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The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.

Cardio-oncology is a growing multi-disciplinary field that focuses on treating and preventing cardiovascular complications in cancer survivors and patients. This review summarizes the current clinical needs and system-based approaches to target barriers of care. The field of cardio-oncology has experienced significant growth in recent years, and an increasing number of programs have been developed across the nation to provide improved and multi-disciplinary care to this patient population. Despite this burgeoning growth, practitioners in the field continue to face important challenges which include lack of administrative and departmental support, funding limitations, and gaps in the areas of mentoring, education, and research. Despite continued growth, cardio-oncology providers continue to face a multitude of challenges. Early inclusion of multi-disciplinary stakeholders, oncologists, cardiovascular team members, and administrative leadership provides an opportunity to collaborate and achieve unique patient care and health system benefits, such as prevention of adverse cardiovascular outcomes, and facilitates the delivery of optimal oncologic treatment.

The complex and often unpredictable course of heart failure (HF) provides many opportunities for communication between clinicians and patients about important subjects as advance care planning, disease state education, therapeutic options and limitations, and end-of-life care. Studies of patients with HF demonstrate that, when engaging in such complex communication, specific language matters in patient experience and in shared decision-making with providers. To date, clinical reports have outlined useful frameworks for communication with patients with HF but have not yet broached specific language crucial to furthering whole person care, particularly in the complex and emotional realm of advancing disease and transitions to end-of-life care. In this work, the investigators unpack language commonly used in advanced HF care and provide explicit suggestions to better provide such pivotal communication. In conclusion, specific phrasing may significantly impact patient experiences and outcomes. Communication that focuses on the disease itself and the therapy or intervention in question may help remove the patient from potential negative emotions, thus facilitating more objective shared decision-making with the clinician.

Background Adult congenital heart disease (ACHD) patients have high rates of untreated depression and anxiety disorders. We evaluated associations among self-reported depression symptoms and alcohol/smoking tobacco use. Methods From 2009 to 2013, 202 ACHD patients (45% male) completed questionnaires on depressive symptoms, anxiety symptoms, and substance use as part of routine clinical care. Data were collected by retrospective chart review. Results Mean age was 31 ± 10 years, 21% reported often feeling depressed and 33% reported feeling nervous or anxious. Sixty-one percent of patients reported some alcohol intake; 25% reported current or previous smoking tobacco use. Patients with depressive symptoms were 3× as likely to report drinking alcohol (OR 2.89; 95% CI 1.29–6.5) and 5× more likely to report smoking tobacco use (OR 5.17; 95% CI 1.49–17.87). Fourteen percent of patients were prescribed antidepressant/antianxiety medications; 43% of patients on medication reported depressive symptoms. In patients reporting symptoms, those who consumed alcohol were less likely to be on antidepressant/antianxiety medications (21%) than those who did not consume alcohol (56%). Conclusion Self-reported depressive symptoms are associated with increased alcohol and smoking tobacco use by ACHD patients. Alcohol use may be a means of self-medicating for untreated depression, but further investigation is needed. Risk factors, including depressive symptoms and substance use, should be routinely assessed and addressed in ACHD patients.

Acute decompensated heart failure is a significant source of morbidity and mortality in the USA. It is the most common reason for admission in the Medicare population and the greatest cause of hospital readmission in both medical and surgical patients. As many of these readmissions are considered preventable, providers and hospital systems are seeking novel strategies to reduce rehospitalization. Several specific interventions have been shown to decrease readmission for heart failure. However, these are typically narrow in scope, focusing on one aspect of patient care and providing a one-size-fits-all approach. We review the data and propose integrating some of these interventions into a comprehensive patient-centered model that is organized into six categories: quality of medical management, early reassessment, health literacy, neuropsychological status, financial means and functional status. By screening for deficiencies in each of these categories, providers and hospital systems can use resources more efficiently to make targeted interventions to improve health outcomes and mitigate readmissions.

