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PurposeCardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers.MethodsRecommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology.ResultsA total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.RecommendationsIt is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

e19009 Background: Ibrutinb is approved for treatment of CLL. Hypertension (HTN) has been reported as a side effect of ibrutinib in 1-23% of patients. We previously reported HTN in CLL patients after 6 months of treatment with ibrutinib. In this study we describe the effects of long-term treatment with ibrutinib on blood pressure (BP). Methods: We performed a retrospective study, evaluating 150 CLL patients on ibrutinib-based clinical trials from 2010 to 2015. Patient demographics, co-morbidities, tobacco use, anti-HTN therapy were recorded. BP was evaluated at baseline and sequentially for up to 5 yrs. New onset HTN was defined as systolic BP (SBP) of ≥ 130 mmHg and/or diastolic BP (DBP) ≥ 80 on two separate visits with no prior HTN or anti-HTN therapy. An increase in baseline SBP by ≥10 and/or increase in DBP by ≥10 was considered significant regardless of the absolute BP. Univariate logistic regression analysis was performed to assess relationship of HTN risk factors and new HTN. Results: Patients’ median age was 65 yrs (68% male and 88% white). Median follow-up was 3 yrs. Pre-existing HTN was present in 44% of patients, 40% were on anti-HTN therapy prior to ibrutinib. New HTN developed in 65% of patients without prior diagnosis of HTN; 32 % of patients were started on anti-HTN therapy or received additional anti-HTN therapy. Of the patients who experienced an increase in BP, 33% experienced isolated systolic HTN. Median SBP was 130 at baseline, 132 at 1mo, 137 at 3mo, 135 at 6mo, 139 at 12mo, 138 at 3yrs, 144 at 5yrs (mean increase in SBP: 7.2, P < 0.001). In patients whose SBP was < 130 at baseline the median SBP was 119 at baseline, 122 at 1mo, 134 at 3mo, 130 at 6mo, 134 at 12mo, 135 at 3yrs and 141 at 5yrs (mean increase in SBP: 15.7, p < 0.001). 74% of patients experienced and increase in SBP ≥10. New HTN on ibrutinib was not associated with: tobacco use, obesity, chronic kidney disease or obstructive sleep apnea (p > 0.05). Conclusions: In this study we demonstrated a high rate of new HTN in patients on prolonged ibrutinib treatment. HTN in these patients is persistent, linear and independent of other risk factors. The increase in BP remained despite initiation of anti-HTN therapy. Additional studies are ongoing to define cardiovascular and renal complications associated with HTN in these patients.

e21526 Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT > 0.01 ng/ml and NT-proBNP levels > 97.5th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- < 20 Gy RR 1.62 [CI 1.07-2.46], 20- < 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend < 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m2 RR 1.39 [1.01-1.91], 201-350mg/m2 RR 2.28 [1.74-2.99], > 350mg/m2 RR 2.99 [2.27-3.95]; p for trend < 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( < 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.

e14121 Background: Various immune-related adverse events (IRAE) have been reported with the use of immune checkpoint inhibitors (ICI). Although a rare event, the increasing incidence of ICI related myocarditis and its reported high mortality raises concern. Cardiovascular IRAE such as pericardial effusions (PE) have been documented in case reports and case series but their clinical significance is unclear. Methods: Retrospective chart review was performed on 1075 patients receiving ICI between 2015 and 2017 with baseline echocardiograms without pericardial effusions and follow up echocardiograms at MD Anderson Cancer Center. We collected baseline characteristics, laboratory findings, echocardiograms, and dates of ICI initiation, PE development, last follow up and death. Overall survival (time from first ICI therapy to death or last follow up) was calculated. Univariate Fine-Gray regression analyses were conducted to identify variables associated with PE to account for death as a competing risk event. A p-value of less than 0.05 indicated statistical significance. Results: After initiation of ICI, 78 patients (7.3%) developed PE of which 45 patients died (58%) compared to 347 deaths (35%) out of the 997 patients without PE. The median follow-up time was 445 days. Univariate Fine-Gray analyses predicting PE demonstrated lower body surface area, lowest nadir in left ventricular ejection fraction (LVEF), higher troponin levels, lower platelet counts, absence of ectopy and hyperlipidemia, and lack of avelumab in therapy as well as a history of heart failure with preserved or reduced ejection fraction, hematologic cancer, and peripheral artery stents were significantly associated with higher incidence of PE. Conclusions: While the development of PE is an IRAE or progression of cancer itself cannot be determined, this study indicates patients receiving ICI who developed PE had higher mortality. Those with greater troponin levels and substantial decline in LVEF were shown to have a greater propensity of developing PE, suggesting the possibility of an underlying myopericarditis. If PE develops during ICI therapy, providers should consider an expedited workup and treatment of ICI related myocarditis.

