Heart Failure In Adolescents Research Articles

Antigen-specific T cell tolerance in the prevention of post-infectious myocarditis induced with Coxsackievirus B3

Abstract Of the many types of heart disease, myocarditis is a predominant cause of heart failure in adolescents, and 10–20% of those affected can develop dilated cardiomyopathy (DCM) with infiltrates in their hearts. Autoimmunity resulting from exposure to infectious agents such as Coxsackievirus B3 (CVB) has been suggested as a possible underlying mechanism of chronic myocarditis in the development of DCM. We recently demonstrated that CVB infection could lead to the generation of pathogenic autoreactive T cells leading to a suggestion that their effector functions can be suppressed by developing antigen-specific T cell therapies. To this end, we sought to generate induced Treg cells by using biodegradable nanoparticle delivery system made of chitosan and poly(lactic-co-glycolic acid) (PLGA) entrapped with interleukin-2 and transforming growth factor termed, nanocytokines. Our data suggest that the PLGA nanocytokines can stably induce Forkhead box protein P3, a molecular marker of Treg cells accompanied with complete suppression of interferon-γ production. Our preliminary data indicate that the Treg cells induced with nanocytokines can suppress non-Treg cells in vitro leading to a suggestion that they could be used to prevent the expansion of autoreactive T cells generated in mice affected with viral myocarditis.

Advanced Heart Failure in Adolescents: A Challenge for A Newly Established Program in the Middle East

Introduction Management of advanced heart failure (HF) is challenging enough in the adult population and significantly more so in adolescents. Our newly established advanced HF and transplant program predominantly caters for adults. Nevertheless, being the only center in the country and one of two in the Gulf Region, we are faced with managing younger patients presenting with advanced HF. This is different from adults in many respects, including HF etiology to overall outcomes. In this case series, we highlight characteristics and outcomes of adolescent patients managed with advanced HF therapies (ventricular assist devices (VAD) and/or heart transplant (HT)). Methods We present data of 10 consecutive patients under the age of 20 who presented to our institution between July 2014 and December 2019. All patients initially required intensive cardiac care, subsequently they went on to receive advanced therapies. Donor scarcity mandated that some patients were referred abroad for HT. All VAD were implanted at our center. Results Table 1 outlines patient characteristics. Mean age at the time of advanced therapy was 15.2 years (range 11-19 years). Seventy percent were males and 40% had familial cardiomyopathy with mean follow 29.9± 24 months. Four patients required a VAD as bridge to transplant, with one of them currently on the waiting list. One patient was bridged to transplantation with extracorporeal membrane oxygenation support. As expected with the younger population the incidence of renal dysfunction was low as was post HT biopsy proven acute rejection (BPAR). One patient had donor transmitted coronary vascular disease and subsequently developed cardiac allograft vasculopathy eventually requiring surgical revascularization. One patient developed perioperative coagulopathy and subsequently anoxic brain injury as he was bridged from VAD to HT. He was later declared brain dead. There was one death due to severe graft failure secondary to non-compliance with medical therapy or follow up. Conclusion Advanced HF in the adolescent population presents a significant challenge to newly established HF programs. In addition to unique clinical aspects, issues like insight, compliance, and parent trust can contribute to delayed presentation and intervention. Our outcomes are comparable to high-volume centers in western countries. Patient and family education and involvement in therapy and decisions is imperative to long-term success with this age group.

Percutaneous Impella RP use for refractory right heart failure in adolescents and young adults-A multicenter U.S. experience.

To assess the outcomes of the use of the percutaneous Impella RP device (Abiomed, Danvers, MA) in adolescents and young adults. Results of the Impella RP device have been reported in adults, but a multicenter experience in adolescents and young adults has yet to be reported. Patients ≤21 years of age who underwent implantation of an Impella RP device for refractory right heart failure from June, 2016 to April, 2018 at nine U.S. Centers were included. A total of 12 adolescents, median age of 18 (14-21) years and median weight 74.4 (49-112.4) kg underwent Impella RP implantation (INTERMACS Profile 1 in nine and Profile 2 in three patients. The central venous pressure decreased from 20 (16-35) to 12 (7-17) mmHg, (p = .001). One patient was concomitantly supported with an intra-aortic balloon pump (IABP) and the rest with a percutaneous/surgically placed left ventricular assist device. There was one adverse event related to the Impella RP device (thrombosis requiring explant). The support duration was 6.5 days (4.8 hr-18.4 days) and survival to hospital discharge was 83%. At a median follow-up of 11 months (5 days-2.5 years), 8 of 12 (67%) patients are alive. In this multicenter experience, the Impella RP device was found to be efficacious and safe when used in adolescents and young adults. Further studies are warranted to identify suitable young/pediatric candidates for Impella RP therapy for right heart failure.

