A Path to Implement Precision Child Health Cardiovascular Medicine.

Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is multifactorial, involving genetic, epigenetic, and/or environmental contributors. Clear dissection of the underlying mechanism is a powerful step to establish individualized therapies. However, the majority of CHDs are yet to be clearly diagnosed for the underlying genetic and environmental factors, and even less with effective therapies. Although the survival rate for CHDs is steadily improving, there is still a significant unmet need for refining diagnostic precision and establishing targeted therapies to optimize life quality and to minimize future complications. In particular, proper identification of disease associated genetic variants in humans has been challenging, and this greatly impedes our ability to delineate gene-environment interactions that contribute to the pathogenesis of CHDs. Implementing a systematic multileveled approach can establish a continuum from phenotypic characterization in the clinic to molecular dissection using combined next-generation sequencing platforms and validation studies in suitable models at the bench. Key elements necessary to advance the field are: first, proper delineation of the phenotypic spectrum of CHDs; second, defining the molecular genotype/phenotype by combining whole-exome sequencing and transcriptome analysis; third, integration of phenotypic, genotypic, and molecular datasets to identify molecular network contributing to CHDs; fourth, generation of relevant disease models and multileveled experimental investigations. In order to achieve all these goals, access to high-quality biological specimens from well-defined patient cohorts is a crucial step. Therefore, establishing a CHD BioCore is an essential infrastructure and a critical step on the path toward precision child health cardiovascular medicine

Unrepaired Tetralogy of Fallot with Absent Pulmonary Valve in a Mildly Symptomatic 16-Year-Old Boy

Absent pulmonary valve is a rare and severe variant seen in only 3% to 6% of patients with tetralogy of Fallot. Fetuses with this combined condition who survive through birth typically need intervention in infancy or early childhood because of respiratory distress, heart failure, or failure to thrive. We describe the unusual case of a mildly symptomatic 16-year-old boy with these conditions who underwent successful primary repair. Our search of the medical literature yielded fewer than 5 cases of tetralogy of Fallot with absent pulmonary valve (or variants with an absent left pulmonary artery) and survival without repair into later adolescence or adulthood

Use of Bivalirudin for Anticoagulation during Implantation of Total Artificial Heart

Heparin-induced thrombocytopenia presents a challenge for anticoagulation techniques during cardiac surgery and ventricular assist device implantation. Bivalirudin is currently recommended for use during cardiopulmonary bypass for patients with heparin-induced thrombocytopenia but requires the use of special techniques to avoid blood stagnation. We report the successful use of bivalirudin during cardiopulmonary bypass for implantation of the Total Artificial Heart with late operative bleeding likely resulting from heavy cell saver use

A Path to Implement Precision Child Health Cardiovascular Medicine.

Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is multifactorial, involving genetic, epigenetic, and/or environmental contributors. Clear dissection of the underlying mechanism is a powerful step to establish individualized therapies. However, the majority of CHDs are yet to be clearly diagnosed for the underlying genetic and environmental factors, and even less with effective therapies. Although the survival rate for CHDs is steadily improving, there is still a significant unmet need for refining diagnostic precision and establishing targeted therapies to optimize life quality and to minimize future complications. In particular, proper identification of disease associated genetic variants in humans has been challenging, and this greatly impedes our ability to delineate gene-environment interactions that contribute to the pathogenesis of CHDs. Implementing a systematic multileveled approach can establish a continuum from phenotypic characterization in the clinic to molecular dissection using combined next-generation sequencing platforms and validation studies in suitable models at the bench. Key elements necessary to advance the field are: first, proper delineation of the phenotypic spectrum of CHDs; second, defining the molecular genotype/phenotype by combining whole-exome sequencing and transcriptome analysis; third, integration of phenotypic, genotypic, and molecular datasets to identify molecular network contributing to CHDs; fourth, generation of relevant disease models and multileveled experimental investigations. In order to achieve all these goals, access to high-quality biological specimens from well-defined patient cohorts is a crucial step. Therefore, establishing a CHD BioCore is an essential infrastructure and a critical step on the path toward precision child health cardiovascular medicine

Implantation of a Berlin Heart EXCOR

A previously healthy two-month-old infant born at thirty-six weeks presented with increasing fussiness, a respiratory rate of sixty breaths per minute and an oxygen saturation of 85 percent. A chest X-ray revealed significant cardiomegaly. A transthoracic echocardiogram demonstrated a severely dilated left ventricle with an ejection fraction of 26 percent. The patient’s hemodynamic stability was supported by milrinone at 0.5 mcg/kg/min and epinephrine at 0.04 mcg/kg/min. Because of her diagnosis of cardiomyopathy and critical status, the surgical team decided to proceed with operative implantation of the Berlin Heart EXCOR.The SurgeryFirst, a midline sternotomy was performed. Aortic cannulation was conducted high on the patient's left lateral aortic arch to ensure enough space for future placement of the inflow cannula. The team commenced cardiopulmonary bypass, and the patient remained warm throughout the procedure. Next, the cardiac mass was elevated out of the pericardial well, and a single 5-0 polypropylene stitch was placed in the right ventricle to facilitate exposure. A pen was used to mark the site for the proposed cannula in the cardiac apex followed by identification of the left obtuse marginal and left anterior descending coronary arteries. A 2-0 silk suture was placed in the cardiac apex to serve as a retraction suture for ventriculotomy. An 11-blade scalpel was then used to make a ventriculotomy and all obstructing muscle below was excised. The inflow cannula was anchored with two pledgets at the nine o’clock and three o’clock positions. The remainder of the graft was sewn counterclockwise with 4-0 polypropylene in a running fashion between the pledgets. The inflow tunnel site was created superior to the rectus muscle, and the inflow cannula was brought through the tunnel.Attention was then turned to the outflow cannula anastomosis. An 8-French Hemashield (collagen impregnated polyester) graft was connected to the Berlin cannula and tied with 2-0 silk ligature twice. An angled c-clamp was positioned on the right lateral anterior wall of the ascending aorta. An aortotomy was then created. The anastomosis of the graft to the aorta was performed using 5-0 polypropylene in a running continuous fashion. Similar tunneling was carried out to externalize the outflow cannula.The cannulae were then deaired and connected to the pneumatic pump. A needle was inserted into the pump to withdraw remaining air. The pump chamber and valves were inspected for air bubbles, and none were found. The team then began to step up the pneumatic flow to thirty beats per minute. As the LVAD rate was increased, flow rates on the cardiopulmonary bypass machine were decreased. Deairing was continued through the needle in the pump until no air was present on the transesophageal echo. The patient successfully came off cardiopulmonary bypass with stable hemodynamics. Evaluation of the Berlin Ikus showed a well-functioning ventricular assist device. The total pump time was 59 minutes. Intraoperative TEE demonstrated a well-positioned apical inflow cannula in the LV apex with adequate decompression of the LV. There was no aortic insufficiency and good RV function.Bivalirudin was started forty-eight hours postoperatively. Institutional protocol aims for a goal PTT of seventy to ninety seconds and to titrate the dose of bivalirudin accordingly. The patient’s dose ranged from 0.48-0.77 mg/kg/hr. The patient was extubated on postoperative day fourteen. She remains in the CVICU and is currently listed as status 1A for a heart transplant.</p