Cardiovascular Effects of Cancer Therapies:  How Do We Diagnose and Treat in 2021

Dr. Ana Barac, M.D., Ph.D., F.A.C.C.

Director, Cardio-Oncology Program
Medstar Heart and Vascular Institute
Associate Professor of Medicine
Georgetown University
Washington, DC

Dr.Barac kicked off the session with an update on the current challenges in cancer patients receiving cardiotoxic chemotherapy.  One of the major emphasis was on the newer definitions of cardiotoxicity and the challenges with cardiac imaging in patients with breast cancer who undergo mastectomy and breast implants. Dr. Barac stated that breast implants lead to technical difficulty in assessing the left ventricular ejection fraction accurately using 2 D echocardiography.  With new breast implants cardiac MRI is also challenging for up to 6 months post-surgery.  Dr. Barac also presented data supporting the use of global longitudinal strain abnormality. As a biomarker of future drop in LVEF in patients receiving cardiotoxic chemotherapy (anthracycline based and HER2 receptor antagonists such as Trastuzumab/Pertuzumab) for breast cancer, lymphoma and certain other malignancies . She emphasized that there is potentially a role for the use of beta blockers and/or ACE inhibitors (blood pressure permitting) to prevent a further drop in left ventricular ejection fraction.  Dr. Barac provided an update on immune checkpoint inhibitor associated myocarditis (rare with < 1% incidence) and emphasized the utility of both cardiac MRI and endomyocardial biopsy for the diagnosis. She summarized by stating that there is a growing unmet need for further development of this field of cardio oncology and allocation of resources for both clinical and research purposes to effectively identify patients at risk of cardiotoxicity and to develop cardio safe treatment strategies and therapies to continue to improve survival in cancer patients.

Role of Atrial Dysfunction and Atrial Valvular Regurgitation in HFpEF

Yogesh Reddy, M.D., M.Sc.

Senior Associate Consultant
Mayo Clinic
Rochester, MN

Dr. Reddy provided a fascinating talk using pathophysiological examples of atrial dysfunction in HFpEF and atrial fibrillation.  Specifically, he stated that as atrial fibrillation progresses and as the patients develop heart failure with preserved ejection fraction the left atrial compliance decreased.  Using classic illustrations, he noted that the stiffening of the left atrium could potentially be identified based on invasive hemodynamics using a right atrial pressure tracing which would show a prominent "v" wave.  He emphasized that clinicians could use this as a marker of significant left atrial stiffening.  Dr. Reddy also brought to light the concept of interdependence of left ventricular end-diastolic pressure, left ventricular transmural pressure and pericardial pressure coupling underlying the pathophysiology of atrial fibrillation and heart failure with preserved ejection fraction.  He stated that the right atrial pressure could potentially serve as a good surrogate of pericardial pressures during invasive hemodynamic study.  Dr. Reddy described the concept of “atrial mitral regurgitation” which is essentially the presence of significant mitral regurgitation in the absence of significant mitral valve pathology or left ventricular dilatation.  He noted that this entitiy is associated with atrial dilatation that could lead to tethering of the posterior mitral leaflet leading to a predominantly "eccentric" mitral regurgitation.  Similarly, he commented on atrial tricuspid regurgitation which is seen in the absence of pulmonary arterial hypertension or heart failure with reduced ejection fraction and presence of structurally normal tricuspid valve .  Dr. Reddy concluded by illustrating the utility of invasive inferior vena caval occlusion test to uncover the presence of pericardial constraint.  He noted that during an IVC occlusion a decrease in the right atrial pressure but no significant change in the wedge pressure is suggestive of more pericardial constraint as opposed to abnormal left ventricular end-diastolic/left ventricular transmural pressures (where both the right atrial and the wedge pressures were decreased with IVC occlusion).

This session highlighted novel concepts of atrial mitral and tricuspid regurgitation, effects of pericardial constraint on cardiac hemodynamics and the interdependence with atrial stiffening/loss of compliance.

Is Earlier Consideration of Atrial Fibrillation Catheter Ablation Beneficial for Patients?

Sana M. Al-Khatib, M.D., M.H.S., F.A.C.C.

