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Objectives: We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.Background: Hospital admission for CHF is an important problem amenable to improved outpatient management.Methods: Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.Results: The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.Conclusions: This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF. [ABSTRACT FROM AUTHOR]

Swimming exercise at optimal speed may optimize growth performance of yellowtail kingfish in a recirculating aquaculture system. Therefore, optimal swimming speeds (Uopt in m s-1 or body lengths s-1, BL s-1) were assessed and then applied to determine the effects of long-term forced and sustained swimming at Uopt on growth performance of juvenile yellowtail kingfish. Uopt was quantified in Blazka-type swim-tunnels for 145 mm, 206 mm and 311 mm juveniles resulting in values of: 1) 0.70 m s-1 or 4.83 BL s-1, 2) 0.82 m s-1 or 3.25 BL s-1 and 3) 0.85 m s-1 or 2.73 BL s-1. Combined with literature data from larger fish, a relation of Uopt (BL s-1) = 234.07(BL)-0.779 (R2= 0.9909) was established for this species. Yellowtail kingfish, either forced to perform sustained swimming exercise at an optimal speed of 2.46 BL s-1 (‘swimmers’) or allowed to perform spontaneous activity at low water flow (‘resters’) in a newly designed 3,600 L oval flume (with flow created by an impeller driven by an electric motor), were then compared. At the start of the experiment, ten fish were sampled representing the initial condition. After 18 days, swimmers (n= 23) showed a 92% greater increase in BL and 46% greater increase in BW as compared to resters (n= 23). As both groups were fed equal rations, feed conversion ratio (FCR) for swimmers was 1.21 vs. 1.74 for resters. Doppler ultrasound imaging showed a statistically significant higher blood flow (31%) in the ventral aorta of swimmers vs. resters (44 ± 3 mL min-1 vs. 34 ± 3 mL min-1, respectively, under anesthesia). Thus growth performance can be rapidly improved by optimal swimming, without larger feed investments.

Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative) have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines – a phenomenon that we call ‘Disciplinary Double Consciousness’ (DDC). Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature), we argue that ‘neuro-collaborations’ inevitably engage researchers in DDC – a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a home discipline and a secondary discipline. Our case study is a five-year case study in fMRI lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations.

Abstract Background Lymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for Case presentation An 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome. Conclusion To the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy.

Abstract Introduction Posterior reversible leukoencephalopathy syndrome refers to a constellation of neurologic symptoms related to temporary white matter changes. The disease typically presents in the context of an abrupt and drastic elevation in blood pressure (>180/110 mmHg). We report an unusual case of posterior reversible leukoencephalopathy syndrome in a post-operative setting, with a blood pressure parameter generally tolerated by most patients. Case presentation We report the case of a 22-year-old Caucasian man who suffered acute onset visual acuity loss four days after an ileocecal anastomosis. A head magnetic resonance imaging scan revealed findings typically associated with posterior reversible leukoencephalopathy syndrome. His symptoms developed in the context of blood pressure parameters that are typically well tolerated in a post-operative setting (150-160/80-90 mmHg). He did not have a history of renal failure or immunosuppression. His symptoms resolved with aggressive blood pressure management. Conclusions Posterior reversible leukoencephalopathy syndrome can occur in a post-operative setting with blood pressure parameters typically well-tolerated in most post-surgical patients. Timely diagnosis and treatment will minimize the risk of permanent neurologic injury.

Abstract Background Microclip placement during AVM resection is generally accepted to be a safe practice in neurosurgery. Here, we describe an unusual complication involving cranio-spinal clip migration discovered five years after the initial AVM surgery. Case Presentation A 53-year-old man underwent resection of a superior vermian AVM that required the placement of two microclips during the procedure. Five years after surgery, the patient suffered from descending sensory radiculopathy that resolved spontaneously. The workup revealed cranio-spinal migration of one of the previously placed microclips. Conclusions AVM clip migration is a rare phenomenon; however, the diagnosis should be entertained in patients with posterior fossa instrumentation who suffer from unusual neurologic symptoms.

