Lower Extremity Edema Research Articles

Cardiac Involvement in Neurosarcoidosis: A Single-Center Investigation

Sarcoidosis is a multisystem inflammatory granulomatous disease. Among systemic sarcoidosis manifestations, cardiac or nervous system involvement can result in significant morbidity and mortality. We describe the overlapping incidence of cardiac sarcoidosis (CS) within a neurosarcoidosis (NS) cohort and determine the frequency of other nonsarcoid cardiac diseases in these patients. We performed a retrospective chart review of patients evaluated at the University of Utah from 2010 to 2022. Patients were included if they had (1) at least one instance of a diagnostic code for sarcoidosis in their medical record-International Classification of Diseases (ICD) 9 code 135 or ICD 10 code D86; (2) at least one outpatient visit in the Neurology Department within the University of Utah electronic health record with a diagnosis of definite, probable, or possible NS based on 2018 consensus criteria; (3) at least one outpatient visit in the Cardiology Department within the University of Utah electronic health record; and (4) ECG available in their medical record for review. Of 64 definite, probable, or possible patients with NS in the University of Utah cohort, 52 met our inclusion criteria and were included in this study. Of 52 patients with NS who met our inclusion criteria, 65.38% were female, with an average age of 60.9 years (range 38-84). More than half (58%) were obese (BMI ≥ 30). CS was diagnosed in 6 patients with NS (12%). Symptoms suggestive of possible cardiac dysfunction included lower extremity edema (50%), palpitations (46%), chest pain (44%), and shortness of breath (27%). ECG abnormalities included nonspecific T-wave change (40%) and right bundle branch block (17%). Three patients experienced ventricular tachycardia: sustained in one patient and nonsustained in 2 patients. Cardiac MRI was performed in 17 patients (32.7%) and in 3 patients (17.6%), which revealed diffuse myocardial enhancement suggesting CS. In this cohort, 12% of patients with NS also had confirmed CS. In addition, these patients had a high burden of cardiovascular disease not directly attributed to sarcoidosis. Our data suggest that patients with NS require comprehensive cardiac evaluation. Future studies are needed to clarify the extent of the direct contribution of granulomatous inflammation on the cardiovascular system from the indirect contribution of treatments such as glucocorticoids that lead to increased risk of cardiovascular disease in sarcoidosis.

Advanced osteoarthritis of the hip as reason for extensive asymmetric leg edema: a rare case report and review of the literature.

An enlarged iliopectineal bursa (IB) can cause pressure on iliofemoral veins. Clinical presentation can manifest as asymmetrical lower extremity edema. This case report demonstrates extensive asymmetrical leg edema caused by femoral vein compression based on iliopectineal bursitis (IB-itis) associated with advanced osteoarthritis (OA) of the left hip joint with an outline of relevant current literature. A female patient presented with left hip pain and edema in the leg. X-ray showed severe OA of the left hip. Computed Tomography (CT) concluded a cystic abnormality at the left iliopsoas muscle associated with the joint consistent with IB-itis, associated with a degenerative left hip joint. Hybrid total hip replacement was performed. At three-month follow-up her left leg showed no longer signs of extensive edema and she walked without the use of walking aids. IB-itis is mostly associated with rheumatoid arthritis (RA). There are no reports which only describe OA as cause of IB-itis. Extensive asymmetrical leg edema can be caused by venous compression of the femoral vein by an IB-itis. If the latter is the consequence of advanced hip OA, a total hip replacement can yield excellent clinical outcomes both functionally and with regard to the edema.

Maternal and fetal arrhythmia as a sign of hemodynamic deterioration: a case report

The co-existing maternal (MA) and fetal arrythmia (FA) are associated with maternal goiter disease, chorioamnionitis, or Ballantyne’s syndrome. The aim of the study - to determine the involvement of maternal arrhythmia and fetal arrhythmia in the pathogenic scenario of hemodynamic deterioration in Ballantyne’s syndrome. Clinical case. It is presented the case of sustained several weeks of MA and FA. A pregnant woman aged 36 years was admitted to the division of maternal and fetal medicine at 34 weeks of gestation. She was gravida 4 and para 3. She had complaints of rapid heartbeat, left-side chest discomfort, and lower extremities edema. The diagnosis of maternal sinus tachycardia was supported via electrocardiography. The indices of fetal, umbilical, and uteroplacental hemodynamics detected via Doppler ultrasound were appropriate. However, fetal heart rate was 209 beats/min. The transplacental attack of oral sotalol 80 mg thrice daily was prescribed. But maternal and fetal tachycardia persisted to stay. The tricuspid regurgitation was detected via Doppler ultrasound next day. The fetus was hydropic. The male baby of 2400 g, 46 cm length, 31 cm head circumference, and Apgar score 3→5 was delivered via caesarean. The newborn was discharged in 21 days. He was admitted again in one month for rehabilitation. Maternal heart rate reduced to 72 beats/min and edema regressed in three days after birth. Conclusions. MA and FA before fetal hydrops are supposed to be the early signs of mirror syndrome. This speculation needs further investigation. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Protein-losing enteropathy: is it Crohn's disease?

