Alkurashi, Adham K.

Background: The bicuspid aortic valve (BAV) exhibits abnormal geometry and transvalvular flow and is susceptible to calcification with subsequent cardioembolic stroke from calcific embolic material. However, the description of embolic ischemic strokes in patients with BAV is limited to case reports. Methods: Consecutive patients from 1975-2015 with BAV (n=5401) at our institution were retrospectively identified. Patients with ischemic stroke before aortic valve replacement (AVR) were analyzed, and the stroke was characterized. Patients were grouped according to stroke etiology: calcific embolism from a BAV (BAV stroke); large artery atherosclerotic or lacunar stroke (LA stroke); and non-BAV, non-large artery embolic stroke (nLA stroke). Results: There were 83/5401 (1.5%) patients with ischemic stroke. Mean age was 54 ± 12 years and 28% were female. Stroke etiology was BAV stroke in 26/83 (31%), LA stroke in 23/83 (28%), nLA stroke in 30/83 (36%), and other in 4/83 (5%). Stroke was embolic in 72/83 (87%), as shown in Figure 1. CHA 2 DS 2 -VASc score was not different in patients with BAV stroke (1.4 ± 1.2) versus nLA stroke (1.8 ± 1.2, p=0.188) but was higher in LA stroke (2.3 ± 1.2, p=0.005 vs. BAV stroke). Recurrent stroke occurred in 41% overall (50% BAV stroke vs. 30% LA stroke vs. 47% nLA stroke, both p=NS vs. BAV stroke). BAV stroke was more commonly located in the retinal circulation (39% BAV stroke vs. 13% LA stroke [p=0.044] vs. 0% nLA stroke [p=0.002]). Patients with BAV and LA stroke were more likely to have moderate-to-severe aortic stenosis and undergo AVR sooner after stroke compared to patients with nLA stroke. Conclusions: Stroke is an important complication in patients with BAV. The most common type of stroke in BAV is embolic. Greater than one-third of embolic stroke resulted from embolism from a calcific aortic valve. Patients with BAV stroke commonly have a history of recurrent cerebral ischemic events, severe valvular disease, and proceed to AVR soon after stroke.

Background Description of cerebral and retinal infarction in patients with bicuspid aortic valve (BAV) is limited to case reports. We aimed to characterize cerebral and retinal infarction and examine outcomes in patients with BAV. Methods and Results Consecutive patients from 1975 to 2015 with BAV (n=5401) were retrospectively identified from the institutional database; those with confirmed cerebral or retinal infarction were analyzed. Infarction occurring after aortic valve replacement was not included. Patients were grouped according to infarction pathogenesis: embolism from a degenerative calcific BAV (BAVi); non‐BAV, large artery atherosclerotic or lacunar infarction (LAi); and non‐BAV, non‐large artery embolic infarction (nLAi). There were 83/5401 (1.5%) patients, mean age 54±12 years and 28% female, with confirmed cerebral or retinal infarction (LAi 23/83 [28%]; nLAi 30/83 [36%]; BAVi 26/83 [31%]; other 4/83 [5%]). Infarction was embolic in 72/83 (87%), and 35/72 (49%) were cardioembolic. CHA 2 DS 2 ‐VASc score was 1.4±1.2 in BAVi ( P =0.188 versus nLAi) and 2.3±1.2 in LAi ( P =0.005). Recurrent infarction occurred in 41% overall (50% BAVi, P =0.164 and 0.803 versus LAi and nLAi). BAVi was more commonly retinal (39% BAVi versus 13% LAi, P =0.044 versus 0% nLAi, P =0.002). Patients with BAVi and LAi were more likely to have moderate‐to‐severe aortic stenosis and undergo aortic valve replacement compared with patients with nLAi. Conclusions Cardioembolism, often from degenerative calcification of the aortic valve, is a predominant cause of cerebral and retinal infarction in patients with BAV and is frequently recurrent. Cerebral and retinal infarction should be regarded as a complication of BAV.

