RESUMO

OBJECTIVES: The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric ventricular assist device. The fourth-generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. METHODS: Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh-led Consortium evaluated fourth-generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). RESULTS: With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery-sized fourth-generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. CONCLUSIONS: Designated a Humanitarian Use Device for "mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery" by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth-generation PediaFlow design to provide chronic pediatric cardiac support.

Assuntos

Fontes de Energia Elétrica , Insuficiência Cardíaca/terapia , Coração Auxiliar , Hemodinâmica , Implantação de Prótese/instrumentação , Função Ventricular , Fatores Etários , Animais , Animais Recém-Nascidos , Peso Corporal , Pré-Escolar , Fontes de Energia Elétrica/efeitos adversos , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar/efeitos adversos , Hemólise , Humanos , Lactente , Recém-Nascido , Teste de Materiais , Miniaturização , Desenho de Prótese , Carneiro Doméstico

RESUMO

OBJECTIVE: Heterotaxy (HTX) congenital heart disease (CHD) patients with ciliary dysfunction (CD) have been shown to have increased postoperative respiratory morbidity. We hypothesized that non-HTX CHD infants with CD also will have increased postoperative morbidity, particularly respiratory complications. METHODS: Sixty-three infants with non-HTX CHD undergoing cardiac surgery were enrolled. Tests commonly used to assess for CD, nasal nitric oxide (nNO) measurements and nasal epithelial ciliary motion (CM) assessment, were obtained. Baseline characteristics and postoperative outcomes were collected and analyzed. RESULTS: Non-HTX CHD infants exhibited a high prevalence of abnormal CM (32%) and low nNO (39%). This finding was not correlated with demographics or surgical complexity. Infants with abnormal CM had increased odds of requiring noninvasive positive pressure ventilation (odds ratio [OR], 6.5; 95% confidence interval [CI], 1.5-29.4; P = .016) and respiratory medication use (OR, 4.4; 95% CI, 1.5-13.3; P = .01). In contrast, infants with low nNO showed evidence of abnormal pre- and postoperative systolic function (40% vs 4%; P = .004, and 34% vs 13%; P = .056, respectively) and had greater odds of acquiring infections (OR, 4.9; 95% CI, 1.4-17; P = .014). CONCLUSIONS: Non-HTX CHD infants with abnormal CM showed increased postoperative morbidity associated with poor respiratory outcomes. In contrast, low nNO correlated with reduced hemodynamic function. These findings suggest screening for abnormal CM may allow perioperative interventions to reduce pulmonary morbidities. Whether low nNO may prognosticate poor hemodynamic function warrants further investigation.

Assuntos

Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transtornos da Motilidade Ciliar/complicações , Cardiopatias Congênitas/cirurgia , Pulmão/fisiopatologia , Mucosa Nasal/fisiopatologia , Respiração , Doenças Respiratórias/etiologia , Biomarcadores/metabolismo , Transtornos da Motilidade Ciliar/metabolismo , Transtornos da Motilidade Ciliar/patologia , Transtornos da Motilidade Ciliar/fisiopatologia , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica , Humanos , Lactente , Recém-Nascido , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Óxido Nítrico/metabolismo , Estudos Prospectivos , Doenças Respiratórias/fisiopatologia , Doenças Respiratórias/terapia , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Função Ventricular

RESUMO

OBJECTIVE: To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) STUDY DESIGN: We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound scan and brain magnetic resonance imaging were obtained pre- and/or postoperatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. RESULTS: A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury but was correlated with increased extraaxial cerebrospinal fluid volume (P < .001), delayed brain maturation (P < .05), and a spectrum of subtle dysplasia including the hippocampus (P < .0078) and olfactory bulb (P < .034). Abnormal CM was associated with higher composite dysplasia score (P < .001), and both were correlated with elevated preoperative serum lactate (P < .001). CONCLUSIONS: Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks.

Assuntos

Encefalopatias/epidemiologia , Encéfalo/patologia , Transtornos da Motilidade Ciliar/complicações , Cardiopatias Congênitas/complicações , Encéfalo/diagnóstico por imagem , Encefalopatias/complicações , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos

RESUMO

The PediVAS blood pump is a magnetically levitated centrifugal pump designed for pediatric bridge-to-decision or bridge-to-recovery in pediatric patients from 3-20kg in weight. In preparation for submission of an investigational device exemption (IDE) application, we completed a final six-animal series of pre-clinical studies. The studies were conducted under controlled conditions as prescribed by the recently released FDA guidance document for animal studies for cardiovascular devices. Three 30-day chronic left ventricular support studies were completed in a juvenile lamb model to demonstrate the safety and hemocompatibility of the PediVAS pump. Three additional 8-hour acute biventricular support studies were performed to demonstrate the feasibility of this approach from a hemodynamic and systems standpoint. It is estimated that 50% of pediatric patients who require left ventricular support also require right ventricular support. All studies were successfully completed without complications, device malfunctions, or adverse events. End-organ function was normal for the chronic studies. We noted small surface lesions on one kidney from each chronic study as well as the presence of ring thrombus on connectors, as expected for these types of studies in animal models. The strategy and challenges imposed by performing a controlled cardiovascular device study in a juvenile lamb model are discussed. We believe that these successful implants demonstrate safety and performance for the PediVAS device for support of an IDE application to initiate human clinical trials and provide a roadmap for other researchers.