e14118 Background: A rare and often fatal spectrum of NM immune-related adverse events (irAEs) includes myositis, myocarditis, and myasthenia gravis (MG). A deeper understanding of their clinical and immunologic features may improve outcomes. Methods: Sixteen patients (pts) with genitourinary cancers who were treated with ICI and developed myositis, myocarditis, MG, or overlap syndrome (≥2) were identified. Diagnostic criteria included serum CK (n=16), aldolase (n=14), troponin (n=12), BNP (n=15), autoantibodies (n=16), and cytokines (n=9). Biopsies of skeletal muscle (n=13) and endomyocardium (n=4) were also obtained. Immune profiling is being performed on blood and tissue for pts consented to an institutional-approved laboratory protocol. Results: ICI-associated NM irAEs consisted of isolated myositis (n=8, 50%), myocarditis (n=1, 6%), MG (n=1, 6%), or overlap syndrome (n=6, 38%), with the most common presenting symptom being weakness (n=9, 56%). CK levels were elevated in 15 (94%) pts, and autoantibodies were detected in 9 (56%). Muscle biopsies showed predominantly T cell infiltration. All 16 pts received corticosteroids, 12 (75%) were treated with other immunosuppressive agents, and 14 (88%) underwent plasmapheresis. Five pts (50%) with isolated irAEs achieved symptom resolution, and none in the overlap group. (Table) Conclusions: NM irAEs occurred more frequently with combination ICI, and were associated with weakness, and elevated CK level and serum autoantibodies. Both T and B cells appear to drive disease pathogenesis. The presence of one toxicity on the spectrum warrants evaluation for associated irAEs. Compared to isolated NM irAEs, the overlap syndrome appears to be more treatment refractory. Current guidelines require refinement to identify effective treatments to improve outcomes. [Table: see text]

e15692 Background: Carcinoid Heart Disease (CHD) complicates 50% of carcinoid syndrome cases and represents a major cause of mortality in these patients. Surgery continues to be the only strategy to improve survival in CHD. We aimed to evaluate predictors of mortality following surgery for CHD. Methods: We retrospectively analyzed patients with CHD and a history of valve surgery presenting at a tertiary cancer center between November 2005 and March 2018. Data regarding symptoms, clinical findings, and CHD treatment were collected. Overall survival (OS, time interval from heart surgery to death) was calculated. Univariate Cox proportional hazards regression analyses were conducted to identify variables that were associated with OS. Results: We identified 25 patients with CHD who underwent surgical replacement with bioprosthetic valves: 10 (40%) the tricuspid valve (TV), 11 (44%) TV and pulmonary valve (PV), 3 (12%) TV, PV, and aortic valve, and 1 (4%) all 4 valves. Among them, 19 (76%) survived at least 12 months after the surgery. Clinical factors associated with decreased OS are presented in Table 1. Conclusions: OS following surgery is dictated by the severity of CHD at the time of surgery. Worse outcomes are predicted by a history of congestive heart failure, the number of symptoms, and ascites. Better selection criteria are needed in order to choose the candidates for surgery who will benefit the most. [Table: see text]

79 Background: Checkpoint Inhibitors have become first line therapy for a variety of solid and liquid malignancy. Immunotherapeutic agents predominantly target CTLA-4 and PD-L1. Efficacy has been demonstrated, and toxicities, especially cardiac manifested as myocarditis. The incidence of myocarditis is relatively low, fatality with monotherapy approaches 50% and with dual Immunotherapy is over 75%. No screening biomarkers or cardiac imaging predict a priori whom will develop myocarditis, nor which patients will be at risk. The frequency of these targets are unknown in the human heart. Methods: We present a case study of a patient with a diagnosis of urothelial carcinoma to lung and lymph nodes treated with systemic nivolumab plus NKTR after cycle 2 he presented with one week history of shortness of breath and hemodynamically unstable complete heart block requiring temporary transvenous pacemaker. Initial Troponin = 356, BNP = 2106. Given high suspicion for cardiovascular disease and or myocarditis, a left heart angiogram, right heart catheterization and endomyocardial biopsy of right ventricle were performed. RV biopsies were obtained percutaneously from right internal jugular approach with fluoroscopic guidance. Pulmonary capillary wedge pressure was 23mmHg. Persistent complete heart block was present during weaning attempts from temporary pacemaker and a percutaneous dual chamber pacemaker was implanted. Results: Coronary angiogram showed non obstructive disease, endomyocardial biopsy revealed lymphocytic infiltrate with necrosis based on Dallas Criteria. Immunohistochemistry showed, predominance of CD3,CD4,CD8,CD20,CD68 and PD-L1 staining was grossly positive compared to control samples. The patient was treated with methylprednisone 1mg/kg IV BID, plasmapheresis times 5 cycles, mycophenolate mofetil 500mg IV BID with resolution of symptoms and discharged to home. Conclusions: We present a patient with nivolumab induced myocarditis complicated with myocarditis and complete heart block. The pathological approach of T-Cell phenotyping is unique and identifies a novel approach to precision driven diagnosis, the incidence of PD-L1 expression in the human heart is unknown.

