1. Lindsey, Heather

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The rapidly evolving specialty of cardio-oncology is becoming an increasingly necessary one for managing the health of cancer patients, especially with the aging population in this country and the complexity of some cancer treatment regimens, according to experts.

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With the baby boomer generation, "there is a real mandate for more expertise in cardio-oncology," said Robert Masci, MD, Cardio-Oncologist at Morristown Medical Center's Carol G. Simon Cancer Center and Gagnon Cardiovascular Institute in New Jersey. In older cancer patients, cardiovascular comorbidities can be exacerbated by certain cancer treatments, he explained. For younger patients, certain cancer treatments may play a role in causing cardiovascular disease.


Cardiovascular disease is the leading cause of mortality worldwide, followed by cancer, noted Arturo Loaiza-Bonilla, MD, MSEd, FACP, Chief of Medical Oncology and Medical Director of Research at Cancer Treatment Centers of America (CTCA) at Eastern Regional Medical Center, Philadelphia. "It makes sense oncologists and cardiologists are joining forces and making sure these disciplines are aligned so patients are living longer, healthier lives," he said.


Benefits of Cardio-Oncology

Cardiologists can provide ongoing monitoring of cancer patients for cardiovascular side effects associated with cancer treatments, said Mark M. Applefeld, MD, Director of the Heart Center and Chief of the Department of Cardiology at Mercy Medical Center in Baltimore, where he often sees cancer patients as part of his practice. "They can also consult on which agents are going to least likely exacerbate or cause cardiovascular disease in a given patient," he said. Helping oncologists navigate the effects of radiation therapy is another skill cardiologists can offer.


When evaluating patients, Amit K. Pursnani, MD, Cardio-Oncologist at NorthShore University HealthSystem outside of Chicago, assesses patient-related risk factors, such as high blood pressure, diabetes, high cholesterol, and a family history of coronary artery disease, in addition to treatment-related risk factors such as the chemotherapy regimen and radiation treatment plan. With this information, he offers risk-reduction strategies, such as treating existing hypertension, high cholesterol, diabetes, and obesity. Primary prevention therapies may also be an option.


Chemotherapy & Other Cancer Drugs

Several decades ago, the number of chemotherapy agents available was limited, so cardiologists did not routinely consult on cancer treatment decisions with oncologists, noted Applefeld. Today, however, with the number of agents and complex treatment regimens available, cardio-oncology is a growing subspecialty.


One of the most notable first-line agents to cause cumulative dose-dependent cardiotoxicity is the anthracycline doxorubicin. The literature indicates that identifying cardiac damage early and treating it with ACE inhibitors and beta-blockers may help mitigate this damage, said Barry Trachtenberg, MD, a cardiologist who established the cardio-oncology program at Houston Methodist DeBakey Heart & Vascular Center. With delayed diagnosis, treatment is less likely to improve heart function.


In patients at high risk of developing cardiovascular comorbidities, a liposomal anthracycline may be less cardiotoxic, said Trachtenberg. In addition, using the cardioprotective medication dexrazoxane may be considered in certain high-risk populations.


Trastuzumab is another drug associated with cardiotoxicity, noted Applefeld. "If you recognize the cardiomyopathy, you can stop the drug to reverse the heart failure," he said. Once the patient recovers, oncologists typically resume treatment. However, Applefeld has seen patients in whom cardiomyopathy recurs once trastuzumab is resumed.


Oncologists may be able to continue to complete a course of trastuzumab in patients with mildly diminished left ventricular (LV) function, while closely being monitored by a cardiologist, noted Masci. "If LV function becomes diminished, what we have done is temporarily hold the trastuzumab and put the patient on medications such as carvedilol aiding the heart's recovery, then restarting trastuzumab to complete the planned course of therapy," he said. "This increases the patient's chance of disease-free survival."


