For many years, researchers around the world have been exploring the connections between cancer treatments and the heart—better known as cardio-oncology. However, many oncologists may be less familiar with this emerging field and what they might need to know in terms of heart health to keep their patients on effective cancer treatments while minimizing the risk of cardiovascular diseases. At the 2023 Global Cardio-Oncology Summit (GCOS) in Madrid, experts from Milan, New York, and Houston discussed the role of cardiac imaging and biomarkers in cardio-oncology.1-3
Cardiac Biomarkers
Daniela Cardinale, MD, PhD, FESC
“Evidence of the usefulness of cardiac biomarkers in cancer patients has been available for more than 20 years, but only recently have guidelines emerged regarding their use,” stated Daniela Cardinale, MD, PhD, FESC, Director of the Cardioncology Unit, European Institute of Oncology, Milan, Italy. Guidelines suggest these biomarkers, specifically cardiac troponins and natriuretic peptides, may be useful in several areas for patients with cancer. They include baseline risk stratification, early diagnosis of cardiotoxicity during and after therapy, identification of patients who may benefit from cardioprotective treatments, and detection of those who may require closer and long-term follow-up.
A position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology (ESC) emphasized the important role played by serum biomarkers in baseline risk assessments.4 “Most of the literature supports the use of cardiac troponins and natriuretic peptides for their use for diagnosis, monitoring, and prognostication of cardiovascular disease,” noted Dr. Cardinale.
A closer look at these two biomarkers shows they provide different but complementary types of information, she noted. Cardiac troponins serve as the “gold standard” for myocardial cell injury, Dr. Cardinale said. Elevated troponin levels during cancer treatment predict left ventricular dysfunction; troponin has a high negative predictive value, which makes it possible to identify patients at low risk who do not need intense surveillance.
As for natriuretic peptides, they focus on hemodynamic index and are considered the second most frequently studied cardiac biomarker in patients with cancer, according to Dr. Cardinale. B-type natriuretic peptide (BNP) may show preexistent cardiac disease. Also, during and after cancer treatments, an increase in BNP may be linked to a drop in left ventricular ejection fraction (LVEF), even in asymptomatic patients.
When should these cardiovascular biomarkers be assessed? According to Dr. Cardinale, the timing of biomarker assessment depends on the level of cardiovascular risk and the type of cancer treatment.
The ESC and the International CardioOncology Society (ICOS) suggest baseline assessment of both markers to quantify the risk of developing cardiotoxicity in patients with cancer. It should include previous cardiovascular disease, both cardiac biomarkers, demographics, cardiovascular risk factors (eg, age, hypertension, diabetes, chronic kidney disease), type of cancer treatment (eg, anthracycline exposure, prior radiotherapy to the left side of the chest or mediastinum, and previous nonanthracycline-based chemotherapy), and lifestyle risk factors (eg, smoking history, obesity). Both cardiac markers may be assessed at each chemotherapy cycle using the same venous route, to avoid additional hospital visits and venesection, or, Dr. Cardinale suggests, it can be done at the already scheduled blood sample requested by oncologists during cancer treatment.
For those found to be at high or very high risk for cardiotoxicity, more intense surveillance is recommended, noted Dr. Cardinale. An increase in cardiac biomarkers should “stimulate a proactive discussion between the oncologist and the cardiologist regarding the possible benefits and harms of all further cancer treatment, in accordance with the principles of permissive cardiotoxicity,” she added. “This paradigm5 shifts the mind set of cancer care providers from should this therapy be discontinued to how can we safely continue this therapy. Increased biomarkers are not enough of a cause or event to stop an effective cancer therapy.”
In daily clinical practice, Dr. Cardinale might consider starting the angiotensin-converting enzyme (ACE) inhibitor enalapril for those found to be at high risk, when the troponin level is 23.8 ng/L and the LVEF is 60%. According to the ICOS-1 trial,6 giving enalapril before chemotherapy or only after an increase in troponin occurred during or after chemotherapy yielded similar results, with stable LVEF in both groups.
Use of Global Longitudinal Strain Imaging in Patients With Cancer
Jennifer Liu, MD, FACC
Jennifer Liu, MD, FACC, Chief of Cardiology at Memorial Sloan Kettering Cancer Center, New York, and Professor of Medicine at Cornell University, reviewed the role of global longitudinal strain (GLS) imaging in cardio-oncology. This echocardiographic method, which measures the cyclic deformity of cardiac chambers during the cardiac cycle, is used to describe the elastic properties of the cardiac muscle. “Strain is negative when the fiber is shortening and positive when it is lengthening or thickening,” Dr. Liu explained. Derived from speckle tracking and analyzed by postprocessing of apical images of the left ventricle, it allows for the early detection of subclinical left ventricular dysfunction.
In terms of its role in oncology, GLS is reliable and reproducible for detecting cancer treatment–related cardiotoxicity. “It can be obtained on standard apical views during routine transthoracic echocardiogram,” Dr. Liu explained. GLS also can be used in risk stratification, identifying high-risk patients. According to Dr. Liu, GLS should be done before, during, and after cancer treatment.
The prognostic value of GLS for early prediction of cardiotoxicity has been shown in multiple studies. In one meta-analysis,7 which focused on more than 1,700 patients with cancer (including breast, hematologic, or sarcoma) treated with anthracycline with or without trastuzumab, the incidence of cancer therapy–related cardiac dysfunction ranged from 9.3% to 43.8% (as defined by a drop in LVEF). Given the heterogeneity of published studies, Dr. Liu stated, further multicenter studies of GLS in this role are needed.