Abstract Introduction: Hepatopulmonary syndrome (HPS) is characterized by hypoxemia, portal hypertension, and intrapulmonary shunting and manifests as dyspnea. The portal hypertension may be a result of cirrhosis or non-cirrhotic causes such as nodular regenerative hyperplasia of the liver that is associated with drug therapy. Progressive hypoxemia often occurs despite stable liver function. Ado-trastuzumab emtansine (T-DM1; KADCYLA) is an antibody-drug conjugate comprised of a humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent maytansine. T-DM1 is prescribed in the postneoadjuvant setting in persons with residual invasive HER2-positive (HER2+) breast cancer (BC) as well as in persons with metastatic HER2+ BC who were previously treated with trastuzumab and a taxane. Liver toxicities including an asymptomatic, transient increase in transaminases and nodular regenerative hyperplasia that results in portal hypertension have been described; however, HPS secondary to noncirrhotic portal hypertension occurring with long-term exposure to T-DM1 has not been reported. We have identified patients (pts) with this infrequent, yet serious complication, and we aim to better characterize their clinical course to guide earlier detection and hopefully prevent irreversible hypoxic respiratory failure. Methods: Institutional search tools were utilized to identify pts at Mayo Clinic with HER2+ BC treated with T-DM1 in either the postneoadjuvant or metastatic setting. Electronic health records were manually reviewed for HPS criteria including 1) hypoxemia 2) portal hypertension and 3) intrapulmonary shunt/vasodilation confirmed by contrast echocardiogram or macroaggregated albumin lung perfusion scan. For pts meeting criteria for HPS, imaging was independently reviewed by a hepatologist to determine whether there was preexisting liver disease or if changes occurred after initiation of T-DM1. Results: We identified 259 pts with HER2+ BC treated with T-DM1 in the postneoadjuvant (n=70) or metastatic setting (n=185). Four pts met criteria for HPS (1.5%) while receiving T-DM1 for metastatic disease (Table 1; listed in chronological order of onset of HPS). Median age was 43 (range 35 - 53 years), median prior lines of treatment was 1.5 (range 0 - 7), and the median number of cycles of T-DM1 prior to discontinuation was 68.5 (range 51 - 90). All pts had evidence of left atrial enlargement on echocardiogram, and evidence of portal hypertension as determined by the presence of varices, and splenomegaly. Three pts had documented telangiectasias as well as Grade 1-2 elevations in serum transaminases and bilirubin. Elevations in hemoglobin were noted in 2 pts during treatment with T-DM1. All pts had a confirmed intrapulmonary shunt via contrast echocardiogram and a lung perfusion scan. Three pts discontinued T-DM1 after diagnosis of HPS and experienced some clinical improvement in hypoxia. One pt died two months after stopping T-DM1 due to progression of BC. Conclusion: HPS may occur in the setting of prolonged exposure to T-DM1 and can be associated with severe hypoxic respiratory failure. Further data are required to characterize the spectrum of liver injury that occurs with long-term use of T-DM1 to provide further guidance to clinicians as regards monitoring for these adverse effects. Patients who developed hepatopulmonary syndrome while on T-DM1Age, yrsSites of metastases# lines of prior txCycles of T-DM1Presenting sign or symptomsNon-contrast ECHO findingsSupplemental oxygenTransaminitis; hyperbilirubinemiaEvidence of portal hypertensionTelangiectasiasHgb prior to T-DM1Hgb end of txLung perfusion studyContrast ECHOPt 153LN, bone090DOE, hypoxemia, clubbingleft atrial enlargement (62 mg/m2)YesNovarices, splenomegalyNot documented12.9 g/dL10.7 g/dL13.5%Yes, small shuntPt 235LN, bone, liver751DOEleft atrial enlargement (54 mg/m2)YesGrade 1; Grade 2varices, splenomegaly; thrombocytopeniaYes, face and handsn/a11.9 g/dL24%Yes, large shuntPt 338LN, bone251Hyperbilirubinemiaborderline left atrial enlargementYesGrade 1; Grade 2varices, splenomegalyYes, trunk, extremities, face11.7 g/dL16.2 g/dL17.8%Yes, moderate shuntPt 448LN, liver186DOEleft atrial enlargement (49 mg/m2)NoGrade 1; Grade 2varices, splenomegalyYes, trunk12.5 g/dL16.1 g/dL7.9%Yes, large shunt Citation Format: Ally Higgins, Adham K Alkurashi, Patrick S Kamath, Vivek N Iyer, Ciara O'Sullivan, Tufia C Haddad. Hepatopulmonary syndrome with long term use of ado-trastuzumab emtansine (T-DM1) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-03.

Abstract Introduction: Blastomycosis is an uncommon; potentially life threatening granulomatous fungal infection. The aim of this study is to report hospital and intensive care unit (ICU) outcomes of patients admitted with blastomycosis. Methods: All patients admitted for treatment of blastomycosis at the Mayo Clinic-Rochester, Minnesota between 01/01/2006 and 09/30/2019 were included. Demographics, comorbidities, clinical presentation, ICU admission, and outcomes were reviewed.Results: A total of 84 Patients were identified with 93 unique hospitalizations primarily for blastomycosis. The median age at diagnosis was 49 (IQR 28.1-65, range: 6-85) years and 56 (66.7%) were male. The most frequent comorbidities incl­uded hypertension (n=28, 33.3%); immunosuppressed state (n=25, 29.8%) and diabetes mellitus (n=21, 25%). The lungs were the only organ involved in 56 (66.7%) cases and the infection was disseminated in 19 (22.6%) cases. A total of 29 patients (34.5%) underwent ICU admission due to complications of blastomycosis. ICU related events included mechanical ventilation (n=21, 25%), acute respiratory distress syndrome (ARDS) (n=13, 15.5%), tracheostomy (n=9, 10.7%), renal replacement therapy (n=8, 9.5%), and extracorporeal membrane oxygenation (ECMO) (n=4, 4.8%). A total of 12 patients (14.3%) died in the hospital; all of whom had undergone ICU admission. In-hospital mortality was associated with renal replacement therapy (RRT) (P=0.0255).Conclusions: Blastomycosis is a serious, potentially life-threatening infection that results in significant morbidity and mortality with a 34.5% ICU admission rate. Renal replacement therapy was associated with in-hospital mortality.