Purpose To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. Results Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all Ptrend < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). Conclusion Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

Purpose To compare two-dimensional (2D) echocardiography, the current method of screening for treatment-related cardiomyopathy recommended by the Children's Oncology Group Guidelines, to cardiac magnetic resonance (CMR) imaging, the reference standard for left ventricular (LV) function. Patients and Methods Cross-sectional, contemporaneous evaluation of LV structure and function by 2D and three-dimensional (3D) echocardiography and CMR imaging in 114 adult survivors of childhood cancer currently median age 39 years (range, 22 to 53 years) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy. Results In this survivor population, 14% (n = 16) had an ejection fraction (EF) less than 50% by CMR. Survivors previously undiagnosed with cardiotoxicity (n = 108) had a high prevalence of EF (32%) and cardiac mass (48%) that were more than two standard deviations below the mean of normative CMR data. 2D echocardiography overestimated the mean EF of this population by 5%. Compared with CMR, 2D echocardiography (biplane method) had a sensitivity of 25% and a false-negative rate of 75% for detection of EF less than 50%, although 3D echocardiography had 53% and 47%, respectively. Twelve survivors (11%) had an EF less than 50% by CMR but were misclassified as ≥ 50% (range, 50% to 68%) by 2D echocardiography (biplane method). Detection of cardiomyopathy was improved (sensitivity, 75%) by using a higher 2D echocardiography cutoff (EF < 60%) to detect an EF less than 50% by the reference standard CMR. Conclusion CMR identified a high prevalence of cardiomyopathy among adult survivors previously undiagnosed with cardiac disease. 2D echocardiography demonstrated limited screening performance. In this high-risk population, survivors with an EF 50% to 59% by 2D echocardiography should be considered for comprehensive cardiac assessment, which may include CMR.

e22092Background: Cancer patients with thrombocytopenia are at risk of developing significant bleeding complications during cardiac catheterization. Little data is currently available on the outcom...

e22106Background: Unique considerations apply regarding percutaneous coronary intervention (PCI) in cancer patients. Evidence supports lesion assessment using fractional flow reserve (FFR), but its...

Purpose Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity. Patients and Methods Over a 4-year period, 38 patients with HER2/neu–positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy. Results After doxorubicin but before trastuzumab, the mean (± standard deviation) left ventricular ejection fraction (LVEF) was 0.61 ± 0.13, and the LVEF decreased to 0.43 ± 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 ± 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen. Conclusion Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.

e14011 Background:Variants of the classic Tako-tsubo syndrome or stress induced cardiomyopathy (SC) includes mid ventricular or basal left ventricular wall motion abnormalities. Midcavitary dyskinesia and ballooning is considered a unique presentation, and there is no published data showing midcavitary involvement in cancer patients. Methods: All cancer patients who fulfilled the diagnostic criteria for SC at MD Anderson Cancer Center over a 6–year period were included in the study. We selected and retrospectively reviewed the medical records of 8 patients who had midcavitary SC. Clinical presentation, ECG, laboratory data, transthoracic echocardiogram and left ventriculography results were reviewed. Results: Out of30 cancer patients who fulfilled the diagnostic criteria for SC, 8 patients (26.7%) (4 females, 4 men, mean age 57.37 yo) had midcavitary SC. 62,5 % patients were diagnosed with a solid malignancy. Trigger factors for midcavitary SC were: systemic infection (3 patients with neutropenia), emotional stress (2 patients), chemotherapy (1 patient undergoing treatment with Ibrutinib), and surgical interventions (3 patients). Clinical presentation included chest pain (37.5%), shortness of breath (50%) and non specific symptoms (12.5%). T wave inversion was the most common electrocardiographic presentation (37.5 %), followed by ST elevation (25 %). All patients had changes of the cardiac biomarkers (BNP mean 2224. 4 pg/dl, TN I mean 2. 8 ng/dl, CK-MB mean 14 ng/dl) and significant LV dysfunction (LVEF < 50%). All patients underwent coronary angiography which showed no obstructive CAD; left ventriculography identified basilar and apical hyperkinesis and midventricular hypokinesia. Cancer therapy was interrupted; aspirin and beta blockers were initiated in all patients. The most common complications of midcavitary SC were: respiratory failure requiring intubation (37, 5%), pulmonary edema (25%), and hypotension (25%). No cardiac deaths were registered. None of the patients experienced recurrence of SC. Conclusions: Mid cavitary SC remains a rare entity, and raises further questions about the causal association between the mid cavitary involvement and cancer, and its impact on cancer therapy and overall survival in this cohort of patients.

