Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Is the practice of using oversized organs for recipients with elevated pulmonary vascular resistance justified?

OBJECTIVE: The purpose of this study was to assess post-transplantation outcomes in recipients with increased pulmonary vascular resistance (PVR) in relation to donor size. METHODS: The United Network for Organ Sharing database was used to identify patients ages 0 to 18 years at time of listing who underwent transplantation from 2010 to 2019 and for whom cardiac catheterization and donor-recipient weight ratio data were available. Patients were divided according to listing PVR into <3, 3 to 6, and >6 Wood units. Donor-recipient weight ratio was categorized as undersized (≤0.80), midsize (0.81-1.2), and oversized (>1.2). Subgroup analysis was done with an additional supersized group (>2.0). RESULTS: Fourteen hundred ninety-one patients met study criteria. Median age was 10 (interquartile range, 3-15) years and 45% were female. Four percent of heart transplantation cases used undersized, 45% used midsize, and 51% used oversized organs. More patients with PVR >6 were received an oversized organ transplant compared with patients with PVR <3; 59% (148/252) versus 48% (430/894); P = .003. There was no difference in survival among organ size groups regardless of PVR; this includes patients with PVR >6 at listing who received an oversized organ transplant versus an undersized (P = .359) or midsized (P = .956) organ. In subgroup analysis, even in patients who received a supersized organ transplant, there was no survival difference noted regardless of PVR. CONCLUSIONS: Despite a persistent practice pattern to transplant oversized organs in high-PVR patients, there remains no difference in post-transplantation survival among these patients and those who received smaller organ transplants. Therefore, transplants in patients with high PVR should not be delayed by waiting for larger donors.

Outcomes of Femoropopliteal Bypass for Lifestyle-Limiting Claudication in the Endovascular Era.

INTRODUCTION: Outcomes after femoropopliteal bypass for intermittent claudication (IC) remain unclear in the endovascular era. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures performed between 1995 and 2020. Demographics, operative details, and outcomes were documented. A statistical analysis included Kaplan-Meier curves and Cox proportional hazards ratios (HR). RESULTS: A total of 282 patients underwent femoropopliteal bypass surgery for IC. Median age was 68 y (interquartile range, 61-73 y). Bypass conduits included great saphenous vein (GSV) (48.2%), prosthetic grafts (48.9%), and non-GSV autogenous grafts (2.8%). Distal bypass target was above-knee in 62.1% and below-knee in 37.9% of patients. The most common postoperative complications were wound infections (14.2%) followed by unplanned 30-d hospital readmissions (12.4%). Mortality rates were low at 0.4% (30 d) and 3.2% (1 y). Five-year primary patency rates trended highest for claudicants undergoing above-knee bypass with GSV conduit (log-rank P = 0.065). Five-year amputation-free survival rates were highest using GSV conduit regardless of distal bypass target (log-rank P = 0.017). On a multivariable analysis, age (HR 1.02 [1.00-1.04], P = 0.023) and active smoking (HR 1.48 [1.06-2.06], P = 0.021) were identified as risk factors for diminished primary graft patency. Risk factors for amputation-free survival included age (HR 1.03 [1.01-1.05], P < 0.001) and GSV conduit type (HR 0.65 [0.46-0.90], P = 0.011). CONCLUSIONS: Femoropopliteal bypass among claudicants is associated with high rates of wound infection and hospital readmission. Active smoking portends worse outcomes in this population. These data may inform clinical decision-making regarding surgical intervention for claudication in the endovascular era.

Endocarditis in Bovine Vein Grafts in the Pulmonary Position Placed Surgically & Percutaneously.

