A Novel Model for Xenograft Right Ventricle to Pulmonary Artery Conduit.

The last 40 years have shown dramatic improvement in outcomes for neonatal cardiac surgery for a spectrum of congenital heart disease diagnoses. With more patients surviving into adulthood, the long-term impact of initial management strategies of these patients has come into focus. This is particularly true for patients with pediatric heart valve disease. Many patients born with right ventricular to pulmonary artery (RVPA) discontinuity require placement of a valved conduit in the neonatal period. Valved conduit options are limited in this patient population due to patient size and inability to respond to somatic growth. Genetically engineered porcine (GEP) donors may offer a xenograft conduit alternative that can grow with the patient. We have developed a model utilizing GEP donor RVPA conduits placed in infantile nonhuman primate (NHP) recipients. Our recipient is maintained on single-drug immunosuppression and demonstrates no evidence of pulmonary valve insufficiency or stenosis during short-term follow-up. Further studies and long-term outcomes are necessary to determine the utility of this technology in human application.

Anatomic considerations in the management of complete atrioventricular canal.

OBJECTIVE: Patients with complete atrioventricular canal have a variable clinical course prior to repair. Many patients balance their circulations well prior to elective repair. Others manifest clinically significant pulmonary over circulation early in life and require either palliative pulmonary artery banding or complete repair. The objective of this study was to assess anatomic features that impact the clinical course of patients. METHODS: In total, 222 patients underwent complete atrioventricular canal repair between 2012 and 2022 at a single institution. Twenty-seven (12%) patients underwent either pulmonary artery banding (n = 15) or complete repair (n = 12) at less than 3 months of age (Group 1). The remaining 195 (88%) underwent repair after 3 months of age (Group 2). Patient records and imaging were reviewed. RESULTS: The median post-operative length of stay following complete repair was 25 [7,46] days for those patients in Group 1 and 7 [5,12] days for those in Group 2 (p < 0.0001). There was relative hypoplasia of left-sided structures in Group 1 versus Group 2. Mean z-score for the ascending aorta was -1.2 (±0.8) versus -0.3 (±0.9) (p < 0.0001), the aortic isthmus was -2.1 (±0.8) versus -1.4 (±0.8) (p = 0.005). The pulmonary valve to aortic valve diameter ratio was median 1.47 [1.38,1.71] versus 1.38 [1.17,1.53] (p 0.008). CONCLUSIONS: Echocardiographic evaluation of the systemic and pulmonary outflow of patients with complete atrioventricular canal may assist in predicting the clinical course and need for early repair vs pulmonary artery banding.

Ross procedure in neonates and infants: A valuable operation with defined limits.

OBJECTIVE: The Ross procedure is an important tool that offers autologous tissue repair for severe left ventricular outflow tract (LVOT) pathology. Previous reports show that risk of mortality is highest among neonates and infants. We analyzed our institutional experience within this patient cohort to identify factors that most affect clinical outcome. METHODS: A retrospective chart review identified all Ross operations in neonates and infants at our institution over 27 years. The entire study population was analyzed to determine risk factors for mortality and define outcomes for survival and reintervention. RESULTS: Fifty-eight patients underwent a Ross operation at a median age of 63 (range, 9-156) days. Eighteen (31%) were neonates. Eleven (19%) patients died before hospital discharge. Multiple regression analysis of the entire cohort identified young age (hazard ratio [HR], 1.037; P = .0045), Shone complex (HR, 17.637; P = .009), and interrupted aortic arch with ventricular septal defect (HR, 16.01; P = .031) as independent predictors of in-hospital mortality. Receiver operating characteristic analysis (area under the curve, 0.752) indicated age younger than 84 days to be the inflection point at which mortality risk increases. Of the 47 survivors, there were 2 late deaths with a mean follow-up of 6.7 (range, 2.1-13.1) years. Three patients (6%) required LVOT reintervention at 3, 8, and 17.5 years, respectively, and 26 (55%) underwent right ventricular outflow tract reintervention at a median of 6 (range, 2.5-10.3) years. CONCLUSIONS: Ross procedure is effective in children less than one year of age with left sided obstructive disease isolated to the aortic valve and/or aortic arch. Patients less than 3 months of age with Shone or IAA/VSD are at higher risk for morbidity and mortality. Survivors experience excellent intermediate-term freedom from LVOT reintervention.