e22536 Background: Pathologic examination is essential for definite diagnosis of both primary and secondary (metastatic) cardiac tumors. Limited data exists on the risks and benefits of catheterization with endomyocardial biopsy (EMB) of cardiac tumors. The present study aims to assess the safety of EBM in diagnosing cardiac tumors. Methods: We retrospectively reviewed therecords of cancer patients who presented with cardiac masses at MD Anderson Cancer Center between 2011 and 2016. Clinical presentation, transthoracic/transesophageal echocardiogram and pathology laboratory results for patients who underwent cardiac catheterization & EMB were reviewed. Results: Out of 8 patients with cardiac tumors (4 females, 4 men, average age of 59.7 y.o.), 5 patients had cardiac catheterization with EMB (5.4 French with Jaw Volume of 2.2, specimens are typically 5 to 20 mg per sample). Clinical presentation included shortness of breath and dyspnea (3 patients), syncope and palpitations (1 patient), and fatigue and slurred speech, as result of a hemispheric stroke (1 patient). Diameter of the cardiac tumors ranged between 4 – 6.5 cm, with no wall abnormalities or hemodynamic compromise as identified by echocardiography. Right atrium (RA) was the most common location (4 patients). One patient had extension of bronchus squamous cell tumor extending into a coronary artery bypass graft (LIMA). Review of the pathological specimens obtained from EMB performed under TEE and fluoroscopic guidance identified 2 patients with cardiac sarcomas in the RA, 1 patient with atrial metastatic melanoma (RA) and 1 patient with lymphoma (right ventricle). EMB was performed with minimal blood loss in all patients. During procedure, one patient developed rapid accumulation of fluid in the pericardial space requiring emergent echo-guided pericardiocentesis. Conclusions: EMB is suggested for the diagnosis of selected cardiac tumors, if the potential benefits from the procedure outweighs the risks. A more invasive approach for rapid histological diagnosis allows appropriate therapy to be promptly initiated. To ensure the safety, EMB should be performed by an experienced operator with fluoroscopy and with transthoracic, transesophageal or intra-cardiac echocardiography guidance.

e14012 Background: Vasospasm and arrhythmias are the main cardiac toxic effects of cancer treatment with Paclitaxel. Chemotherapy induced stress cardiomyopathy (SC) (Tako-tsubo syndrome) has been linked to antineoplastic agents associated with abnormal vasoreactivity. We aimed to identify if there is a causal relationship between SC and Paclitaxel administration. Methods: All cancer patients who fulfilled the diagnostic criteria for SC at MD Anderson Cancer Center over a 6–year period were included in the study. We selected and retrospectively reviewed the medical records of all the patients who had chemotherapy induced SC. Clinical presentation, ECG, laboratory data, transthoracic echocardiogram and coronary angiography results were reviewed. Results: Out of30 patients who fulfilled the diagnostic criteria for SC, 5 patients (16.6%) had SC triggered by chemotherapy. Three patients (2 females, 1 male, mean age 71.3 yo) had Paclitaxel induced SC (60%); two patients received a combination of Paclitaxel and Carboplatin for ovarian cancer, and one patient had combination of Paclitaxel and Cyclophosphamide for prostate cancer. Two patients had cardiac manifestations in the first day of Paclitaxel administration. All three patients presented with chest pain; T wave inversion was the main finding on the electrocardiography. All patients had changes in the cardiac biomarkers (BNP mean 1459.7 pg/dl, TN I mean 1.36 ng/dl, CK-MB mean 8.6 ng/dl) and significant LV dysfunction (LVEF < 50%). Characteristic apical ballooning pattern was identified in all cases from left ventriculogram. Chemotherapy was interrupted ; aspirin and beta blockers were initiated in all patients. Two patients were rechallenged with chemotherapy after 10 days, respectively 20 days after SC. None of the patients experienced recurrence of SC, nor arrhythmias while on aspirin and beta blockers. Conclusions: To our knowledge there are no published data on the association of Paclitaxel administration and SC. In cancer patients who develop acute chest pain after administration of Paclitaxel, evaluation for SC is important to exclude NSTEMI diagnosis, which can impact further cancer therapy. Cancer patients with SC whom have complete recovery may early resume cancer therapy.