Background: Infective endocarditis (IE) is one of the major complications following pulmonary valve replacement (PVR). This analysis hopes to evaluate the incidence, outcomes and possible risk factors of IE associated with trans-catheter and surgical placement of a bovine jugular vein (BJV) graft in the pulmonary position. Methods: In this single-center retrospective study, all records of trans-catheter and surgical PVR from 3/2010 to 12/2019 were reviewed. IE was defined as positive blood cultures, with vegetations seen on echocardiography or sudden increase in peak gradient across the valve or vegetations confirmed at time of valve replacement. Poor dental hygiene:1.dental procedures without S.B.E prophylaxis AND/OR 2.one or more dental cavities, caries, dental abscess. Results: 165 patients had PVR with BJV:107 trans-catheter and 63 surgical. 7%(12/170) of PVRs developed IE(catheter:n = 10, surgery:n = 2) at a median time from valve placement of 38 months. The incidence of IE in the catheter group:3-per-100patient-years and in surgical group:1-per-100patient-years. Multivariate cox regression showed that poor dental hygiene was significantly associated with IE [HR(95% CI):16.9(4.35-66.2)](p value <.001). Kaplan-Meier curves showed a significant difference in freedom from IE between patients with poor and appropriate dental hygiene (p value<.001). Conclusions: There is a 7% incidence of IE with the use of BJV grafts in the pulmonary position at mid-term follow-up. Though the rate in catheter placed BJV seems 3x higher than surgically placed ones, their cohorts are quite different making this comparison flawed. Poor dental hygiene is a strong predictor for post-operative IE and offers a significant opportunity for lowering the rate of infective endocarditis.

Heart-kidney listing is better than isolated heart listing for pediatric heart transplant candidates with significant renal insufficiency.

OBJECTIVES: Significant renal insufficiency is identified as a risk factor for post-transplantation mortality in pediatric heart transplant recipients. This study evaluates simultaneous heart-kidney transplantation listing outcomes compared with heart transplant for pediatric candidates with significant renal insufficiency. METHODS: The United Network for Organ Sharing registry was searched for patients (January 1987 to March 2020) who were simultaneously listed for a heart-kidney transplantation or for heart transplant with significant renal insufficiency at the time of listing. Significant renal insufficiency was defined as needing dialysis or having a low estimated glomerular filtration rate (<40 mL/min). Survival was calculated using Kaplan-Meier analysis. RESULTS: A total of 427 cases were identified; 109 were listed for heart-kidney transplantation, and 318 were listed for heart transplant alone. Median time on the waitlist was 101 days (interquartile range, 28-238) for heart-kidney transplantation listings compared with 39 days (14-86) and 23.5 days (6-51) for heart transplant recipients with a low estimated glomerular filtration rate (P = .002) or on dialysis (P < .001), respectively. Of all heart-kidney transplantation listings, 66% (n = 71) received a transplant compared with 54% (n = 173) of heart transplantation with significant renal insufficiency (P = .005) with a mean survival of 14.6 years (12.7-16.4 years) for heart transplant without significant renal insufficiency at transplantation and 7.6 years (5.4-9.9 years) for heart transplant with significant renal insufficiency at transplantation. At 1 year after listing, 69% of heart-kidney transplantation listed recipients were alive, compared with 51% of heart transplant listed recipients (P = .029). Heart-kidney transplantation recipients had better 1-year post-transplantation survival (86%) than heart transplantation with significant renal insufficiency at transplant (66%) (P = .001). There was no significant difference in the 1- and 5-year survivals of those undergoing heart transplantation listed with significant renal insufficiency but no significant renal insufficiency at the time of transplant (89% and 78%) and heart-kidney transplantation recipients (86% and 81%; P = .436). CONCLUSIONS: Pediatric candidates with significant renal insufficiency listed for heart-kidney transplantation have superior waitlist and post-transplantation outcomes compared with those listed for heart transplant alone. Patients with significant renal insufficiency should be listed for heart-kidney transplantation, however; if their renal function improves significantly, heart transplant alone appears judicious.

Distal Bypass Versus Infrageniculate Endovascular Intervention for Chronic Limb-Threatening Ischemia.

Chronic limb-threatening ischemia (CLTI) carries a high risk of amputation and warrants urgent intervention. CLTI involving the infrageniculate vessels, in particular, carries a considerably higher risk of major limb amputation. Open surgical bypass is the historical gold standard for the treatment of tibial arterial disease; however, endovascular therapy provides an attractive alternative in this high-risk patient population. In this article, we review the existing literature regarding distal bypass and infrageniculate endovascular intervention in patients with CLTI.