Case of a 24-year-old woman presenting due to edema in lower extremities. The patient had had infectious mononucleosis three weeks prior and had medical history of suspicion of Crohn's disease (CD) (due to a non-specific ileocolitis in a colonoscopy/EnteroRM). No ongoing medication. Laboratory evaluation unveiled hypoproteinemia with severe hypoalbuminemia, no renal abnormalities. A PLE was assumed, with post-infectious or CD being the most likely culprits. Alternative causes were extensively excluded. A videocapsule revealed white-tipped or granular villi, some white nodular villi and diffuse edema of the mucosa, and multiple extensive erosions and superficial ulcers in the jejunum and proximal ileum, not suggestive of CD. A push enteroscopy revealed unspecific histopathology. After incomplete response to enteral nutrition, corticotherapy was initiated resulting in sustained improvement. A follow-up Ileocolonoscopy and double balloon enteroscopy revealed no abnormalities. Six months post-treatment, the patient remains asymptomatic, with unremarkable laboratory results and no need for medication.

Delayed Diagnosis of Constrictive Pericarditis Resulting in Recurrent Heart Failure: A Case Report

Constrictive pericarditis can lead to compromised diastolic ventricular filling due to pericardial inflammation and fibrosis. A diagnosis of constrictive pericarditis was established by identifying structural and hemodynamic features through echocardiography. We present a case of constrictive pericarditis, which manifested in the form of gradually worsening dyspnea and lower-extremity edema over a 7 years period. The patient was diagnosed with constrictive pericarditis using echocardiography, and underwent a pericardiectomy.

Heyde Syndrome as Cause of New-onset Heart Failure in the Setting of Bioprosthetic Aortic Valve: A Case Report

This report describes the case of a 70-year-old female with a history of bioprosthetic aortic valve replacement. She presented to the emergency department with significant shortness of breath and bilateral lower extremity edema, which was found to be secondary to new-onset acute symptomatic congestive heart failure in the setting of Heyde syndrome.

Cardiac Manifestation of Rosai-Dorfman Disease: A Case Report and a Systematic Review

Background: Rosai-Dorfman disease is a rare condition that typically presents as a nodal disease. Cardiac involvement is extremely uncommon, occurring in 0.1–0.2% of cases, which has hindered our understanding. We report a case of Rosai-Dorfman disease (RDD) related cardiac manifestation in a patient without nodal involvement. Further, we conduct a comprehensive review of the literature to consolidate data on how patients with cardiac manifestations of RDD are typically managed and treated. Methods: A systematic review of PubMed, Web of Science, and Embase was conducted to identify cases of RDD with cardiac involvement. Out of 464 studies identified, 42 publications encompassing 43 patients met the criteria and were incorporated in this review. We gathered data on patient demographics, as well as their management and treatment approaches. Additionally, we share our own experience with a patient who presented with a cardiac mass related to RDD. Results: Out of the 43 patients, only 20.9% (n = 9) had a documented history of RDD prior to cardiac manifestations. Nodal involvement was reported in 32.6% (n = 14), while extranodal extracardiac involvement was reported in 46.5% (n = 20). Upon presentation, the most prevalent symptoms were dyspnea (48.8%, n = 21), chest discomfort (41.9%, n = 18), and lower extremity edema (16.3%, n = 7). Cardiac manifestations were most frequently found in the right atrium (41.9%, n = 18) and pericardium (18.6%, n = 8). Treatment encompassed systemic medical therapy (34.9%, n = 15) and cardiac surgery (39.5%, n = 17). The median follow-up period was 12 months (with a range of 1 to 36), and 8 patients (18.6%) experienced mortality. Our patient, who had a cardiac mass in the left atrium, underwent resection and has remained symptom-free without any recurrence for the past 5 years. Conclusion: The frequency of cardiac related-RDD manifestations may be greater than initially perceived. These results underscore the significance of identifying RDD and its cardiac-related presentations, facilitating timely diagnosis and treatment for affected individuals.

December 2023 Medical Image of the Month: Metastatic Pulmonary Calcifications in End-Stage Renal Disease

No abstract available. Manuscript truncated after 150 words. A 51-year-old African-American man with medical history of obesity (BMI 36) and hypertension was seen in pulmonary consultation for preoperative evaluation of kidney transplantation. End-Stage renal disease (ESRD) was diagnosed 7 years before evaluation secondary to resistant hypertension. The patient has been on hemodialysis since then. The patient was on carvedilol, hydralazine, losartan, and calcitriol. He had prescribed sevelamer and prednisone, but he was not taking them. His main symptoms were 3-year chronic dyspnea on exertion and mild morning cough productive of small amounts of clear sputum. He has had no chest pain, wheezes, hemoptysis, fevers, or dizziness. He had trace lower extremity edema. He worked as a forklift operator. He has had no relevant exposures and was a lifetime nonsmoker. The patient was diagnosed with cryptogenic organizing pneumonia 5 years ago and was on prednisone taper with subjective improvement of symptoms. He has not had lung function testing or …