The Ross Procedure in Children: The Gold Standard?

The management of aortic valve disease in the pediatric population is complex and requires an individualized approach and opportune application of techniques focused on each individual patient's specific anatomy, pathology, and clinical presentation. Though some patients may require variations in the approach to management, the ultimate goal should be to perform a Ross procedure when aortic valve replacement is indicated.

The utility of aortic valve leaflet reconstruction techniques in children and young adults.

OBJECTIVES: The treatment of aortic valve disease in children and adolescents requires an individualized approach to provide a long-term solution with optimal hemodynamic profile. The role of aortic leaflet reconstruction techniques is evolving. METHODS: We retrospectively reviewed the charts of 58 patients who underwent aortic valve tricuspidalization either by an Ozaki procedure (neo-tricuspidalization) or single leaflet reconstruction between 2015 and 2019. Immediate operative results as well as hospital and short-term outpatient follow-up data were evaluated. RESULTS: Fifty-eight patients underwent leaflet reconstruction with 40 (69%) receiving a neo-tricuspidalization and 18 patients (31%) undergoing single leaflet reconstruction, using either a glutaraldehyde fixed autologous pericardium or tissue engineered bovine pericardium (CardioCel; Admedus, Queensland, Australia). The median age at the time of surgery was 14.8 years (interquartile range, 10.6-16.8 years). Twenty-three patients (40%) had isolated aortic regurgitation. The peak velocity across the aortic valve decreased from 3.4 ± 1.2 meters per second (m/s) preoperatively to 2.0 ± 0.4 m/s (P < .001) after surgery and remained stable (2.2 ± 0.7 m/s) during a median echocardiographic follow-up of 14.1 months (7.2-20.1 months) for the whole cohort. Freedom from reoperation or moderate and greater aortic regurgitation at 1, 2, and 3 years was 94.2% ± 3.3%, 85.0% ± 5.8%, and 79.0% ± 8.0%, respectively, with no difference between the neo-tricuspidalization and single leaflet reconstruction groups (P = .635). There were 6 late reoperations (10%) of which 3 were due to endocarditis. CONCLUSIONS: Aortic leaflet reconstruction provides acceptable short-term hemodynamic outcomes and proves the utility of this technique as an adjunctive strategy for surgical treatment of aortic valve disease in children and young adults.

Simultaneous Systemic to Pulmonary Shunt and Pulmonary Artery Banding is a Viable Option for Neonatal Palliation of Single Ventricle Physiology.

A subset of neonates with single ventricle (SV) physiology has antegrade pulmonary blood flow that is deemed unlikely to be reliable until Glenn. We have used systemic to pulmonary shunt (SPS) with pulmonary artery banding (PAB) to optimize pulmonary blood flow while maintaining reserve antegrade flow. We hypothesize that this is an effective strategy that can be accomplished without the routine need for cardiopulmonary bypass. We retrospectively reviewed the records of 60 neonates who underwent combined SPS + PAB between 2004 and 2015. Data are presented as median with quartiles. Children were 8 (4-19) days old at surgery and included 38 (63%) boys. Atresia or severe stenosis of the subpulmonary atrioventricular (AV) valve associated with pulmonary blood flow across a bulboventricular foramen was present in 37 (62%). In 20 (33%), heterotaxy-associated unbalanced AV canal with pulmonary stenosis with or without anomalous pulmonary venous drainage was present. First-stage palliation was accomplished without cardiopulmonary bypass in 44 patients (73%). There were 7 (12%) hospital deaths, 4 among the 20 (20%) with heterotaxy. Fifty-three children were followed for a median 5.1 (1.8-8.2) years. Three early reinterventions were required after initial palliation (1 PAB adjustment, 2 SPS balloon angioplasties). Five additional heterotaxy patients experienced late mortality during follow-up. There were no early or emergent Glenn. Thirty-nine patients have reached Fontan circulation with a median pre-Fontan PA pressure of 14 (12-18) mm Hg. One patient converted to biventricular physiology and the remaining await completion Fontan. Heterotaxy was the only independent predictor of mortality (hazard ratio 10 (2.3-44, P < 0.001). In SV patients with unreliable antegrade PA flow, SPS + PAB is an effective first-stage palliation. SV patients with heterotaxy are at increased risk for mortality.

