ImmunoGlobe: enabling systems immunology with a manually curated intercellular immune interaction network.

BACKGROUND: While technological advances have made it possible to profile the immune system at high resolution, translating high-throughput data into knowledge of immune mechanisms has been challenged by the complexity of the interactions underlying immune processes. Tools to explore the immune network are critical for better understanding the multi-layered processes that underlie immune function and dysfunction, but require a standardized network map of immune interactions. To facilitate this we have developed ImmunoGlobe, a manually curated intercellular immune interaction network extracted from Janeway's Immunobiology textbook. RESULTS: ImmunoGlobe is the first graphical representation of the immune interactome, and is comprised of 253 immune system components and 1112 unique immune interactions with detailed functional and characteristic annotations. Analysis of this network shows that it recapitulates known features of the human immune system and can be used uncover novel multi-step immune pathways, examine species-specific differences in immune processes, and predict the response of immune cells to stimuli. ImmunoGlobe is publicly available through a user-friendly interface at www.immunoglobe.org and can be downloaded as a computable graph and network table. CONCLUSION: While the fields of proteomics and genomics have long benefited from network analysis tools, no such tool yet exists for immunology. ImmunoGlobe provides a ground truth immune interaction network upon which such tools can be built. These tools will allow us to predict the outcome of complex immune interactions, providing mechanistic insight that allows us to precisely modulate immune responses in health and disease.

Percutaneous Paravalvular Leak Repair.

Paravalvular leaks (PVLs) are challenging lesions that require a comprehensive understanding of surgical and transcatheter heart therapies, multimodality imaging, and transcatheter techniques. Approach to a transcatheter heart valve (THV) or surgical prosthesis for PVL differs in terms of options and varies according to the location (aortic or mitral). A suggested framework for transcatheter PVL repair is defect localization, access planning, defect crossing, sheath delivery. and occluder deployment. Careful planning facilitates success, but operators begin the case with a flexible mindset because many initial strategies may not succeed.

Short term outcomes after transcatheter mitral valve repair.

BACKGROUND: Outcome data following transcatheter mitral valve repair (TMVR) with the MITRACLIP® device are scarce outside the pivotal randomized controlled trials. METHODS: The Nationwide Readmission Data base (NRD) was utilized for years 2013-2017 to identify the study population. Thirty-day readmission pattern, in-hospital complications, causes of readmissions, and multivariate predictors for readmission, complications and mortality were explored. RESULTS: We noted a total of 14,647 index admissions related to MITRACLIP of which 48% of procedures were performed at high volume centers (Annual hospital volume ≥ 25). A total of 15% of patients were readmitted within 30 days of discharge most frequently due to cardiac causes. Approximately 33% of patients were discharged within 24 h of the procedure. The in-hospital mortality rate was 2.8% and in-hospital complication rate was 14.6%. The most common complications were cardiac complications (8.2%), bleeding related complications (5.9%) and vascular complications (0.65%). On multivariate modeling, female sex, CHF, Atrial fibrillation, prior PCI, COPD, CKD, transfer to skilled nursing facility, length of stay ≥2 days were associated with a high risk of readmission. Additionally, coagulopathy, chronic kidney disease and lengthier hospital stays were associated with high risk of complication or death. CONCLUSION: The 30-day readmission rate following commercial treatment with the MITRACLIP device is 15%. Half of these admission were from a cardiac etiology. Heart failure, atrial arrhythmias and clip related complications round out the top 3 cardiac reasons for readmission. There was no impact of hospital size, teaching status or case volume on mortality and in hospital complication rates.

Patient Attributes Associated With Better Long-Term Outcomes on Palliative Milrinone.

