Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial.

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

Development and Initial Validation of a Frailty Score for Pediatric Patients with Congenital and Acquired Heart Disease.

Frailty is a multi-dimensional clinical syndrome that is associated with increased morbidity and mortality and decreased quality of life. Children/adolescents with heart disease (HD) perform significantly worse for each frailty domain compared to non-HD peers. Our study aimed to create a composite frailty score (CFS) that can be applied to children/adolescents with HD and evaluate associations between the CFS and outcomes. Children and adolescents (n = 30) with HD (73% single ventricle, 20% heart failure, 7% pulmonary hypertension) were recruited from 2016 to 2017 (baseline). Five frailty domains were assessed at baseline using measures validated for pediatrics: (1) Slowness: 6-min walk test; (2) Weakness: handgrip strength; (3) Fatigue: PedsQL Multi-dimensional Fatigue Scale; (4) Body composition: triceps skinfold thickness; and (5) Physical activity questionnaire. Frailty points per domain (range = 0-5) were assigned based on z-scores or raw questionnaire scores and summed to produce a CFS (0 = least frail; 25 = most frail). Nonparametric bootstrapping was used to identify correlations between CFS and cross-sectional change in outcomes over 2.2 ± 0.2 years. The mean CFS was 12.5 ± 3.5. In cross-sectional analyses of baseline data, correlations (|r|≥ 0.30) were observed between CFS and NYHA class, the number of ancillary specialists, total prescribed medications, heart failure medications/day, exercise test derived chronotropic index and percent predicted VO2peak, and between child and parent proxy PEDsQL. At follow-up, CFS was correlated with an increase in the number of heart failure medications (r = 0.31). CFS was associated with cross-sectional outcomes in youth with heart disease. Longitudinal analyses were limited by small sample sizes due to loss to follow-up.

Cough and Progressive Pleuritic Chest Pain With an Enlarging Cavity on Imaging.

CASE PRESENTATION: A 49-year-old woman sought treatment at the hospital for evaluation of an enlarging cavitary mass of the right lung associated with worsening ipsilateral pleuritic chest pain and cough. She had recent hospitalizations for complications relating to recurrent lung abscesses, including one in which she underwent wedge resection of the right lung. She had been treated with several courses of antibiotics, which only temporarily relieved her symptoms. She did not report any fevers, chills, skin changes, diarrhea, or changes to her bowel habits. Her long-term medications included albuterol, dapsone, and prednisone 15 mg or 20 mg doses alternating daily. Her only past medical history was asthma and primary cutaneous pyoderma gangrenosum. The patient never smoked and did not report any recent sick contacts.

Current Practices in Treating Cardiomyopathy and Heart Failure in Duchenne Muscular Dystrophy (DMD): Understanding Care Practices in Order to Optimize DMD Heart Failure Through ACTION.

Cardiac disease has emerged as a leading cause of mortality in Duchenne muscular dystrophy in the current era. This survey sought to identify the diagnostic and therapeutic approach to DMD among pediatric cardiologists in Advanced Cardiac Therapies Improving Outcomes Network. Pediatric cardiology providers within ACTION (a multi-center pediatric heart failure learning network) were surveyed regarding their approaches to cardiac care in DMD. Thirty-one providers from 23 centers responded. Cardiac MRI and Holter monitoring are routinely obtained, but the frequency of use and indications for ordering these tests varied widely. Angiotensin converting enzyme inhibitor and aldosterone antagonist are generally initiated prior to onset of systolic dysfunction, while the indications for initiating beta-blocker therapy vary more widely. Seventeen (55%) providers report their center has placed an implantable cardioverter defibrillator in at least 1 DMD patient, while 11 providers (35%) would not place an ICD for primary prevention in a DMD patient. Twenty-three providers (74%) would consider placement of a ventricular assist device (VAD) as destination therapy (n = 23, 74%) and three providers (10%) would consider a VAD only as bridge to transplant. Five providers (16%) would not consider VAD at their institution. Cardiac diagnostic and therapeutic approaches vary among ACTION centers, with notable variation present regarding the use of advanced therapies (ICD and VAD). The network is currently working to harmonize medical practices and optimize clinical care in an era of rapidly evolving outcomes and cardiac/skeletal muscle therapies.

Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

Heterogeneous outcomes of liver disease after heart transplantation for a failed Fontan procedure.