Over-expression of c-fos may play a role in some diseases. Research pertaining to the expression of c-fos in acute myocardial ınfarction (AMI) is rare, and the detailed role of c-fos in AMI has not been reported. Therefore, the purpose of this project was to elucidate the detailed effect of c-fos on AMI rats and evaluate the effect of a metoprolol intervention. An AMI rat model was established for the purposes of this study. The expression of c-fos in AMI was evaluated via immunohistochemical analysis and in situ hybridization. Simultaneously, we investigated the effect of c-fos on AMI rats via medicinal treatment with c-fos monoclonal antibody, isoproterenol, and metoprolol. Positive c-Fos protein expression and c-fos mRNA expression in cardiomyocytes were increased at 1, 3, 7, and 10 days after ligation in AMI rats compared with a sham-operated group. Peak expression occurred at 3 days after ligation. The weight percentage fraction of infarct size was decreased in rats treated with c-fos monoclonal antibody compared with the control normal saline treatment group. The weight percentage fraction of infarction size was increased after c-fos was increased via the administration of isoproterenol. c-Fos protein expression and the infarct size in rats treated with metoprolol were also decreased compared with the control normal saline treatment group. The results showed that c-fos expression rapidly increased after coronary ligation; c-fos plays an important role in myocardial lesions and is likely to be involved in the pathogenesis of AMI as well. Metoprolol can inhibit the expression of c-fos and has a positive therapeutic effect on rats after AMI; the involvement effect of metoprolol on myocardial infarction might be correlated with its effect on the inhibition of c-fos.

Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially fatal cardiopulmonary syndrome that imposes a significant burden on patients in terms of morbidity and mortality, and on managed care organizations in terms of resource utilization. The majority of PAH-approved therapies are high-touch, high-management, high-cost treatments dispensed through specialty pharmacies. Current treatment guidelines recommend combination therapy for patients who show inadequate clinical response or who deteriorate on monotherapy. Combination therapies target 2, or sometimes 3, distinct PAH-associated signaling pathways: the endothelin, prostacyclin, and nitric oxide pathways. Registry data suggest that combination therapy is utilized in more than half of patients with PAH in the United States. Evidence supporting the use of combination therapy is provided through clinical trials, retrospective research, registry data, and expert guidelines. Managed care decision makers are charged with making population-based decisions on resource allocation. These decision makers must always consider cost, but must also be aware that clinical evidence suggests that early treatment with combination therapy can significantly reduce disease burden, may reduce hospitalizations, and should be considered when making coverage decisions.

Adult congenital heart disease (ACHD) patients have high rates of untreated depression and anxiety disorders. We evaluated associations among self-reported depression symptoms and alcohol/smoking tobacco use.From 2009 to 2013, 202 ACHD patients (45% male) completed questionnaires on depressive symptoms, anxiety symptoms, and substance use as part of routine clinical care. Data were collected by retrospective chart review.Mean age was 31 ± 10 years, 21% reported often feeling depressed and 33% reported feeling nervous or anxious. Sixty-one percent of patients reported some alcohol intake; 25% reported current or previous smoking tobacco use. Patients with depressive symptoms were 3× as likely to report drinking alcohol (OR 2.89; 95% CI 1.29-6.5) and 5× more likely to report smoking tobacco use (OR 5.17; 95% CI 1.49-17.87). Fourteen percent of patients were prescribed antidepressant/antianxiety medications; 43% of patients on medication reported depressive symptoms. In patients reporting symptoms, those who consumed alcohol were less likely to be on antidepressant/antianxiety medications (21%) than those who did not consume alcohol (56%).Self-reported depressive symptoms are associated with increased alcohol and smoking tobacco use by ACHD patients. Alcohol use may be a means of self-medicating for untreated depression, but further investigation is needed. Risk factors, including depressive symptoms and substance use, should be routinely assessed and addressed in ACHD patients.

Background Several studies have focused on stratifying patients according to their level of readmission risk, fueled in part by incentive programs in the U.S. that link readmission rates to the annual payment update by Medicare. Patient-specific predictions about readmission have not seen widespread use because of their limited accuracy and questions about the efficacy of using measures of risk to guide clinical decisions. We construct a predictive model for readmissions for congestive heart failure (CHF) and study how its predictions can be used to perform patient-specific interventions. We assess the cost-effectiveness of a methodology that combines prediction and decision making to allocate interventions. The results highlight the importance of combining predictions with decision analysis. Methods We construct a statistical classifier from a retrospective database of 793 hospital visits for heart failure that predicts the likelihood that patients will be rehospitalized within 30 days of discharge. We introduce a decision analysis that uses the predictions to guide decisions about post-discharge interventions. We perform a cost-effectiveness analysis of 379 additional hospital visits that were not included in either the formulation of the classifiers or the decision analysis. We report the performance of the methodology and show the overall expected value of employing a real-time decision system. Findings For the cohort studied, readmissions are associated with a mean cost of $13,679 with a standard error of $1,214. Given a post-discharge plan that costs $1,300 and that reduces 30-day rehospitalizations by 35%, use of the proposed methods would provide an 18.2% reduction in rehospitalizations and save 3.8% of costs. Conclusions Classifiers learned automatically from patient data can be joined with decision analysis to guide the allocation of post-discharge support to CHF patients. Such analyses are especially valuable in the common situation where it is not economically feasible to provide programs to all patients.

