A prospective multicenter feasibility study of a miniaturized implantable continuous flow ventricular assist device in smaller children with heart failure.

BACKGROUND: There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant. METHODS: Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure. RESULTS: Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1-4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient. CONCLUSION: The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, clinicaltrials.gov 02954497).

Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children.

BACKGROUND: Despite growing cardiogenic shock (CS) research in adults, the epidemiology, clinical features, and outcomes of children with CS are lacking. OBJECTIVES: This study sought to describe the epidemiology, clinical presentation, hospital course, risk factors, and outcomes of CS among children hospitalized for acute decompensated heart failure (ADHF). METHODS: We examined consecutive ADHF hospitalizations (<21 years of age) from a large single-center retrospective cohort. Patients with CS at presentation were analyzed and risk factors for CS and for the primary outcome of in-hospital mortality were identified. A modified Society for Cardiovascular Angiography and Interventions shock classification was created and patients were staged accordingly. RESULTS: A total of 803 hospitalizations for ADHF were identified in 591 unique patients (median age 7.6 years). CS occurred in 207 (26%) hospitalizations. ADHF hospitalizations with CS were characterized by worse systolic function (P = 0.040), higher B-type natriuretic peptide concentration (P = 0.032), and more frequent early severe renal (P = 0.023) and liver (P < 0.001) injury than those without CS. Children presenting in CS received mechanical ventilation (87% vs 26%) and mechanical circulatory support (45% vs 16%) more frequently (both P < 0.001). Analyzing only the most recent ADHF hospitalization, children with CS were at increased risk of in-hospital mortality compared with children without CS (28% vs 11%; OR: 1.91; 95% CI: 1.05-3.45; P = 0.033). Each higher CS stage was associated with greater inpatient mortality (OR: 2.40-8.90; all P < 0.001). CONCLUSIONS: CS occurs in 26% of pediatric hospitalizations for ADHF and is independently associated with hospital mortality. A modified Society for Cardiovascular Angiography and Interventions classification for CS severity showed robust association with increasing mortality.

Long-term implantable ventricular assist device support in children.

BACKGROUND: In pediatrics, implantable continuous-flow ventricular assist devices (IC-VAD) are often used as a "temporary" support, bridging children to cardiac transplantation during the same hospital admission. METHODS: We conducted a retrospective review of our consecutive patients undergoing IC-VAD support at a tertiary pediatric heart center between 2008 and 2022. RESULTS: We identified 100 IC-VAD implant encounters: HeartWare HVAD (67; 67%), HeartMate II (17; 17%), and HeartMate 3 (16; 16%). The median (range) age, weight, and body surface area at implantation were 14.1 (3.0-56.5) years, 54.8 (13.3-140) kg, and 1.6 (0.6-2.6) m2, respectively. Cardiomyopathy (58; 58%) was the most common etiology, followed by congenital heart disease (37; 37%, including 13 single ventricle). At 6 months of IC-VAD support, 94 (94%) encounters achieved positive outcomes: ongoing support (59; 59%), transplant (33; 33%), and cardiac recovery (2; 2%). Eighty-two encounters (82%) resulted in home discharge with ongoing VAD support, including 38 (46%, out of 82) requiring readmission and 7 (9%, out of 82) resulting in death. There was a clinically significant decrease in morbidity rates before versus after home discharge: bleeding (1.55 vs 0.06), infection (0.84 vs 0.37), and stroke (0.84 vs 0.15 event per patient-year). Overall, 86 encounters (86%) reached positive end points at the latest follow-up (64 transplant, 15 ongoing support, and 7 recovery). Infection (29%; 4 of 14) was the most common cause of negative outcomes, followed by cerebrovascular accident (21%; 3), and unresolved frailty (21%; 3). The estimated overall survival at 1, 2, and 5 years was 90%, 86%, and 77%, respectively. CONCLUSIONS: This study suggests the feasibility of outpatient management of pediatric IC-VAD support. The ability to offer true long-term support maximizes the potential of IC-VAD support, not limited to a temporary bridging tool for heart transplantation.

Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-ß Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-ß (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans. METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR (clustered regularly interspaced short palindromic repeats)-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated and subjected to ECG, histological, and transcriptional analysis. RESULTS: We report 2 probands with loss-of-function PRDM16 variants and pediatric left ventricular noncompaction cardiomyopathy. One proband hosts a PRDM16-Q187X variant with left ventricular noncompaction cardiomyopathy and demonstrated infant-onset heart failure, which was selected for further study. Induced pluripotent stem cell-derived cardiomyocytes prepared from the PRDM16-Q187X proband demonstrated a statistically significant impairment in myocyte proliferation and increased apoptosis associated with transcriptional dysregulation of genes implicated in cardiac maturation, including TGF-ß-associated transcripts. Homozygous Prdm16Q187X/Q187X mice demonstrated an underdeveloped compact myocardium and were embryonically lethal. Heterozygous Prdm16Q187X/WT mice demonstrated significantly smaller ventricular dimensions, heightened fibrosis, and age-dependent loss of TGF-ß expression. Mechanistic studies were undertaken in H9c2 cardiomyoblasts to show that PRDM16 binds TGFB3 promoter and represses its transcription. CONCLUSIONS: Novel loss-of-function PRDM16 variant impairs myocardial development resulting in noncompaction cardiomyopathy in humans and mice associated with altered TGF-ß signaling.

Atypical infiltrates on endomyocardial biopsy are associated with adverse outcomes in pediatric heart transplantation.

BACKGROUND: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes. METHODS: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis. RESULTS: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002). CONCLUSIONS: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

Pediatric Pericarditis: Update.

PURPOSE OF REVIEW: While there have now been a variety of large reviews on adult pericarditis, this detailed review specifically focuses on the epidemiology, clinical presentation, diagnosis, and management of pediatric pericarditis. We have tried to highlight most pediatric studies conducted on this topic, with special inclusion of important adult studies that have shaped our understanding of and management for acute and recurrent pericarditis. RECENT FINDINGS: We find that the etiology of pediatric pericarditis differs from adult patients with pericarditis and has evolved over the years. Also, with the current COVID-19 pandemic, it is important for pediatric clinicians to be aware of pericardial involvement both due to the infection and from vaccination. Oftentimes, pericarditis maybe the only cardiac involvement in children with COVID-19, and so caregivers should maintain a high index of suspicion when they encounter children with pericarditis.  Large-scale contemporary epidemiological data regarding incidence and prevalence of both acute and recurrent pericarditis is lacking in pediatrics, and future studies should focus on highlighting this important research gap. Most of the current management strategies for pediatric pericarditis are from experiences gathered from adult data. Pediatric multicenter trials are warranted to understand the best management strategy for those with acute and recurrent pericarditis. CASE VIGNETTE: A 6-year-old child with a past history of pericarditis almost 2 months ago comes in with a 2-day history of chest pain and fever. Per mother, he stopped his steroids about 2 weeks ago, and for the last 2 days has had a temperature of 102F and has been complaining of sharp mid-sternal chest pain that gets worse when he lies down and is relieved when he sits up and leans forward. On examination, he is tachycardic (heart rate 160 bpm), with normal blood pressure for age. He appears to be in pain (5/10), and on auscultation has a pericardial friction rub. His lab studies are notable for elevated white blood cell count and inflammatory markers (CRP and ESR). His electrocardiogram reveals sinus tachycardia and diffuse ST-elevation in all precordial leads. His echocardiogram demonstrates normal biventricular function and a trace pericardial effusion. His cardiac MRI confirms recurrent pericarditis. He is started on indomethacin and colchicine. He has complete resolution of his symptoms by day 3 of admission and is discharged with close follow-up.

Temporary ventricular assist device support with a catheter-based axial pump: Changing the paradigm at a pediatric heart center.

