Call for Formalized Pathways in Vascular Medicine Training: JACC Review Topic of the Week.

The burden of vascular diseases and complexity of their management have been growing. Vascular medicine specialists may help to bridge gaps in care, especially as part of multidisciplinary teams. However, there is a limited number of vascular medicine specialists because of constraints in training. Despite established pathways for training in vascular medicine, there are obstacles that restrict completion of training in dedicated programs. A key factor is lack of funding as a result of inadequate recognition by key national accrediting and credentialing organizations. A concerted effort is required to overcome the obstacles to expand vascular medicine training programs and ultimately the pool of vascular medicine specialists. Well-trained vascular medicine specialists will be well positioned to ease the burden of vascular disease and optimize patient outcomes.

Use of echocardiography as an essential tool for targeted transcatheter biopsy of cardiac masses.

Echocardiography has emerged as an essential tool to guide targeted, transcatheter biopsy of cardiac masses. Options for imaging include transthoracic or transesophageal echocardiography and intracardiac echocardiography, with appropriate use being dictated by specific patient characteristics and institutional experience. The authors present a case of three-dimensional (3-D) transesophageal echocardiography-guided transcatheter biopsy of a right ventricular mass and review the current use of echocardiography to guide these procedures.

Effects of Crushed Ticagrelor Versus Eptifibatide Bolus Plus Clopidogrel in Troponin-Negative Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Randomized Clinical Trial.

Background After a loading dose of ticagrelor, the rate of high on-treatment platelet reactivity remains elevated, which increases periprocedural myocardial infarction and injury. This indicates that faster platelet inhibition with crushed ticagrelor (CTIC) or eptifibatide is needed to reduce high on-treatment platelet reactivity. The efficacy of CTIC versus eptifibatide bolus plus clopidogrel is unknown. Methods and Results A total of 100 P2Y12 naïve, troponin-negative patients with acute coronary syndrome were randomized to CTIC (180 mg) versus eptifibatide bolus (180 µg/kg×2 intravenous boluses) plus clopidogrel (600 mg) at the time of percutaneous coronary intervention. High on-treatment platelet reactivity was markedly higher with CTIC versus eptifibatide bolus plus clopidogrel (42% versus 0%; P<0.001) at 30 minutes and persisted up to 2 hours (12% versus 0%; P=0.01, respectively). Platelet aggregation by adenosine diphosphate dropped faster from baseline with eptifibatide bolus plus clopidogrel versus CTIC (0.5 versus 2 hours, respectively) and was higher with CTIC versus eptifibatide bolus plus clopidogrel at 0.5, 2, and 4 hours after loading dose (53±12% versus 1.3±2%; 35±11% versus 0.34±1.0%; and 23±9% versus 3.5±2%, respectively; P<0.001). Eptifibatide bolus plus clopidogrel, but not CTIC, significantly inhibited platelet aggregation induced by thrombin-receptor activating peptide. Periprocedural myocardial infarction and injury was higher with CTIC versus eptifibatide bolus plus clopidogrel (48% versus 28%, respectively; P=0.035). Post-percutaneous coronary intervention hemoglobin levels were not different between groups. Conclusions Eptifibatide bolus plus clopidogrel led to faster and more potent platelet inhibition than CTIC and reduced periprocedural myocardial infarction and injury in troponin-negative acute coronary syndrome patients undergoing percutaneous coronary intervention, with no significant hemoglobin drop after percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02925923.

Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction: Association With Baseline Disease Severity and Subsequent Outcome.

