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Papers by Edward Kasper

ABSTRACTBackgroundPeople with autoimmune or inflammatory conditions who take immunomodulatory/sup... more ABSTRACTBackgroundPeople with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences.ObjectiveAssess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care.DesignLongitudinal registry studyParticipants4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns HopkinsMeasurementsPeriodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcareResultsA total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) w...

Journal of Cardiac Failure, 2020

Background: Cardiac sarcoidosis (CS) is an increasingly recognized cause of cardiomyopathy; howev... more Background: Cardiac sarcoidosis (CS) is an increasingly recognized cause of cardiomyopathy; however, data on immunosuppressive strategies are limited. Treatment with tumor necrosis factor (TNF) alpha inhibitors is not well described; moreover, there may be heart failureÀrelated safety concerns. Methods: Retrospective multicenter study of patients with CS treated with TNF alpha inhibitors. Baseline characteristics, treatments, and outcomes were adjudicated. Results: Thirty-eight patients with CS (mean age 49.9 years, 42% women, 53% African American) were treated with TNF alpha inhibitor (30 infliximab, 8 adalimumab). Prednisone dose decreased from time of TNF alpha inhibitor initiation (21.7 § 17.5 mg) to 6 months (10.4 § 6.1 mg, P = .001) and 12 months (7.3 § 7.3 mg, P = .002) after treatment. On pre-TNF alpha inhibitor treatment positron emission tomography with 18-flourodoxyglucose (FDG-PET), 84% of patients had cardiac FDG uptake. After treatment, there was a significant decrease in number of segments involved (3.5 § 3.8 to 1.0 § 2.5, P = .008) and maximum standardized uptake value (3.59 § 3.70 to 0.57 § 1.60, P = .0005), with 73% of patients demonstrating complete resolution or improvement of cardiac FDG uptake. The left ventricular ejection fraction remained stable (45.0 § 16.5% to 47.0 § 15.0%, P = .10). Four patients required inpatient heart failure treatment, and 8 had infections; 2 required treatment cessation. Conclusions: TNF alpha inhibitor treatment guided by FDG-PET imaging may minimize corticosteroid use and effectively reduce cardiac inflammation without significant adverse effect on cardiac function. However, infections were common, some of which were serious, and therefore patients require close monitoring for both infection and cardiac symptoms.

JACC. Cardiovascular imaging, 2017

This study sought to evaluate the effects of inflammatory sarcoid disease on coronary circulatory... more This study sought to evaluate the effects of inflammatory sarcoid disease on coronary circulatory function and the response to immune-suppressive treatment. Although positron emission tomography assessment of myocardial inflammation is increasingly applied to identify active cardiac sarcoidosis, its effect on coronary flow and immune-suppressive treatment remains to be characterized. Thirty-two individuals, who were referred for positron emission tomography/computed tomography, were evaluated for known or suspected cardiac sarcoidosis applying (18)F-fluorodeoxyglucose to determine inflammation and (13)N-ammonia to assess for perfusion deficits following a high-fat/low-carbohydrate diet and fasting state >12 h to suppress myocardial glucose uptake. Inflammation was quantified with standardized uptake value and regional myocardial blood flow at rest and during regadenoson-stimulated hyperemia was determined in ml/g/min. Positron emission tomography studies were repeated in 18 cases...

$Research paper thumbnail of PET-measured longitudinal flow gradient correlates with invasive fractional flow reserve in CAD patients$

European heart journal cardiovascular Imaging, Jan 19, 2016

We aimed to evaluate whether a PET-determined longitudinal decrease in myocardial blood flow (MBF... more We aimed to evaluate whether a PET-determined longitudinal decrease in myocardial blood flow (MBF) or gradient, assumed as a more specific flow parameter for epicardial resistance, correlates with invasively measured fractional flow reserve (FFR) in coronary artery disease (CAD) patients. In 29 patients with suspected or known CAD, myocardial perfusion and MBF in mL/g/min was determined with (13)N-ammonia PET/CT during regadenoson stimulation and at rest, and corresponding myocardial flow reserve (MFR = MBF stress/MBF rest) was calculated. MBF parameters were assessed in the myocardial region with stress-related perfusion defect and with stenosis ≥50% (Region 1), without defect but with stenosis ≥50% (Region 2), or without stenosis ≥50% (Region 3). Hyperaemic MBFs were significantly lower in the mid-distal than in the mid-left ventricular myocardium in Regions 1-3 [median and IQ range: 1.57 (1.24, 1.84) vs. 1.87 (1.61, 2.00), and 1.23 (1.11, 1.86) vs. 1.89 (1.80, 1.97), and 1.78 (1....