Milrinone is a phosphodiesterase three inhibitor used as an inotrope in patients with advanced heart failure with reduced ejection fraction (HFrEF). Its action is independent of ß-receptor stimulation, which makes it preferable in patients who are on ß blockers as part of a guideline-directed neurohormonal blockade. There have been numerous studies evaluating the risks, benefits, and mortality associated with milrinone in the management of chronic heart failure patients. Time and again, there has been concern regarding the undesirable outcomes associated with it, including higher mortality and cardiac arrhythmias. Additionally, it has been difficult to determine whether milrinone or disease progression is responsible for adverse outcomes and mortality. In light of such discrepancy, the selection of patients for milrinone remains challenging. We hypothesized that there are underlying patient characteristics that influence the response to milrinone and may predict milrinone's adverse outcomes in spite of milrinone. A retrospective study review of 10 patients on palliative milrinone was conducted to identify these factors with a mean follow-up of 36 months. During the study period, four of 10 patients died. These four patients were on milrinone for a mean of 11.5 months. The attributes of the survivors compared to the deceased included lower age at start of therapy (67.5 vs 79 y), female gender (66% vs 33%), non-ischemic cardiomyopathy (33% vs 50%), associated diagnosis of atrial fibrillation/flutter(50% vs 25%), hyperlipidemia (66% vs 50%), or anemia (83% vs 75%), presence of chronic resynchronization therapy (CRT) (66% vs 25%), and implantable cardioverter-defibrillator (ICD) (16% vs 0%), as well as lower sodium (136 vs 140 mEq), chloride (101.5 vs 104.5 mEq), potassium (4.07 vs 4.23 mEq), and creatinine (1.3 vs 1.8 mg/dL)  Conversely, the deceased patients were more likely to have coronary artery disease (75% vs 33%), diabetes mellitus (50% vs 16%), hypertension (100% vs 83%), chronic kidney disease (75% vs 66%), peripheral vascular disease (25% vs zero), higher pulmonary artery pressures (54 vs 50.5%), and history of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) (50% vs 16%). These trends exhibit patient characteristics that may predict better outcomes on long-term milrinone although larger studies are needed to assess the statistical significance of these findings.

An Observation of Racial and Gender Disparities in Congestive Heart Failure Admissions Using the National Inpatient Sample.

Background Congestive heart failure (CHF) is a frequent cause of inpatient admissions in the United States. The purpose of this study was to analyze the racial and gender disparities that occur in CHF admissions and determine the impact of these disparities on medical expenditure. Methods We analyzed the National Inpatient Sample (NIS) database from 2009 to 2014 for patients with a primary discharge diagnosis of CHF, and further stratified the cohort on the basis of race and sex. Multivariate analysis was performed to identify the association between CHF and total charges along with other variables such as mortality, length of stay (LOS), and number of procedures. Results There were a total of 5,491,050 admissions with a primary diagnosis of CHF from 977,850 in 2009 to 901,425 in 2014. Females accounted for 49.7%. Total charges for CHF admission were highest in Asians at an average cost of $59,668. African Americans had the lowest mortality rate at 1.75%, however, they also had an average age of admission of 63.47 years, compared to Caucasian at 76.76 (p<0.05). Total charges for males were $42,920 and $36,744 for females (p <0.05). Males also had more procedures at 1.16 vs 0.98 for females (p <0.05). Elixhauser mortality score was higher in males than females at 5.95 vs 5.42 (p <0.05). Conclusion Healthcare disparities exist in CHF admissions in both contexts of race and gender. Further studies are required to pinpoint the source of these differences not only to address mortality but also expenditure costs.

Acute Myocarditis Presenting as Acute Coronary Syndrome.

A 50-year-old male presented to the hospital with an approximate three-week history of nausea, fever, and back pain. Upon initial evaluation he had an electrocardiogram with ischemic changes and initial labs significant for a troponin of >25.0 ng/ml (<0.30 ng/ml), pro b-type natriuretic peptide (proBNP) of 9884 pg/ml (<125 pg/ml), and a lactic acid of 4.3 mmol/L (0.5-1.9 mmol/L). There was a concern for an acute coronary syndrome presenting as cardiogenic shock, but the patient was unable to tolerate left heart catheterization. He had a rapid clinical decline and despite all efforts, he passed away. The initial cause of death was thought to be due to an acute myocardial infarction, however, autopsy results were consistent with acute myocarditis. This case highlights the presentation of acute myocarditis as an acute coronary syndrome with complete heart block.