BACKGROUND: Fontan-associated liver disease (FALD) uniformly affects patients with long-term Fontan physiology. The effect of isolated heart transplant (HT) on the course of FALD post-HT is not well understood. METHODS: We evaluated serial liver imaging pre- and post-HT to assess liver changes over time in a single-center retrospective analysis of Fontan HT recipients who had pre- and ≥1-year post-HT liver imaging. Available patient demographic and clinical data were reviewed, including available liver biopsy results. RESULTS: Serial liver imaging was available in 19 patients with a median age at HT of 12 years (range 3-23), the median age from Fontan to HT of 5.7 years (range 0.8-16), and the median time from imaging to follow up of 27 months (range 12-136 months). Pre-HT liver imaging was classified as follows: normal (n=1), congested (n=9), fibrotic (n=7), and cirrhotic (n=2). The majority of transplanted patients (15/19) had improvement in their post-HT liver imaging, including 13 patients with initially abnormal imaging pre-HT having normal liver imaging at follow-up. One patient had persistent cirrhosis at 26-month follow-up, one patient had unchanged fibrosis at 18-month follow-up, and one patient progressed from fibrosis pre-HT to cirrhosis post-HT at 136 months. No patients had overt isolated liver failure during pre- or post-HT follow-up. Liver biopsy did not consistently correlate with imaging findings. CONCLUSIONS: Post-HT liver imaging evaluation in Fontan patients reveals heterogeneous liver outcomes. These results not only provide evidence for the improvement of FALD post-HT but also show the need for serial liver imaging follow-up post-HT.

Intermittent Cough and Hemoptysis With Tree-in-Bud Opacities on Imaging.

CASE PRESENTATION: A 44-year-old man with hyperthyroidism and no smoking history presented to his internist with 5 months of intermittent cough and hemoptysis. The patient's family history was remarkable only for non-Hodgkin's lymphoma in his father. He had a history of a 25-day exposure to a home renovation at work 2 years prior to presentation. He was treated with oral clarithromycin with no improvement in his symptoms. A chest radiograph showed bilateral nodular opacities with a left lower lobar consolidative opacity (Fig 1A, 1B); the patient underwent CT scanning of the chest, which showed areas of nodular infiltration in the lower lobes with tree-in-bud-like opacities. He was referred to a pulmonologist.

A 54-Year-Old Man With Chronic Cough and Recurrent Upper Respiratory Infection.

CASE PRESENTATION: A 54-year-old man sought treatment at the ED for a productive cough with green phlegm of approximately 6 months' duration that was accompanied by a 10-pound weight loss, night sweats, and occasional subjective fevers. He had made several prior visits to the ED for the cough and was hospitalized 4 months earlier for similar symptoms, at which time he underwent a bronchoscopy with BAL and was discharged with antibiotics for presumed pneumonia. He did not report any itching, rashes, sinus infections, joint swelling, joint pain, or GI symptoms. His long-term medications included omeprazole and amlodipine. The patient had a past medical history of grade III follicular lymphoma for which he completed six cycles of bendamustine 4 years before presentation and had been in remission since. He was a never smoker, had a recent travel history to the Dominican Republic 8 months before admission, and had no recent sick contacts.

Physical Activity Patterns in Children and Adolescents With Heart Disease.

PURPOSE: To quantify the differences in daily physical activity (PA) patterns, intensity-specific volumes, and PA bouts in youth with and without heart disease (HD). METHODS: Seven-day PA was measured on children/adolescents with HD (n = 34; median age 12.4 y; 61.8% male; 70.6% single ventricle, 17.7% heart failure, and 11.8% pulmonary hypertension) and controls without HD (n = 22; median age 12.3 y; 59.1% male). Mean counts per minute were classified as sedentary, light, and moderate to vigorous PA (MVPA), and bouts of MVPA were calculated. PA was calculated separately for each hour of wear time from 8:00 to 22:00. Multilevel linear mixed modeling compared the outcomes, stratifying by group, time of day, and day part (presented as median percentage of valid wear time [interquartile range]). RESULTS: Compared with the controls, the HD group had more light PA (33.9% [15%] vs 29.6% [9.5%]), less MVPA (1.7% [2.5%] vs 3.2% [3.3%]), and more sporadic bouts (97.4% [5.7%] vs 89.9% [9.2%]), but fewer short (2.0% [3.9%] vs 7.1% [5.7%]) and medium-to-long bouts (0.0% [1.9%] vs 1.6% [4.6%]) of MVPA. The HD group was less active in the late afternoon, between 15:00 and 17:00 (P < .03). There were no differences between groups in sedentary time. CONCLUSION: Children/adolescents with HD exhibit differences in intensity-specific volumes, PA bouts, and daily PA patterns compared with controls.

Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease.

Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8-17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score -3.9 ± 1.3 vs -1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes.Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438.

Use of Mechanical Circulatory Support in Isolated Right Heart Failure: A Bridge to Transplantation.

Acute myocarditis may lead to left ventricular dysfunction and subsequent need for cardiac transplantation. We describe a 15-month-old child who presented with right heart failure of unclear cause. Echocardiography showed normal left ventricular function; however, right ventricular function was markedly reduced. The patient required extracorporeal membrane oxygenation followed by placement of a right-sided Berlin EXCOR ventricular assist device. There was little recovery, and the child underwent cardiac transplantation. Subsequent pathologic examination revealed lymphocytic myocarditis. We believe this is the first use of an isolated right ventricular assist device as a bridge to heart transplantation.

Obstructive Sleep Apnea and Pulmonary Hypertension in Children.