Journal of Heart and Lung Transplantation, Aug 1, 2005

Background: Pulmonary hypertension (PH) is common in severe heart failure, but the effect of mild... more Background: Pulmonary hypertension (PH) is common in severe heart failure, but the effect of mild PH on posttransplantation PH and survival after heart transplantation has not been well described. Methods: This cohort study examined preoperative and postoperative hemodynamics in 172 heart transplant recipients at Johns Hopkins Hospital followed for up to 15.1 years. PH was defined as pulmonary vascular resistance Ն2.5 Wood units, as measured during routine right heat catheterization; mild to moderate PH was defined as PVR between 2.5 and 4.9 Wood units; and severe PH was defined as PVR Ն5.0 Wood units. Results: Seventy-one patients (41.3%) had PH, mostly of mild/moderate severity (77.5%), at the last routine hemodynamic monitoring before transplantation (median time before transplantation, 2.7 months). During follow-up, 105 patients (62.9%) developed PH at some point after transplantation, and 48 patients died (cumulative incidence, 76.5%). Mild/moderate preoperative PH was associated with increased risk of posttransplantation PH at 1, 3, and 6 months, but not with later episodes of PH. Mild/moderate preoperative PH was not associated with a higher mortality rate, but each 1 Wood unit increase in preoperative PVR demonstrated a trend toward increased mortality. Severe preoperative PH was associated with death within the first year after adjusting for potential confounders, but not with overall mortality or mortality at other time points. Conclusions: Mild to moderate preoperative PH is associated with increased risk of developing early but not late posttransplantation PH and may suggest different management strategies. Although PH was not consistently associated with mortality, increasing severity of the preoperative PH suggests potentially worse prognosis.

American Heart Journal, Sep 1, 2005

Background Sarcoidosis is a systemic granulomatous disorder of unknown etiology. In patients with... more Background Sarcoidosis is a systemic granulomatous disorder of unknown etiology. In patients with cardiomyopathy, the diagnosis of sarcoidosis has important treatment implications. We studied the prognostic implications of a cardiac biopsy diagnosis of sarcoidosis in patients with unexplained cardiomyopathy. Methods We evaluated 1235 patients with unexplained cardiomyopathy who underwent endomyocardial biopsy (EMBx) between 1982 and 1997 at the Johns Hopkins Hospital. Twenty-eight patients were referred with a clinical diagnosis of sarcoidosis. Results Seven of these 28 patients (25%) plus 3 more with other initial diagnoses had sarcoidosis on heart biopsy. Of these 10 patients, 3 (30%) died with a median survival time after biopsy of 0.69 years. Of the remaining 21 patients with a clinical diagnosis of sarcoidosis, 20 had negative biopsy results for sarcoidosis and 7 (35%) died with a median survival time of 2.34 years. The odds of death within 1, 2, and 3 years were higher for those with than for those without an EMBx-proven cardiac sarcoid (crude OR 4.75 [ P = .23], 8.1 [ P = .09], and 1.28 [ P = .78], respectively), but the differences failed to reach significance at the .05 level. However, the difference in the odds of death within 2 years did achieve marginal significance. Conclusions Only a quarter of patients with cardiomyopathy and clinical diagnosis of sarcoid have a noncaseating granuloma on EMBx. Of those with a clinical diagnosis of sarcoidosis, heart biopsy results that are positive for sarcoidosis appear to be associated with a shorter median survival time than heart biopsy results that are negative for sarcoidosis. Finally, a noncaseating granuloma on EMBx is a rare finding in patients with cardiomyopathy without a history of sarcoidosis.

Journal of Cardiac Failure

BMC medical education, Jan 6, 2017

Physicians spend less time at the bedside in the modern hospital setting which has contributed to... more Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiop...

Journal of the American Medical Informatics Association : JAMIA, Jan 5, 2015

To develop and prospectively evaluate a web-based tool that forecasts the daily bed need for admi... more To develop and prospectively evaluate a web-based tool that forecasts the daily bed need for admissions from the cardiac catheterization laboratory using routinely available clinical data within electronic medical records (EMRs). The forecast model was derived using a 13-month retrospective cohort of 6384 catheterization patients. Predictor variables such as demographics, scheduled procedures, and clinical indicators mined from free-text notes were input to a multivariable logistic regression model that predicted the probability of inpatient admission. The model was embedded into a web-based application connected to the local EMR system and used to support bed management decisions. After implementation, the tool was prospectively evaluated for accuracy on a 13-month test cohort of 7029 catheterization patients. The forecast model predicted admission with an area under the receiver operating characteristic curve of 0.722. Daily aggregate forecasts were accurate to within one bed for ...