Refractory Vasospastic Angina: When Typical Medications Don't Work.

Vasospastic angina (VSA) is defined as spasm of the coronaries leading to transient constriction and eventual myocardial ischemia. VSA is treated typically with calcium-channel blockers (CCBs) and nitrates. However, there are times when the vasospasm is refractory to typical medications. When this occurs, unconventional treatment modalities may be employed for symptomatic relief. We present a case of a 48-year-old-male with a history of inferior ST-elevation myocardial infarction (STEMI) status post percutaneous coronary intervention (PCI) with drug-eluting stent (DES) to the distal right coronary artery (RCA), who presented with recurrent angina. The pain was described as pressure-like, substernal, radiating to both arms, and similar to his previous STEMI presentation. On presentation to the emergency room, he had an elevated serum troponin with no electrocardiogram (EKG) changes. He was taken to the cath lab where it was found that he revealed severe focal stenosis just proximal to the previously placed stent. Immediately after guidewire passage into the RCA, acute vasospasm developed, resulting in diffuse, severe stenosis, extending over previously normal segments to the proximal RCA, resolving with intracoronary nicardipine and nitroglycerin, including the initial focal stenosis. The patient was diagnosed with VSA. Unfortunately, despite optimal medical therapy, he developed refractory VSA, requiring the use of unconventional treatment methods. Our patient presented with a lesser-known phenomenon called refractory VSA, where intermittent vasospasm continues despite being on a combination of two medications. Treatment for VSA is well-documented, however, little data is available for refractory VSA.

Severe Coronary Artery Disease Disguised as Myocarditis.

Serum troponin is a marker of cardiac myocyte damage that is typically used to assess for myocardial infarction in the setting of acute coronary syndrome. However, many conditions, including cardiomyopathy, pulmonary embolism, or myocarditis, can cause an elevation in serum troponin. The most common use of this tool is to determine whether acute coronary syndrome (ACS) is occurring, but other differentials include cardiomyopathy, pulmonary embolism, and even acute heart failure. We present the case of a patient who presented with symptoms consistent with viral myocarditis but ultimately was found to have severe coronary artery disease (CAD). A 33-year-old Caucasian male with no cardiac risk factors other than a five-pack year smoking history, presented with progressively worsening upper respiratory symptoms, including sore throat and a non-productive cough that began a few weeks ago. These symptoms were associated with fevers, and 24 hours prior to admission, he developed intermittent chest pain at rest, radiating to the back, worsening in the supine position. In the emergency room (ER), the patient was found to have an elevated serum troponin of 15.61 ng/L (normal <0.05 ng/L). The electrocardiogram (EKG) showed T-wave inversions in the lateral leads. Based on his presentation and age, there was a high suspicion of viral myocarditis. However, non-ST elevation myocardial infarction (NSTEMI) had not yet been ruled out and the patient was started on started on a heparin infusion per the ACS protocol. A transthoracic echocardiogram showed wall motion abnormalities with low-normal left ventricular ejection fraction. A coronary angiogram showed severe CAD and he underwent staged a percutaneous coronary intervention with the resolution of symptoms. CAD and viral myocarditis, at times, can share common presenting symptoms, EKG changes, and laboratory findings. Out of all possible diagnoses, an elevation in serum troponin correlates to an MI up to 60% of the time. Myocarditis is the second leading cause of troponin elevation and accounts for 25% of cases. We highlight this case to discuss the importance of maintaining a broad differential and pursuing complete work-up when treating younger patients with chest pain and elevated serum troponin who lack typical risk factors for CAD.

Metastatic squamous cell carcinoma to the heart: an unusual cause of ST elevation-a case report.

