Publications by authors named "Pedro J Del Nido"

328 Publications

The Association of Age and Repair Modification with Outcome after Cone Repair for Ebstein's Malformation.

Semin Thorac Cardiovasc Surg 2021 May 6. Epub 2021 May 6.

Department of Cardiac Surgery, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA. Electronic address:

Cone repair (CR) uses native tissue for tricuspid valve (TV) repair and provides potential for growth. Results after CR were investigated in different age groups including several surgical modifications. Single institution retrospective analysis of all CR excluding neonatal procedures. Endpoints included TV reoperation, late tricuspid regurgitation (TR) and death. Between April 2006 and August 2019, 157 patients underwent CR at a median age of 11.7 years (range, 0.3-57.2). 20% (n=32) of patients had previous surgery. Repair modifications included atrial reduction (n=111,71%), right ventricular plication (n=85,55%), leaflet augmentation (n=36,23%), papillary muscle repositioning (n=50,32%), ring annuloplasty (n=70,45%). Early re-operation for recurrent TR occurred in 11 patients. Median follow-up time was 4.3 years (range, 9d-12.3y). There was no significant association between age at repair and time to TV reoperation (p=0.25). However, age <4 years at CR was identified as the most discriminating binary age threshold for the patients with TV reoperation (25.0% in <4y group vs. 9.3% in the ≥4y group). Placement of an annuloplasty ring was protective against ≥moderate TR (OR=0.39, 95% CI 0.16-0.95, p=0.039). Freedom from late TV re-operation was 94.1% at 7 years. Survival was 97.9% at 6 years. Repair after age 18 years was associated with mortality in early follow-up (p=0.037). Mid-term results for CR are favorable in children and adults. Time to TV reoperation may be shorter when Cone repair is performed before age four years, but this result requires confirmation in a larger sample. An annuloplasty ring should be considered when appropriate.
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http://dx.doi.org/10.1053/j.semtcvs.2021.03.034DOI Listing
May 2021

Long-term outcomes of truncus arteriosus repair: A modulated renewal competing risks analysis.

J Thorac Cardiovasc Surg 2021 Feb 12. Epub 2021 Feb 12.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

Objective: In this study, we sought to identify independent risk factors for mortality and reintervention after early surgical correction of truncus arteriosus using a novel statistical method.

Methods: Patients undergoing neonatal/infant truncus arteriosus repair between January 1984 and December 2018 were reviewed retrospectively. An innovative statistical strategy was applied integrating competing risks analysis with modulated renewal for time-to-event modeling.

Results: A total of 204 patients were included in the study. Mortality occurred in 32 patients (15%). Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were significantly associated with overall mortality (right ventricle to pulmonary artery conduit size: hazard ratio, 1.34; 95% confidence interval, 1.08-1.66, P = .008; truncal valve insufficiency: hazard ratio, 2.5; 95% confidence interval, 1.13-5.53, P = .024). truncal valve insufficiency at birth, truncal valve intervention at index repair, and number of cusps (4 vs 3) were associated with truncal valve reoperations (truncal valve insufficiency: hazard ratio, 2.38; 95%, confidence interval, 1.13-5.01, P = .02; cusp number: hazard ratio, 6.62; 95% confidence interval, 2.54-17.3, P < .001). Right ventricle to pulmonary artery conduit size 11 mm or less was associated with a higher risk of early catheter-based reintervention (hazard ratio, 1.54; 95% confidence interval, 1.04-2.28, P = .03) and reoperation (hazard ratio, 1.96; 95% confidence interval, 1.33-2.89, P = .001) on the right ventricle to pulmonary artery conduit.

Conclusions: Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were associated with overall mortality after truncus arteriosus repair. Quadricuspid truncal valve, the presence of truncal valve insufficiency at the time of diagnosis, and truncal valve intervention at index repair were associated with an increased risk of reoperation. The size of the right ventricle to pulmonary artery conduit at index surgery is the single most important factor for early reoperation and catheter-based reintervention on the conduit.
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http://dx.doi.org/10.1016/j.jtcvs.2021.01.136DOI Listing
February 2021

Super Glenn for staged biventricular repair: impact on left ventricular growth?

Eur J Cardiothorac Surg 2021 Mar 15. Epub 2021 Mar 15.

Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.

Objectives: The Super Glenn procedure involves targeted increased in blood flow to left sided heart structures with fenestrated atrial septation. The objective of this study was to examine the outcomes of patients who had this procedure as a part of biventricular staging and specifically evaluate the effect on dimensions of left heart structures.