Patients with early repair of an isolated atrial septal defect (ASD) are expected to have unremarkable right ventricular (RV) and pulmonary circulation physiology. Some studies, however, suggest persistent functional impairment. We aimed to examine the role of abnormal RV and pulmonary vascular response to exercise in patients who had undergone ASD closure. Using a previously published data set, we reviewed invasive exercise cardiopulmonary testing with right-sided hemodynamic data for 12 asymptomatic patients who had undergone ASD closure. The 5 (42%) patients with impaired maximal oxygen uptake ([Formula: see text]) were older and exhibited a lower peak cardiac index (5.6 ± 0.8 vs. 9.0 ± 1.2 L/min/m(2); P = .005) because of abnormal stroke volume augmentation (+3.2 ± 3.9 vs. +17.4 ± 10.2 mL/m(2); P = .02). While all resting hemodynamic variables were similar, patients with low [Formula: see text] tended to have abnormal total pulmonary vascular resistance change during exercise (+11% ± 41% vs. -28% ± 26%; P = .06) and had a steeper relation between mean pulmonary arterial pressure and cardiac index (5.8 ± 0.6 vs. 2.2 ± 0.1 L/min/m(2); P = .02). The increase in peak mean RV power during exercise was also significantly lower in the impaired-[Formula: see text] patients (4.7 ± 1.6 vs. 7.6 ± 2.1 J/s; P = .04). As described in the original study, despite normal resting hemodynamics, a subset of asymptomatic patients with repaired ASD had diminished exercise capacity. Our analysis allows us to conclude that this is due to a combination of abnormal pulmonary vascular response to exercise and impaired RV function.

Advances in cardiovascular care and cardiothoracic surgical expertise have enabled many patients with congenital heart disease to live well into adulthood. With lengthened life expectancies, congenital heart disease patients are more frequently undergoing noninvasive nuclear cardiac imaging to exclude perfusion abnormalities. We present the Tc-99m sestamibi SPECT findings of a patient with an uncommon congenital malformation. Case history. A 45-year-old man with doubleinlet left ventricle, pulmonary stenosis, pulmonary hypertension, status postmultiple systemic-pulmonary shunt procedures, and, most recently, a Potts anastamosis (descending aorta to the left pulmonary artery anastamosis) at age 31, presented to the cardiology clinic complaining of burning epigastric pain on exertion. The patient had known pulmonary artery hypertension but had improved his oxygen saturation and exercise tolerance on a regimen of bosentan, coumadin, digoxin, and verapamil. Initially, the patient underwent a modified walk test and was able to walk on a level surface at increasing speed for 15 minutes, achieving a peak speed of 1.8 miles per hour, HR 97, BP 148/69, when he complained of progressive chest burning. His pulse oximetry at rest was 84% and dropped to 72% with exercise. The electrocardiogram showed no change from baseline (sinus rhythm, left ventricular hypertrophy with strain, and ST elevation in the right precordial leads). In light of the reproducible symptoms and the patient’s strong preference for noninvasive evaluation, he underwent adenosine Tc-99m sestamibi SPECT to evaluate for coronary artery disease. The patient was infused with 140 mcg per kilogram per minute of adenosine over a 6-minute period; at 3 minutes into the infusion, 99mTc sestamibi was injected. There were no reported electrocardiogram changes or symptoms during adenosine infusion. Images were acquired with 180° SPECT approximately 30 minutes later. Findings. The adenosine sestamibi SPECT images showed a large left-ventricle cavity with no definite myocardial perfusion abnormality. Low counts were seen along the middle inferior wall because of adjacent tracer activity in a loop of small bowel. On both stress and rest images, the short-axis projection showed a smaller, rounded structure with a central lumen from the middle anterior to basal ventricular cavity, consistent with a rudimentary right ventricle (Figure 1). Because this is essentially a single functioning chamber, absent were the typical-appearing interventricular septum or right ventricle (compare with the normal right ventricle and septum in Figure 2). Despite the unusual anatomy, the gated SPECT perfusion images showed normal left ventricular myocardial wall motion and systolic thickening with an ejection fraction of 51%. The cardiac chambers were further clarified by viewing the patient’s transesophageal echocardiogram to evaluate mitral insufficiency (Figures 3 and 4).