136 Background: Chemotherapy-induced left ventricular dysfunction (CILVD) leading to heart failure (HF) is a clinical problem of emerging importance particularly with the 14.5 million cancer survivors who are alive in the United States today, and projected to increase to almost 19 million in 2024. Many of these survivors have received cardiotoxic anticancer agents such as anthracycline and trastuzumab. Research showed that those exposed to anthracyclines are expected to have some degree of cardiac dysfunction 10 to 20 years after treatment and 5% of those patients will develop overt HF. This pilot study investigated whether cancer survivors with CILVD who achieved recovery of cardiac function will maintain their left ventricular ejection fraction (LVEF) if HF medications were discontinued. Methods: We conducted a prospective pilot study on 20 cancer survivors with history of CILVD with recovered cardiac function. HF medications were weaned off in a stepwise process per protocol. Cardiac function was monitored with LVEF measurement per echocardiography and cardiac biomarkers performed at baseline, 2, 4 and 6 months. Patients monitor their heart rate, blood pressure, and symptoms and reported changes based on set parameters. Results: Cancer survivors who maintained their LVEF after discontinuation of HF medications were younger (mean age 47.9 years SD+12.0), 65% female, 55% breast cancer survivors, with no history ofischemic heart disease, hypertension, diabetes mellitus and cardiac dysrhythmias. Chemotherapeutic agents (mean dose) used in the treatment of these patients include doxorubicin (363 mg/m2), epirubicin (527mg /m2), cyclophosphamide (5062 mg), and trastuzumab (6317 mg). There was no significant change from baseline measurements of LVEF and global longitudinal strain (GLS) of 55.1% (± 3.7) GLS of -18.3% (± 2.7) prior to weaning the HF medication to 56% (± 1.6) GLS of -18.2% (± 2.3). after complete withdrawal of HF medications. Conclusions: With the increasing number of young cancer survivors, CILVD may become a frequent clinical issue. Clearly, there is a need to examine the safety of withdrawing HF medications in cancer survivors with CILVD and if lifelong therapy with HF medications is necessary.

7060 Background: Vascular toxicities (eg, peripheral arterial occlusive disease [PAOD]) have been associated with BCR-ABL tyrosine kinase inhibitor (TKI) treatment (tx). Methods: We evaluated vascu...

e20664 Background: Vascular endothelial growth factor (VEGF) inhibitors such as bevacizumab (BV) can result in side-effects such as hypertension (HTN), proteinuria and acute kidney injury (AKI). The objectives are to evaluate practice patterns of BV-induced HTN; to assess frequency of BV dose reduction, withdrawal and delay due to HTN, proteinuria and AKI; and to determine the time course for initial resolution of BV-induced HTN, proteinuria and AKI. Methods: We retrospectively reviewed random charts of 75 cancer patients (pts) treated with BV from 1/1/2009 to 9/30/2011. This included demographic, clinical and outcome parameters. Descriptive statistics were utilized. Results: 37 (56%) were males with median age 56 years (range 19-84). Most had lung (14, 19%), breast (11, 15%), and colorectal cancer (10, 13%). 69 (92%)had metastatic disease. 70 (93%) pts were on BV with other antineoplastic agents. 37 (49%) had a diagnosis of HTN at study entry. The median days from first BV treatment (tx) to first hypertensive reading was 7 (0-279) and days to receiving new or dose increase of HTN meds was 49 (0-283). 44 (59%) pts had 2 consecutive readings ≥ 140 or ≥ 90 mmHg during BV tx and 49 (65%) during post-tx follow-up of 6 months or less. 14 pts received new or dose increase of HTN meds during tx. The most frequent HTN meds used were diuretics (26%), beta blockers (21%) and calcium channel blockers (17%). The average number of new HTN meds at last BV tx was 1.5. No pt had BV dose reduced due to HTN, proteinuria or AKI. BV was withdrawn in 2 (3%) due to HTN, 2 (3%) due to proteinuria and 1 (1%) due to AKI. 5 pts had a delay due to HTN (4) and AKI (1). 57% (8 /14) of pts receiving additional HTN meds during BV tx had first dose decrease of additional HTN meds post-tx at a median of 30.5 (11-162) days. The median number of days to resolve first proteinuria and first AKI was 20 (1-193) and 14 (0-34) days, respectively. Conclusions: HTN occurred in a majority with few receiving extra HTN meds although meeting HTN criteria. Patients continued to have HTN post-tx. However, despite HTN, few stopped BV due to cardiovascular events. Further education regarding HTN guidelines may be necessary and should be considered.

123 Background: Heart failure (HF) is a clinical problem of emerging importance in cancer care. The advances in cancer detection and complex treatment regimens have resulted in increased cancer treatment induced HF. The literature indicates that more than 50% of all patients exposed to anthracyclines will show some degree of cardiac dysfunction either acutely or 10 to 20 years after treatment, and 5% of those patients will develop overt HF. Successful management requires a collaborative, interdisciplinary approach. The purpose of this presentation is to discuss how the “Heart Success Program” (HSP) resulted in cost effective and clinical quality outcomes in patients with cancer and HF. Methods: The HSP was piloted in the emergency center and telemetry units with high volume admission of HF patients. The HSP includes comprehensive education of patients, families, and health care providers regarding HF management in cancer patients. HSP implementation includes a HF order set, patient education booklet, and educational videotape specific for patients with cancer and HF. Weekly interdisciplinary clinical rounds provide a forum for discussion of identified patient’s problems and formulation of solutions. Endpoint outcomes include compliance with the Center for Medicare and Medicaid Services (CMS) core measures for HF, as well as decreasing HF readmissions. Results: The pilot implementation of the HSP resulted in decreased hospital length of stay by 57%, and average hospital admission cost by 60%. Despite multiple co morbid conditions, patients were discharged with improved functional status and compliance with CMS HF core measures. Conclusions: The findings from this quality improvement project showed significant impact in clinical and cost outcomes for patients with cancer and HF. The multidisciplinary team approach that provided support to patients and their families and allowed for patients to continue their cancer treatment resulting in improved outcomes. As we move toward value-based purchasing, the HSP provides an example of how collaboration and standardized process improvement impacts cost and quality in the oncology population.