Methods: Data for patients who had this procedure between 2005 and 2019 were retrospectively identified.

Results: Thirty-seven patients were identified. Most common diagnosis was hypoplastic left heart syndrome in 40% (n = 15). On echocardiography, the median mitral valve z score was -2.26. On cardiac magnetic resonance imaging, median indexed left ventricular end-diastolic volume was 31.5 ml/m2 and mitral/tricuspid inflow ratio was 0.35. The median age at Super Glenn was 2.3 years (interquartile range 1.5-3.6) while median weight was 12 kg (interquartile range 9.8-14). There were no early/hospital deaths. The median intensive care unit length of stay was 4 days, and median hospital length of stay was 10 days. Median follow-up for the entire cohort was 3 years (range 15 days to 13.2 years). There was a statistically significant increase in indexed left ventricular dimensions. There were 5 deaths (14%). Three patients (8%) underwent heart transplant. Freedom from death/transplant was 79% at 5 years. Seven patients (19%) needed a reoperation. Twenty-three patients (62%) underwent biventricular conversion after a median of 11.3 months after Super Glenn.

Conclusions: The Super Glenn procedure achieves consistent increase in left ventricular dimensions. This may be a useful strategy to help achieve a successful biventricular circulation in patients with borderline left ventricle. The superiority/non-inferiority of this approach over the conventional Fontan pathway is unclear.
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http://dx.doi.org/10.1093/ejcts/ezab126DOI Listing
March 2021

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion.

J Vis Exp 2021 02 2(168). Epub 2021 Feb 2.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School;

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries. The renal arteries are occluded for 60 min by introducing the balloon-catheters through the femoral and carotid artery and advancing them into the proximal portion of the arteries. Iodinated contrast is injected in the aorta to assess any opacification of the kidney vessels and confirm the success of the artery occlusion. This is furtherly confirmed by the flattening of the pulse waveform at the tip of the balloon catheters. The balloons are deflated and removed after 60 min of bilateral renal artery occlusion, and the animals are allowed to recover for 24 h. At the end of the study, plasma creatinine and blood urea nitrogen significantly increase, while eGFR and urine output significantly decrease. The need for iodinated contrast is minimal and does not affect renal function. Bilateral renal artery occlusion better mimics the clinical scenario of perioperative renal hypoperfusion, and the percutaneous approach minimizes the impact of the inflammatory response and the risk of infection seen with an open approach, such as a laparotomy. The ability to create and reproduce this clinically relevant swine model eases the clinical translation to humans.
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http://dx.doi.org/10.3791/62230DOI Listing
February 2021

Congenital aortic and truncal valve reconstruction using the Ozaki technique: Short-term clinical results.

J Thorac Cardiovasc Surg 2021 May 19;161(5):1567-1577. Epub 2020 Feb 19.

Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston Children's Hospital, Boston, Mass.

Objectives: Aortic valve reconstruction (AVRec) with neocuspidization or the Ozaki procedure with complete cusp replacement for aortic valve disease has excellent mid-term results in adults. Limited results of AVRec in pediatric patients have been reported. We report our early outcomes of the Ozaki procedure for congenital aortic and truncal valve disease.

Methods: A retrospective analysis was performed on all 57 patients with congenital aortic and truncal valve disease who had a 3-leaflet Ozaki procedure at a single institution from August 2015 to February 2019. Outcome measures included mortality, surgical or catheter-based reinterventions, and echocardiographic measurements.

Results: Twenty-four patients had aortic regurgitation (AR), 6 had aortic stenosis (AS), and 27 patients had AS/AR. Two patients had quadricuspid valves, 26 had tricuspid, 20 had bicuspid, and 9 had unicusp aortic valves. Four patients had truncus arteriosus. Thirty-four patients had previous aortic valve repairs and 5 had replacements. Preoperative echocardiography mean annular diameter was 20.90 ± 4.98 cm and peak gradient for patients with AS/AR was 53.62 ± 22.20 mm Hg. Autologous, Photofix, and CardioCel bovine pericardia were used in 20, 35, and 2 patients. Eight patients required aortic root enlargement and 20 had sinus enlargement. Fifty-one patients had concomitant procedures. Median intensive care unit and hospital length of stay were 1.87 and 6.38 days. There were no hospital mortalities or early conversions to valve replacement. At discharge, 98% of patients had mild or less regurgitation and peak aortic gradient was 16.9 ± 9.5 mm Hg. Two patients underwent aortic valve replacement. At median follow-up of 8.1 months, 96% and 91% of patients had less than moderate regurgitation and stenosis, respectively.