Background: Patients with obstructive hypertrophic cardiomyopathy have increased symptomatic burden. Mavacamten was recently approved for treatment of obstructive hypertrophic cardiomyopathy based on 2 randomized controlled trials. However, its use under real-world conditions and in diverse populations is under-studied., Methods and Results: This was a prospective observational cohort study of patients seen at the Johns Hopkins HCM center and prescribed mavacamten for obstructive hypertrophic cardiomyopathy between July 7, 2022 and January 6, 2024. Patients were followed longitudinally, with serial echocardiography and clinical evaluation as mandated by the risk evaluation and mitigation strategy program. Sixty-six patients received mavacamten (mean age 59 years, 47% male, 29% non-White [Black, Hispanic/Latino, Asian, Native Hawaiian or Pacific Islander], 47% obese). Before treatment, all patients had New York Heart Association class II (51.5%) or III (48.5%) heart failure symptoms. Initial maximum peak left ventricular outflow tract gradient was 107±46 mm Hg. Median treatment duration was 9 months. For patients on mavacamten after ≥6 months (n=43), symptoms improved by ≥1 New York Heart Association class in 72% of patients, and peak left ventricular outflow tract gradient decreased by 80±46 mm Hg, eliminating hemodynamically significant left ventricular outflow tract obstruction in 79.1% of patients. Mavacamten was temporarily discontinued in 3 patients due to left ventricular ejection fraction decrease <50%. There were no medication-related adverse events. Effectiveness and safety were similar between White and non-White patients, but symptomatic relief was attenuated in patients with body-mass index ≥35 kg/m 2 ., Conclusions: Mavacamten was effective and safe when used under real-world conditions in a racially diverse population of symptomatic patients with obstructive hypertrophic cardiomyopathy. Patients with comorbid obesity were less likely to experience symptomatic improvement while on mavacamten.