Results of a Phase 1/2 Study of Lower Dose CPX-351 for Patients with Int-2 or High Risk IPSS Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia after Failure to Hypomethylating Agents

INTRODUCTION: Hypomethylating agents (HMAs) are the standard of care for patients (pts) with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). HMA failure (HMA-F) is associated with poor outcomes and median survival of 4 to 6 months. CPX-351 is a drug liposomal encapsulation of cytarabine (araC) and daunorubicin (dauno) at a synergistic 5:1 molar ratio approved for the treatment of pts with therapy-related acute myeloid leukemia (AML) or AML with MDS-related changes. Here we present the results of a phase I-II study of lower dose CPX-351 for HR-MDS and CMML after HMA-F. METHODS: We conducted a phase I/II clinical trial of CPX-351 for pts with MDS or CMML after HMA-F with Int-2 or High risk by IPSS, or Int-1 with >10% bone marrow (BM) blasts. The study included an initial phase I dose-escalation portion, following a 3+3 design, followed by a phase II dose expansion portion. Dose escalation included 4 dose levels of CPX-351: 10 units/m 2 (dauno 4.4mg/m 2 and araC 10mg/m 2), 25 units/m 2 (dauno 11mg/m 2 and araC 25mg/m 2), 50 units/m 2 (dauno 22mg/m 2 and araC 50mg/m 2) and 75 units/m 2 (dauni 33mg/m 2 and araC 75mg/m 2). Therapy was administered intravenously on days 1, 3 and 5 of 28-day cycles during induction and on days 1 and 3 of re-induction or consolidation. Re-induction was allowed in pts not achieving response after induction. The primary end point was to evaluate safety and determine the maximum tolerated dose of CPX-351. Responses were evaluated following 2006 IWG criteria. The Kaplan-Meir product-limit method was used to estimate median survival. RESULTS: Between June 2019 and September 2022, 23 pts have been treated: 15 in the phase I portion, and 8 in the phase II. A total of 17 pts had MDS, and 6 had CMML. Four (17%) pts had intermediate-1 risk IPSS and >10% blasts, 15 (65%) had intermediate-2 and 4 (17%) had high-risk IPSS. Median number of prior therapies was 1 (range 1-4) including 4 (17%) pts with failure to prior venetoclax therapy and 2 (9%) with prior HSCT. In the phase I portion, 3 pts received CPX-351 at dose level 1, 3 at dose level 2, 3 at dose level 3 and six at dose level 4. One pt treated at dose level 4 developed grade 2 congestive heart failure with grade 2 reduction in left-ventricular ejection fraction (LVEF). No additional DLTs were detected during the 28-day DLT evaluation window. The initial two pts treated at the P2RD of 75units/m 2 during phase II experienced cardiac complications: grade 3 congestive heart failure without reduction in LVEF and grade 3 right-sided heart failure, respectively. Study was amended to continue further treatment in phase II at dose level 3 (50units/m 2). Most common adverse events (AEs) were lower extremity edema (n=12, 52%), febrile neutropenia (n=11, 48%), dyspnea (n=10, 44%), mucositis (n=10, 44%), constipation (n=9, 39%), diarrhea (n=9, 39%), and generalized muscle weakness (n=9, 39%). Most common grade 3-4 AEs were febrile neutropenia (n=11, 48%), neutropenia (n=5, 22%), lung infection (n=4, 17%), diarrhea (n=4, 17%) and thrombocytopenia (n=3, 13%). The 4-week and 8-week cumulative incidences of mortality were 0% and 4%, respectively. Median number of days to cycle 2 was 47 days (range 30-83). Dose reductions of CPX-351 occurred in 4 (17%) pts. Median number of cycles was 3 (range 1-9). Median cycles to best response was 1 (range 1-3). Among pts with HR-MDS, the ORR was 71% (n=12): CR in 1 (6%), mCR with HI in 1 (6%) and mCR in 11 (59%) pts (Fig 1A). Among pts with BM blast reduction to <5% by the end of cycle 1, 11 (65%) and 9 (53%) had ANC recovery to >0.5x10 9/L and >1x10 9/L, respectively, and 8 (47%) and 6 (35%) had platelet recovery to >50x10 9/L and >100x10 9/L, respectively. Based on 2023 IWG response criteria, the ORR was 59% (n=10) including CR in 1 (6%), CR bilineage (CRbi) in 4 (24%) and CR unilineage in 5 (29%). Of 11 (65%) pts with baseline cytogenetic abnormalities, 2 (18%) and 2 (18%) achieved complete and partial cytogenetic responses, respectively. Three (13%) pts underwent HSCT at time of best response. Among pts with CMML (n=6), only one (17%) achieved response. Median response duration was 4.5 months (95% CI 0.7-8.2 months) and the median OS was 12.6 months (95% CI 3.6-21.7 months) (Fig 1B). CONCLUSIONS: Lower doses of CPX-351 in HR-MDS after HMA-F can induce clinically meaningful responses and be used as a bridge to allogeneic stem-cell transplant. Therapy is associated with median OS of 12.6 months in this population with expected survival of 4-6 months.