Importance: Among myriad changes occurring during the evolution of heart failure with preserved ejection fraction (HFpEF), cardiomyocyte-extracellular matrix interactions from excess collagen may affect microvascular, mechanical, and electrical function. Objective: To investigate whether myocardial fibrosis (MF) is similarly prevalent both in those with HFpEF and those at risk for HFpEF, similarly associating with disease severity and outcomes. Design, Setting, and Participants: Observational cohort study from June 1, 2010, to September 17, 2015, with follow-up until December 14, 2015, at a cardiovascular magnetic resonance (CMR) center serving an integrated health system. Consecutive patients with preserved systolic function referred for CMR were eligible. Cardiovascular magnetic resonance was used to exclude patients with cardiac amyloidosis (n = 19). Exposures: Myocardial fibrosis quantified by extracellular volume (ECV) CMR measures. Main Outcome and Measures: Baseline BNP; subsequent hospitalization for heart failure or death. Results: Of 1174 patients identified (537 [46%] female; median [interquartile range {IQR}] age, 56 [44-66] years), 250 were "at risk" for HFpEF given elevated brain-type natriuretic peptide (BNP) level; 160 had HFpEF by documented clinical diagnosis, and 745 did not have HFpEF. Patients either at risk for HFpEF or with HFpEF demonstrated similarly higher prevalence/extent of MF and worse prognosis compared with patients with no HFpEF. Among those at risk for HFpEF or with HFpEF, the actual diagnosis of HFpEF was not associated with significant differences in MF (median ECV, 28.2%; IQR, 26.2%-30.7% vs 28.3%; IQR, 25.5%-31.4%; P = .60) or prognosis (log-rank 0.8; P = .38). Over a median of 1.9 years, 61 patients at risk for HFpEF or with HFpEF experienced adverse events (19 hospitalization for heart failure, 48 deaths, 6 with both). In those with HFpEF, ECV was associated with baseline log BNP (disease severity surrogate) in multivariable linear regression models, and was associated with outcomes in multivariable Cox regression models (eg, hazard ratio 1.75 per 5% increase in ECV, 95% CI, 1.25-2.45; P = .001 in stepwise model) whether grouped with patients at risk for HFpEF or not. Conclusions and Relevance: Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.

Diffuse Myocardial Fibrosis Reduces Electrocardiographic Voltage Measures of Left Ventricular Hypertrophy Independent of Left Ventricular Mass.

BACKGROUND: Myocardial fibrosis quantified by myocardial extracellular volume fraction (ECV) and left ventricular mass (LVM) index (LVMI) measured by cardiovascular magnetic resonance might represent independent and opposing contributors to ECG voltage measures of left ventricular hypertrophy (LVH). Diffuse myocardial fibrosis can occur in LVH and interfere with ECG voltage measures. This phenomenon could explain the decreased sensitivity of LVH detectable by ECG, a fundamental diagnostic tool in cardiology. METHODS AND RESULTS: We identified 77 patients (median age, 53 [interquartile range, 26-60] years; 49% female) referred for contrast-enhanced cardiovascular magnetic resonance with ECV measures and 12-lead ECG. Exclusion criteria included clinical confounders that might influence ECG measures of LVH. We evaluated ECG voltage-based LVH measures, including Sokolow-Lyon index, Cornell voltage, 12-lead voltage, and the vectorcardiogram spatial QRS voltage, with respect to LVMI and ECV. ECV and LVMI were not correlated (R2=0.02; P=0.25). For all voltage-related parameters, higher LVMI resulted in greater voltage (r=0.33-0.49; P<0.05 for all), whereas increased ECV resulted in lower voltage (r=-0.32 to -0.57; P<0.05 for all). When accounting for body fat, LV end-diastolic volume, and mass-to-volume ratio, both LVMI (ß=0.58, P=0.03) and ECV (ß=-0.46, P<0.001) were independent predictors of QRS voltage (multivariate adjusted R2=0.39; P<0.001). CONCLUSIONS: Myocardial mass and diffuse myocardial fibrosis have independent and opposing effects upon ECG voltage measures of LVH. Diffuse myocardial fibrosis quantified by ECV can obscure the ECG manifestations of increased LVM. This provides mechanistic insight, which can explain the limited sensitivity of the ECG for detecting increased LVM.

Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding.