BACKGROUND: Cardiac tumours are typically secondary in nature, and the most common malignancies metastasizing to the heart are cancers of the lung, breast, oesophagus, melanoma, and lymphoma. We present a unique case of squamous cell carcinoma of the tongue, metastasizing to the heart and manifesting with ST elevation in the inferior-leads on electrocardiogram (ECG). CASE SUMMARY: A 25-year-old woman was initially diagnosed with squamous cell carcinoma of the tongue at the age of 23 and treated with hemi-glossectomy with clear-margins. Sixteen months later, the tumour recurred in the oropharynx and the left upper lobe of the lung. She was treated with chemotherapy; however, the tumour progressed. Thus, she was initiated on immunotherapy and radiation therapy. One month later, she presented with chest pain. Electrocardiogram revealed ST elevation in the inferior-leads. Troponin-I was elevated. Transthoracic echocardiogram revealed focal areas of thickening within the left and right ventricular myocardium with associated hypokinesis. These findings suggested ECG changes were likely secondary to infiltrative metastases and not acute-coronary-syndrome. Cardiac magnetic resonance imaging showed infiltrative masses with increased T2-signal and heterogeneous enhancement on perfusion and delayed enhancement sequences. Imaging also demonstrated numerous extra-cardiac metastases. She was treated with analgesics and discharged to home hospice. DISCUSSION: Head and neck cancers are a rare cause of cardiac metastasis. ST elevation and troponin release are thought to be due to tumour extension into the myocardium. Cardiac metastases usually present in patients with advanced widespread malignancy. In a cancer patient with cardiac symptoms or ECG changes, it is important to consider a broad differential diagnosis and entertain the possibility of cardiac metastasis.

Still's Disease and Myopericarditis.

Adult-onset Still's disease (AOSD) has a vast array of clinical presentations. Myopericarditis is one of the rarest cardiopulmonary manifestations of the disease and due to its rarity, the literature on the association of myocarditis with AOSD is sparse. Herein, we describe an interesting case of a 44-year-old male who presented with chest pain following exertion. He was febrile at the time of presentation and exam revealed inflammation in various joints. Electrocardiogram showed diffuse ST segment elevations in the precordial leads. Laboratory results revealed elevated troponin of 3.17 (<0.05 ng/mL) and CK-MB of 6 ng/mL along with elevated ferritin of 6225 (16-336 ng/mL). Cardiac MRI showed early and late gadolinium enhancement consistent with myocarditis. The patient was started on steroids and non-steroidal anti-inflammatory drugs (NSAID) resulting in clinical improvement. This case highlights the critical importance of diagnosis of pericarditis and myocarditis in patients with AOSD, as a missed diagnosis can lead to significant morbidity and mortality.

Acute Myopericarditis with Crohn's Disease Flare-up.

Cardiac involvement is rare in inflammatory bowel disease (IBD) but can occur as a complication of either the disease itself or drug therapy. We describe an interesting clinical scenario of acute myopericarditis during Crohn's flare-up. A 37-year-old patient with severe Crohn's disease started having multiple bloody bowel movements associated with abdominal pain. These symptoms were attributed to Crohn's disease flare-up, prompting the addition of steroids and an increase in the dose of mesalamine without any significant relief. Two weeks later, he presented to the emergency department with pleuritic chest pain. Electrocardiogram (EKG) revealed ST segments elevation in leads I and aVL. Laboratory work revealed elevated troponin I of 1.82 ng/mL, with increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) of 121 mm and 180.1 mg/L, respectively. Cardiac magnetic resonance imaging (MRI) revealed early gadolinium enhancement consistent with myocarditis. The patient was started on colchicine with an increase in the dose of steroids, resulting in clinical improvement. The patient reported having similar chest pain during a previous episode of Crohn's disease flare-up, suggesting underlying IBD as the likely etiology.