Journal of Cardiac Failure, 2015

Journal of Transplant Coordination, 1998

Review of the Literature Messerli 1 describes cardiac adaptation to obesity and hypertension in t... more Review of the Literature Messerli 1 describes cardiac adaptation to obesity and hypertension in the general population as left ventricular dilation and increased left ventricular mass. Other researchers have reported similar results. 2,3 Weight gain, resulting in obesity and its attendant problems, has also been reported in the cardiac transplant literature. 4-7 Baker et al 6 noted significant weight gain among transplant recipients at 2, 4, 6, 8, and 10 months following transplantation. However, except for an inverse relationship between age at transplantation and weight gain (P < .05), the researchers found no relationship between weight

Transplantation, 2001

Background. Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is... more Background. Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is associated with activation of the coagulation system. We investigated whether plasma markers of coagulation predict the presence of allograft rejection. Methods. A total of 132 blood specimens and endomyocardial biopsies were collected from 35 patients, between February of 1997 and May of 1998. We measured plasma prothrombin fragment 1.2 (PF1.2) and p-selectin, fibrinogen, thrombomodulin, and d-dimer. Biopsies were graded according to the International Society of Heart and Lung Transplantation system, with a range of 0 to 4. Grades 0 and 1A were grouped as "no rejection," and the higher grades as "rejection." Linear and logistic regression, accounting for longitudinal data, were the principal analytic tools. Results. p-Selectin level increased progressively with increasing rejection grade (P<0.001). With multivariate analysis, both p-selectin and prothrombin fragment levels significantly predicted rejection. p-Selectin levels were predictive of prothrombin fragment levels (P<0.0001) but not of d-dimer, fibrinogen, or thrombomodulin levels. This model allowed correct prediction of rejection, based on p-selectin and prothrombin fragment values, up to 85% of the time. Dichotomizing patients by a p-selectin level of 65 ng/ml resulted in an odds of rejection of 21.4 [95% C.I. 7.1-64.7] for the patients in the high-compared with the lower risk group. Conclusions. In heart transplant recipients, p-selectin levels and PF 1.2 levels are highly predictive of organ rejection. The elevation of PF 1.2 suggests that there is systemic generation of thrombin generation. These markers may be useful for noninvasively monitoring patients for organ rejection or for after response to treatment.

Transplantation, 2002

Chlamydia pneumoniae has been associated with atherosclerosis, although its role in the process i... more Chlamydia pneumoniae has been associated with atherosclerosis, although its role in the process is not clearly defined. Heart transplant recipients are known to have high titers of antibodies to C. pneumoniae, and the organism has been recovered from the coronary arteries of both transplant recipients and donors. This study evaluated association between C. pneumoniae infection and accelerated graft arteriosclerosis (AGA), also known as cardiac allograft vasculopathy (CAV), after cardiac transplantation. A case-control study was performed with 54 heart transplant recipients at the Johns Hopkins Hospital. Severe cases had &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% luminal narrowing on cardiac catheterization, mild cases &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50% narrowing, and controls were free of arteriosclerotic disease. Blood specimens were examined for C. pneumoniae serology and DNA detection by polymerase chain reaction (PCR) assays. For every twofold increase in geometric mean C. pneumoniae immunoglobulin (Ig)G titer, the odds ratio for severe AGA versus controls was 3.13 (P=0.03) and for mild AGA versus control patients was 1.61 (P=0.45). On Kaplan-Meier survival analysis there was a nonsignificant trend toward faster development of CAV in patients with higher C. pneumoniae antibody titers. Overall, 29% of heart transplant patients evaluated had evidence of circulating C. pneumoniae DNA by PCR, without a statistical difference between groups. C. pneumoniae IgG titer correlates with severity of allograft arteriosclerosis after cardiac transplantation. Circulating C. pneumoniae DNA is detectable by PCR in up to 30% of cardiac transplant recipients, but this does not correlate with severity of allograft vasculopathy.