OBJECTIVE: We report the largest pediatric single-center experience with an Impella (Abiomed Inc) catheter-based axial pump support. METHODS: We conducted a retrospective cohort study of all patients with acute decompensated heart failure or cardiogenic shock requiring catheter-based axial pump support between October 2014 and February 2022. The primary outcome per individual encounter (hospital admission) was defined as bridge-to-recovery, bridge-to-durable ventricular assist device support, bridge-to-cardiac transplantation, or death at 6 months after catheter-based axial pump explantation. Adverse events were defined according to the Pediatric Interagency Registry for Mechanical Circulatory Support criteria. RESULTS: Our final study cohort included 37 encounters with 43 catheter-based axial pump implantations. A single catheter-based axial pump device was used for support in 33 encounters (89%), with 2 catheter-based axial pump devices used in 3 (8%) separate encounters and 3 catheter-based axial pump devices used in 1 (3%) encounter. The median [range] age, weight, and body surface area at implantation were 16.8 [6.9-42.8] years, 61.1 [23.1-123.8] kg, and 1.7 [0.8-2.5] m2, respectively. The predominant causes of circulatory failure were graft failure/rejection in 16 patients (43%), followed by cardiomyopathy in 7 patients (19%), arrhythmia refractory to medical therapies in 6 patients (16%), myocarditis/endocarditis in 4 patients (11%), and heart failure due to congenital heart disease in 4 patients (11%). Competing outcomes analysis showed a positive outcome with bridge-to-recovery in 58%, bridge-to-durable VAD support in 14%, and bridge-to-cardiac transplantation in 14% at 6 months. Fourteen percent of encounters resulted in death at 6 months. CONCLUSIONS: We demonstrate that catheter-based axial pump support in children results in excellent 1- and 6-month survival with an acceptable adverse event profile.

Ventricular assist device support for failing Glenn circulation: Impact of concomitant Fontan completion in select patients.

BACKGROUND: Ventricular assist device (VAD) support for failing Glenn circulation represents a unique challenge. METHODS: We conducted a retrospective review of clinical outcomes in patients with VAD support for failing Glenn circulation between 2010 and 2020 at a tertiary pediatric institution. RESULTS: Ten patients were included: INTERMACS profiles were 1 in 3 patients and 2 in 7 patients. The median age, weight, and body surface area were 3.2 years, 13.0 kg, and 0.5 m2, respectively. Seven patients (70%) were implanted with continuous-flow devices and 3 with para-corporeal devices. Nine patients (90%) received heart transplant, with a median support duration of 77 days. Four (67%) out of 6 patients supported with discharge-capable devices were managed as outpatients. Post-transplant survival was 100%, with a median (range) follow up duration of 3.5 (1.8-11.9) years. There were 3 neurologic complications in 3 patients (0.9 events per patient-year); 2 intraoperative events (fatal hypoxia and symptomatic embolic stroke) and 1 postoperative (asymptomatic subarachnoid hemorrhage). Pump thrombosis occurred in one patient (0.3 events per patient-year), requiring pump exchange at day 65. Five patients (50%) received concomitant Fontan completion (fenestrated in 1). The Fontan-upgraded patients (vs Glenn) tended to be larger (median (range): 15.9 (12.6-22.9) vs 9.1 (7.7-22.8) kg), older (4.7 (3.1-6.5) vs 1.1 (0.9-10.1) years) and had a higher PaO2/FiO2 ratio (192 (52-336) vs 76 (59-78) mm Hg) on postoperative day 1. CONCLUSION: Our experience suggests the feasibility of durable VAD support for failing Glenn circulation. Concomitant Fontan completion may be considered in select patients to improve oxygen delivery.

Correlating decline in left ventricular ejection fraction and longitudinal strain in pediatric cancer patients.