Results of a Phase II Study of Cladribine, Low Dose Cytarabine and Venetoclax, Alternating with Azacitidine and Venetoclax in Patients with Higher Risk Chronic Myelomonocytic Leukemia or Myelodysplastic Syndromes

INTRODUCTION: Clinical responses to hypomethylating agents (HMAs) in patients (pts) with higher-risk myelodysplastic syndromes (HR-MDS) and myeloproliferative chronic myelomonocytic leukemia (CMML) remain short-lived, with high risk of transformation to acute myeloid leukemia (AML). Prior data suggests use of the purine analogue cladribine can induce monocyte apoptosis and is active in AML, particularly in combination with low dose cytarabine (LDAC) and venetoclax. We aimed to evaluate the safety and activity of cladribine, LDAC and venetoclax in HR-MDS and CMML. METHODS: We designed a phase II basket clinical trial of cladribine combined with LDAC and venetoclax alternating with azacitidine and venetoclax for pts with HR-MDS or CMML. Pts were divided into 4 cohorts: cohort A: MDS with int-1 to high risk by IPSS and >5% blasts with prior HMA-failure (HMA-F); cohort B: CMML-1/CMML-2 with prior HMA-F; cohort C: previously untreated MDS with Int-2 or High risk by IPSS and >10% bone marrow (BM) blasts; cohort D: previously untreated CMML-2 or CMML-1 with at least one high-risk feature (extramedullary disease, splenomegaly of >5cm below costal margin, platelets <100x10 9/L, Hgb level <10g/dL, WBC >13x10 9/L, clonal cytogenetic abnormality [other than monosomy Y]). HMA-F was defined as no response after 6 cycles of therapy with HMA or relapse/progression after any number of cycles. Induction consisted of cladribine 5mg/m 2 daily IV on days 1-3, cytarabine 20mg s.c bid days 1-5 and venetoclax 400mg daily days 1-5. Re-induction was allowed in pts not achieving response after induction. Consolidations consisted of azacitidine 75mg/m 2 daily days 1-7 with venetoclax 400mg daily days 1-7 alternating with cladribine 5mg/m 2 days 1-3, cytarabine 20mg s.c bid days 1-5 and venetoclax 400mg days 1-5 every two 28-day cycles. The primary end point was to evaluate safety, efficacy, and tolerability of the combination. Responses were evaluated following 2006 IWG criteria. The Kaplan-Meir product-limit method was used to estimate median survival. RESULTS: Between October 2022 and June 2023, 20 pts have been treated: 10, 5, 3 and 2 in cohorts A, B, C and D, respectively. Thirteen pts had MDS, and 7 had CMML. Median age was 74 years (range 52-83). Among MDS pts, 8 (62%) had int-2 and 5 (38%) had high risk by IPSS. By the Molecular IPSS, 10 (79%) had very high, 1 (8%) had high, 1 (8%) had moderate high and 1 (8%) had low risk. Among CMML pts, 4 (57%) had high, 2 (29%) had intermediate-2 and 1 (14%) had intermediate-1 risk by the CPSS Molecular score. Among HMA-F cohorts, median number of prior therapies was 1 (range 1-4), median cycles of prior HMA was 6 (range 2-63) and 4 (27%) pts had failure to prior venetoclax therapy. Most common adverse events (AEs) were hypoalbuminemia (40%), nausea (40%), sinus bradycardia (40%), alanine aminotransferase increase (35%), constipation (35%), lower extremity edema (35%), fatigue (35%) and hypocalcemia (35%) Most common grade 3-4 AEs were leukopenia (20%) and febrile neutropenia (15%). The 4-week and 8-week cumulative incidences of mortality were 0%. Median number of cycles was 2 (range 1-6). Median cycles to best response was 1 (range 1-3). Among HMA naïve pts (cohorts C and D), the ORR was 80% (n=4): CR in 2 (40%), mCR in 2 (40%). Based on 2023 IWG response criteria, responses in cohort C (n=3) included: CR in 2 (67%) and CR bilineage (CRbi) in 1 (33%). Based on 2015 IWG MDS/MPN criteria, responses in cohort D (n=2) included optimal marrow response and clinical benefit in 1 (50%) and 1 (50%) pts, respectively. Among HMA-F pts (cohorts A and B) the ORR was 20%: 1 CR (10%) and 1 (10%) mCR with HI. Median follow up is 5.3 months (95% CI 2.4-81). Median EFS is 2.1 months in cohorts A and B and not reached in C and D (Fig 1A). Median OS has not been reached for all cohorts (Fig 1B). At the time of data cut-off, all pts in cohorts C and D discontinued study to proceed with hematopoietic stem-cell transplantation (HSCT). Among cohorts A and B, 2 pts (13%) discontinued study to proceed with HSCT, 5 (33%) due to transformation to AML, 2 (13%) due to no response, 2 (13%) due to physician choice, 1 (7%) due to patient choice and 2 (13%) pts remain on study. CONCLUSIONS: Preliminary data suggests the use of cladribine, LDAC and venetoclax can be safely administered in pts with very high risk MDS and CMML with early promising results in pts with de novo disease.