Conclusions: The AVRec procedure has acceptable short-term results and should be considered for valve reconstruction in pediatric patients with congenital aortic and truncal valve disease. Longer-term follow-up is necessary to determine the optimal patch material and late valve function and continued annular growth.
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http://dx.doi.org/10.1016/j.jtcvs.2020.01.087DOI Listing
May 2021

Human endothelial colony-forming cells provide trophic support for pluripotent stem cell-derived cardiomyocytes via distinctively high expression of neuregulin-1.

Angiogenesis 2021 Jan 17. Epub 2021 Jan 17.

Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Ave., Enders 349, Boston, MA, 02115, USA.

The search for a source of endothelial cells (ECs) with translational therapeutic potential remains crucial in regenerative medicine. Human blood-derived endothelial colony-forming cells (ECFCs) represent a promising source of autologous ECs due to their robust capacity to form vascular networks in vivo and their easy accessibility from peripheral blood. However, whether ECFCs have distinct characteristics with translational value compared to other ECs remains unclear. Here, we show that vascular networks generated with human ECFCs exhibited robust paracrine support for human pluripotent stem cell-derived cardiomyocytes (iCMs), significantly improving protection against drug-induced cardiac injury and enhancing engraftment at ectopic (subcutaneous) and orthotopic (cardiac) sites. In contrast, iCM support was notably absent in grafts with vessels lined by mature-ECs. This differential trophic ability was due to a unique high constitutive expression of the cardioprotective growth factor neuregulin-1 (NRG1). ECFCs, but not mature-ECs, were capable of actively releasing NRG1, which, in turn, reduced apoptosis and increased the proliferation of iCMs via the PI3K/Akt signaling pathway. Transcriptional silencing of NRG1 abrogated these cardioprotective effects. Our study suggests that ECFCs are uniquely suited to support human iCMs, making these progenitor cells ideal for cardiovascular regenerative medicine.
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http://dx.doi.org/10.1007/s10456-020-09765-3DOI Listing
January 2021

Commentary: Cone reconstruction for Ebstein's anomaly is here to stay.

Authors:
Pedro J Del Nido

J Thorac Cardiovasc Surg 2021 03 5;161(3):1110-1111. Epub 2020 Dec 5.

Department of Cardiac Surgery, Boston Children's Hospital, and Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.12.004DOI Listing
March 2021

Discussion.

Authors:
Pedro J Del Nido

J Thorac Cardiovasc Surg 2021 Mar 5;161(3):1165-1166. Epub 2021 Jan 5.

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.155DOI Listing
March 2021

Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury.

J Thorac Cardiovasc Surg 2020 Dec 1. Epub 2020 Dec 1.

Department of Cardiovascular Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

Objectives: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI).

Methods: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control).

Results: Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO-defined as freedom from ECMO reinstitution within 1 week after initial separation-was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (-23.0%; range, -20.0% to -28.8%) compared with the Control group (-16.8%; range, -13.0% to -18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04) CONCLUSIONS: In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.151DOI Listing
December 2020

A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

J Extra Corpor Technol 2020 Dec;52(4):303-313

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts.
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http://dx.doi.org/10.1182/ject-2000034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728502PMC
December 2020

Bilateral Erector Spinae Blocks Decrease Perioperative Opioid Use After Pediatric Cardiac Surgery.

J Cardiothorac Vasc Anesth 2020 Oct 12. Epub 2020 Oct 12.

Harvard Medical School, Boston, MA; Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, MA.

Objective: The present study examined the feasibility and efficacy of continuous bilateral erector spinae blocks for post-sternotomy pain in pediatric cardiac surgery.

Design: Prospective cohort study; patients were retrospectively matched 1:2 to control patients. Conditional logistic regression was used to compare dichotomous outcomes, and generalized linear models were used for continuous measures, both accounting for clusters.

Setting: Quaternary children's hospital, university setting.

Participants: The study comprised 10 children ages five-to-17 years undergoing elective cardiac surgery requiring cardiopulmonary bypass.

Interventions: Ultrasound-guided bilateral erector spinae blocks at the conclusion of the cardiac surgical procedure, with postoperative infusion of ropivacaine until chest tube removal. Postoperative management otherwise followed standardized guidelines.