A History of Thoracic Aortic Surgery.

Ancient historical texts describe the presence of aortic pathology conditions, although the surgical treatment of thoracic aortic disease remained insurmountable until the 19th century. Surgical treatment of thoracic aortic disease then progressed along with advances in surgical technique, conduit production, cardiopulmonary bypass, and endovascular technology. Despite radical advances in aortic surgery, principles established by surgical pioneers of the 19th century hold firm to this day.

The Utility of Nurse-Managed Extracorporeal Life Support in an Adult Cardiac Intensive Care Unit.

BACKGROUND: The use of extracorporeal life support (ECLS) worldwide has increased exponentially since 2009. The patient requiring ECLS demands an investment of hospital resources, including personnel. Educating bedside nurses to manage ECLS circuits broadens the availability of trained providers. METHODS: Experienced cardiothoracic intensive care unit (CTICU) nurses underwent training to manage ECLS circuits, including volume assessment, treatment of arterial blood gas values, the physiology of ECLS, and recognition of common emergencies. In addition to lectures and a written examination, simulation using water circuits and an ICU model allowed assessment of skills and understanding of concepts. Performance assessments were completed regularly at the bedside, and skills revalidation occurred every 6 months. A sequential cohort of 40 patients was tracked over 1 year. RESULTS: Despite doubling the census of ECLS patients in 1 year, management by specially trained CTICU nurses has positively affected patient care and outcomes. At a single institution, 40 patients had a median of 6 days (interquartile range, 2 to 226 days) of support in 2014, leading to 767 patient-days of support. Survival to hospital discharge increased to 45% in 2014. Most survivors were weaned from support. Neurologic injury was the most common cause of death, followed by failure to qualify for advanced therapies. CONCLUSIONS: With on-going education and assessment, including crisis training, physiology, and cannulation strategies, CTICU nurses can safely operate ECLS circuits and can increase the availability of appropriately trained providers to accommodate the exponential increase in ECLS occurrences without negatively affecting outcomes and generally at a lower cost.

Arterioplasty for Right Ventricular Outflow Tract Obstruction After Arterial Switch Is a Durable Procedure.

BACKGROUND: Right ventricular outflow tract obstruction (RVOT) is the most common late complication requiring intervention after arterial switch operation (ASO). The durability of surgical management of this complication has not been well established. METHODS: We retrospectively reviewed the charts of 38 consecutive patients who underwent RVOT reconstruction after ASO at our institution between 2004 and 2013. During the same time period, 223 consecutive patients underwent ASO for transposition of the great arteries at our institution. Thirty-five (16%) of the 223 patients developed RVOT obstruction, and 3 additional patients who had ASO done elsewhere presented to us with RVOT obstruction. Patient characteristics, site of stenosis, type of intervention, and outcomes were analyzed. Data are presented as median with interquartile ranges. RESULTS: The time interval between ASO and echocardiographic diagnosis of significant RVOT obstruction was 12.5 (3 to 23.7) months. After echocardiographic diagnosis, 33 (87%) children underwent cardiac catheterization. Obstruction involved the supravalvar main pulmonary artery (PA) in 21 (64%), branch PA in 14 (42%), pulmonary valve in 4 (12%), and sub-valvar area in 1 (3%). Ten of 33 patients who underwent catheterization had attempted percutaneous intervention, with 4 (40%) demonstrating significant response. Surgical intervention was performed at a median of 4 months in responders compared with 2.3 months in non-responders. Surgical repair included main PA plasty (36), extended to 1 or both branch PAs (26), or crossed the RVOT annulus (7). Surgical morbidity was 13% and there was no hospital or late mortality. At last follow-up, 41.2 months (21.4 to 81) after RVOT reconstruction, all patients had New York Heart Association grade 0 or 1 symptoms, and RV pressure was a median 36% of systemic pressure. Five (13%) patients underwent catheterization 26 months after surgery, with 2 requiring dilation at site of arterioplasty and 3 requiring distal branch PA intervention. One patient required reoperation for main PA stenosis. Freedom from re-intervention after surgery is 89%, 86%, and 86% at 2, 3, and 5 years, respectively. CONCLUSIONS: Surgical management of RVOT obstruction after ASO is an effective and durable intervention in the intermediate term. Our results serve as a benchmark for expected outcomes in this disease process.