Pacing and Clinical Electrophysiology, 2003

NASIR, K., ET AL.: Filtered QRS Duration on Signal-Averaged Electrocardiography Predicts Inducibi... more NASIR, K., ET AL.: Filtered QRS Duration on Signal-Averaged Electrocardiography Predicts Inducibility of Ventricular Tachycardia in Arrhythmogenic Right Ventricle Dysplasia. Treatment of arrhythmogenic right ventricular dysplasia (ARVD) is mostly based on the prevention of sudden cardiac death that results from arrhythmias. A clinical history suggestive of ARVD requires careful evaluation including electrophysiological study. The potential ability to identify those patients who will have inducible VT with electrophysiological study will enable better risk stratification and selection of vulnerable patients for electrophysiologically guided therapy. The purpose of the study was to evaluate the predictive ability of signal-averaged electrocardiography (SAECG) to predict inducibility of VT in patients with ARVD. The patient population consisted of 31 ARVD patients diagnosed with McKenna's criteria who underwent electrophysiological study. Electrophysiological study was considered positive if sustained monomorphic VT was induced. The sensitivity, specificity, and predictive accuracy of various SAECG criteria for inducibility of sustained monomorphic VT were also calculated. Twenty-one patients had inducible VT. The filtered QRS duration (fQRS), duration of signal <40 uV (LAS40), and root mean square voltage in the last 40 ms of QRS duration (RMS40) in ARVD patients induced versus noninduced were 122 ± 21 and 103 ± 8 ms (P = 0.007), 45 ± 20 and 28 ± 14 ms (P = 0.02), 19 ± 19 and 32 ± 22 uV (0.03), respectively. The ejection fractions were comparable in both groups. fQRS duration ≥110 ms had sensitivity of 91%, specificity of 90%, and a total predictive accuracy of 90% in predicting inducibility of VT in these patients. Filtered QRS duration on SAECG is predictive of electrophysiological study outcome in ARVD. Further studies will be needed to determine if SAECG results can predict the development of ventricular arrhythmias during follow-up.

Journal of the American College of Cardiology, 2008

Objectives-This study was designed to analyze how patient preferences for survival versus quality... more Objectives-This study was designed to analyze how patient preferences for survival versus quality of life change after hospitalization with advanced heart failure (HF). Background-Although patient-centered care is a priority, little is known about preferences to trade length of life for quality among hospitalized patients with advanced HF, and it is not known how those preferences change after hospitalization. Methods-The time trade-off utility, symptom scores, and 6-minute walk were measured at hospitalization and again in 287 patients during 6 months after therapy to relieve congestion in the ESCAPE trial. Results-Willingness to trade was bimodal. At baseline, the median trade for better quality was 3 months survival time, with modest relation to symptom severity. Preference for survival time was stable for most patients, but increase after discharge occurred in 98/145(68%) patients initially willing to trade survival time, and was more common with symptom improvement, and after therapy guided by pulmonary artery catheters (p=0.034). Adjusting days alive out of hospital for patients' survival preference reduced overall days by 24%, with largest reduction in patients dying early after discharge (p=0.0015).

Journal of the American College of Cardiology, 1998

Heart, Lung and Circulation, 2009

Diabetes Care, 2003

OBJECTIVE—Controversy exists regarding the relation between diabetes and nonischemic idiopathic c... more OBJECTIVE—Controversy exists regarding the relation between diabetes and nonischemic idiopathic cardiomyopathy (ICM), and only limited data on the incidence of ICM in adults with diabetes are available. Therefore, we used the 1995 Nationwide Inpatient Sample (NIS) to determine discharge rates and test the hypothesis that diabetes is independently associated with ICM. RESEARCH DESIGN AND METHODS—The 1995 NIS includes demographic and diagnostic data on all discharges from >900 representative hospitals in 19 states. ICD-9 codes were used to identify ICM, defined as discharges with a diagnosis of primary cardiomyopathy but without established risk factors for cardiomyopathy. Control subjects were selected by stratified random sampling by age to yield 10 per ICM case. The analyzed covariates included age, race, median income, diabetes, and hypertension. Multivariate logistic regression was used to conduct case-control analyses. RESULTS—Using sampling weights, we estimated that in 1995...

Clinica Chimica Acta, 2001

Due to myocyte damage and an associated inflammatory response, it is possible that cardiac tropon... more Due to myocyte damage and an associated inflammatory response, it is possible that cardiac troponin T and C-reactive Ž. protein CRP concentrations may correlate with the histologic grade of rejection in endomyocardial biopsy samples obtained from patients who have received a heart transplant. In this study, 704 blood samples were obtained from 145 different heart transplant recipients just prior to endomyocardial biopsy. Plasma specimens were assayed for troponin T and CRP concentration and the results compared with the assigned International Society of Heart and Lung Transplantation Ž. ISHLT histologic grade. Rejection was defined as an ISHLT grade of 3A or higher. The negative predictive values were near 80% in all cases, and a statistically significant increase in median troponin T concentration was observed across ISHLT Ž. grades. After the first month posttransplantation, the specificity of the troponin T test cutoff 0.1 ngrml was 95% and increased to 98% when false positives seen in renal disease patients were excluded. Both tests demonstrated poor sensitivity and positive predictive value for rejection. Neither CRP nor troponin T had sufficient sensitivity to serve as an alternative to endomyocardial biopsy in the diagnosis of acute cardiac allograft rejection. However, the troponin T test had a high specificity, especially when patients with renal insufficiency were excluded, and could serve as an adjunct test in this setting. When combined with a normal serum creatinine, a troponin T G 0.1 ngrml prior to endomyocardial biopsy correlated with graft rejection in almost all cases, making biopsy unnecessary.