e13506 Background: Relationship between elevated blood pressure and clinical response in patients with advanced cancers treated with anti-VEGF treatment was evaluated. Methods: We performed an analysis of 438 consecutive patients from 19 clinical trials treated with therapy that included an anti-VEGF agent starting January, 2006. Clinical response was determined by RECIST 1.0. Blood pressures (BP) were scored as shown in Table. BP scores were calculated from an average mean BP of all BP readings for each patient, taken at each visit, and then divided into time points: baseline, 4, 8 and 12 months. Other factor included number of medication. Scores at each time point were compared to baseline value and divided into: increasing, decreasing and stable. Chi-square was used to correlate increased BP scores with clinical response. Additional analysis was also done by using CTCAE v4.02 for grading of BP. Results: The median age was 57 years (13 to 88) and 54% were male; 10% of patients received more than one anti-VEGF therapy. The median number of anti-VEGF therapies was 2 (1 to 3). Within the first four months, 52% of patients who achieved partial response (PR) had increased BP scores from baseline compared to 18% of those with progressive disease (PD) and 25% of those with stable disease (SD) (p

3023 Background: PBI-05204 (Oleandrin), a cardiac glycoside, inhibits the α-3 subunit Na-K ATPase pump. Relative expression of the α-3 subunit in tumor cells correlates with proliferation. Oleandrin inhibits FGF-2 export, activation of NF-Kβ, phosphorylation of Akt, p70S6K, decreasing mTOR activity. In this first-in-human study, we sought to determine the MTD/recommended phase II dose and to define the pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in advanced cancer patients (pts). Methods: Trial was a 3+3 phase I design. PBI-05240 was given for 21 of 28 days. Dose was increased by 100% if no related grade 2 adverse event (AE) emerged and increased by 50% if a grade 2 AE occurred. Blood samples were drawn for PK and drug-mediated changes in pAkt, p70S6K, and S6 (mTOR effectors) expression in peripheral blood mononuclear cells (PBMCs) for PD analysis. Results: 46 pts were dosed at 8 dose levels (DL) of PBI-05204 (0.6 to 10.2 mg/day). 2 dose-limiting toxicities occurred at DL 8 (grade 3 prote...

9507 Background: Childhood cancer survivors have an increased risk of late-onset treatment-related cardiotoxicity. How traditional cardiovascular disease risk factors (CVRFs) modify this risk is unknown. Methods: Analyses included 14,358 >5 yr survivors of childhood cancer diagnosed 1970-86 (median age at last follow-up 31.9 yrs, range 5.6-58.9). Rates of obesity (BMI≥30), CVRFs requiring medical treatment (diabetes, hypertension, dyslipidemia) and cardiac outcomes (coronary artery disease, congestive heart failure, valvular abnormality, stroke and arrhythmia) were collected at baseline and subsequent follow-up questionnaires and compared to a sibling cohort (n=4,023). Associations between CVRFs and cardiac outcomes and the predictive ability of CVRFs for future cardiac events were assessed. Results: Survivors reported higher rates of diabetes (3.7% vs. 2.5%, OR= 1.7, 95% CI 1.4-2.1), hypertension (15.1% vs. 9.7%, OR= 2.1, 95% CI 1.9-2.4),dyslipidemia (8.2% vs. 5.7%, OR= 1.9, 95% CI 1.7-2.3), but not obes...

8053 Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et.al. NEJM,2002). Doxorubicin, a key drug in the regimen, has risk for cardiotoxicity, and thus of concern in older patients (pts) with higher incidence of cardiovascular (CV) disease. In breast cancer pts pegylated liposomal doxorubicin (D) has shown greater cardiac safety and similar efficacy to doxorubicin. We thus replaced doxorubicin with D in RCHOP (DRCOP). Methods: The regimen is: rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1-5. Eligibility criteria were: > 60 years of age; untreated confirmed DLBCL (no discordant histology); Ann Arbor stage II-IV; baseline LVEF 50%. CV disease was permitted, if symptoms controlled, but consult at baseline by Cardiologist and at follow-up required. Troponin and brain natriuretic peptide (BNP) levels were monitored. Granulocyte grow...