Measurements And Main Results: Patient characteristics were similar in the two groups. The median time to completion of the bilateral blocks was 16.0 minutes (interquartile range [IQR] 14.8-19.3), and no major adverse events were identified. Pain scores were low in both groups. Postoperative opioid use at 48 hours, rendered as oral morphine equivalents, was significantly reduced in the patients receiving the blocks. Cluster-adjusted squared-root-transformed means ± standard error were 0.89 ± 0.06 mg/kg for patients receiving the blocks versus 1.05 ± 0.06 mg/kg for control patients (p = 0.04; raw medians 0.81 [IQR 0.41-1.04] v 1.10 [IQR 0.78-1.35] mg/kg, respectively). There were no differences in recovery metrics, length of stay, or complications.

Conclusions: Bilateral erector spinae blocks were associated with a reduction in opioid use in the first 48 hours after pediatric cardiac surgery compared with a matched cohort from the enhanced recovery program. Larger studies are needed to determine whether this can result in an improvement in recovery and patient satisfaction.
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http://dx.doi.org/10.1053/j.jvca.2020.10.009DOI Listing
October 2020

Professor Ajit P. Yoganathan, PhD: "From bench to bedside": Celebrating his contributions to cardiac surgery with an honorary fellowship from the American Association for Thoracic Surgery.

J Thorac Cardiovasc Surg 2021 Mar 18;161(3):728-729. Epub 2020 Sep 18.

Department of Cardiovascular Surgery, Mount Sinai Hospital, New York, NY; Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1016/j.jtcvs.2020.09.073DOI Listing
March 2021

Aortic valve neo-cuspidation using the Ozaki technique for acquired and congenital disease: where does this procedure currently stand?

Indian J Thorac Cardiovasc Surg 2020 Jan 9;36(Suppl 1):113-122. Epub 2020 Jan 9.

Boston Children's Hospital, Harvard Medical School, Boston, MA USA.

The surgical treatment options for pediatric aortic valve disease are limited. The Ozaki procedure, which involves templated creation of new aortic valve leaflets, has proved to be a promising surgical technique. This review aims at elaborating the indications, technical intricacies, and outcomes of the aortic valve neo-cuspidization procedure (Ozaki procedure) in the pediatric population.
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http://dx.doi.org/10.1007/s12055-019-00917-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525707PMC
January 2020

Autogenous mitochondria transplantation for treatment of right heart failure.

J Thorac Cardiovasc Surg 2020 Aug 10. Epub 2020 Aug 10.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

Background: Right ventricular hypertrophy and failure are major causes of cardiac morbidity and mortality. A key event in the progression to right ventricular hypertrophy and failure is cardiomyocyte apoptosis due to mitochondrial dysfunction. We sought to determine whether localized intramyocardial injection of autologous mitochondria from healthy muscle treats heart failure.

Methods: Mitochondria transplanted from different sources were initially tested in cultured hypertrophic cardiomyocytes. A right ventricular hypertrophy/right ventricular failure model created through banding of the pulmonary artery in immature piglets was used for treatment with autologous mitochondria (pulmonary artery banded mitochondria injected/treated n = 6) from calf muscle, versus vehicle (pulmonary artery banded vehicle injected/treated n = 6) injected into the right ventricular free-wall, and compared with sham-operated controls (sham, n = 6). Animals were followed for 8 weeks by echocardiography (free-wall thickness, contractility), and dp/dt max was measured concomitantly with cardiomyocyte hypertrophy, fibrosis, and apoptosis at study end point.

Results: Internalization of mitochondria and adenosine triphosphate levels did not depend on the source of mitochondria. At 4 weeks, banded animals showed right ventricular hypertrophy (sham: 0.28 ± 0.01 cm vs pulmonary artery banding: 0.4 ± 0.02 cm wall thickness; P = .001), which further increased in pulmonary artery banded mitochondria injected/treated but declined in pulmonary artery banded vehicle injected/treated (0.47 ± 0.02 cm vs 0.348 ± 0.03 cm; P = .01). Baseline contractility was not different but was significantly reduced in pulmonary artery banded vehicle injected/treated compared with pulmonary artery banded mitochondria injected/treated and so was dp/dtmax. There was a significant difference in apoptotic cardiomyocyte loss and fibrosis in sham versus hypertrophied hearts with most apoptosis in pulmonary artery banded vehicle injected/treated hearts (sham: 1 ± 0.4 vs calf muscle vs vehicle: 13 ± 1.7; P = .001 and vs pulmonary artery banded mitochondria injected/treated: 8 ± 1.9, P = .01; pulmonary artery banded vehicle injected/treated vs pulmonary artery banded mitochondria injected/treated, P = .05).