Background: Although sex- and race-based patterns have been described in the extracardiac organ involvement of sarcoidosis, cardiac sarcoidosis (CS)-specific studies are lacking., Methods: We studied CS presentation, treatment and outcomes based on sex and race in a tertiary-center cohort. Multivariable adjusted Cox proportional hazards and survival analyses were performed for primary composite outcomes (left ventricular assist device, heart transplantation, all-cause death) and for secondary outcomes (ventricular arrhythmia and all-cause death., Results: We identified 252 patients with CS (108 female, 109 Black). At presentation with CS, females vs males (P = 0.001) and Black vs White individuals (P = 0.001) more commonly had symptomatic heart failure (HF), with HF most common in Black females (ANOVA P < 0.001). Treatment differences included more corticosteroid use (90% vs 79%; P = 0.020), higher 1-year prednisone dosage (13 vs 10 mg; P = 0.003) and less frequent early steroid-sparing agent use in males (29% vs 40%; P = 0.05). Black participants more frequently received a steroid-sparing agent (75% vs 60%; P = 0.023). Composite outcome-free survival did not differ by sex or race. Male sex had an adjusted hazard ratio of 2.34 (95% CI 1.13, 4.80; P = 0.021) for ventricular arrhythmia., Conclusion: CS course may differ by sex and race and may contribute to distinct clinical CS phenotypes., Competing Interests: Disclosures The authors have no relevant disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiac sarcoidosis (CS) is an important cause of cardiomyopathy. The trajectory of left ventricular ejection fraction (LVEF) in patients with CS undergoing treatment remains unclear. Patients with CS who were treated with corticosteroids and who underwent transthoracic echocardiography were studied. Baseline characteristics, treatment, echocardiographic data (including baseline to follow-up change in LVEF), and outcomes were retrospectively evaluated. Among 100 patients, 55 had baseline reduced LVEF (<50%), and 45 had preserved LVEF (≥50%). At follow-up, 82% of patients demonstrated stable or improved LVEF. Change in LVEF was significantly higher in the baseline reduced than in the preserved LVEF group (5% [interquartile range 0 to 15] vs 0% [interquartile range -10% to 5%], p = 0.001). There was no difference in corticosteroid exposure or use of heart failure guideline-directed medical therapy between patients who did experience improvement in LVEF and those who did not experience improvement in LVEF. On multivariable analysis, baseline reduced LVEF (Odds ratio 54.89, 95% confidence interval 3.84 to 785.09, p = 0.003) and complete heart block (Odds ratio 28.88, 95% confidence interval 2.17 to 383.74, p = 0.011) at presentation were significantly associated with reduced LVEF after treatment. In conclusion, most patients with CS treated with corticosteroids maintain or improve LV systolic function. Cardiac characteristics at presentation impact prognosis in CS, despite treatment., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described., Methods: A retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed., Results: There were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups., Conclusion: Patients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: Heart failure is an increasingly recognized later stage manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) that can require heart transplantation (HT) to appropriately treat. We aimed to study contemporary ARVC HT outcomes in a national registry., Methods and Results: The United Network for Organ Sharing registry was queried for HT recipients from 1/1994 through 2/2020. ARVC patients were compared with non-ARVC dilated, restrictive, and hypertrophic cardiomyopathy HT patients (HT for ischaemic and valvular disease was excluded from analysis). Post-HT survival was assessed using Kaplan-Meier estimates. A total of 189 of 252 (75%) waitlisted ARVC patients (median age 48 years, 65% male) underwent HT, representing 0.3% of the total 65 559 HT during the study time period. Annual frequency of HT for ARVC increased significantly over time. ARVC patients had less diabetes (5% vs. 17%, P < 0.001), less cigarette use (15% vs. 23%, P < 0.001), lower pulmonary artery and pulmonary capillary wedge pressures, and lower cardiac output than the 33 659 non-ARVC patients (P < 0.001). Ventricular assist device use was significantly lower in ARVC patients (8% vs. 32%, P < 0.001); 1 and 5 year post-HT survival was 97% and 93% for ARVC vs. 95% and 82% for non-ARVC HT recipients (P < 0.001). On adjusted multivariable Cox regression, ARVC had decreased risk of post-HT death compared with non-ARVC aetiologies (hazard ratio 0.48, 95% confidence interval 0.28-0.82, P = 0.008). Patients with ARVC also had lower risk of death or graft failure than non-ARVC patients (hazard ratio 0.51, 95% confidence interval 0.32-0.81, P = 0.004)., Conclusions: In the largest series of HT in ARVC, we found that HT is increasingly performed in ARVC, with higher survival compared with other cardiomyopathy aetiologies. The right ventricular predominant pathophysiology may require unique considerations for heart failure management, including HT., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences., Methods: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health., Results: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income., Conclusions: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment., Methods and Results: This retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200-2760 mg] vs 2710 mg [IQR, 1200-5080 mg]; P = .06). On 18 F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7-9.0, P = .002) and 2.9 (IQR 0-5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac 18 F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated., Conclusions: Mycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 failure-related 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients with end-stage cardiomyopathy due to cardiac sarcoidosis (CS) may be referred for mechanical circulatory support (MCS) and heart transplantation (HT). We describe outcomes of patients with CS undergoing HT, focusing on the use of MCS as a bridge to transplant (BTT)., Methods: Using the United Network for Organ Sharing Scientific Registry of Transplant Recipients, we identified all adult waitlisted patients and isolated HT recipients from 2006 to 2015. These were divided into those with and without CS and further divided into those who did or did not receive MCS as BTT. Outcomes included 1- and 5-year post-transplantation freedom from mortality and 5-year freedom from primary graft failure., Results: Over the study period, 31,528 patients were listed for HT, 148 (0.4%) of whom had CS. Among the CS patients, 34 (23%) received MCS as BTT. 18,348 patients (58%) eventually underwent HT, including 67 (0.4%) with CS, 20 (30%) of whom had received BTT MCS. Compared with non-CS diagnoses, CS patients had similar 1-year (91% vs 90%; log rank P = .88) and 5-year (83% vs 77%; log rank P = .46) freedom from mortality. Survival was also similar between CS BTT and non-CS BTT groups at 1 year (89% vs 89%; log-rank P = .92) and 5 years (72% vs 75%; log-rank P = .77)., Conclusions: Survivals after HT were similar between CS and non-CS patients out to 5 years, and were also similar between CS and non-CS BTT cohorts. Both HT and BTT MCS should be considered in patients with CS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared with isolated postcapillary. However, it remains unclear whether increased mortality in combined post- and precapillary pulmonary hypertension is simply a result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) is a measure of total right ventricular afterload, reflecting both resistive and pulsatile components. We aimed to test whether pulmonary Ea discriminates survivors from nonsurvivors in patients with pulmonary hypertension due to left heart disease and if it does so better than other hemodynamic parameters associated with combined post- and precapillary pulmonary hypertension., Methods and Results: We combined 3 large heart failure patient cohorts (n=1036) from academic hospitals, including patients with pulmonary hypertension due to heart failure with preserved ejection fraction (n=232), reduced ejection fraction (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models, pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance and the transpulmonary gradient. Along with pulmonary arterial compliance, pulmonary Ea remained predictive of survival in patients with normal pulmonary vascular resistance. The diastolic pulmonary gradient did not predict mortality. In addition, in a subset of patients with echocardiographic data, Ea and pulmonary arterial compliance were better discriminators of right ventricular dysfunction than the other parameters., Conclusions: Pulmonary Ea and pulmonary arterial compliance more consistently predicted mortality than pulmonary vascular resistance or transpulmonary gradient across a spectrum of left heart disease with pulmonary hypertension, including patients with heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and pulmonary hypertension with a normal pulmonary vascular resistance., (© 2018 American Heart Association, Inc.)