May Thurner Syndrome: Diagnostic and Therapeutic Outcomes in an Institutional Setting

Introduction: May-Thurner syndrome (MTS), a chronic compression of left common iliac vein (CIV) against the lumbar vertebrae by overlying common iliac artery is an underappreciated contributor to left leg deep venous thrombosis. Even though the estimated prevalence of MTS is high in left-leg deep vein thrombosis (DVT) cases per autopsy studies, the clinical association remains low. Since the screening for MTS in patients with recurrent left-leg DVTs is not a common practice, diagnosis can either be incidental or a combination of clinical presentation and objective testing. Diagnosis is challenging via ultrasound (US) due to the deep anatomical location of iliac veins; therefore, invasive imaging including Contrast venography (CTV) is needed for confirmation. The management of MTS has been reformed over the years with the advances in minimally invasive therapeutic tools. We sought to review the management and outcomes of the MTS adult population by conducting a retrospective review to identify all adult cases of MTS at our academic safety net hospital between 2010 and 2022. Methods: Data was extracted and analyzed for baseline parameters including age, gender, ethnicity, and body mass index (BMI). Presenting symptoms, imaging used for MTS diagnosis (including US Doppler, magnetic resonance venography or CTV), and interventional approaches (catheter or systemic thrombolysis, thrombectomy, balloon angioplasty and/or stent placement) were additionally documented. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 19 cases, predominantly females 68% (13/19), with a median age of 48 years and a mean BMI of 28.84 kg/m 2 diagnosed with MTS were identified. The predominant initial presentation was left lower extremity edema and pain 36% (7/19) later found to have a DVT, followed by non-healing venous ulcer 15% (3/19) and pelvic congestion syndrome 0.05 % (1/19). Whereas 42% (8/19) of the patients were diagnosed with MTS while undergoing evaluation for chronic and recurrent DVTs. All patients were diagnosed following CTV using transvenous pressures with the formation of collateral veins and a pressure gradient of more than 2 mm Hg across iliofemoral stenosis at rest. Sixteen patients (84%) underwent endovascular stent placement, while one patient underwent Balloon Angioplasty only. One patient refused any intervention for MTS however underwent great saphenous vein ablation for chronic venous wounds. In view of anticoagulation therapy, the initial choice in the most cases was low molecular weight heparin (LMWH), which was later transitioned to other choices, 81 % (10/16) were switched to direct oral anticoagulants, (apixaban= 10, rivaroxaban=3) due to ease of administration and compliance, while 19 % (3/16) were continued on LMWH for patient preference and pregnancy. Post-intervention complications consisted of stent failure in 25% (4/16) patients; related to stent thrombosis and Post-thrombotic Syndrome (PTS) in 12.5 % (2/16) patients. No bleeding complications were seen post any case of endovascular stent placement. Conclusion: This review was a highly educational experience giving us insight into this unacknowledged syndrome. Multiple factors could be contributing to this underdiagnosis, including invasive gold standard imaging for MTS, more easily recognizable risk factors for DVTs that can overshadow MTS, and a smaller number of data and studies. Some authorities have advocated a need to rule out MTS in young women with acute left lower extremity DVT, a clear female predominance was also noted (68%) in our analysis. Post-stent placement, systemic anticoagulation for 3-6 months is recommended, in our review, all patients (100%) who underwent stent placement were started on anticoagulation for at least 3 months. A small sample size, patients lost to follow-up (poor outcomes and complications could have been missed) and a single institutional review were some limitations of our study, however with a rare disease such as MTS with 2-3% prevalence it is difficult to conduct a large size, multi- institutional analysis. This study contributes to the limited literature available on MTS.

Quantitative measurement of pitting edema with a novel edema ruler

Lower extremity edema is a symptom of chronic venous disease and venous insufficiency. However, clinical evaluations rely on the qualitative evaluation of the pitting depth, which is neither well-defined nor quantitative. We created a novel three-dimensionally printed edema ruler as a quantitative method to measure pitting depth. Twenty-five patients (50 legs) with chronic venous disease were evaluated for ankle edema using the edema ruler. The results demonstrate excellent intraclass correlation for both single (0.944, P < .001) and average (0.971, P < .001) measurements. The edema ruler is a noninvasive, useful, and objective tool for the clinical measurement of lower extremity edema.