3537 Background: PBI-05204 contains oleandrin, a cardiac glycoside, which inhibits the α-3 subunit Na-K ATPase pump. Over-expression of the α-3 subunit in malignant cells correlates with the tumor proliferation. Oleandrin inhibits FGF- 2 export and activation of NF-Kβ and inhibits phosphorylation of Akt. PBI-05204 also inhibits p70S6K, decreasing mTOR activity. In this ongoing study of PBI-05204, we sought to determine the DLTs, MTD and recommended phase II dose in advanced solid tumors patients (pts) and to characterize its’ pharmacokinetics (PK) and pharmacodynamics (PD). Methods: This was a standard 3+3 phase I design. PBI-05240 was given orally for 21 days of 28 days. Dose was increased by 100% if no related grade 2 adverse event (AE) was observed and increased by 50% if a grade 2 AE occurred. If no other grade 2 AE were observed then subsequent dose escalation was resumed at 100%. In order to determine drug-mediated changes in pAkt, p70S6K, and S6 (mTOR effectors) expression as a surrogate marker of target effect, peripheral blood mononuclear cells (PBMCs) were obtained in addition to PKs. Results: To date 15 pts have received PBI-05204 at 5 dose levels (0.6 mg to 10.2 mg/day), 2 pts are currently active at dose level 5. No DLT has been observed thus far. 10 out of 15 pts (67%) experienced only grade 1 AEs, most common: fatigue and constipation (20%). No significant cardiac toxicities have been observed, only first degree AV block and grade 2 PVC's. Of the 15 evaluable pts, 3 had stable disease for > 4 months, with bladder, colorectal, and fallopian tube cancer pts having an 11, 16, and 10% reduction by RECIST respectively. PKs initially show dose-dependent peak plasma oleandrin concentrations are reached at 2–4 hr following administration with > 50% cleared in 6 hrs. Western blots of PBMCs showed PBI-05204 markedly reduced phosphorylation of Akt, p70S6K, and S6 in a time dependent manner in 4 pts (1 at dose level 2, and 3 and 2 at dose level 5). Reduction of these effectors was observed concomitantly with relatively higher levels of Na, K-ATPase α-3 subunit expression. Conclusions: PBI-05204 is tolerated up to 10.2/mg/day with very little AE's or cardiotoxicity. Initial response evaluation shows activity in diverse tumors with PD analysis suggesting target effect. [Table: see text]

e19506 Background: Troponin and BNP are markers that rise acutely during myocardial injury and cardiac dysfunction, respectively. Doxorubicin (Dox) is an effective drug for treatment of DLBCL, in the regimen RCHOP (Coiffier, et.al. NEJM, 2002). Dox has risk of myocardial toxicity, which is higher in older patients (pts). Pegylated liposomal doxorubicin (D) has greater cardiac safety yet similar efficacy to Dox in breast cancer. D replaced Dox in RCHOP (DRCOP) in a phase II study in patients >60 yrs of age, with troponin and BNP levels pre and post-treatment to see if they would predict a fall in LVEF secondary to DRCOP. Methods: DRCOP is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria: > 60 years; untreated DLBCL; Ann Arbor stage II-IV; baseline LVEF ≥ 50%. Consult at baseline by Cardiologist required, and at follow-up as indicated. The Wilcoxon rank sign test was used to compare baseline BNP with subsequent BNP. A linear mixed model was used to assess the effect of time on troponin at baseline, midpoint and endpoint. All tests were two-sided and p-values of 0.05 or less were considered statistically significant.. Statistical analysis was carried out using SAS version 9 (SAS Institute, Cary, NC). Results: 60 patients are enrolled; only one patient has developed systolic dysfunction, (LVEF to [Table: see text] No significant financial relationships to disclose.

20505 Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et. Al. NEJM, 2002). Doxorubicin, a key drug in the regimen, has r...

19521 Cancer chemotherapy (CHEMO), especially anthracycline-containing regimens, may result in heart failure and left ventricular dysfunction (LVD) due to cardiotoxicity (CVTx). The ability to detect CVTx currently utilizes techniques to assess LVD, such as MUGA or echocardiography (Echo), which have substantial limitations and only detect LVD well after it occurs. Cardiac biomarkers, troponin (Trop I) and B-Type Natriuretic Peptide (BNP) are well established for detecting myocardial injury and LVD in patients without cancer. Limited evidence suggests that these may be important predictors of subsequent CVTx during CHEMO, but these markers have not been systematically investigated prospectively. Methods: Patients undergoing anthracycline-containing combination CHEMO were evaluated at baseline with: history and physical; electrocardiogram; Echo; and BNP and Trop I. Biomarkers were repeated before and after up to 6 cycles of CHEMO. ECHO was repeated after 6 cycles or at 6 months from baseline. Cardiac events (heart failure, LVD, sudden death, or arrhythmia) were documented, if present. Results: To date, 111 (53M/58F) patients, age 56±14 (mean±SD), with either lymphoma (n=39, 35%), sarcoma (n=60, 54%), or breast cancer (n=12, 11%) were enrolled. At least one traditional cardiac risk factor was identified in 77 (69%) and 2 or more risk factors noted in 46 (41%). Baseline ECHO parameters including ejection fraction (EF) and biomarkers were normal. With CHEMO, the mean post CHEMO BNP value (pg/ml) for the group did not change significantly; however, in the 8 patients with cardiac events, the BNP post CHEMO was elevated. The Trop I values were not abnormal except in 2 patients with events. Conclusion: Preliminary data collected to date indicates that BNP values during CHEMO remain normal unless cardiac events occur. Additionally, elevated BNP levels appear to detect CVTx, but LVEF did not. Furthermore, patients receiving CHEMO frequently have cardiac risk factors that may promote CVTx. [Table: see text] No significant financial relationships to disclose.