Conclusions: Mitochondrial transplantation allows for prolonged physiologic adaptation of the pressure-loaded right ventricular and preservation of contractility by reducing apoptotic cardiomyocyte loss.
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http://dx.doi.org/10.1016/j.jtcvs.2020.08.011DOI Listing
August 2020

Mitochondrial transplantation for myocardial protection in ex-situ‒perfused hearts donated after circulatory death.

J Heart Lung Transplant 2020 Jun 29. Epub 2020 Jun 29.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts.

Methods: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 × 10 in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MT]; n = 6) received a second injection of mitochondria (5 × 10 in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia.

Results: At the end of 4 hours of reperfusion, MT and MT groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MT groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion.

Conclusions: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool.
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http://dx.doi.org/10.1016/j.healun.2020.06.023DOI Listing
June 2020

Mitochondrial transplantation by intra-arterial injection for acute kidney injury.

Am J Physiol Renal Physiol 2020 09 20;319(3):F403-F413. Epub 2020 Jul 20.

Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, Massachusetts.

Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters. Following 60 min of ischemia, the balloon catheters were deflated and animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of the cortex and medulla. There were no safety-related issues detected with mitochondrial transplantation. Following 24 h of reperfusion, estimated glomerular filtration rate and urine output were significantly increased while serum creatinine and blood urea nitrogen were significantly decreased in swine that received mitochondria compared with those that received vehicle. Gross anatomy, histopathological analysis, acute tubular necrosis scoring, and transmission electron microscopy showed that the renal cortex of the vehicle-treated group had extensive coagulative necrosis of primarily proximal tubules, while the mitochondrial transplanted kidney showed only patchy mild acute tubular injury. Renal cortex IL-6 expression was significantly increased in vehicle-treated kidneys compared with the kidneys that received mitochondrial transplantation. These results demonstrate that mitochondrial transplantation by intra-arterial injection provides renal protection from ischemia-reperfusion injury, significantly enhancing renal function and reducing renal damage.
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http://dx.doi.org/10.1152/ajprenal.00255.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509287PMC
September 2020

Technical Performance Score's Association With Arterial Switch Operation Outcomes.

Ann Thorac Surg 2021 04 27;111(4):1367-1373. Epub 2020 Jun 27.

Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Outcomes after the arterial switch operation (ASO) for dextro-transposition of the great arteries have improved significantly since its inception in the 1980s. This study reviews contemporaneous outcomes and predictors for late reinterventions after ASO.

Methods: We retrospectively reviewed patients who underwent ASO for dextro-transposition of the great arteries from 1997 to 2017. Technical performance score (TPS) class (class 1, trivial or no residua; class 2, minor residua; class 3, major residua or reintervention) was assigned at discharge based on echocardiographic evaluation of components of the ASO. Multivariable Cox regression identified patient- and procedure-specific factors associated with postdischarge reinterventions.

Results: Among 598 patients, 410 (69%) underwent ASO and 188 (31%) underwent ASO with ventricular septal defect repair. Median age at surgery was 5 days (interquartile range, 3 to 7); median follow-up time was 8.2 years; 408 (68%) were male; 50 (8.3%) were premature; and 10 (1.7%) had noncardiac anomalies or syndromes. Survival to hospital discharge was 98% (n = 591). Among 349 patients with follow-up, freedom from unplanned reintervent2ion at 5 years was 99% for TPS class 1, compared with 84% for class 2 and 30% for class 3. On multivariable Cox regression, classes 2 and 3 had significantly higher hazard for reintervention (class 2 hazard ratio 10.6; 95% confidence interval, 2.5 to 44.2; P = .001; class 3 hazard ratio 58.2, 95% confidence interval, 13.1 to 259; P < .001).

Conclusions: At our center, ASO was associated with relatively low mortality. Class 2 and class 3 TPS were the most important independent predictors of reinterventions after discharge. Therefore, TPS can serve as a tool for identifying high-risk patients who warrant closer follow-up.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.057DOI Listing
April 2021

Experience and Outcomes of Surgically Implanted Melody Valve in the Pulmonary Position.

Ann Thorac Surg 2021 03 27;111(3):966-972. Epub 2020 Jun 27.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Multiple congenital cardiac malformations require pulmonary valve replacement and/or right ventricular outflow (RVOT) reconstruction. Pulmonary valve replacement remains challenging in children owing to the limited growth potential of prosthetic valves. We evaluated outcomes in patients undergoing surgical implantation of a Melody valve in the RVOT.

Methods: Data were retrospectively collected for 23 patients undergoing surgical Melody valve implantation at Boston Children's Hospital between 2009 and 2019. We assessed postoperative valve function, reintervention rates, and mortality.