AIM: To compare outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it. METHODS: Patients not known to have any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups. RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics (control group). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group (P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25 (27%) vs 31 (112%) and 44 (47%) vs 74 (28%) respectively, (P = 0.001)], as well as dyslipidemia [21 (22%) vs 16 (6%), P < 0.0001). Smoking was more frequent in the aspirin group [34 (41%) vs 60 (27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower in-hospital mortality rates (2.1% vs 13.7%, P = 0.002), shorter hospital stay (4.9 d vs 7 d, P = 0.01), and fewer composite outcomes (10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups. CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits.

Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements.

BACKGROUND/AIMS: Echocardiographic abnormalities are common after resuscitation from cardiac arrest. The association between echocardiographic findings with vasopressor requirements and mortality are not well described. We sought to determine the associations between echocardiographic abnormalities and mortality, vasopressor requirements and organ failure after cardiac arrest. METHODS: We prospectively evaluated 55 adult subjects undergoing transthoracic echocardiography within 24h after resuscitation from cardiac arrest. We evaluated the association between 2D echocardiographic and Doppler measurements and mortality, Sequential Organ Failure Assessment (SOFA) scores and vasopressor requirements. RESULTS: Inpatient mortality was 60%. Mean left ventricular ejection fraction (LVEF) was 43.6%; LVEF was <40% in 36% of subjects. None of the measured echocardiographic parameters (including LVEF) was significantly associated with inpatient mortality (all p>0.1). Subjects with LVEF <40% more often had shockable arrest rhythms and patients resuscitated from shockable rhythms had lower mean LVEF (36.2% vs. 52.3%, p=0.001). There was no correlation between markers of right and left ventricular systolic or diastolic function (including LVEF and Doppler parameters) with vasopressor requirements, lactate levels or SOFA scores. CONCLUSION: Echocardiographic parameters (including LVEF) were not associated with inpatient mortality after cardiac arrest. Vasopressor requirements and organ failure severity were not associated with multiple echocardiographic markers of systolic function.

Clinical Characteristics and Outcomes of Older Cardiac Resynchronization Therapy Recipients Using a Pacemaker versus a Defibrillator.

BACKGROUND: Cardiac resynchronization therapy (CRT) is commonly used to manage heart failure, yet published guidelines do not distinguish between recommendations for pacemakers (CRT-P) and defibrillators (CRT-D) despite significant differences in size, longevity, and cost between these devices. The purpose of this study is to compare the clinical characteristics and outcomes between elderly recipients of CRT-P and CRT-D. METHODS AND RESULTS: Data from 512 patients (405 CRT-D, 107 CRT-P) aged ≥75 years with LV ejection fraction ≤35% and QRS duration >120 milliseconds were retrospectively analyzed for baseline characteristics and followed to the primary outcome of all-cause mortality. Cox proportional hazards models were used to adjust for possible confounders. Results were further validated through propensity matching cohorts. Compared to CRT-D recipients, CRT-P patients were older (83 years vs. 81 years, P < 0.001) and had more comorbid conditions (Charlson index = 5 [3-6] vs. 4 [3-5], P = 0.007). During 40.8 months of follow-up, there were 280 deaths. Compared to CRT-D patients, CRT-P recipients had higher unadjusted mortality (HR 1.54, 95% CI 1.15-2.08, P = 0.004). However, this difference lost significance after adjusting for baseline differences between the groups (HR 1.18, 95% CI 0.78-1.77, P = 0.435). CONCLUSION: Higher all-cause mortality in older CRT-P versus CRT-D patients is largely explained by baseline clinical and demographic differences between the two groups, which are likely the drivers of device selection in real-world clinical practice, where the published guidelines remain ambiguous. There is a need for randomized studies to determine optimal CRT device selection.

Radionuclide Assessment of Left Ventricular Dyssynchrony.