PURPOSE: Left ventricular ejection fraction (LVEF) is routinely used to monitor cardiac function in cancer patients. Global longitudinal strain (GLS) detects subclinical myocardial dysfunction. There is no consensus on what constitutes a significant change in GLS in pediatric cancer patients. We aim to determine the change in GLS associated with a simultaneous decline in LVEF in pediatric cancer patients. METHODS: This is a retrospective longitudinal study of pediatric cancer patients treated with anthracyclines between October 2017 and November 2019. GLS was measured by 2-dimensional speckle tracking. The study outcome was a decline in LVEF, defined as a decrease in LVEF of ≥ 10% points from baseline or LVEF < 55%. We evaluated two echocardiograms per patient, one baseline, and one follow-up. The follow-up echocardiogram was either (1) the first study that met the outcome or (2) the last echocardiogram available in patients without the outcome. Statistical analyses included receiver operator characteristic curves and univariable and multivariable Cox proportional hazards regression. RESULTS: Out of 161 patients, 33 (20.5%) had a decline in LVEF within one year of follow-up. GLS reduction by ≥ 15% from baseline and follow-up GLS >-18% had sensitivities of 85% and 78%, respectively, and specificities of 86% and 83%, respectively, to detect LVEF decline. GLS reduction by ≥ 15% from baseline and follow-up GLS >-18% were independently associated with simultaneous LVEF decline [hazard ratio (95% confidence intervals): 16.71 (5.47-51.06), and 12.83 (4.62-35.63), respectively]. CONCLUSION: Monitoring GLS validates the decline in LVEF in pediatric cancer patients.

Arrhythmogenic cardiomyopathy is under-recognized in end-stage pediatric heart failure: A 36-year single-center experience.

BACKGROUND: Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies. METHODS: We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases. RESULTS: Forty-five percent (n = 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205 = 4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p = .012) and transplant (11.1 years vs. 6.5 years, p = .010), had more ventricular arrhythmias (80.0% vs 32.8%, p = .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p = .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n = 5/5, 100%). CONCLUSION: AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC.

Outcomes of temporary ventricular assist device: A pediatric institutional experience over 25 years.

BACKGROUND: There are scarce data describing outcomes of pediatric temporary ventricular assist device support. METHODS: A retrospective single-center study was conducted to review clinical outcomes of all consecutive patients with temporary ventricular assist device between 1996 and 2021. Given the complex clinical course in some patients requiring multiple temporary ventricular assist device runs, outcome analysis was based on "encounters" (hospitalizations with temporary ventricular assist device, regardless of the number of devices used). RESULTS: In total, 126 temporary ventricular assist devices were implanted in 108 patients, resulting in a total of 114 encounters: 70 (61%) extracorporeal centrifugal pumps and 44 (39%) catheter-based axial pumps. The median (range) age and weight at temporary ventricular assist device implant were 10.1 years (1 day to 42.8 years) and 33.6 (2.5-128) kg, respectively. Underlying etiologies of cardiac dysfunction were cardiomyopathy (34, 30%), cardiac transplant graft dysfunction (29, 25%), congenital heart disease (23, 20%; 9 single ventricle), myocarditis (22, 19%), and other (6, 5%). Interagency Registry for Mechanically Assisted Circulatory Support Profile was 1 in 75 (66%) and 2 in 39 (34%). Support configuration was left ventricular assist device (104, including 9 systemic ventricular assist devices), right ventricular assist device (5), and biventricular assist device (5). The median (range) support duration was 6 (1-61) days. Overall, 97 (85%) encounters reached a positive primary end point: bridge-to-recovery (55), bridge-to-bridge (31), and bridge-to-transplant directly with temporary ventricular assist device (11). Seventeen (15%) encounters resulted in death during temporary ventricular assist device support: multiorgan failure (12), stroke (4), and cardiac arrest (1). The 6-month survivals with catheter-based axial pumps and extracorporeal centrifugal pumps were 84% (95% confidence interval, 74-96) and 67% (95% confidence interval, 57-79), respectively (P = .08). The 1- and 5-year survivals of 82 hospital survivors were 90% and 84%, respectively. CONCLUSIONS: This study suggests temporary ventricular assist device support is feasible in children with favorable outcomes.

Relation of Low Chloride Concentration to Diuretic Efficiency and Transplant-Free Survival in Children Hospitalized With Heart Failure.