Results: Median age was 1.7 years (range, 2 months to 6 years); 12 patients were aged greater than 2 years (52%). Diagnosis was tetralogy of Fallot in 15 patients (65%); 15 had a prior RVOT operation (65%). The Melody valve was dilated before surgery to a median diameter of 14 mm (range, 10-20 mm). No patients had acute pulmonary regurgitation. One required transcatheter RVOT reintervention before discharge. Median follow-up was 3.7 years (range, 0.02-8.7 years) with moderate or greater pulmonary regurgitation in 2 patients. Catheter-based interventions (mean, 0.83 ± 1.07/patient) occurred at a median of 1 year (range, 16 days to 5.4 years) and included valve expansion for somatic growth (n = 10) and subsequent valve-in-valve replacement (n = 3). Three patients (13%) required surgical valve explant or replacement at a median of 1.0 year (range, 0.6-3.7 years) for Melody-specific indications. One-, 3-, and 5-year freedom from Melody-driven reoperation was 90%, 90%, and 83%, respectively.

Conclusions: The Melody valve can be surgically implanted in the RVOT of young patients with acceptable early results. These valves can be successfully dilated through transcatheter reintervention to accommodate growth.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.061DOI Listing
March 2021

1.5-Ventricle Repair Using Left Ventricle as the Subpulmonary Ventricle.

Ann Thorac Surg 2020 12 3;110(6):e529-e530. Epub 2020 Jun 3.

Department of Cardiac Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

The use of the left ventricle as the subpulmonary ventricle to achieve a 1.5 or biventricular circulation is feasible in heterotaxy patients with complex intracardiac anatomy and acceptable right ventricular function. It is an alternative in patients who are not ideal candidates for single-ventricle palliation. We highlight 2 cases in which patients were rescued from a failed Fontan palliation and demonstrated improved functional status with normal saturations.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.071DOI Listing
December 2020

Modified Ozaki Procedure Including Annular Enlargement for Small Aortic Annuli in Young Patients.

Ann Thorac Surg 2020 10 23;110(4):1364-1371. Epub 2020 May 23.

Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Aortic valve neocuspidization (AVNeo) (Ozaki procedure) has excellent midterm results in adults. Outcomes in patients with a small native aortic annulus are unknown. We report early outcomes in young patients with small native aortic valve annuli.

Methods: Retrospective data of patients undergoing AVNeo between 2015 and 2019 were reviewed. Patients with native aortic annulus less than 21 mm undergoing 3-leaflet AVNeo were included.

Results: A total of 51 patients were identified (median age 7.9 years; median weight 21 kg), and 80% patients were less than or equal to 12 years age. Preoperative indication was aortic regurgitation (AR) (n = 23), aortic stenosis (AS) (n = 22), or mixed AS and AR (n = 6). Baseline anatomy was quadricuspid (n = 1), tricuspid (n = 23), bicuspid (n = 15), or unicuspid (n = 12) valve. Preoperative peak gradient for AS and mixed AS and AR patients was 55.36 mm Hg. Median native annulus diameter was 17 mm; sinus and annular enlargements were required in 22 patients and 9 patients, respectively. Median intensive care unit and hospital length of stay were 2.0 days and 7.2 days, respectively. There were no reinterventions, and there was 1 hospital mortality unrelated to aortic valve. At discharge, 94% of patients had less than or equal to mild AR, and the median peak gradient was 18 mm Hg. At mean follow-up of 11.9 months, 80% and 82% of patients had less than moderate AR and AS, respectively. Three patients required surgical reintervention. In annular enlargement patients, mean annulus Z score remained greater than 0 at follow-up.

Conclusions: The Ozaki procedure has acceptable short-term results in young patients with small aortic annuli. A larger aortic annulus can be achieved with surgical annular enlargement. Long-term follow-up is necessary to determine late valve function and potential continued annular growth.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.025DOI Listing
October 2020

Discussion.

Authors:
Pedro J Del Nido

J Thorac Cardiovasc Surg 2020 Apr 29. Epub 2020 Apr 29.

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http://dx.doi.org/10.1016/j.jtcvs.2019.11.151DOI Listing
April 2020

Minimally Invasive Cardiac Surgical Procedures in Children.

Authors:
Pedro J Del Nido

Innovations (Phila) 2020 Mar/Apr;15(2):95-98

1811 Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, MA, USA.