Amniotic fluid-derived mesenchymal stem cells (AF-MSC) are newly described, excellent seed cells that have good differentiation capability and are convenient to obtain. However, it is important to develop a method to isolate and culture AF-MSC efficiently. Amniotic fluid samples were obtained from rabbits and the adherence method was used for AF-MSC culture. Flow cytometry, western blot, and immunofluorescence studies were used to analyze the phenotypic characteristics of the cultured AF-MSC. Amniotic fluid-derived mesenchymal stem cells were successfully isolated and cultured from amniotic fluid. Flow cytometric analysis demonstrated that these cells expressed CD29 and CD44, while they did not express CD34. The expression of transcription factor Oct-4 was confirmed by western blot and immunofluorescence analysis. Using the adherence method, we developed a successful, reproducible protocol for the isolation of AF-MSC from amniotic fluid. The results of our phenotypic analysis revealed that the AF-MSC isolated in the present study were multipotent cells.

Background c-fos may play a role in the pathogenesis of some diseases. The expression and function of c-fos in viral myocarditis (VMC) have not yet been reported. To study the change and significance of proto-oncogene c-fos in VMC is the objective of this experiment. Methods An animal model of VMC was established via coxsackie virus B3 inoculation. VMC mice were then treated with a c-fos monoclonal antibody and isoproterenol and the protein and mRNA expression of c-fos were studied via immunohistochemical analysis and in situ hybridization. Results were simultaneously analyzed for the significance of c-fos expression in mice with VMC. Results Myocardial necrosis and cell infiltration decreased after treatment with c-fos monoclonal antibody compared to control mice, while myocardial necrosis and cell infiltration were increased after treatment with isoproterenol. Positive cardiomyocytes with c-Fos expression increased at 3, 5, 7, 9, and 15 days after virus inoculation in VMC mice compared to control mice, while returning to almost normal levels at 35 days. The expression level of c-fos mRNA at 3 and 7 days after virus inoculation in VMC mice was also higher than that of control mice. Conclusions c-fos expression in the cardiomyocytes of VMC mice is significantly increased, c-fos plays an important role in myocardial lesions. The apparent increase in expression of c-fos is likely to be involved in the pathogenesis of VMC.

s S201 Methods: On April 1, 2014, we started using the protocol for prevention of pump thrombosis. The key points included checking for hypercoagulable state at the baseline and raising INR goals to 2.5-3.5 for patients with such state or for those with spikes in lactatedehydrogenase (LDH), full dose aspirin (325 mg) and dipyridamole 25 mg three times a day for patients without history of bleeding, coverage with low molecular weight heparin when INR drops below therapeutic, and admission with immediate full work-up for pump thrombosis when LDH exceeds 600 IU/mL for HeartMate II or 400 IU/mL for Heartware (LDH spikes). Comparison for LDH spikes was made between first three months of the year (before the protocol), second three months (transition), and third quarter (on the protocol). The comparison was done with chi square test. Results: In the 1st quarter of 2014, we followed 33 patients (5 with Heartware), and 7 (20.6) had LDH spikes. In the 2nd quarter, there were 37 patients (8 with Heartware) with 6 (15.7%) having LDH spikes. In the third quarter, there were 37 patients (10 with Heartware) with 2 LDH spikes (5.1%, p= 0.05 for the difference between the 1st and the 3rd quarter). The distribution of LDH values is shown on figure 1. There was one clinical pump thrombosis in each of the first two quarters and none in the third quarter. There was no increase in bleeding events or decrease in hematocrit after the protocol was started. Conclusion: Targeted higher level of anticoagulation in LVAD patients decreases the rate of LDH spikes used as a surrogate indicator of pump thrombosis.