“Strain has been shown to be a reliable and reproducible parameter for detecting cancer therapy–related cardiac dysfunction that is superior to two-dimensional LVEF,” stated Dr. Liu. “Reproducibility is a recognized limitation of two-dimensional LVEF.”
In one study, investigators developed a baseline risk score to determine the risk of heart failure in patients being treated for acute leukemia with anthracyclines.8 “GLS less than 15% was a powerful predictor of development of heart failure, and it was independently associated with all-cause mortality, after adjusting for age and leukemia type,” Dr. Liu commented. “When GLS is less than 16%, subclinical left ventricular dysfunction can be assumed.”
The recent SUCCOUR trial, however, shed less positive light on the role of GLS in guiding cardioprotective treatment in patients undergoing treatment for breast cancer.9 In this study, a GLS-based strategy for early detection and treatment of cancer therapy–related cardiac dysfunction was not superior to an LVEF-based strategy when applied broadly in the breast cancer population. Dr. Liu noted, however, this group was a very healthy, low-risk population. And, she noted, there was a slightly higher incidence of cancer therapy–related cardiac dysfunction in the LVEF-guided group and a lower final ejection fraction in the LVEF-treated cardioprotective group than in the GLS group, suggesting a potential benefit with GLS in guiding cardioprotective treatment in a higher-risk population.
Update on Consensus for Multimodality Imaging During and After Cancer Therapy
Juan Carlos Plana, MD, FASE, FACC
Juan Carlos Plana, MD, FASE, FACC, Chief of Cardiovascular Service, Baylor St. Luke’s Medical Center and Associate Professor of Medicine, Baylor College of Medicine, Houston, revisited the expert consensus for multimodality imaging of adults during and after cancer treatment from nearly 10 years ago.10 This report was from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACI).
In terms of cancer treatment–related cardiac dysfunction, Dr. Plana believes some changes in the criteria will be made on the next iteration of these guidelines. Ten years ago, the definition included both a drop of 10 absolute points of LVEF and an LVEF of less than 53%. However, Dr. Plana, commented, “I think that probably in the next version of the document, we’re going to shut off the requirement of the drop of 10 points of ejection fraction.” So, stage B heart failure, which Dr. Plana called pre–heart failure, and LVEF less than 53% would be the criteria for cancer treatment–related cardiac dysfunction. “A lot of the patients I see will end up with heart failure with mildly reduced ejection fraction,” he noted.
According to Dr. Plana, the only category 2A recommendation for patients who have heart failure with mildly reduced ejection fraction is the use of an SGLT2 (sodium-glucose transport protein 2) inhibitor. “The medications we have been using historically [ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists] work when you get very close to the LVEF of 40% but don’t for those patients between 41% and 49%,” declared Dr. Plana.
As for echocardiographic evaluation of cardiac structure and function in patients receiving cancer treatment, “I can say without hesitation that three-dimensional echo and global longitudinal strain is a class 1 indication,” stated Dr. Plana. In clinical practice, he added, those with moderate, high, and very high cardiovascular risk “are the ones I tell oncology to send my way [for assessment].”
Finally, Dr. Plana turned to the detection of subclinical left ventricular dysfunction in patients with cancer. Although the use of GLS is intentionally not included the ASE/EACI guidelines at this time, it can be useful in those being treated for cancer. “If you are in the middle in terms of ejection fraction, such as between 50% and 60%, this is when global longitudinal strain may be helpful,” he said. However, given the somewhat negative results with GLS from the SUCCOUR trial,9 Dr. Plana believes GLS should not be used for surveillance after cancer treatment. “It just doesn’t work,” he noted. “We don’t have the data right now.”
DISCLOSURE: Dr. Cardinale has received honoraria from Siemens Healthineers, Ipsen SpA, and Gilead Sciences. Dr. Liu has received honoraria from GE Healthcare and Philips Medical. Dr. Plana is a consultant to General Electric.
REFERENCES
1. Cardinale D: Tips and tricks for cardiac biomarkers in daily practice. 2023 Global Cardio-Oncology Summit. Presented September 28, 2023.
2. Liu J: When is strain needed in patients with cancer? 2023 Global Cardio-Oncology Summit. Presented September 28, 2023.
3. Plana JC: Organizing cardio-oncology imaging pathways. 2023 Global Cardio-Oncology Summit. Presented September 28, 2023.
4. Pudil R, Mueller C, Celutkiene J, et al: Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: A position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail 22:1966-1983, 2020.
5. Porter C, Azam TU, Mohananey D, et al: Permissive cardiotoxicity: The clinical crucible of cardio-oncology. JACC CardioOncol 4:302-312, 2022.
6. Cardinale D, Ciceri F, Latini R, et al: Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. Eur J Cancer 94:126-137, 2018.
7. Oikonomou EK, Kokkinidis DG, Kampaktsis PN, et al: Assessment of prognostic value of left ventricular global longitudinal strain for early prediction of chemotherapy-induced cardiotoxicity: A systematic review and meta-analysis. JAMA Cardiol 4:1007-1018, 2019.
8. Kang Y, Assuncao BL, Denduluri S, et al: Symptomatic heart failure in acute leukemia patients treated with anthracyclines. JACC CardioOncol 1:208-217, 2019.
9. Negishi T, Thavendiranathan P, Penicka M, et al: Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy: 3-Year results of the SUCCOUR trial. JACC Cardiovasc Imaging 16:269-278, 2023.
10. Plana JC, Galderisi M, Barac A, 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. Eur Heart J Cardiovasc Imaging 15:1063-1093, 2014.