17009 Background: Cardiac risk assessment in cancer patients has not extensively been studied. We evaluated the role of stress myocardial perfusion scan (SMPS) in predicting cardiovascular outcomes in cancer patients. Methods: A retrospective chart review was performed on 787 patients who had a SMPS from 01/2002 - 03/2003. All patients were followed for at least 1.5 years. Cox proportional hazard model was used to determine the time-to-first event [cardiac death, myocardial infarction (MI) and coronary revascularization]. Cardiac death was defined as documented cardiac death or sudden unexplained death. Results: A total of 501/787 (64%) patients had normal SMPS, whereas 286/787 (36%) had abnormal SMPS. Adenosine [430/787 (55%)] and dobutamine [144/787 (14%)] were used for chemical stress while 213/787 (23%) patients underwent exercise testing. Mean age was 66±11 years and median follow-up duration was 1.8 years. The 3- year event-free survival rate was 0.71 (0.64–0.78) for abnormal SMPS and 0.87 (0.8–0.94) for normal SMPS (p No significant financial relationships to disclose.

16512 Background: Little is known regarding management or treatment of cardiac failure after bone marrow transplantation. We investigated the management, treatment and outcome of new onset acute decompensated heart failure (ADHF) after bone marrow transplantation (BMT) with beta blockers, ace-inhibitors and adjuvant intravenous immune globulin (IVIG) therapy. Methods: We retrospectively examined 25 patients with ADHF. Eleven of these patients developed congestive heart failure within 100 days of BMT. Baseline echocardiograms were normal prior to admission and all patients were hospitalized and evaluated for left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class. Patients with acute heart failure were treated with standard heart failure medications and patients post-BMT were treated with standard heart failure therapy plus adjuvant (IVIG) (500mg/Kg/day) for 48 hours. Baseline LVEF and NYHA class of 11 patients pre- and post-BMT were compared with LVEF and NYHA class of 14 patients with ADHF that did not receive a BMT. Results: The baseline diagnosis for all patients in the BMT group was NYHA class 4 and post-therapy improved to class 1.2. The baseline diagnosis for all patients in the non-BMT group were NYHA class 3.7 and improved to class 1.2 with medical therapy. The mean LVEF in the BMT group at diagnosis of ADHF was 27.5% and the mean post-therapy with IVIG was 57.6%. The mean baseline LVEF in the group not undergoing BMT and at diagnosis of ADHF was 28.2% and improved post-therapy to 45.2%. Conclusions: Acute decompensated heart failure in the cancer patient is highly treatable with aggressive medical management. Patients with ADHF after BMT and treated with IVIG may have potential clinical benefits with IVIG and standard medical therapy. Significant improvement in LVEF and NYHA were present in the BMT group versus the non-BMT group. These data suggest that BMT outcomes may be improved with routine heart failure management. Further randomized studies should be conducted. [Table: see text] No significant financial relationships to disclose.

9044 Background: Despite the effectiveness of doxorubicin (D) in sarcomas, its use is limited by cardiotoxicity. Both delivery by continuous infusion (CI) and use of the cardioprotectant dexrazoxane (Z) have been used to reduce cardiotoxicity. Since 1998 patients with Ewing’s sarcoma seen at MDACC have been treated with a total of 540 mg/m2 D given with Z (ZD). During this period patients with osteosarcoma have been treated with 360–540 mg/m2 D given as a 48-hour infusion (CID). Methods: To compare the cardiotoxicity of ZD versus CID, we did a retrospective review of patients seen on the pediatric service at MDACC since 1998. Patients included needed to have had 1) planned therapy of at least 360 mg/m2 D, given either as ZD or CID; 2) measurement of ejection fraction (EF) prior to any D; and 3) routine monitoring of cardiotoxicity with EF. Patients were recorded as having cardiotoxicity for any EF [Table: see text] No significant financial relationships to disclose.