Purpose: Position of the inflow cannula (IC) within the left ventricle may affect optimal function of the LVAD and contribute to the risk of complications. We evaluated the intraventricular position of the IC in Heartmate II (HM2) and Heartware (HW) LVADs. Methods: A single-center retrospective review of the most recent cardiac CT (CCT) of all continuous flow LVAD implants between 10/2006 and 9/2013 was performed. CT acquisitions were completed on a 64 or 256 slice platform using ECG gated helical technique. Measurements were performed in standard 2-chamber and short-axis views. Fisher’s exact and Wilcoxon-MannWhitney tests were used to determine statistical difference between groups. Results: A total of 195 patients underwent LVAD implants (101 HM2, 94 HW). At least one CCT was performed on 63 patients. Mean LV end diastolic diameter was 63 ± 11 mm. Apical tip of the IC was more frequently in contact with anterior wall in the HM2 patients (15/24, 62%) compared to HW pumps (5/38, 13%, p< 0.001). Basal tip did not abut the anterior wall in any patient. Septal wall contact was 25% vs. 5 % (p= 0.05) and lateral wall contact was 29% vs. 25% (p= 0.7) in HM2 and HW pumps, respectively. In the total population, the IC was angulated towards the mitral annulus plane (median 33 degrees, IQR 22, 46) and formed a 77-degree horizontal angle in the short axis (IQR 57, 95, figure 1). Angle of the IC was significantly different between HM2 and HW LVADs (table 1). Conclusion: Significant variation exists among patients and between two different types of continuous-flow LVAD with regards to intraventricular position of the inflow cannula. Clinical significance of these variations remains to be determined.

Objective: To survey attitudes about abortion in a sample of physicians practicing in the Bronx, New York, identify factors associated with those attitudes, and investigate how attitudes about abortion influence willingness to do it. Methods: A questionnaire mailed to obstetricians and gynecologists affiliated with a medical school in the Bronx elicited information on attitudes about abortion and the willingness to do it. Attitude scores were measured on a Likert scale ranging from 1 to 5, with 5 indicating a proponent attitude about abortion. The practice score ranged from 0 to 2, with 2 indicating proponent attitude about practicing abortion. Results: The median attitude score was 3.8. Physicians were receptive to reasons for abortion that were medically indicated. A proponent attitude was found in non-Catholics and those who were trained in residency programs that required observing abortions. The median practice score was 1.2. The most important personal factors influencing a physician’s decision not to perform abortions included lack of proper training and ethical and religious beliefs. There was a significant positive correlation between the attitude score and practice score ( r = .42, P Conclusion: Personal beliefs and past experience with abortion are associated with attitudes about abortion that, besides competence doing them, influence physicians’ willingness to do them. Offering training in abortion might benefit physicians who are proponents and willing to perform abortions.

Purpose Optimal function of a left ventricular assist device (LVAD) requires proper positioning of the inflow cannula (IC) within the left ventricle. Cardiac computed tomography (CT) is emerging as the preferred method for evaluation of the IC position. We sought to evaluate the frequency of contact between the IC and the left ventricular wall (LV) in patients with axial flow and centrifugal flow devices. Methods and Materials This single center study included all patients who received a continuous flow implantable LVAD between 5/2008 & 8/2011 and who underwent a contrast cardiac CT. Patients were stratified into 2 groups, based on whether the indication for the CT scan was a clinical event (arrhythmia, etc) or a routine study (redo sternotomy evaluation prior to transplantation). Each CT was evaluated for the presence of contact between the IC and the LV. Results The study included 28 patients:14 patients (16 scans) with HeartMate II (HMII) and 14 patients (16 scans) with HeartWare (HW). Characteristics of the cohort are shown in Table 1 . Contact between the IC and the LV was observed in all 16 scans (100%) of patients who received a HMII. In contrast, contact between the IC and the LV was observed in only 5/16 (31%) scans of patients who received a HW: 2/7 performed for a clinical indication and 3/9 performed as routine study. In both the HMII and HW groups, wall contact was observed throughout the cardiac cycle in all but one case, where it was only noted during end-systole. In all cases, contact with the LV involved the outside tip of the IC but did not appear to cause inflow obstruction. Conclusions Contact between the IC and the LV appears to be very common among patients with HM II and less common among patients with HW. In this cohort, cannula tip contact with the LV was not associated with any obstruction to inflow and is therefore unlikely to have any clinical significance. Patient Characteristics HMII HW Age (yrs) 51 ± 11 51 ± 16 Female 2/14 5/14 Time from LVAD implant to CT (days) 233 ± 204 275 ± 203 LV dimension (cm) 6.4 ± 1.3 6.3 ± 1.9