CTNI-15. PILOT STUDY OF HIGH-DOSE PEMETREXED FOR PROGRESSIVE CHORDOMA

Abstract INTRODUCTION Chordomas are ultra-rare tumors of the spine, and no systemic therapy is approved for refractory disease. Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase (TS) and other enzymes involved in nucleotide biosynthesis. Considering the majority of chordomas do not express TS, we sought to evaluate the therapeutic activity and safety of high-dose pemetrexed. METHODS Adults with previously-treated chordoma were enrolled on an open-label, single-institution, single-arm, pilot clinical trial. Pemetrexed 900 mg/m2 was administered intravenously every 3 weeks, with supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary and exploratory endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in potential tissue and blood-based biomarkers before and after treatment. RESULTS Fifteen patients with chordoma received a median of 15 (range 4-31) doses of pemetrexed. Median PFS was 10.5 months (95% CI 9 months-undetermined) and 6-month PFS was 67%. Out of 14 response-evaluable patients, two (14%) achieved a partial response and ten (71%) demonstrated stable disease. Adverse events were generally mild at grades 1-2, the most common being fatigue, rash, nausea, constipation, diarrhea, mucositis, vomiting, alopecia, pruritus, lower extremity edema, and alanine transaminase increased. One Grade 3 creatinine increase, one Grade 3 lymphopenia, and one Grade 4 lymphopenia occurred and there were no Grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities. Clinical improvement in disease-related symptoms occurred in several patients. Tumor molecular profiling revealed low mutational burden and though not statistically significant, positive TS expression trended negatively with disease progression. Cell-free microRNAs (cfmiRs) were concordantly detected in plasma and tissues and a blood cfmiR signature was identified that distinguished chordoma from health donors. CONCLUSION High-dose pemetrexed is safe and well-tolerated in chordoma patients. A phase II study is in development. (NCT03955042)

Abstract 14822: Portopulmonary Hypertension Unveiled: Effects of Transjugular Intrahepatic Portopulmonary Shunt Placement

Introduction: Transjugular intrahepatic portosystemic shunts (TIPS) treat portal hypertension by connecting the portal vein to the hepatic vein in the liver. The resultant shunting of portal venous flow to the systemic circulation helps reduce the portosystemic gradient and is used to treat complications of portal hypertension. Right heart failure and the development of pulmonary hypertension after TIPS are known complications; however, portopulmonary hypertension (POPH) is rare. Description of Case: A 61-year-old male presents to the clinic for six months of exertional dyspnea, weight gain, and lower extremity edema. He has a history of coronary artery disease and nonalcoholic steatohepatitis cirrhosis, with TIPS placement four years prior for esophageal variceal bleeding. An echocardiogram revealed right ventricular (RV) dilatation with moderately reduced function, a flattened left ventricular septum, and an estimated pulmonary artery systolic pressure of 91 mmHg. An echocardiogram and right heart catheterization (RHC) performed before his TIPS showed normal RV function and pulmonary artery pressures (PAP). Decision Making: The patient was promptly started on furosemide and spironolactone, and after adequate diuresis, a repeat RHC was obtained, which showed significantly elevated PAP, and normal left-sided filling pressures and cardiac output. Other causes of pulmonary hypertension were ruled out, and the patient was started on tadalafil monotherapy for severe POPH, with significant improvement in his PAP (Table 1). Conclusion: POPH after TIPS is a rare complication that should be suspected in patients presenting with signs of right-sided volume overload. The mechanism by which TIPS leads to POPH is not entirely understood. The degree of RV dysfunction correlates with mortality, and prompt treatment is warranted.

Abstract 14216: Acute Heart Failure and Mitral Stenosis in a Patient With Spindle Cell Sarcoma of the Mitral Valve

A 27-year-old male with no past medical history presented with a productive cough, intermittent hemoptysis, dyspnea, orthopnea, and lower extremity edema. He underwent an echocardiogram that was significant for a large 6.2 cm x 3.5 cm left atrial mass moving into the left ventricle across the mitral valve concerning for a myxoma. Other pertinent findings were an ejection fraction of 50-55%, severe mitral stenosis with a mean mitral valve gradient of 23, severely reduced right heart function, and severe tricuspid regurgitation. Cardiovascular surgery was consulted for evaluation of atrial mass. He underwent left atrial mass resection. The left atrial mass was attached to the mitral valve, so the mitral valve was repaired with Onyx mechanical valve. After the surgery, there was a significant improvement in right heart function, mitral valve gradient, and velocities were within the expected range. Pathology from atrial mass back with high-grade spindle cell sarcoma so Oncology was consulted. Further studies were negative for metastatic spread. He was started on adjuvant chemotherapy and currently, he is undergoing his fourth cycle. Follow-up TEE six months later noted a left atrial mass located in or where the left atrial appendage should be approximately that was 2.5cm x 1.5cm concerning for recurrence of his sarcoma. This case demonstrates a rare primary cardiac tumor, spindle cell sarcoma, which is generally aggressive and therefore has a poor prognosis. The clinical symptoms are more related to the location of the sarcoma than the histopathology. Depending on location, cardiac sarcomas generally present with heart failure as in this patient. About 25% of cardiac tumors are malignant with the majority of those being sarcomas. Initial evaluation of primary cardiac sarcomas should include echocardiography. The primary treatment is surgical resection of the mass with adjuvant chemotherapy, however, there is a high rate of recurrence and metastatic spread.

