Cardiotoxicity of Immune Checkpoint Inhibitors in Patients with Lung Cancer

S50 Journal of Cardiac Failure Vol. 25 No. 8S August 2019 126 Barriers to Weight Loss in a Heart Failure with Preserved Ejection Fraction Clinic Weihan Chen, Scott Hummel, Sonja Schuetz, Benjamin Palleiko, Taleen Shahrigian, Jen McNamara, Sue Ryskamp, Matthew Konerman; University of Michigan, Ann Arbor, MI

incur a troponin elevation compared to patients on conventional chemotherapy. Elevated troponin is associated with an increased likelihood of MACE, especially early during treatment with ICIs. This data supports closer monitoring, including serial troponin measurements during the early phase of ICI therapy.

Introduction: Obesity is common in HFpEF, and likely contributes to its development and progression. Cohort studies and clinical trials suggest that weight loss is beneficial, but barriers to weight loss in this population may be substantial. Methods: We performed a chart review of patients presenting to our HFpEF Clinic from 1/2015 to 9/2018. Obesity was defined as a body mass index
30 kg/m2. We evaluated physical activity using the Godin Leisure-Time Questionnaire. We evaluated for anxiety and depression with General Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9) scores. Pittsburgh Sleep Quality Index scores were used in combination with chart data to calculate risk of obstructive sleep apnea (OSA) using the STOP-BANG criteria. The Short Physical Performance Battery (SPPB) was used to assess frailty. Patient electronic medical records were reviewed for polysomnograms (PSG), outpatient nutrition consults, and bariatric surgery and cardiac rehabilitation referrals. Results: We identified 127 obese HFpEF patients (61% female) with an average age of 69 § 6.6 years. Comorbid conditions were common (85% hypertension, 70% hyperlipidemia, 59% diabetes mellitus). Of the 50 patients with adequate data to calculate a STOP-BANG score, 96% met criteria for high risk of OSA. All 35 patients that had a PSG tested positive for OSA. Barriers to weight loss were common including anxiety, depression, and frailty (see Table). Most did not meet the Government Advisory Committee recommended 500 MET-min/week and over half reported no exercise at all. The overall utilization of resources to facilitate weight loss was suboptimal. Fewer than one-third received an outpatient dietitian consultation. Less than half meeting criteria for bariatric surgery were offered the intervention. Three-quarters of patients with indications for cardiac rehabilitation were referred; however, many did not have Medicare-reimbursed indications. Conclusion: Barriers to weight loss are highly prevalent in HFpEF, with many patients struggling with anxiety, depression, frailty, and decreased activity levels. Opportunities exist to facilitate weight loss and improve quality of life in HFpEF through multidisciplinary interventions to address these challenges. Barriers to Weight Loss among Obese HFpEF Patients (BMI
30 kg/m2) Barriers to Weight Loss Anxiety Depression Physical Activity

SPPB Nutrition Consult Bariatric Surgery Cardiac Rehabilitation

# Completed GAD7 % with Anxiety # Completed PHQ9 % with Depression # Completed Godin Leisure Score % < 500 Met-min/week % 0 Met-min/week # Completed SPPB % Frail (SPPB<10 points) % Referred # Patients with Indications % Referred # Patients with Indications % Referred

28 21% 34 50% 84 85% 55% 125 59% 28% 44 46% 49 76%

127 Cardiotoxicity of Immune Checkpoint Inhibitors in Patients with Lung Cancer Kalyan R. Chitturi, Raquel Araujo-Gutierrez, Edward T. McLean, Jiaqiong Xu, Arvind Bhimaraj, Ashrith Guha, Imad Hussain, Barry H. Trachtenberg; Houston Methodist Hospital, Houston, TX Background: Immune checkpoint inhibitors (ICIs) activate the host immune system to target cancer cells. However, the unchecked systemic inflammatory response may result in cardiovascular immune-related adverse events, as myocarditis, pericardial disease, stress-induced, and dilated cardiomyopathy are increasingly reported in case series and pharmacovigilance databases. We sought to further investigate ICI-related cardiotoxicity in a cohort of patients with lung cancer. Methods: We performed a retrospective analysis of patients with a pathologically confirmed diagnosis of primary lung cancer treated with ICIs or non-ICI systemic therapy over three years to assess the likelihood of major adverse cardiovascular events, defined as cardiovascular death, non-fatal MI, non-fatal stroke, and hospitalization for heart failure. Data was collected on co-morbidities, cardiovascular medications, past or concurrent radiation or systemic therapies, serum troponin, brain natriuretic peptide levels, pre- and post-treatment electrocardiograms, echocardiography, angiography, and total ICI dose. Each factor was compared between patients treated with ICIs and non-ICI systemic therapy. Results: We included 252 patients in our study. During a median follow-up of 6 months (interquartile range: 2-14 months), patients treated with ICIs (n = 135) who had a troponin elevation were more likely to sustain a MACE (hazard ratio: 6.9, 95% confidence interval: 3.2-15, p <0.001) with a median time to event of 33 days (Figure 1). Discussion: Patients with lung cancer on ICIs are more likely to

Figure 1.

128 Outcomes of Heart Failure in Adult Patients with Muscular Dystrophy: A Single Center Experience Tanya Doctorian, David Farchadi, Shuktika Nandkeolyar, Dmitry Abramov, Liset Stoletniy, Antoine Sakr; Loma Linda University Medical Center, Loma Linda, CA Introduction: Cardiomyopathies associated with Duchenne (DMD) or Becker (BMD) muscular dystrophy have been historically noted to have poor outcomes in the pediatric population, but studies in the adult population are sparse. Hypothesis: The goal of this study was to determine the rates of ejection fraction (EF) decline and overall survival outcomes in a cohort of adult patients with dystrophinopathic cardiomyopathies on contemporary heart failure therapies. Methods: This is a retrospective cohort study of 41 adults with muscular dystrophy (29 with DMD, 7 with BMD, 5 with other types of muscular dystrophy) out of 1582 heart failure patients followed in the Loma Linda University International Heart Institute clinic who were evaluated using the following outcome measures: mortality and rate of EF decline comparing first and most recent echocardiogram. Results: The cohort had a mean age of 32 years (DMD was 31 and BMD was 35 years), 71% with DMD, 17% with BMD, 100% male, 44% Caucasian, 37% Hispanic, and 12% African American. Mean follow up time in clinic was 6.79 years. Mortality within 5 years was 29% (17% in the DMD group and 33% in the BMD group). Mean EF on the most recent echocardiogram was 31.7% for the DMD group and 28.0% for the BMD group. Of the patients who are still alive (n=29), 83% are on a beta blocker and 93% are on an ACEi, ARB, or ARNI. Of those who have died (n=12), 92% were on a beta blocker and 75% were on ACEi, ARB, or ARNI. Twelve out of 31 survivors were on ivabradine versus 0 out of 12 who died (p=0.08). The mean rate of EF decline in the overall cohort was about 3.1% per year (3.0% per year for DMD, 4.4% year for BMD); see Figure 1. The mean rate of EF decline in those who died was 3.7% per year, and 2.8% in those who are still alive. Conclusions: Dystrophinopathic cardiomyopathies are associated with progressive left ventricular remodeling and about 3% per year mean drop in EF. Survival tended to be greater in patients treated with ivabradine. Further research is needed in the adult muscular dystrophy population to evaluate the effectiveness of contemporary heart failure therapy including ivabradine in slowing the progression of their cardiomyopathy