Professor of Medicine
Duke Clinical Research Institute
Duke University
Durham, NC

Dr. Al-Khatib provided a very detailed overview of all the major clinical trials of radiofrequency catheter ablation in paroxysmal atrial fibrillation ablation in patients with heart failure with reduced ejection fraction.  She focused on major trials such as CASTLE AF, CABANA, EARLY AF NET, EARLY AF and LVEF trial.  Dr. Katab summarized all of these trials and concluded that an individualized approach needs to be employed for every patient with paroxysmal atrial fibrillation and heart failure with reduced ejection fraction in order to ensure successful outcomes.  She stated that prior to radiofrequency catheter ablation, strict risk factor control strategy should be employed to control hypertension, obesity and obstructive sleep apnea.  Specifically, she stated that in those with paroxysmal atrial fibrillation and in selected cases of persistent atrial fibrillation with no significant left atrial myopathy or fibrosis or underlying significant structural heart disease, radiofrequency catheter ablation could provide symptom relief and a reduction in cardiovascular hospitalizations.  She emphasized that the trials do not point to a significant mortality reduction with the use of early catheter-based ablation in HFrEF patients with paroxysmal atrial fibrillation.  When posed a question on use of catheter ablation in morbid obesity patient's Dr. Katab stated that her approach would be to delay such procedures in those who are greater than 300 pounds and such group could benefit from referral to bariatric surgery program.  She also clarified the current definitions of atrial fibrillation and summarized as follows: #1 paroxysmal atrial fibrillation-patient is going in and out of atrial fibrillation on their own with no assisted medical therapies, #2 persistent atrial fibrillation-group of patients requiring cardioversion to get them out of atrial fibrillation, #3 longstanding persistent atrial fibrillation-group of patients who have had atrial fibrillation for at least 1 year and #4 permanent atrial fibrillation-where decision has been taken by the patient and the provider to remain in atrial fibrillation.

Omega-3 Fatty Acids-Role in CV Prevention

Amit Khera, M.D., M.Sc., F.A.C.C.

Professor of Medicine
Director, Preventive Cardiology
U.T. Southwestern Medical Center
Dallas, TX

Dr. Khera presented an update on the current controversies associated with the use of both prescription and nonprescription, omega-3 fatty acid supplements, to reduce cardiovascular adverse events.  Dr. Khera provided an overview on the use of EPA and DHA fish oil.  He stated that there are several commercial formulations in use such as Vascepa (which has 1 g of EPA), Lovaza (as a combination of EPA plus DHA).  He summarized all the major trials associated with the use of omega-3 fatty acids and cardiovascular disease prevention such as ASCEND, VITAL, REDUCE IT, EVAPORATE, STRENGTH, JELLID study.  While each of these trials used different formulations of EPA and DHA and assessed endpoints which were nonuniform Dr. Khera helped summarize the data in recommending the following strategy for providers encountering patients specifically with elevated triglyceride levels.
Recommendation #1: For primary prevention of cardiovascular disease in patients with normal triglycerides he stated that there is currently no data to support the use of either EPA or DHA supplements.
Recommendation #2: For both primary and secondary prevention in a group of patients with triglycerides greater than 500 current recommendation is to use 2 g of omega-3 fatty acids 2 times a day primarily to reduce the incidence of pancreatitis.
Recommendation #3: For secondary prevention in the group of patients with triglycerides between 150 and 499 he recommended that the initial strategy should imply a combination of statin therapy or PCSK9 inhibitors with or without SGLT2 inhibitors and if adequate control is not achieved such patients good benefit from use of 2 g twice a day of Icosapentanoic acid.

He also emphasized that the fish oil supplements in general (based on the trials mentioned above) are associated with an increased risk of atrial fibrillation and hence patients need to be informed about the potential risks prior to initiation of treatment.

Summary Prepared by:

Tarun W. Dasari,  M.D., M.P.H., F.A.C.C., F.H.F.S.A.
Associate Professor of Medicine
Cardiovascular Section,
Director of Coronary Care Unit, OU Medical Center
University of Oklahoma HSC