Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes.

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.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

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.

Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review.

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.

Management of Cardiac Sarcoidosis Using Mycophenolate Mofetil as a Steroid-Sparing Agent.

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 18F-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 18F-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.

Clinical and Imaging Response to Tumor Necrosis Factor Alpha Inhibitors in Treatment of Cardiac Sarcoidosis: A Multicenter Experience.

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.

A Contemporary Analysis of Heart Transplantation and Bridge-to-Transplant Mechanical Circulatory Support Outcomes in Cardiac Sarcoidosis.

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.

A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training.

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.

Eighteen-Month Real-World Experience Using Mavacamten for Treatment of Obstructive Hypertrophic Cardiomyopathy in a Racially Diverse Population.

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/m2. 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.

Transcriptomic biomarkers for the accurate diagnosis of myocarditis.

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.

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure.

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.

The variable natural history of idiopathic dilated cardiomyopathy.

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.

Heart transplantation outcomes in arrhythmogenic right ventricular cardiomyopathy: a contemporary national analysis.

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.

Effect of Corticosteroids on Left Ventricular Function in Patients With Cardiac Sarcoidosis.

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.

Cardiac sarcoidosis outcome differences: A comparison of patients with de novo cardiac versus known extracardiac sarcoidosis at presentation.

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.

The gene expression profile of patients with new-onset heart failure reveals important gender-specific differences.

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.

Use of novel and conventional biomarkers for management of patients with heart failure.

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.

RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES.

Background: People 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. Objective: Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care. Design: Longitudinal registry study. Participants: 4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins. Measurements: Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. Results: A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%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 chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption. Limitations: Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported. Conclusions: Exposure to glucocorticoids 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.

Transcriptomic biomarkers for individual risk assessment in new-onset heart failure.

BACKGROUND: Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF. METHODS AND RESULTS: Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions. CONCLUSIONS: These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.