Background: 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., Methods: 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 cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE)., Results: Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE., Conclusions: A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs.

Objectives: This study sought to evaluate the effects of inflammatory sarcoid disease on coronary circulatory function and the response to immune-suppressive treatment., Background: 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., Methods: 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 with a median follow-up of 2.5 years (interquartile range [IQR]:1.3 to 3.4 years)., Results: Twenty-five exams had normal perfusion but evidence of regional inflammation (group 1), and 21 exams presented a regional perfusion deficit associated with inflammation (group 2). Median myocardial blood flow did not differ between inflamed and noninflamed myocardium in both groups (0.86 ml/g/min [IQR: 0.66 to 1.11 ml/g/min] vs. 0.83 ml/g/min [IQR: 0.64 to 1.12 ml/g/min] and 0.74 ml/g/min [IQR: 0.60 to 0.93 ml/g/min] vs. 0.77 ml/g/min [IQR: 0.59 to 0.95 ml/g/min], respectively). As regards median hyperemic myocardial blood flows, they were significantly lower in the inflamed than in the remote regions in group 1 and 2 (2.31 ml/g/min [IQR: 1.81 to 2.95 ml/g/min] vs. 2.70 ml/g/min [IQR: 2.07 to 3.30 ml/g/min] and 1.61 ml/g/min [IQR: 1.17 to 2.18 ml/g/min] vs. 1.94 ml/g/min [IQR: 1.49 to 2.39 ml/g/min]; p < 0.001, respectively). Immune-suppression-mediated decrease in inflammation was associated with preserved myocardial flow reserve (MFR) at follow-up, whereas MFR significantly worsened in regions without changes or even increases in inflammation (median ΔMFR: 0.07 [IQR: -0.29 to 0.45] vs. -0.24 [IQR: -0.84 to 0.21]; p < 0.001). There was an inverse correlation between pronounced alterations in myocardial inflammation (Δ regional myocardial volume with standardized uptake value >4.1) and ΔMFR (r = -0.47; p = 0.048)., Conclusions: Sarcoid-mediated myocardial inflammation is associated with a regional impairment of coronary circulatory function. The association between immune-suppressive treatment-related alterations in myocardial inflammation and changes in coronary vasodilator capacity suggests direct adverse effect of inflammation on coronary circulatory function in cardiac sarcoidosis., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Over the last decades, beta-blockers have been a key component of heart failure therapy. However, currently there is no method to identify patients who will benefit from beta-blocking therapy versus those who will be unresponsive or worsen. Furthermore, there is an unmet need to better understand molecular mechanisms through which heart failure therapies, such as beta-blockers, improve cardiac function, in order to design novel targeted therapies. Solving these issues is an important step towards personalized medicine. Here, we present a comprehensive transcriptomic analysis of molecular pathways that are affected by beta-blocking agents and a transcriptomic biomarker to predict therapy response.

