is limited data here.
  • Patients with a history of pre-transplant malignancy are at increased risk of recurrence and PTLD. You can consider decreasing immunosuppression or switching to mTOR inhibitor-based regimen to reduce the risk.

What must we know about de-novo malignancy post-heart transplant?

• Risk factors: history of prior malignancy, heavier immunosuppression, older recipient age, smoking history, radiation exposure, genetic variants.
  • Treatment: reduce immunosuppression as much as possible and switch to an mTOR-based regimen.
  • What about immune checkpoint inhibitors post-transplant?
    • These work by upregulating T cell activity, which counteracts our transplant immunosuppression. High risk of rejection, but some successful case reports of use.

References – Advanced Heart Failure in CardioOncology

1. Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the C ardio‐ O ncology S tudy G roup of the H eart F ailure A ssociation of the E uropean S ociety of C ardiology in collaboration with the I nternational C ardio‐ O ncology S ociety. Eur J Heart Fail. 2020;22(11):1945-1960. doi:10.1002/ejhf.1920
2. Neilan TG, Quinaglia T, Onoue T, et al. Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial. JAMA. 2023;330(6):528. doi:10.1001/jama.2023.11887
3. Singh JP, Solomon SD, Fradley MG, et al. Association of Cardiac Resynchronization Therapy With Change in Left Ventricular Ejection Fraction in Patients With Chemotherapy-Induced Cardiomyopathy. JAMA. 2019;322(18):1799. doi:10.1001/jama.2019.16658