Obstructive sleep apnea (OSA) is a common pediatric breathing disorder, affecting 1-5% of all children. Pulmonary hypertension (PH), a severe complication of OSA, is associated with significant morbidity and mortality. Despite this important relationship between OSA and PH, there is sparse literature addressing this subject in children. This review will examine the putative relationship between OSA and PH, synthesize the available literature in children, and suggest a reasonable approach, despite limited data, for clinicians. We conclude that available evidence suggests many children with OSA have evidence of PH (estimates ranging from 0% to 85%) and vice versa (estimates ranging from 6% to 24%). Furthermore, previous studies demonstrate that treatment of the OSA, either with surgery or non-invasive ventilation, ameliorates pulmonary artery pressures to the extent of cure in a substantial number of cases. Future studies are required to better delineate the true co-occurrence of these diseases and help predict which patients are at greater risk for this serious complication. Clinicians who maintain a healthy vigilance for this important interaction of disease states will likely recognize opportunities to intervene and improve prognoses in these patients.

Intravenous home inotropic use is safe in pediatric patients awaiting transplantation.

BACKGROUND: Intravenous inotropic therapy can be used to support children awaiting heart transplantation. Although use of this therapy is discouraged in adults because of poor outcomes, its use in children, particularly outpatient, has had limited evaluation. We aimed to evaluate the safety and efficacy of this practice. METHODS AND RESULTS: A retrospective analysis of an intent to treat protocol was completed on United Network for Organ Sharing status 1A patients discharged on inotropic therapy from 1999 until 2012. Intravenous inotropic therapy was initiated for cardiac symptoms not amenable to oral therapy. Patients who were not status 1A or required >1 inotrope were excluded. Efficacy was analyzed by time to first event: transplantation; readmission until transplantation; improvement leading to inotrope withdrawal; or death. Safety included analysis of infection rates, line malfunctions, temporary hospitalization, neurological events, and arrhythmias. One hundred six patients met inclusion criteria. The mean age was 10.1±6.4 years, 47% of patients had congenital heart disease, and 80% of these patients had single ventricle physiology. In patients without congenital heart disease, 53% had dilated cardiomyopathy, 91% of patients received milrinone, 85% of patients underwent transplantation, 8% of patients successfully weaned from support as outpatients, whereas 6% died. Fifty percent of patients were readmitted before transplantation or weaning from support, of which 64% required only 1 readmission. The majority of readmissions were for heart failure. CONCLUSIONS: Outpatient intravenous inotropic therapy can be safely used as a bridge to transplantation in pediatric patients. A minority of patients can discontinue inotropic therapy because of clinical improvement.

Heart transplantation in pediatric cardiomyopathies.

Cardiomyopathies represent an uncommon but serious cause of heart disease in the pediatric population and can be categorized as dilated, hypertrophic, restrictive and left ventricular non-compaction. Each of these subtypes has multiple potential genetic etiologies in addition to possible non-genetic causes. Many patients with cardiomyopathies can benefit from transplantation, although there is not insignificant morbidity and mortality for those patients. Outcomes both prior to and following transplantation depend on the underlying etiology, the amount of support needed prior to transplantation and the illness severity of the patient prior to transplantation. Mechanical circulatory support is frequently used to bridge patients to transplantation, and newer technologies are currently in development.

Echocardiographic parameters that predict outcome in aortic atresia patients undergoing comprehensive stage II procedure.

BACKGROUND: The hybrid procedure is one option for palliating patients with hypoplastic left heart syndrome. As experience increases with this palliation, the physiology and its influence on outcome can be better assessed. The goal of this study was to determine if echocardiographic parameters correlate with post-operative variables in patients with aortic atresia undergoing the comprehensive Stage II procedure. METHODS: Retrospective chart review on all patients with aortic atresia, who underwent the comprehensive Stage II procedure from January 2002 to December 2008, was performed. Echocardiographic indices were evaluated and correlations were made with peri-operative and hospital variables. Pair-wise Pearson's correlation tests were used to analyze the associations between continuous measures. RESULTS: Thirty-four patients met inclusion criteria. Age at comprehensive Stage II procedure was 0.45 ± 0.13 years and body surface area was 0.31 ± 0.04 m(2). Right ventricle (RV) percentage change was 45 ± 10%, eccentricity index was 1.96 ± 0.45, estimated systemic cardiac output was 7.68 ± 2.56 L/min/m(2) and estimated effective systemic cardiac output was 5.15 ± 2.24 L/min/m(2). Retrograde patent ductus arteriosu (PDA) velocity time integral (VTI) correlated with log pre-bypass lactate and maximum lactate (r = 0.53, 0.44). PDA regurgitant fraction correlated with log post-bypass lactate, length of intubation, and urine output on day four (r = 0.39, 0.46, -0.37). RV percentage change correlated with log pre-bypass lactate, and urine output on days four and five (r =-0.38, 0.43, 0.54). No echocardiographic parameter predicted renal or liver insufficiency, dialysis, extracorporeal membrane oxygenation use, or hospital death. CONCLUSION: Retrograde PDA VTI and RV percent change correlated with some peri-operative variables though no echocardiographic parameter was associated with any major morbidities or mortality. Newer echocardiographic techniques may better predict comprehensive stage II outcomes.