Phase analysis of gated myocardial perfusion single-photon emission computed tomography is a widely available and reproducible measure of left ventricular (LV) dyssynchrony, which also provides comprehensive assessment of LV function, global and regional scar burden, and patterns of LV mechanical activation. Preliminary studies indicate potential use in predicting cardiac resynchronization therapy response and elucidation of mechanisms. Because advances in technology may expand capabilities for precise LV lead placement in the future, identification of specific patterns of dyssynchrony may have a critical role in guiding cardiac resynchronization therapy.

Aspirin Has a Protective Effect Against Adverse Outcomes in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

OBJECTIVE: To determine the effect of aspirin and anticoagulants on clinical outcomes and cause of in-hospital death in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). METHODS: Patients were identified from a tertiary center database that included all patients with UGIB. Clinical outcomes including (1) in-hospital mortality, (2) severe bleeding, (3) rebleeding, (4) in-hospital complications, and (5) length of hospital stay were examined in patients taking (a) aspirin only, (b) anticoagulants only, and (c) no antithrombotics. RESULTS: Of 717 patients with NVUGIB, 56 % (402) were taking at least one antithrombotic agent. Seventy-eight (11 %) patients died in hospital, and 310 (43 %) had severe bleeding (BP < 90 mmHg, HR > 120 b/min, Hb < 7 g/dL on presentation, or transfusion of >3 units). On multivariate analysis, being on aspirin was protective against in-hospital mortality [OR 0.26 (0.13-0.53)], rebleeding [OR 0.31 (0.17-0.59)], and predictive of a shorter hospital stay (coefficient = -4.2 days; 95 % CI -8.7, 0.3). Similarly, being on nonaspirin antiplatelets was protective against in-hospital mortality (P = 0.03). However, being on anticoagulants was predictive of in-hospital complications [OR 2.0 (1.20-3.35)] and severe bleeding [OR 1.69 (1.02-2.82)]. Compared to those not taking any antithrombotics, patients who bled on aspirin were less likely to die in hospital of uncontrolled gastrointestinal bleeding (3.6 vs 0 %, P ≤ 0.01) and systemic cancer (4.9 vs 0 %, P ≤ 0.002), but equally likely to die of cardiovascular/thromboembolic disease, sepsis, and multiorgan failure. CONCLUSION: Patients who present with NVUGIB on aspirin had reduced in-hospital mortality and fewer adverse outcomes, while those on anticoagulants had increased in-hospital complications.

Effects of rosiglitazone (PPAR†γ agonist) on the myocardium in non-hypertensive diabetic rats (PPAR γ).

BACKGROUND: There is ongoing controversy regarding the safety of rosiglitazone and its effects on the myocardium, in some cases causing severe cardiac pathology and even in some instances mortality. In this study we aimed at examining the effects of pharmacologic doses of rosiglitazone on cardiomyocytes in diabetic non-cardiac rats receiving sub-optimal doses of insulin. METHODS: Animals were distributed into six groups: normal, diabetic, and diabetic receiving insulin, each subdivided into a control group and an experimental group receiving pharmacologic doses of rosiglitazone. Cardiomyocyte hypertrophy was assessed using heart to body weight index and microscopic examination using the number of cardiomyocytes per quadrant of high power field and intercalated disks in a sector of 100 × field. Fibrosis was assessed using Masson Trichrome staining. A number of sections of each group were stained with periodic acid Shiff and others with Sudan III for glycogen and fat accumulation, respectively. One way ANOVA was used for statistical analysis as appropriate. RESULTS: Diffuse cardiomyopathic changes in diabetic control animals were observed consisting of cardiomyocyte hypertrophy, loss of striations and widespread vacuolation. These changes were reduced and even prevented by treatment with insulin and rosiglitazone. Masson staining showed that all rat groups had no more than +1 fibrosis that is equal to what was present in the normal controls. CONCLUSION: Rosiglitazone, in combination with even sub-optimal doses of insulin therapy, has protective effects on cardiac muscle in diabetic animals especially those expressed as muscle hypertrophy, muscle cell death, and fibrosis.