MILESTONE: More Than 1,200 Children Bridged to Heart Transplantation with Mechanical Circulatory Support.

Pediatric mechanical circulatory support (MCS) has been successfully used to bridge numerous children to transplantation who otherwise would have been unlikely to survive on the waitlist and, in many cases, make them better transplant candidates. The purpose of this study was to analyze what the pediatric heart failure community has achieved over the last 15 years in reaching 1,200 cases of bridging children to heart transplantation. The United Network for Organ Sharing database was used to identify MCS patients ages 0-18 at the time of listing for heart transplantation between 2005 and 2019, divided into three eras: first (2005-2009), second (2010-2014), and third (2015-2019). From 2005 to 2019, 1,289 pediatric cases were identified. More patients were successfully bridged to transplantation with MCS in the third-era (28%) [vs. first-era (16%), second-era (24%), p ≤ 0.004]. The proportion of discharges on ventricular assist device has increased as well from 3% to 22% (p < 0.001). Post-transplant survival was significantly better in the third era (1-year survival: 96%; 3-year survival: 89%) compared to the two previous eras (p = 0.006). On MCS, renal dysfunction, ventilator dependence, inotrope use, and functional status improved from the time of listing to transplantation (p < 0.01). Hepatic dysfunction (p < 0.001), renal dysfunction (p = 0.004), congenital heart disease (p = 0.023), and infant age (p = 0.002) were risk factors for post-transplant mortality. Over the last 15 years, pediatric MCS has become an accepted and increasingly used strategy for bridging children to transplantation. MCS therapy is associated with improved end-organ function at the time of transplantation, perhaps contributing to the increasing post-transplantation survival of patients bridged with MCS.

Effect of ischemic time on pediatric heart transplantation outcomes: is it the same for all allografts?

BACKGROUND: Studies have shown that the optimal ischemia time (IT) threshold in pediatric heart transplantation (PHT) is up to 4 h, independent of other donor organ factors. The purpose of this study was to examine the relationship between IT and donor left ventricular ejection fraction (LVEF) and study their impact on PHT outcomes. METHODS: This is a retrospective cohort study of PHT (<18 years) identified in UNOS between January 2000 and March 2020. Post-transplantation survival analysis of patients receiving donor hearts with IT<4, 4-6, and >6 h was performed using Kaplan-Meier curves. Cohort was divided according to donor LVEF median value, and survival was analyzed. Cox regression was performed. RESULTS: Median LVEF was 65% in the study cohort (6669 PHT). Overall, IT>6 h was associated with worse survival compared to <4 h regardless of donor LVEF. For allografts with LVEF < 65%, IT = 4-6 h was associated with worse survival compared with IT < 4 h (p = .006) but had similar survival compared with IT > 6 h (p = .315). For allografts with LVEF ≥ 65%, IT = 4-6 h had similar survival compared with <4 h (p = .175) but improved survival compared with >6 h (p = .003). After adjusting for donor and recipient variables, Cox regression showed that IT = 4-6 h was not associated with increased mortality for LVEF ≥ 65%. CONCLUSIONS: The IT threshold of 4 h does not apply to all allografts. Recipients of hearts with LVEF≥65% can tolerate an IT up to 6 h without any detriment to survival. Routine acceptance of these donor hearts could mitigate longer waiting times and poor donor availability for many candidates.

Children who stroke on VAD support: When is it safe to transplant and what are their outcomes?