Serum chloride plays an important role in fluid homeostasis and is associated with impaired diuretic responsiveness and mortality in adults with heart failure (HF). We sought to characterize the relationship of serum chloride and diuretic efficiency (DE) and to determine its prognostic importance in children hospitalized with acute decompensated HF (ADHF). We studied DE, defined as net fluid output/kg+constant per mg of loop diuretic/kg, in 200 children hospitalized with ADHF. Median serum chloride at admission was 102 mmol/L (interquartile range 99 to 105 mmol/L), and hypochloremia (chloride ≤96 mmol/L) was present in 16% of the population at admission. Serum chloride correlated with serum sodium (r = 0.66; p < 0.001) and bicarbonate (r = -0.39; p < 0.001). In the adjusted analysis, lower chloride was associated with reduced DE (p < 0.001). Serum sodium was associated with DE on the unadjusted analysis; however, the association was eliminated when added to the model with chloride (p = 0.442). Lower chloride was also associated with features of inadequate decongestion during hospitalization: a positive fluid balance (p = 0.003), greater cumulative loop diuretic dose per weight (p = 0.001), addition of a thiazide diuretic during hospitalization (p < 0.001), less weight loss (p = 0.025), and longer length of stay (p = 0.003). Chloride concentration was independently associated with death or transplant 1 year after admission (hazard ratio 0.94; p < 0.001). As a dichotomous variable, hypochloremia was independently associated with reduced DE (p < 0.001) and decreased 1-year transplant-free survival (hazard ratio 2.3, p < 0.001). Lower serum chloride at hospital admission is strongly and independently associated with impaired DE and reduced transplant-free survival in children hospitalized with ADHF.

Reductions in anxiety, depression and insomnia in health care workers using a non-pharmaceutical intervention.

The COVID-19 pandemic has caused significant medical and psychological challenges worldwide, and not only exceeded the capacity of hospitals and intensive care units but also an individuals' ability to cope with life. Health-care workers have continued to provide care for patients despite exhaustion, fear of transmission to themselves and their family, illness or death of friends and colleagues, and losing many patients. They have also faced additional stress and anxiety due to long shifts combined with unprecedented population restrictions, including personal isolation. In this study, we study the effect of an app-based Yoga of Immortals (YOI) intervention on mental health of healthcare workers. In this study, the health care workers were digitally recruited, and their psychological parameters were measured using validated questionaries. The participants were randomly grouped into control and test groups. The validated psychological measures were the Patient Health Questionnaire-8 (PHQ-8), Insomnia Severity Index (ISI) and generalized anxiety disorder (GAD-7) scales. The digital YOI intervention significantly reduced the anxiety, depression symptoms, and insomnia in healthcare workers of all age groups. In contrast, there was no improvement in the control group. This study details the effectiveness of an app-based YOI intervention in healthcare workers.

App-Based Yoga of Immortals: A Novel, Easy-to-use Intervention in the Management of Urinary Incontinence.

OBJECTIVE: To study the effectiveness Yoga of Immortals (YOI) intervention in participants with urinary incontinence (UI) of all types. YOI uniquely combines specific yogic postures, breathing exercises, sound therapy & meditation and is practiced by many for general well-being. MATERIALS AND METHODS: In this App-based cohort study, a survey was sent to the YOI app subscribers. Those who identified with UI and consented were sent the ICIQ-UI- SF (for mean symptom score & severity of UI), and the ICIQ-LUTS-QOL (for impact of UI on QOL) Questionnaires at baseline, 4, and 8 weeks. Global impression of improvement was assessed by PGI-I scale. RESULTS: 258/422 participants (18-74 years) were included and showed significant decrease in mean scores on the ICIQ-UI-SF (4.06 ± 0.24 at baseline; 2.90 ± 0.22 at 4-weeks [p ≤ 0.001] and 3.44 ± 0.23 at 8 weeks [p ≤ 0.001]) and ICIQ-LUTS-QOL (28.36± 0.74 at baseline; 24.46± 0.70 at 4-weeks [p ≤ 0.001] and 25.78± 0.70 at 8 weeks [p≤ 0.001]). Additionally, the 55-60 year subgroup also had significant decrease in mean scores on ICIQ-LUTS-QOL (25.06 ±1.20 at base line; 21.69 ± 1.07 at 4 weeks [p ≤ 0.01] and 22.28 ± 0.96 at 8 weeks [p ≤ 0.01]). CONCLUSION: YOI intervention resulted in significant improvement in mean scores on ICIQ-LUTS-QOL; ICIQ-UI-SF; frequency and severity of urinary leak; and daily life activity. Majority of the participants felt 'very much better' on PGI-scale. Being app- based, it has the added advantage of the ability to be used anytime and anywhere.