Also of note, targeted VEGF inhibitors such as bevacizumab can cause hypertension, which can be problematic in patients who are already at risk of stroke or heart failure, said Loaiza-Bonilla. Additionally, the tyrosine kinase inhibitor imatinib can cause fluid retention, leading to heart failure.


To better understand the impact of chemotherapy and other drugs on cardiovascular health, "we're trying to establish a protocol where we put different drugs in different buckets of risk," said Loaiza-Bonilla.


The goal with CTCA's cardio-oncology program is to increase awareness among oncologists and create a consensus-based approach to care when considering medications that may cause or exacerbate cardiovascular morbidity. "It's a dynamic program because we're learning more as additional information comes along from phase III trials," noted Loaiza-Bonilla. Ongoing surveillance is also valuable.


Radiation Therapy

Cardiovascular side effects from radiation therapy such as coronary artery disease and aortic stenosis may occur decades after treatment, although some patients may not survive long enough to experience these, said Applefeld. Other side effects, such as pericarditis, may occur as soon as 6-12 months after radiation therapy, although this adverse event may also arise further out from treatment.


Specifically, in patients with left-sided breast cancer, radiation therapy can lead to coronary artery disease by causing inflammation of the coronary arteries, said Masci. Other potential cardiovascular toxicities include fibrosis of the aortic and mitral valves, pericarditis, particularly constrictive pericarditis, and cardiomyopathy.


Adult survivors of childhood cancer should undergo regular cardiovascular health screening by a cardiologist, said Masci. Patients who have received >30-35 Gy units are at particularly high risk. More modern radiation therapy techniques, including intensity-modulated radiation therapy and complex 3D treatment modeling, have helped reduce the risk of cardiac injury and cardiovascular side effects, he noted.


Radiation oncologists, physicists, and cardiologists often discuss patient imaging scans and work together to ensure therapy minimizes cardiovascular damage, said Loaiza-Bonilla. Highly targeted radiation and proton-based therapy allow radiation oncologists to decrease damage to healthy tissue.


Exams such as a coronary CT angiography and stress tests may help cardiologists and oncologists determine whether a patient's arteries are healthy enough for radiation therapy to the chest, especially in individuals with high-risk features, said Trachtenberg. "There's not real long-term evidence that drugs such as statins help mitigate risk of radiation therapy," he added.


Collaboration Key

Loaiza-Bonilla uses a multidisciplinary approach to managing patients with cardiovascular risk factors or whose treatments may raise these risks. A team that includes cardiologists, internal medicine physicians, and oncologists meets to discuss treatment plans.


Multidisciplinary teams consider the intent of treatment and the patient's quality of life, said Loaiza-Bonilla. They weigh the risks and benefits of treatments and consider patient preferences. They also consider the survivorship of patients and the potential for developing cardiovascular complications later in life. An increased risk of complications may be acceptable because the treatment strategy may have a curative intent, he said.


Ongoing communication between the cardiologist and the oncology team can aid in maximizing the ability to achieve a cure, while minimizing potential cardiovascular side effects, said Masci.


Available Guidelines

Medical organizations are gradually reaching a consensus on what recommendations to follow to help prevent cardiotoxicity in cancer patients, said Pursnani. For example, guidelines for the prevention and monitoring of cardiovascular morbidities are available from ASCO (J Clin Oncol 2017; doi:10.1200/JCO.2016.70.5400). Another on imaging evaluation of adult patients during and after cancer therapy is available from the American Society of Echocardiography and the European Association of Cardiovascular Imaging (Eur Heart J Cardiovasc Imaging 2014;15(10):1063-1093).


"We do have guideline-recommended echocardiogram surveillance algorithms to monitor patients who have received anthracyclines and trastuzumab," said Pursnani.


He would like to see evidence on whether following such guidelines helps impact cardiovascular outcomes in patients. "We need to know how often certain patients need echocardiograms, and which ones should be given preventive therapies for cardiac dysfunction," Pursnani concluded.


Heather Lindsey is a contributing writer.