Abstract 16681: Early Left Ventricular Dysfunction in Healthy Young Adults Born Premature

Rationale: Preterm birth, or less than 37 weeks completed gestation, affects one in 10 live births in the United States. Moderate to extreme premature birth, or less than 32 weeks gestation, is associated with up to a 17-fold increased risk for the development of heart failure in adolescents and young adults. Here, we sought to characterize left ventricular (LV) function in young adults born premature. Methods: Adults born preterm (n=11; gestational age 28.2±0.8 weeks; current age 27±1 years) were recruited from the Newborn Lung Project at the University of Wisconsin-Madison, a prospective cohort of infants born 1988-1991 with birth weight <1500 g. Controls were recruited from the general population (n=12; age 26±1 years). All subjects were free from adult cardiopulmonary disease. Subjects underwent cardiac magnetic resonance imaging (MRI) on a 3.0T scanner. Measures included standard assessment of LV function and LV strain. 4D flow imaging was acquired with a radially-undersampled PC VIPR sequence to assess systolic and diastolic LV kinetic energy, and corresponding LV energetic efficiency was defined as stroke volume normalized by the systolic and diastolic kinetic energy . Mann-Whitney tests were performed to assess for statistical significance (p<0.05). Results: Young adults born premature had significantly smaller chamber volumes, even when indexed to body size (table 1). However, stroke volume was maintained due to a higher ejection fraction. Cardiac output and index were significantly higher in young adults born premature, due to a higher resting heart rate. Strain analysis confirmed a hyperdynamic LV. 4D flow demonstrated a significantly higher LV energy cost, resulting in an energetically inefficient LV. Conclusions: Otherwise healthy young adults born premature demonstrate a hypercontractile, energetically inefficient LV, which may provide mechanistic insight into the increased risk for heart failure in this high-risk population.

Choosing medications for chronic subclinical heart failure in adolescents

As a result of the fact that prescription of medications for children and adolescents with early stages of chronic heart failure is not provided by the treatment protocols, and the doctor has to act intuitively, the development of methods for decision-making support gains a special relevance. In this paper, the authors proposed method of optimal selection of medications at subclinical variants of chronic heart failure of adolescents, taking into account the features of multifunctional characteristics of heart on the basis of analytical networks.The main stages of the method and the results of its introduction in the SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine” are described in the paper. Application of this method will allow reasonable choice of the best among the set of alternative variants, taking into account the indicators of the patient’s condition, dependences between these indicators and medications, feedbacks between them in the network structure, and also will promote the prescription of effective therapeutic measures and prevention of progression of early stages of chronic heart failure of adolescents. The proposed method can be easily realized in the outpatient or inpatient conditions, and its use allows to achieve considerable technical result

Abdominal complaints as a common first presentation of heart failure in adolescents with dilated cardiomyopathy

ObjectiveWe hypothesized that isolated gastrointestinal complaints (abdominal pain, nausea, anorexia, weight loss), in the absence of other symptoms, were a common mode of initial presentation in children with congestive heart failure (CHF). Study designNinety-eight patients younger than 18 years hospitalized with dilated cardiomyopathy at a single institution between January 1, 2000, and December 31, 2009, were included. Retrospective review of their presenting complaints was recorded and analyzed according to 3 age groups: 0 to 1 year (infants), 1 to 10 years (children), and 11 to 18 years (adolescents) of age. ResultsRespiratory symptoms were common in all age groups (range, 56%-63%). Gastrointestinal complaints were also common in all age groups (42%, 28%, and 65%, respectively) and were more frequent than respiratory complaints in adolescents. Adolescents were likely to present with abdominal pain as their only complaint (10/43, 23%). Chest pain, syncope, or cardiac arrest occurred rarely. ConclusionsAbdominal complaints are a common component of the presenting symptom complex of CHF in pediatric dilated cardiomyopathy in all age groups. In adolescents, abdominal complaints occur more frequently than respiratory complaints and often in the absence of any other symptoms. Unlike CHF in adults, chest pain, arrhythmia, or cardiac arrest occurs rarely at presentation in pediatric patients. Recognition of the different presenting symptoms of heart failure in children by primary providers is crucial to ensuring prompt diagnosis and timely initiation of therapy.