Opposing effects of aspirin and anticoagulants on morbidity and mortality in patients with upper gastrointestinal bleeding.

OBJECTIVE: We aimed to determine the effect of antithrombotics on in-hospital mortality and morbidity in patients with peptic ulcer disease-related upper gastrointestinal bleeding (PUD-related UGIB). METHODS: The study cohort was retrospectively selected from a tertiary center database of patients with PUD-related UGIB, defined as bleeding due to gastric or duodenal ulcers, or erosive duodenitis, gastritis or esophagitis. Outcomes were compared among patient groups based on their antithrombotic medications before admission. Patients on no antithrombotics served as controls. The composite adverse outcomes, in-hospital mortality, rebleeding and/or need for surgery were measured. Severe bleeding and in-hospital complications were also recorded. RESULTS: Of 398 patients with PUD-related UGIB, 44.5% were on aspirin or anticoagulants only. The composite adverse outcome was most common in patients taking anticoagulants only (40.5%), intermediate in controls (23.1%) and least in those taking aspirin only (12.1%). On multivariate analysis, patients taking aspirin alone had a significantly lower risk of adverse outcome events (odds ratio [OR] 0.4, 95% CI 0.2-0.8) and a shorter length of hospital stay (regression coefficient = -3.4, 95% CI [-6.6, -0.6]). In contrast, taking anticoagulants was associated with a greater risk of adverse outcome events (OR 2.3, 95% CI 1.0-5.3), severe bleeding (OR 2.6, 95% CI 1.2-5.8) and in-hospital complications (OR 2.9, 95% CI 1.3-6.6). CONCLUSIONS: Patients with PUB-related UGIB while taking aspirin had fewer adverse outcomes compared with those taking anticoagulants. Aspirin may have beneficial effects in this population.

Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy in ischemic vs nonischemic cardiomyopathy patients.

BACKGROUND: Echocardiography-guided (EG) left ventricular (LV) lead placement at the site of latest mechanical activation improves outcome in heart failure (HF) patients receiving a cardiac resynchronization therapy (CRT)-defibrillator (CRT-D). OBJECTIVE: The purpose of this study was to examine the effect of a strategy of EG LV lead placement in each of ischemic (ICM) vs nonischemic (NICM) cardiomyopathy patients. METHODS: Patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized trial who were treated with a CRT-D device (108 EG strategy and 75 routine strategy) were followed to the end-points of death, appropriate CRT-D therapy, or HF hospitalization. RESULTS: Of the patients enrolled in STARTER, 115 had ICM and 68 had NICM. Over mean follow-up of 3.7 ± 2.1 years, 62 patients died, 40 received appropriate CRT-D therapy, and 67 had HF hospitalizations. Compared to NICM patients, patients with ICM had worse survival (P = .0003), worse survival free from implantable cardioverter-defibrillator therapy (P = .004), and survival free from HF hospitalization (P = .0001). A strategy of EG LV lead placement improved the outcome of CRT-D therapy-free survival primarily in ICM patients and the outcome of HF hospitalization-free survival in both ICM and NICM patients. Achieving LV resynchronization was most critical in ICM patients in whom arrhythmic and HF outcomes improve with resynchronization to levels comparable to those of NICM patients. CONCLUSION: A strategy of EG LV lead placement improves HF-free survival equally in ICM and NICM patients and CRT-D therapy-free survival more favorably in ICM patients to levels comparable to those of NICM patients.

Celiac disease patients presenting with anemia have more severe disease than those presenting with diarrhea.