Impaired coronary collateral growth in the metabolic syndrome is in part mediated by matrix metalloproteinase 12-dependent production of endostatin and angiostatin.

OBJECTIVE: We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin. APPROACH AND RESULTS: Rats underwent transient, repetitive left anterior descending occlusion and resultant myocardial ischemia (RI) for 0 to 10 days. CCG was measured in the collateral-dependent and normal zones using microspheres, MMP activation by Western blot, and endostatin and angiostatin by ELISA on days 0, 3, 6, 9, or 10 of RI. Endostatin and angiostatin were increased in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Increased endostatin and angiostatin correlated with increased MMP12 (≈ 4-fold) activation in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Inhibition of MMP12 in JCR rats nearly completely blocked endostatin (≈ 85%) and angiostatin (≈ 90%) generation and significantly improved CCG (collateral-dependent zone flow was ≈ 66% of normal zone flow versus ≈ 12% for JCR RI). CONCLUSIONS: Compromised CCG in the metabolic syndrome is, in large part, because of increased MMP12 activation and consequent increased generation of endostatin and angiostatin, which inhibits late-stage collateral remodeling.

MMPs 2 and 9 are essential for coronary collateral growth and are prominently regulated by p38 MAPK.

Transient, repetitive ischemia (RI) stimulates coronary collateral growth (CCG) in normal, healthy (SD) rats, which requires p38 MAPK activation. In contrast, RI does not induce CCG in the metabolic syndrome (JCR) rats, which is associated with lack of p38 MAPK activation. The functional consequences of p38 MAPK activation in CCG remain unknown. Theoretically, effective collateral growth would require extracellular matrix remodeling; however, direct assessment as well as identification of proteases responsible for this degradation are lacking. In this study, we investigated the role of p38 MAPK in the regulation of matrix metalloproteinases 2 and 9 (MMPs 2 and 9) and their requirement for CCG in SD vs. JCR rats. The rats underwent the RI protocol (8 LAD occlusions, 40s each, every 20min, in 8h cycles for 0, 3, 6, or 9days). MMP expression was measured in the ischemic, collateral-dependent zone (CZ) and the normal zone (NZ) by Western blot, and MMP activity by zymography. Expression and activation of MMP 2 and 9 were significantly increased (~3.5 fold) on day 3 of RI in the CZ of SD rats. In vivo p38 MAPK inhibition completely blocked RI-induced MMP 2 and 9 expression and activation. MMP activation correlated with increased degradation of components of the basement membrane and the vascular elastic laminae: elastin (~3 fold), laminin (~3 fold) and type IV collagen (~2 fold). This was blocked by MMP 2 and 9 inhibition, which also abolished RI-induced CCG. In contrast, in JCR rats, RI did not induce expression or activation of MMP 2 or 9 and there was no associated degradation of elastin, laminin or type IV collagen. In conclusion, MMP 2 and 9 activation is essential for CCG and is mediated, in part, by p38 MAPK. Furthermore, compromised CCG in the metabolic syndrome may be partially due to the lack of p38 MAPK-dependent activation of MMP 2 and 9 and resultant decreased extracellular matrix degradation.