Abstract 68: Role of Substance P Signaling in the Pathogenesis of Murine Viral Myocarditis

Viral myocarditis is an important cause of heart failure in adolescents and young adults for which no specific treatment is currently available. Substance P (SP) is a neuropeptide and pain transmitter that activates RhoA, a small G-protein, shown to induce hypertrophy of neonatal rat ventricular myocytes. The current studies were performed to determine if SP signaling contributes to the pathogenesis of encephalomyocarditis virus (EMCV) infection, a well-established murine model of viral myocarditis. Aprepitant (1.2 mg/kg), a SP receptor antagonist, or fasudil (10mg/kg), a Rho A inhibitor, or saline control, was administered daily to mice orally by gavage 3 times for 3 days prior to intraperitoneal infection with 50 PFU of EMCV, and the mice monitored for 14 days. Pretreatment with aprepitant reduced mortality by 40% (25±7% vs. 65±7%), reduced heart-to-body weight ratio by 26% (0.0088±0.0001 vs. 0.0119±0.0001), reduced end systolic diameter (ESD) by 21% (3.0±0.2mm vs. 3.8±0.4mm), improved ejection fraction by 72% (57.2±4.7% vs. 33.2 ±9.3%), reduced chamber volume by 46% (34±5.0 μl vs. 62.7±30.8 μl), increased peak aortic flow velocity by 41% (87.0±24.7 vs. 61.7±20.1), and reduced cardiomyocyte diameter size by13% (11.0±0.1 μM vs. 12.7± 0.2 μM); p<.05 for all, Student’s t-test). Pretreatment with fasudil reduced heart-to-body weight ratio by 18% (0.0097±0.0001 vs. 0.0119±0.0001) and reduced cardiomyocyte diameter size by 12% (11.14±0.51 μM vs. 12.7± 0.2 μM; p<.05 for both), but did not significantly impact heart functional changes or mortality. These findings indicate that SP contributes to cardiac remodeling and dysfunction following ECMV infection and raises the possibility that inhibition of SP signaling may be of benefit in the treatment of patients with viral myocarditis.

Incidence and Risk Distribution of Heart Failure in Adolescents and Adults With Congenital Heart Disease After Cardiac Surgery

Heart failure (HF) is a major problem in the long-term follow-up of adults with congenital heart disease (CHD) after cardiac surgery. The purpose of this study was to evaluate risk factors for HF in patients with CHD. N-terminal-pro-brain natriuretic peptide and maximal oxygen uptake (VO2max) were measured in 345 consecutive patients with CHD. HF was defined as an elevated N-terminal-pro-brain natriuretic peptide level (> or = 100 pg/ml) and reduced VO2max (< or = 25 ml/kg/min). The HF criteria were met by 89 patients. These patients were significantly older (mean +/- SEM 30.8 +/- 0.9 vs 24.8 +/- 0.5 years), had significantly lower maximal heart rates (149 +/- 3 vs 164 +/- 1 beats/min), and had larger end-diastolic right ventricular diameters (36 +/- 1 vs 27 +/- 1 mm) and right ventricular pressure estimated by Doppler flow velocities of tricuspid valve regurgitation (2.9 +/- 0.1 vs 2.3 +/- 0.03 m/s). Mean fractional shortening of the left ventricle was within the normal range. To estimate risk stratification, odds ratios for HF were determined for the most frequently occurring types of congenital heart defects and surgical procedures. In conclusion, HF in adults with CHD predominately depends on diagnosis, age, the frequency of reoperation, and right ventricular function and may be related to chronotropic incompetence indicated by lower maximal heart rates.

Balloon valvotomy for severe aortic stenosis with congestive heart failure in adolescents

Balloon valvotomy for severe aortic stenosis with congestive heart failure in adolescents