BACKGROUND & AIMS: Anemia is considered to be an atypical or silent presentation of celiac disease, compared with the classic presentation with diarrhea. However, little information is available about how these groups compare in terms of disease severity. We compared the severity of celiac disease between patients who present with anemia vs those who present with diarrhea. METHODS: The study cohort was selected from a database of patients with celiac disease who were evaluated at a tertiary referral center between 1990 and 2011. Severity of celiac disease was assessed by the degree of villous atrophy and clinical and serologic parameters. Patients were compared according to mode of presentation and sex. Multivariable analyses, adjusting for age and sex, were conducted to assess the association between the mode of celiac disease presentation and cholesterol level, bone density, severity of villous atrophy, erythrocyte sedimentation rate, and level of anti-tissue transglutaminase. RESULTS: Of 727 patients, 77% presented with diarrhea and 23% with anemia (92% iron deficient). On multiple regression analysis, presentation with anemia was associated with lower levels of total cholesterol (P = .02) and high-density lipoprotein (P = .002) and a higher erythrocyte sedimentation rate (P = .001) and level of anti-tissue transglutaminase (P = .01). Presentation with anemia was associated with lower level of cholesterol only in women. Anemic patients were more than 2-fold more likely to have severe villous atrophy and a low bone mass density at the time they were diagnosed with celiac disease than patients who presented with diarrhea. CONCLUSIONS: Celiac disease patients who present with anemia have more severe disease than those who present with diarrhea. There also appear to be sex-specific differences with regard to the association between anemia and the different features of celiac disease.

Men with celiac disease are shorter than their peers in the general population.

OBJECTIVE: Late diagnosis of celiac disease (CD) is increasingly common, the implications of which are largely unknown. Although short stature is a common sign of childhood CD, the data on the height of adult CD patients is conflicting. This study investigates the final height of men and women diagnosed with CD in adulthood and attempts to identify influencing factors. PATIENTS AND METHODS: We performed a cross-sectional study of 585 adults at the Celiac Disease Center at Columbia University, comparing their height with the control population (NHANES). Patients were included if they were older than 18 years of age at diagnosis and if baseline height and weight were available. In addition, we examined for differences in demographic and physical features, mode of presentation, and concomitant illnesses in shorter versus taller celiac patients. RESULTS: Men (n=162) with CD diagnosed in adulthood were shorter than men in the general population (CD: 169.3 ± 10.5 vs. 177.3 ± 7.0 cm, P<0.01) whereas women (n=423) were not (CD: 166.3 ± 9.4 vs. 163.2 ± 6.7 cm). There were no statistically significant differences in age at diagnosis, BMI, concomitant autoimmune illnesses (hypothyroidism, type I diabetes, dermatitis herpetiformis), or mode of presentation in shorter versus taller CD patients of either sex. Hemoglobin was associated with short stature in CD men (short: 13.9 g/dl, tall: 14.6 g/dl; P=0.01), but not women (short: 12.9 g/dl, tall: 13.0 g/dl, P=0.41). CONCLUSION: Short stature is a well described phenomenon in pediatric CD with the potential for 'catch-up growth' on a gluten-free diet. However, among adults with CD who had attained final height before diagnosis, we found that men, not women, are shorter relative to the general population.

Villous atrophy and negative celiac serology: a diagnostic and therapeutic dilemma.

OBJECTIVES: Patients with villous atrophy (VA) and negative celiac disease (CD) serologies pose a diagnostic and therapeutic dilemma. When a definitive etiology for VA is not determined, patients are characterized as having unclassified sprue (US), the optimal management of which is unknown. METHODS: We studied adult patients with VA on biopsy and negative celiac serologies, evaluated at our tertiary referral center over a 10-year period. Testing for HLA DQ2/8 alleles, antienterocyte antibodies, giardia stool antigen, bacterial overgrowth, total serum immunoglobulins, and HIV was noted. Treatment, response, and repeat-biopsy findings were recorded. RESULTS: The most common diagnoses of the 72 patients were seronegative CD, medication-related villous atrophy, and US. Of those with US, the majority reported symptomatic improvement with immunosuppressive therapy. Some patients initially labeled as unclassified were found to have VA associated with olmesartan use. CONCLUSIONS: The role of medications in the development of VA and the optimal dose and length of immunosuppression for patients with US should be investigated further.