OBJECTIVE: Ventricular assist devices (VADs) increase waitlist survival, yet the risk of stroke remains notable. The purpose of this study was to analyze how strokes on VAD support impact post-transplant (post-Tx) outcomes in children. METHODS: About 520 pediatric (<18 years) heart transplant candidates listed from January 2011 to April 2018 with a VAD implant date were matched between the United Network of Organ Sharing and Pediatric Health Information System databases. Patients were divided into pre-Tx Stroke and No Stroke cohorts. RESULTS: About 81% of the 520 patients were transplanted; 28% (n = 146) had a pre-Tx Stroke; and 59% (n = 89) of the Stroke patients were transplanted at a median of 57 (IQR 17-102) days from stroke. Significantly more No Stroke cohort (90%) were transplanted (p < 0.001). There was no difference in post-Tx survival between the Stroke and No Stroke cohorts (p = 0.440). Time between stroke and transplant for patients who died within 1 year of transplant was 32.0 days (median) compared to 60.5 days for those alive >1 year (p = 0.18). Regarding patients in whom time from stroke to transplant was more than 60 days, one-year survival of Stroke vs. No Stroke patients was 96% vs. 95% (p = 0.811), respectively. CONCLUSION: Patients with stroke during VAD support, once transplanted, enjoy similar survival compared to No Stroke patients. We hypothesize that allowing Stroke patients more time to recover could improve post-Tx outcomes. Unfortunately, the ideal duration of time between stroke and safe transplantation could not be determined and will require more detailed and larger studies in the future.

Management of Neonates Admitted With Tetralogy of Fallot: Changing Patterns Across the United States.

BACKGROUND: This study describes the evolving in-hospital management strategies for neonates who are diagnosed with tetralogy of Fallot (ToF). METHODS: The Pediatric Health Information System (PHIS) database was used to identify admitted patients aged 0 to 1 month old with ToF from 2010 through 2019; era 1, 2010 through 2014; and era 2, 2015 through 2019. International Classification of Diseases codes were used to identify related interventions that occurred during this admission but not necessarily as a neonate: full repair, systemic-to-pulmonary shunt, and percutaneous stent in the right ventricular outflow tract and/or patent ductus arteriosus. RESULTS: Among 6021 neonates diagnosed with ToF, 2030 (34%) underwent an intervention: 60% had total repair, 31% systemic-to-pulmonary shunt, and 9% percutaneous stent. In the no-intervention cohort, in-hospital mortality was 9%. In-hospital mortality between repair (6%), shunt (6%), and stent (3%) patients (P = .446) did not differ. Regarding regional practices, no intervention was most frequently used in the Midwest (69% vs 65% average for all other regions [avg], P = .075) while interventions overall were performed most frequently in the West (36% vs 33.5% avg, P = .075). Among the interventions, full repair was most frequent in the Northeast (76% vs 57% avg, P < .001), shunt was most frequent in the Midwest (39% vs 28% avg, P < .001), and stent was most frequent in the South (11% vs 7% avg, P = .083). Between eras 1 and 2, the type of intervention changed: full repair (52% vs 69%, P < .001) and stent (1% vs 16%, P < .001) increased, while shunt decreased (47% vs 15%, P < .001). CONCLUSIONS: Although most neonates admitted with ToF are discharged with no intervention, more than one-third undergo some intervention with a 3% to 6% mortality. The proportion of these patients who undergo an intervention is unchanged during the past decade, but the types of intervention have changed, and significant regional differences exist.

More Than 400 Uses of an Intestinal Submucosal Extracellular Matrix Patch in a Congenital Heart Program.

BACKGROUND: Repair of complex congenital heart disease frequently requires use of a patch as an anatomic substitute. The study's aim is to evaluate the use, effectiveness, and safety of using small intestine submucosal extracellular matrix (SIS-ECM) patches in a congenital cardiac surgery program. METHODS: This is a single-center, retrospective, cohort study of surgeries using SIS-ECM between 2012 and 2019. The SIS-ECM data were categorized by use and type (four-ply and two-ply). All reinterventions and complications were reviewed by an independent surgeon, a practicing congenital heart surgeon, and a pediatric cardiologist. RESULTS: In all, 408 SIS-ECM patches were used in 309 patients (188 male, 121 female; median age 8.5 months). Use of the patches consisted of 314 arterioplasties (77%), 22 venoplasties (5.4%), 63 intracardiac repairs (15.4%), and 9 valve repairs (2.2%). The most common use was for pulmonary artery repair (n = 181; 44.4%). Median follow-up time was 3.9 years (range, 3 days to 7.4 years). Ten patches (2.5%) required surgical reintervention (2 in the first 30 days and 5 in the first year) and 27 (6.6%) required percutaneous reinterventions (2 in the first 30 days and 22 in the first year). Between four-ply (n = 376) and two-ply (n = 32) SIS-ECM, the rate of surgical (2.1% [n = 8] vs 6.3% [n = 2], P = .18) or percutaneous reinterventions (6.4% [n = 24] vs 9.4% [n = 3], P = .46) was not different. There were no deaths related to the SIS-ECM patch or reports of calcification. CONCLUSIONS: The SIS-ECM is a viable patch option that can be used in various cardiac and vascular reconstructive surgeries with low risk of failure and calcification. Long-term, positive outcomes may be maximized by using consistent techniques and understanding the appropriate applications of the patch.