Objective: 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)., Methods: 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., Results: 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 70.3% of days and within three beds for 97.5% of days during the prospective evaluation period. The web-based application housing the forecast model was used by cardiology providers in practice to estimate daily admissions from the catheterization laboratory., Discussion: The forecast model identified older age, male gender, invasive procedures, coronary artery bypass grafts, and a history of congestive heart failure as qualities indicating a patient was at increased risk for admission. Diagnostic procedures and less acute clinical indicators decreased patients' risk of admission. Despite the site-specific limitations of the model, these findings were supported by the literature., Conclusion: Data-driven predictive analytics may be used to accurately forecast daily demand for inpatient beds for cardiac catheterization patients. Connecting these analytics to EMR data sources has the potential to provide advanced operational decision support., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to evaluate if diastolic pulmonary gradient (DPG) can predict survival in patients with pulmonary hypertension due to left heart disease (PH-LHD)., Background: Patients with combined post- and pre-capillary PH-LHD have worse prognosis than those with passive pulmonary hypertension. The transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) have commonly been used to identify high-risk patients. However, these parameters have significant shortcomings and do not always correlate with pulmonary vasculature remodeling. Recently, it has been suggested that DPG may be better a marker, yet its prognostic ability in patients with cardiomyopathy has not been fully assessed., Methods: A retrospective cohort of 1,236 patients evaluated for unexplained cardiomyopathy at Johns Hopkins Hospital was studied. All patients underwent right heart catheterization and were followed until death, cardiac transplantation, or the end of the study period (mean time 4.4 years). The relationships between DPG, TPG, or PVR and survival in subjects with PH-LHD (n = 469) were evaluated with Cox proportional hazards regression and Kaplan-Meier analyses., Results: DPG was not significantly associated with mortality (hazard ratio [HR]: 1.02, p = 0.10) in PH-LHD whereas elevated TPG and PVR predicted death (HR: 1.02, p = 0.046; and HR: 1.11, p = 0.002, respectively). Similarly, DPG did not differentiate survivors from non-survivors at any selected cut points including a DPG of 7 mm Hg., Conclusions: In this retrospective study of patients with cardiomyopathy and PH-LHD, an elevated DPG was not associated with worse survival., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) remains a condition with high morbidity and mortality. We tested a telephone support strategy to reduce major events in rural and remote Australians with HF, who have limited healthcare access. Telephone support comprised an interactive telecommunication software tool (TeleWatch) with follow-up by trained cardiac nurses., Methods: Patients with a general practice (GP) diagnosis of HF were randomized to usual care (UC) or UC and telephone support intervention (UC+I) using a cluster design involving 143 GPs throughout Australia. Patients were followed up for 12 months. The primary endpoint was the Packer clinical composite score. Secondary endpoints included hospitalization for any cause, death or hospitalization, as well as HF hospitalization., Results: Four hundred and five patients were randomized to CHAT. Patients were well matched at baseline for key demographic variables. The primary endpoint of the Packer score was not different between the two groups (P = 0.98), although more patients improved with UC+I. There were fewer patients hospitalized for any cause (74 vs. 114, adjusted HR 0.67 [95% CI 0.50-0.89], P = 0.006) and who died or were hospitalized (89 vs. 124, adjusted HR 0.70 [95% CI 0.53-0.92], P = 0.011), in the UC+I vs. UC group. HF hospitalizations were reduced with UC+I (23 vs. 35, adjusted HR 0.81 [95% CI 0.44-1.38]), although this was not significant (P = 0.43). There were 16 deaths in the UC group and 17 in the UC+I group (P = 0.43)., Conclusions: Although no difference was observed in the primary endpoint of CHAT (Packer composite score), UC+I significantly reduced the number of HF patients hospitalized among a rural and remote cohort. These data suggest that telephone support may be an efficacious approach to improve clinical outcomes in rural and remote HF patients., (© 2012 John Wiley & Sons Ltd.)