ICD shocks in LVAD patients are not associated with increased subsequent mortality risk.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks are associated with increased mortality risk in heart failure patients. Whether ICD shocks are associated with mortality in continuous flow LVAD (CF-LVAD) patients is unknown. We studied the relationship of ICD shocks and ventricular arrhythmias (VAs) to morbidity and mortality in CF-LVAD-supported patients in our institution. METHODS: Single-center, retrospective study of prospectively collected ICD and LVAD databases. We analyzed data on VA which received ICD therapy in patients who underwent CF-LVAD implantation at Hartford Hospital between 2008 and 2018. RESULTS: A total of 157 patients were studied. During a median follow-up of 10 months (interquartile range 5-20 months), 48 patients (30.6%) experienced post-LVAD sustained VA. Thirty patients (19.1%) had appropriate shocks for VA and 5 patients (3.1%) had inappropriate shocks. Shocks for any arrhythmia were not associated with an increased risk of death (OR 0.836, 95% CI 0.224-3.115, p = 0.789). Neither post-LVAD VA nor the rate of VA was associated with an increased mortality risk (OR 0.662 [0.329-1.334], p = 0.248; OR 1.001 [0.989-1.014], p = 0.817, respectively). Cox multivariate regression analysis revealed pre-LVAD VA as a significant predictor of VA post LVAD implantation (OR 3.284 [1.584-6.808], p = 0.001). Symptoms with VA occurred in 22 (45.8%) patients, ranging from palpitations to near syncope/syncope. None of the variables including the rate of VA was associated with death or symptoms. CONCLUSIONS: VAs are common in CF-LVAD patients and occur with higher frequency in those with pre-LVAD VA and frequently cause symptoms. Neither VA nor ICD shocks are associated with mortality risk.

Coronary Artery Aneurysms: Analysis of Comorbidities from the National Inpatient Sample.

Introduction Coronary artery aneurysms (CAA) are not commonly seen in the general population, with an incidence of approximately 0.37% to 2.53%. Patients are typically asymptomatic but symptomatic presentation varies from dyspnea and angina to myocardial infarction or even sudden cardiac death. Methods We conducted a retrospective analysis using the National Inpatient Sample Healthcare Cost and Utilization Project (NIS-HCUP) database to query individuals with the diagnosis of CAA with the International Classification of Disease (ICD) code 414.11 in all discharge diagnoses for the years 2006-2014. History of Kawasaki disease was determined by ICD code 446.1. Results From 2006 to 2014, there were 23,033 patients identified with CAA, correlating to approximately one case per 10,000 patients or an incidence of close to 0.01%. Of this, 1,405 or approximately 6.1% of these patients had Kawasaki disease. The mortality rate of CAA was 1.79%. In terms of demographics, Caucasians were the most likely to develop CAA, with 73.8% of cases. The mean age was 61.2 years, with a mean length of stay of 5.1 days. The average cost of admission was $70892. The presence of perivascular disease (15.5% vs 4.5% p<0.05), hypertension (66.1% vs 39.1% p<0.05), chronic lung disease (20.2% vs 15.1% p<0.05), diabetes (21.7% vs 15% p<0.05), renal failure (11% vs 8.8% p<0.05), coagulopathy (6.2% vs 3.4% p<0.05), and obesity (13.1% vs 8.2% p<0.05) were all risk factors for CAA as compared to those without. It was noted that weight loss (3.28% vs 1.91% p<0.05), electrolyte abnormalities (18.2% vs 15.5% p<0.05), and blood loss (2.1% vs 0.9% p<0.05) were protective of CAA. Conclusion CAA risk factors appear to be similar to those of coronary artery disease risk factors, with hypertension, diabetes, perivascular disease, and renal failure. Additionally, obesity was noted to be a risk factor but weight loss appeared to be protective. Interestingly, Kawasaki disease was seen at almost similar rates as these cardiac risk factors. The incidence of CAA we found, of almost 0.01%, is much less than in the quoted literature, however, previous studies did not have as many cases as our study.