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http://dx.doi.org/10.1177/1556984520914283DOI Listing
April 2021

Letter by McCully et al Regarding Article, "Mitochondria Do Not Survive Calcium Overload".

Circ Res 2020 04 9;126(8):e56-e57. Epub 2020 Apr 9.

From the Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, MA.

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http://dx.doi.org/10.1161/CIRCRESAHA.120.316832DOI Listing
April 2020

Multi-Band Surgery for Repaired Tetralogy of Fallot Patients With Reduced Right Ventricle Ejection Fraction: A Pilot Study.

Front Physiol 2020 19;11:198. Epub 2020 Mar 19.

School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

Introduction: Right ventricle (RV) failure is one of the most common symptoms among patients with repaired tetralogy of Fallot (TOF). The current surgery treatment approach including pulmonary valve replacement (PVR) showed mixed post-surgery outcomes. A novel PVR surgical strategy using active contracting bands is proposed to improve the post-PVR outcome. In lieu of testing the risky surgical procedures on real patients, computational simulations (virtual surgery) using biomechanical ventricle models based on patient-specific cardiac magnetic resonance (CMR) data were performed to test the feasibility of the PVR procedures with active contracting bands. Different band combination and insertion options were tested to identify optimal surgery designs.

Method: Cardiac magnetic resonance data were obtained from one TOF patient (male, age 23) whose informed consent was obtained. A total of 21 finite element models were constructed and solved following our established procedures to investigate the outcomes of the band insertion surgery. The non-linear anisotropic Mooney-Rivlin model was used as the material model. Five different band insertion plans were simulated (three single band models with different band locations, one model with two bands, and one model with three bands). Three band contraction ratios (10, 15, and 20%) and passive bands (0% contraction ratio) were tested. RV ejection fraction was used as the measure for cardiac function.

Results: The RV ejection fraction from the three-band model with 20% contraction increased to 41.58% from the baseline of 37.38%, a 4.20% absolute improvement. The RV ejection fractions from the other four band models with 20% contraction rate were 39.70, 39.45, and 40.70% (two-band) and 39.17%, respectively. The mean RV stress and strain values from all of the 21 models showed only modest differences (5-11%).

Conclusion: This pilot study demonstrated that the three-band model with 20% band contraction ratio led to 4.20% absolute improvement in the RV ejection fraction, which is considered as clinically significant. The passive elastic bands led to the reduction of the RV ejection fractions. The modeling results and surgical strategy need to be further developed and validated by a multi-patient study and animal experiments before clinical trial could become possible. Tissue regeneration techniques are needed to produce materials for the contracting bands.
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http://dx.doi.org/10.3389/fphys.2020.00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103653PMC
March 2020

Dynamic Augmentation of Left Ventricle and Mitral Valve Function With an Implantable Soft Robotic Device.

JACC Basic Transl Sci 2020 Mar 26;5(3):229-242. Epub 2020 Feb 26.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Left ventricular failure is strongly associated with secondary mitral valve regurgitation. Implantable soft robotic devices are an emerging technology that enables augmentation of a native function of a target tissue. We demonstrate the ability of a novel soft robotic ventricular assist device to dynamically augment left ventricular contraction, provide native pulsatile flow, simultaneously reshape the mitral valve apparatus, and eliminate the associated regurgitation in an Short-term large animal model of acute left ventricular systolic dysfunction.
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http://dx.doi.org/10.1016/j.jacbts.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091510PMC
March 2020

A geometrically adaptable heart valve replacement.

Sci Transl Med 2020 02;12(531)

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Congenital heart valve disease has life-threatening consequences that warrant early valve replacement; however, the development of a growth-accommodating prosthetic valve has remained elusive. Thousands of children continue to face multiple high-risk open-heart operations to replace valves that they have outgrown. Here, we demonstrate a biomimetic prosthetic valve that is geometrically adaptable to accommodate somatic growth and structural asymmetries within the heart. Inspired by the human venous valve, whose geometry is optimized to preserve functionality across a wide range of constantly varying volume loads and diameters, our balloon-expandable synthetic bileaflet valve analog exhibits similar adaptability to dimensional and shape changes. Benchtop and acute in vivo experiments validated design functionality, and in vivo survival studies in growing sheep demonstrated that mechanical valve expansion accommodated growth. As illustrated in this work, dynamic size adaptability with preservation of unidirectional flow in prosthetic valves thus offers a paradigm shift in the treatment of heart valve disease.
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http://dx.doi.org/10.1126/scitranslmed.aay4006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425635PMC
February 2020

Examination of pathologic features of the right atrioventricular groove in hearts with Ebstein anomaly and correlation with arrhythmias.