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic., Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy., Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed., Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF < 25% was 64% (95% CI 41%-79%) and that of NYHA class > 2 was 53% (95% CI 36-69%). A logistic model incorporating these three variables incorrectly classified 29% of patients., Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort. In this study, we tested whether Valsalva-induced changes in the pulse amplitude of finger photoplethysmography (PPG), a technology already widely available in medical settings, correlate with invasively measured left ventricular end-diastolic pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac catheterizations. A finger photoplethysmography waveform was recorded during a Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG waveform amplitude just before release of expiratory effort divided by the waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P < 0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95% confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In conclusion, finger PPG, a technology already ubiquitous in medical centers, may be useful for assessing clinically meaningful categories of left heart filling pressure, using simple analysis of the waveform after a Valsalva maneuver effort that most patients can achieve.

Opinion Statement: Investigation of the complex biochemical pathways that underlie heart failure (HF) has led to the recognition of multiple molecular markers that may help to characterize patients with this disease. Although a myriad of novel biomarkers are being studied, most attention continues to be focused on the natriuretic peptides, brain natriuretic peptide (BNP) and N-Terminal-proBNP (NT-proBNP). Numerous studies have established a role for these hormones in HF diagnosis and prognostication. More contentious has been their role in helping to guide HF management on a routine basis. This article aims to update the body of evidence surrounding conventional HF biomarkers and to highlight some emerging evidence on the use of novel markers. We believe that in select patients there may be a role for monitoring and cautious interpretation of HF biomarker levels to facilitate diagnosis, prognostication, and optimization of tailored therapy. However, there are not yet convincing data to suggest that routine hormone monitoring should be applied broadly and algorithmically to all HF patients. Moreover, to the extent that they are measured, HF biomarkers should serve only as a complement to-never as a substitute for-sound clinical judgment, watchful follow-up, and reliance on expert consultation when necessary.

Background: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures., Methods and Results: Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy., Conclusions: Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.

Aims: We sought to test the hypothesis that inherent biological factors contribute to gender differences in disease pathophysiology of new-onset heart failure (HF), which can be detected from the transcriptome of a single endomyocardial biopsy (EMB)., Methods and Results: We analysed samples from male (n = 29) and female patients (n = 14) with idiopathic dilated cardiomyopathy (IDCM) and new-onset HF with U133 Plus 2.0 microarrays (Affymetrix) and significance analysis of microarrays (SAM). There were 35 overexpressed and 16 downregulated transcripts in men vs. women [q < 5%, fold change (FC) > 1.2]. In addition to overexpression of Y-chromosome-related transcripts (n = 18), such as USP9Y (FC > 13.1), DDX3Y (FC > 11.3), RPS4Y1 (FC > 9.9), and EIF1AY (FC > 11.8) in males, there was overexpression of CD24 (FC > 5.6) and KCNK1 (FC > 1.5). In females, XIST was highly overexpressed (FC > 28.9), together with X-linked zinc finger proteins (FC > 1.9) and autosomal genes GATAD1 (FC > 1.6), SLC2A12 (FC > 2.9), and PDE6B (FC > 1.5). Analysis of a public data set of end-stage IDCM (n = 15) resulted in approximately 85% overlap with our findings., Conclusion: This is the first study that identified gender-specific transcriptomic differences in new-onset HF. Our findings may offer novel insights into fundamental biological differences in the pathophysiology of HF between sexes and provide a platform for personalized medicine.