Abstract 12297: A Rare Case of May-Thurner Syndrome Due to External Compression of the Right and Left Common Iliac Veins

Description of Case: A 54yr male with HTN and CKD stage IIIa presented with asymmetric right greater than left lower extremity (LE) edema. Vital signs were normal. His exam showed asymmetric right greater than left LE edema to the mid-thighs. ECG revealed sinus rhythm. Medical therapy with increasing titration of diuretics was unsuccessful in resolving his asymmetric LE edema. A TTE showed EF of 55-60% with normal bi-ventricular size and function and no significant valve abnormalities. Bilateral duplex US showed no DVT. CT abdomen pelvis showed no hydronephrosis or compressive masses. Right heart catheterization revealed normal bi-ventricular filling pressures. Bilateral peripheral venogram showed bilateral common iliac vein stenosis (Figure 1A). IVUS showed external compression of the right common iliac vein (RCIV) between the right external and internal iliac arteries with external compression of the left common iliac vein (LCIV) by the right common iliac artery (RCIA) against the lumbar spine (Figure 1A). A diagram of the compression observed in this case is included (Figure 1B). The RCIV had an 18mmHg gradient with no significant gradient on the LCIV. The RCIV was stented using an 18x60mm self-expanding stent and balloon dilation. Final IVUS and venogram showed no residual stenosis, edge dissection or perforation (Figure 1D). The patient was discharged on dual-antiplatelet therapy for three months and aspirin thereafter with continued diuretics. He had significant reduction in asymmetric LE edema with marked improvement in ambulation capacity and no further LE asymmetry at the 30-day follow-up visit. Discussion: Here we present a rare case of May-Thurner Syndrome via compression of the LCIV by the RCIA and RCIV by the right internal and external iliac arteries with successful management. We also illustrate the importance of a broad differential diagnosis in patients with persistent asymmetric LE edema refractory to diuretic management

Abstract 14631: A Perfect Storm: Alcoholic Cardiomyopathy, Influenza B and the Battle Against Biventricular Thrombi and Pulmonary Embolism

Introduction: Biventricular thrombi (BT) are a rare occurrence in clinical practice and when they occur in alcoholic dilated cardiomyopathy (ADCM), they are a complication of this condition. Secondary predisposing conditions that can promote thrombus formation include infections like Influenza B. Herein, we report a rare case of ADCM and influenza B propagating the development of biventricular thrombi and pulmonary embolism. Case Presentation: A 47-year-old healthy gentleman with a history of tobacco, marujuana and alcohol abuse presented with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, non-productive cough, fevers and bilateral lower extremity swelling. Initial vitals were significant for tachycardia and slightly elevated blood pressure. On examination, the patient had decreased breath sounds in the right lower lobe with rales and trace lower extremity edema. Initial labs revealed elevated BNP, High-sensitivity troponin and d-dimer. Rapid influenza B was positive. Chest x-ray showed pleural effusion and CT angiogram chest revealed filling defect in the segmental and subsegmental branches of the right pulmonary artery. Echocardiogram revealed biventricular thrombi and LVEF of 10-15% with global LV hypokinesis. He was treated with oseltamivir, enoxaparin and was started on guideline directed medical therapy. Discussion: BT formation can occur in heart failure with reduced ejection fraction. ADCM induces LV dilation which creates a stagnant environment conducive to thrombus development. Influenza B can cause a prothrombotic state due to endovascular injury by proinflammatory mediators. Due to advanced diagnostic techniques, the incidence of BT has increased however, they remain a significant challenge due to embolization risks. This is the first case that highlights that patients with ADCM in combination with influenza B are predisposed to hypercoagulable states inducing fatal BT formation thus, prompt recognition is vital.

Abstract 16856: The Upside Down: A Case of Reverse McConnell’s Sign in Mixed Shock and ARDS