Heart Rhythm 2020 07 22;17(7):1092-1098. Epub 2020 Jan 22.

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Catheter ablation of accessory pathways (APs) in patients with Ebstein anomaly (EA) has a higher recurrence rate than in subjects with normal hearts. Anatomic features could account for suboptimal ablation outcomes.

Objective: The purpose of this study was to examine the right atrioventricular (AV) groove in autopsy hearts with EA, correlate with clinical data, and identify features relevant for catheter ablation.

Methods: Thirty-three specimens with EA from our Cardiac Registry were examined. The right AV groove was inspected for gross anatomic features. Limited microscopy was performed on selected specimens. Premortem clinical data were correlated with anatomic findings.

Results: A prominent ridge along the right AV groove was seen in 15 of 33 specimens (45%). Ten specimens had a clinical history of AP (AP+). The extent of ventricular atrialization did not differ between AP+ and AP- groups (64 ± 63 mm/m vs 76 ± 42 mm/m; P = .61), nor did the presence of visible macroscopic AV tissue connections (45% vs 51%; P = .68). The single item that differed was the presence of an AV groove ridge itself, which was significantly more common in the AP+ group (70% vs 21%; P = .03). Microscopy of ridge tissue revealed a muscular bundle in 1 AP+ specimen penetrating deep into the fibrous AV annulus that was suggestive of an AP, although complete muscular continuity was not verified in the limited sections available for examination.

Conclusion: A prominent ridge along the inferior right AV groove is a common feature in EA and correlates with clinical history of AP. It presents a potential obstacle to catheter ablation and may contribute to recurrence rate.
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http://dx.doi.org/10.1016/j.hrthm.2020.01.013DOI Listing
July 2020

Fontan with lateral tunnel is associated with improved survival compared with extracardiac conduit.

J Thorac Cardiovasc Surg 2020 04 30;159(4):1480-1491.e2. Epub 2019 Nov 30.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

Objectives: The study aim was to compare Fontan patients undergoing lateral tunnel (LT) versus extracardiac conduit (ECC) technique.

Methods: Fontan patients (LT vs ECC) from January 2000 to December 2017 were analyzed retrospectively. Baseline characteristics were analyzed as covariates. Primary outcomes (ie, mortality, Fontan failure, thrombosis, and pacemaker implantation) were compared using time-to-event models. Subgroup analysis including only initially fenestrated cases and propensity score matching were performed.

Results: Eight hundred one Fontan patients: LT (n = 638) versus ECC (n = 163) were included. Median follow-up time was 4.8 years (range, 1.1-10.8 years). Baseline characteristics were similar except for age: LT versus ECC: 2.6 years (range, 2.2-3.2 years) versus 3.1 years (range, 2.6-4.7 years) (P < .01) and mean pulmonary artery pressure: LT versus ECC: 12 mm Hg (11-15 mm Hg) versus 11 mm Hg (10-13 mm Hg) (P < .05). Early mortality was significantly higher in ECC versus LT group (3.1%; vs 0.5%; P < .05). Freedom from death, heart transplantation and Fontan failure were significantly longer in LT vs ECC (P < .01). After correcting for age, diagnosis, surgical technique, surgeon, mean pulmonary artery pressure, and fenestration, the ECC group showed worse freedom from death (hazard ratio, 2.8; P < .01) and Fontan failure (hazard ratio, 3.0; P < .01). No difference in pacemaker implantation rate was demonstrated (P = .25). Early fenestration closure was associated with higher risk of early (hazard ratio, 30.5) and late mortality (hazard ratio, 3.5). After matching, log-rank tests showed significant differences between the 2 groups for Fontan failure at 5 and 10 years (P < .01) and mortality at 5 years (P = .02).

Conclusions: When compared with ECC, LT Fontan is associated with better short and midterm outcomes. Spontaneous fenestration closure is an independent risk factor for early/late mortality.
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http://dx.doi.org/10.1016/j.jtcvs.2019.11.048DOI Listing
April 2020

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy.

JACC Basic Transl Sci 2019 Dec 23;4(8):871-888. Epub 2019 Dec 23.

Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts.

Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one's healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular K channels. Intracoronary mitochondrial delivery after temporary regional ischemia significantly improved myocardial function, perfusion, and infarct size. The authors concluded that intracoronary delivery of mitochondria is safe and efficacious therapy for myocardial ischemia-reperfusion injury.
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http://dx.doi.org/10.1016/j.jacbts.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938990PMC
December 2019