Impact of mechanical circulatory support on pediatric heart transplant candidates with elevated pulmonary vascular resistance.

With the new era of increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study was to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients aged 0-18 at the time of listing for heart transplant between 2010 and 2019 who had PVR documented (n = 2081). Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No MCS groups, then divided by PVR (PVR) at the time of listing: <3, 3-6, and >6 Wood units (WU). MCS was used in 20% overall (n = 426); 57% of those with PVR <3, 27% with PVR 3-6, and 16% with PVR >6. MCS, PVR <3 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .049; vs. PVR 3-6, P = .004; vs. PVR >6, P < .001). MCS, PVR 3-6 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .048; vs. PVR 3-6, P = .009; vs. PVR >6, P < .001). MCS, PVR >6 patients had a higher chance of positive waitlist outcome than No MCS, PVR >6 patients (P = .012). Within the No MCS group, patients with a PVR >6 had a higher incidence of negative waitlist outcome compared to PVR <3 (17% vs. 10%, P = .002); this was not the case in the MCS group (5% vs. 6%, P = .693). More patients in the MCS group were ventilator dependent (15% vs. 9%, P < .001) at the time of listing and less likely to have a functional status >50% (43% vs. 73%, P < .001). No significant differences in post-transplant survival were found in pairwise comparisons of MCS and No MCS PVR subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. This was most pronounced with a PVR greater than 6 WU. MCS compared to No MCS patients had better waitlist survival and equivalent post-transplant survival. MCS patients, despite being more ill, had better overall survival regardless of PVR.

The total artificial heart in patients with congenital heart disease.

BACKGROUND: While ventricular assist devices (VADs) remain the cornerstone of mechanical circulatory support (MCS), the total artificial heart (TAH-t) has gained popularity for certain patients in whom VAD support is not ideal. Congenital heart disease (CHD) patients often have barriers to VAD placement due to anatomic and physiological variation and thus can benefit from the TAH-t. The purpose of this study is to analyze the differences in TAH application and outcomes in patients with and without CHD. METHODS: The SynCardia Department of Clinical Research provided data upon request for all TAH-t implantations worldwide from December 1985 to October 2019. These patients were divided into two groups by pre-implantation diagnosis of CHD and non-CHD. RESULTS: A total of 1,876 patients were identified. Eighty (4%) of these patients also carried a diagnosis of CHD. There was a higher proportion of children in the CHD cohort (16.3% vs. 2.1%, P<0.001) and this translated into a lower average age amongst the two groups (34±13 vs. 49±13 years, P<0.001). There were also significantly more females in the CHD group (22.8% vs. 12.8%, P=0.010). CHD patients were more likely to be supported with a 50 cc TAH-t (11.3% vs. 4.5%, P=0.005) while all other support characteristics, including duration of support, were similar between the groups. All measured outcomes were similar between CHD and non-CHD patients including positive outcome (alive on device or transplanted), 1-month conditional survival, and rate of Freedom Driver use. CONCLUSIONS: TAH-t is an effective means to support patients with CHD. Patients with CHD had similar survival, support characteristics, and frequency of discharge compared to patients without CHD. As MCS continues to grow, its indications broadened, and its contraindications narrowed, more patient populations will see the benefit of the TAH's continuously developing technology.