Introduction: We present a case of reverse McConnell’s sign in shock and respiratory failure. Hospital Course: A 48-year-old woman with cirrhosis presented to the emergency department with hypoxia, hypotension, and tachycardia. She endorsed lower extremity edema and orthopnea. Labs noted elevated BNP, procalcitonin, troponin, and lactate. Urinalysis showed signs of infection. EKG did not reveal ischemic changes. CT pulmonary embolism (PE) protocol was negative for PE but showed pulmonary edema. Parasternal short axis views on bedside ultrasound revealed interventricular septal flattening during systole consistent with right ventricular pressure overload ("D sign"). She received broad-spectrum antibiotics for E. coli bacteremia. Trans-thoracic echocardiogram showed a hyperdynamic LV and decreased RV function with a "reverse McConnell sign (rMS)" (figure 1). Providers initiated diuresis once her vasopressor requirement stabilized. She was soon extubated and her oxygen requirement continued to improve with diuresis. Vasopressors weaned in several days. Prior to discharge, trans-thoracic echocardiogram echo showed recovery of RV function. Discussion: This case of respiratory failure and shock highlights the value of prompt echocardiography. Her rMS was likely caused by increased pulmonary arterial pressure from hypoxic vasoconstriction and V/Q mismatch from ARDS. Other heart failure processes seem unlikely. rMS refers to right apical hypokinesis and basal hyperkinesis, inverted compared to its counterpart. Cases are associated with PE and Takotsubo cardiomyopathy, but rMS likely more generally indicates right heart strain. Evidence suggests that rMS may be associated with higher rates of comorbidities and adverse events. Finally, it may represent the RV’s protective mechanism for abruptly increased afterload. Conclusion: Providers should consider rMS as a sign of RV strain to assist diagnosis and management of undifferentiated shock.

Abstract 19052: Interferon B1A-Induced Dilated Cardiomyopathy

Introduction: Congestive heart failure is a leading causes of morbidity and mortality. Interferon therapy is a rare cause of dilated cardiomyopathy (DCM) and Heart Failure with Reduced Ejection Fraction (HFrEF). Specifically, interferon Alpha has been associated with cardiotoxicity. Here we describe a case of interferon B1A - induced HFrEF and DCM in a patient who took subcutaneous Interferon B1A for 11 years before developing clinical signs of heart failure. To our knowledge, only four other cases have been reported. Case Description: A 70-year-old man with a history of multiple sclerosis managed with Interferon B1A presented with shortness of breath, orthopnea, and lower extremity edema for 10 days. Physical examination revealed jugular venous distension and pitting edema. Brain natriuretic peptide (BNP) was 1580 pg/mL, troponin was 49 ng/L. Lipid panel, complete blood count, complete metabolic panel, Hemoglobin A1c, and thyroid stimulating hormone were within normal limits. Urine drug screen was negative. Chest X-ray revealed pulmonary vascular congestion and small pleural effusions bilaterally. A Transthoracic echocardiogram revealed mild aortic root dilatation (4.1cm), significant four-chamber dilatation, severely reduced left ventricular (LV) systolic function with an estimated ejection fraction of 20%, diastolic LV dysfunction, and moderately reduced systolic RV function, consistent with HFrEF and DCM (LVIDD 6.1cm). Coronary angiography showed normal coronary anatomy. The patient was started on guideline-directed medical therapy for HFrEF. Close follow-up was arranged to track improvement in systolic function after cessation of interferon b1a and consideration for Cardiac MRI and possible RV biopsy to evaluate for other causes of cardiomyopathy. Discussion/Conclusions: Due to the patient’s negative ischemic workup and absence of risk factors for cardiovascular disease, we strongly suspect that the patient’s cardiomyopathy was due to interferon B1A. With only 4 other cases of interferon B1A-induced DCM reported, it is a rare cause of medication-induced DCM. Interferon B1A should be considered a potential risk factor for developing heart failure, especially in high-risk patients.

Abstract 12450: Mystifying Masquerade: Renal Cell Carcinoma Associated Arteriovenous Fistula Presenting as High-Output Heart Failure

Case Presentation: 59 year-old woman with CKD stage 3b and hypertension presented with 3 months of progressive dyspnea, abdominal distension, bilateral lower extremity edema, and a 60-pound weight gain. Physical exam noted diffuse anasarca, with stable hemodynamics on room air. EKG revealed low voltage leads and chest X-ray demonstrated an enlarged cardiac silhouette. CT abdomen was remarkable for significant ascites, body wall edema, and a suspicious large right renal mass. Diagnostic paracentesis indicated cardiac ascites. Echocardiogram showed preserved ejection fraction, moderate pericardial effusion and an enlarged right side of the heart. Right heart catheterization confirmed high-output heart failure (HOHF). A suspected renal mass-related arteriovenous fistula (AVF) was confirmed through inferior vena caval and renal venogram blood gas sampling, indicating arteriovenous shunting within the renal mass. Hepatic venogram excluded portal hypertension. MRI abdomen confirmed a large necrotic right renal mass consistent with renal cell carcinoma (RCC). Symptoms significantly improved after nephrectomy, with aggressive diuresis, and therapeutic paracenteses leading to an 80-pound weight loss. Postoperative echocardiography illustrated decrease in pericardial effusion and right ventricular size. Cardiac MRI and stress test were unremarkable prior to planned immunotherapy for stage III RCC. Discussion: AVF and HOHF associated with malignancy are unusual presentations. RCC is the most prevalent underlying malignancy linked with AVF and is hypothesized to be a result of hypervascularity caused by a VHL gene mutation. The most often utilized imaging modalities for detecting a tumor-related AVF are contrast enhanced CT or MRI. When imaging is inconclusive, a venogram with blood gas sample, as observed in our case, may be considered to establish an RCC-associated AVF.