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study.

OBJECTIVES: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. DESIGN: Retrospective cohort study. SETTING: Single tertiary-quaternary referral center. PATIENTS: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. CONCLUSIONS: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Signal-to-Noise Analysis Can Inform the Likelihood That Incidentally Identified Variants in Sarcomeric Genes Are Associated with Pediatric Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity. Methods and Results: Incidental variants in HCM genes (MYBPC3, MYH7, MYL2, MYL3, ACTC1, TPM1, TNNT2, TNNI3, and TNNC1) were obtained from a clinical ES referral database (Baylor Genetics) and compared to rare population variants (gnomAD) and variants from HCM literature cohort studies. A subset of the ES cohort was clinically evaluated at Texas Children's Hospital. We compared the frequency of ES and HCM variants at specific amino acid locations in coding regions to rare variants (MAF < 0.0001) in gnomAD. S:N ratios were calculated at the gene- and amino acid-level to identify pathogenic hotspots. ES cohort variants were re-classified using ACMG criteria with S:N analysis as a correlate for PM1 criteria, which reduced the burden of variants of uncertain significance. In the clinical validation cohort, the majority of probands with cardiomyopathy or family history hosted likely pathogenic or pathogenic variants. Conclusions: Incidental variants in HCM-associated genes were common among clinical ES referrals, although the majority were not disease-associated. Leveraging amino acid-level S:N as a clinical tool may improve the diagnostic discriminatory ability of ACMG criteria by identifying pathogenic hotspots.

Ventricular assist device support for children with chemotherapy-induced cardiomyopathy and advanced heart failure: Perspectives gained from a single-center experience.

BACKGROUND: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited. METHODS: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support. RESULTS: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m2 (IQR 450-630 mg/m2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation. CONCLUSIONS: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support.

Does Cardiac Catheterization Facilitate Hemodynamic Optimization of Pediatric Patients on Continuous-Flow Ventricular Assist Devices?

Understanding optimal ventricular assist device (VAD) parameters for pediatric patients is valuable given the inherent issue of patient-device size mismatch and heterogeneous cardiac anatomy in children. We evaluated our center's experience of continuous-flow VAD (CF-VAD) optimization using cardiac catheterization. We performed a retrospective analysis of all patients on CF-VAD support who underwent hemodynamic heart catheterization from 2013 to 2018. Fifteen patients had 16 hemodynamic catheterizations performed. The indications for hemodynamic optimization by catheterization included clinical signs of heart failure while on CF-VAD (9 of 16, 56%), pretransplant evaluation of pulmonary hypertension (2 of 16, 13%), or assessment of myocardial recovery (5 of 16, 31%). The median age at catheterization was 12 years (interquartile range: 8-16). Median baseline speed of device was 2333 ± 253 rotations per minute. The goal was to find the speed at which optimal hemodynamics were achieved, defined by low wedge pressure with an acceptable central venous pressure. Of the 16 catheterizations, there were 9 (56%) speed increases to achieve optimal hemodynamics and 5 (33%) speed decreases for hemodynamic optimization or for potential explant. The speed was not changed in 2 (13%) catheterizations as the patients were determined to be at an optimal hemodynamic state. Overall, VAD settings were optimized in 75% (14 of 16) of hemodynamic catheterizations. There were no adverse events related to catheterization. Thus, we conclude that catheterization-based hemodynamic assessment is safe and effective for optimizing VAD speed and provides guidance on medical management in children supported on CF-VAD.

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.