Beta blockers are empirically used in many patients with heart failure (HF) and preserved ejection fraction (HFpEF) because they allow more time for diastolic filling and because they improve outcomes in patients with systolic HF. However, recent data suggest that impaired chronotropic and vasodilator responses to exercise, which can worsen with beta blockade, may play a key role in the pathophysiology of HFpEF. We prospectively examined the association between beta-blocker therapy after hospitalization for decompensated HF and HF rehospitalization at 6 months in 66 consecutive patients with HFpEF (71 +/- 13 years old, 68% women, 42% Black). Subjects were stratified based on receiving (BB+; 15 men, 28 women) or not receiving (BB-) beta-blockers at hospital discharge. In men, HF rehospitalization occurred less frequently in the BB+ than in the BB- group, albeit nonsignificantly (20% vs 50%, p = 0.29). In women, HF rehospitalization occurred more frequently in the BB+ than in the BB- group (75% vs 18%, p <0.001). In univariate analyses, discharge beta-blocker was associated with HF rehospitalization in women (odds ratio [OR] 14.00, 95% confidence interval [CI] 3.09 to 63.51, p = 0.001), but not in men (OR 0.25, 95% CI 0.03 to 1.92, p = 0.18). In a forward logistic regression model that offered all univariate predictors of HF rehospitalization, discharge beta blocker remained an independent predictor of HF rehospitalization in women (OR 11.06, 95% CI 1.98 to 61.67, p = 0.006). In conclusion, this small observational study suggests that beta-blocker therapy may be associated with a higher risk of HF rehospitalization in women with HFpEF. The risks and benefits of beta-blocker therapy in patients with HFpEF should be evaluated in randomized, controlled trials., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection., Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations., Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters., Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

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-min walk distance were measured in 287 patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness) trial at hospitalization and again during 6 months after therapy to relieve congestion., Results: Willingness to trade was bimodal. At baseline, the median trade for better quality was 3 months' survival time, with a modest relation to symptom severity. Preference for survival time was stable for most patients, but increase after discharge occurred in 98 of 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 after hospital discharge for patients' survival preference reduced overall days by 24%, with the largest reduction among patients dying early after discharge (p = 0.0015)., Conclusions: Preferences remain in favor of survival for many patients despite advanced HF symptoms, but increase further after hospitalization. The bimodal distribution and the stability of patient preference limit utility as a trial end point, but support its relevance in design of care for an individual patient.

Background: Cardiac allograft vasculopathy (CAV) poses the greatest threat to the long-term survival of cardiac transplant recipients, and these individuals often exhibit elevated levels of uric acid (UA), a stimulator of T cells. We hypothesized that hyperuricemia is associated with CAV in cardiac transplant recipients., Methods: UA levels were measured in cardiac transplant recipients between January 2003 and January 2005. Surveillance cardiac catheterizations performed 3 months to 1 year after UA measurement were reviewed. The relationship between UA and CAV was adjusted for possible confounders with propensity scores and confirmed with goodness-of-fit tests., Results: The 105 patients included in this study were a median 63.3 months post-transplant and their left heart catheterizations were performed a median 5.6 months after UA measurement. Focal stenosis was evident in 25 angiograms and 31 showed distal pruning of the coronary arteries. Compared with the lowest quartile of UA, the highest quartile had an increased risk of CAV: odds ratio (OR) 6.11 (95% CI 1.47 to 25.5; p = 0.013) for focal stenosis and OR 4.60 (95% CI 1.34 to 15.8; p = 0.015) for distal pruning. After adjustment, this relationship persisted for both focal stenosis (OR 5.53, 95% confidence interval [CI] 1.29 to 23.7; p = 0.021) and distal pruning (OR 4.21, 95% CI 1.15 to 15.4; p = 0.029)., Conclusions: Elevated UA confers an increased risk of CAV. This association may be causal, with pathophysiologic implications for the role of hyperuricemia in allograft failure and, if substantiated, could have clinical implications for the use of xanthine oxidase inhibitors in cardiac transplant recipients.