Abstract Objective To demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model. Methods A left ...mini-thoracotomy was performed on Yorkshire pigs. The pectoralis major was dissected, and skeletal muscle tissue was removed and used for the isolation of autologous mitochondria. The heart was subjected to regional ischemia (RI) by temporarily snaring the circumflex artery. After 24 minutes of RI, hearts received 8 × 0.1 mL injections of vehicle (vehicle-only group; n = 6) or vehicle containing mitochondria (mitochondria group; n = 6) into the area at risk (AAR), and the snare was released. The thoracotomy was closed, and the pigs were allowed to recover for 4 weeks. Results Levels of creatine kinase-MB isoenzyme and cardiac troponin I were significantly increased ( P = .006) in the vehicle-only group compared with the mitochondria group. Immune, inflammatory, and cytokine activation markers showed no significant difference between groups. There was no significant between-group difference in the AAR ( P = .48), but infarct size was significantly greater in the vehicle group ( P = .004). Echocardiography showed no significant differences in global function. Histochemistry and transmission electron microscopy revealed damaged heart tissue in the vehicle group that was not apparent in the mitochondria group. T2-weighted magnetic resonance imaging and histology demonstrated that the injected mitochondria were present for 4 weeks. Conclusions Autologous mitochondrial transplantation provides a novel technique to significantly enhance myocardial cell viability following ischemia and reperfusion in the clinically relevant swine model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US.
We conducted a cross-sectional survey ...from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated.
In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided.
There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Normal pediatric values of three-dimensional (3D) left ventricular (LV) volumes and strain are not well established; moreover, no reports exist of the stress-strain relation and the heart ...rate-corrected velocity of circumferential fiber shortening (VCFc) based upon 3D imaging in children. Three-dimensional LV datasets were obtained in pediatric patients (≤18 years of age) with structurally normal hearts. Ventricular volumes and strain components (longitudinal, GLS; circumferential, GCS; and 3D strain, 3DS) were analyzed using a commercial 3D speckle-tracking analysis package. LV mid-wall global average end-systolic fiber stress was calculated from 3D LV volumes. A total of 238 patients were included in the analysis with a median age of 13.1 years (range 0.4 to 17.9 years). Regression equations were derived for 3D volume parameters, permitting body surface area-based Z score calculation. Overall, 3DS values were more negative than GLS and GCS (mean ± SD = −33.8 ± 2.8; −27.8 ± 2.9; and −21.7 ± 3.1, respectively); only GLS varied significantly with age (r = 0.22; p <0.001). Both global average end-systolic fiber stress and 3D VCFc increased significantly with age (p <0.001 for both). Stress-adjusted 3DS and VCFc both varied with age (p <0.001 for both), consistent with increased contractility. In conclusion, 3D echocardiography may be used to calculate LV stress, strain, and volumes in pediatric patients with strong reproducibility. Among strain parameters, significant age-related changes were seen only in GLS. Both indexes of contractility investigated (3DS and VCFc indexed to wall stress) improved with age. Future studies of the 3D echocardiography stress-strain relation may yield new insights into maturational changes in myocardial contractility.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are ...less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 range, 10.4–17.4 versus 10.0 range, 5.4–14.8 years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.
Cell saver blood reinfusion, a blood conservation technique recently available for pediatric use, is typically limited to 6 hours post processing to guard against bacterial contamination. We ...hypothesize that reinfusion of cell saver blood up to 24 hours post collection in children after cardiac surgery will not increase the incidence of hospital-acquired infections (HAI). The primary aim is to compare incidence of HAI between children receiving cell saver blood ≤6 hours vs. >6 to ≤24 hours from its collection. The secondary aim is to compare mortality and clinical outcomes. Retrospective chart review of children ≤18 years undergoing cardiac surgery with cardiopulmonary bypass (CPB) from 2013 to 2018 when cell saver collection and bedside temperature controlled storage became standard of care. Patients on extracorporeal membrane oxygenation (ECMO) within 48 hours postoperatively and those who did not receive cell saver were excluded. The primary outcome was HAI incidence postoperative days 0-6. Demographic data included diagnosis, surgical severity score, and clinical outcomes. 466 patients, 45% female. No significant between-group differences identified. There was no significant difference in HAI (control 8.5% vs. treatment 8.0%,
= .80) and death (control 7.9% vs. treatment 4.9%,
= .20). Noninferiority testing indicated the treatment group was not statistically inferior to the control group (
= .0028). Kaplan-Meier curve depicted similar status between-group rates of no infection or death; 92% treatment vs. 91% control. Total volume allogeneic red blood cell transfusion (allogeneic blood transfusion ABT) up to 24 hours postoperatively was significantly less in the treatment group,
< .0001. Incidence of HAI or mortality was not increased in patients receiving cell saver blood reinfusion >6 to ≤24 hours post collection. Treatment subjects received significantly less volume of ABT. Considering the risks of ABT, these findings support cell saver blood reinfusion up to 24 hours post collection.
Conclusion: The exercise capacity of ASO survivors is well preserved and is only mildly reduced compared to normal subjects. ...there is only a slight deterioration in exercise capacity over time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cell saver blood reinfusion, a blood conservation technique recently available for pediatric use, is typically limited to 6 hours post processing to guard against bacterial contamination. We ...hypothesize that reinfusion of cell saver blood up to 24 hours post collection in children after cardiac surgery will not increase the incidence of hospital-acquired infections (HAI). The primary aim is to compare incidence of HAI between children receiving cell saver blood ≤6 hours vs. >6 to ≤24 hours from its collection. The secondary aim is to compare mortality and clinical outcomes. Retrospective chart review of children ≤18 years undergoing cardiac surgery with cardiopulmonary bypass (CPB) from 2013 to 2018 when cell saver collection and bedside temperature controlled storage became standard of care. Patients on extracorporeal membrane oxygenation (ECMO) within 48 hours postoperatively and those who did not receive cell saver were excluded. The primary outcome was HAI incidence postoperative days 0–6. Demographic data included diagnosis, surgical severity score, and clinical outcomes. 466 patients, 45% female. No significant between-group differences identified. There was no significant difference in HAI (control 8.5% vs. treatment 8.0%,
p
= .80) and death (control 7.9% vs. treatment 4.9%,
p
= .20). Noninferiority testing indicated the treatment group was not statistically inferior to the control group (
p
= .0028). Kaplan–Meier curve depicted similar status between-group rates of no infection or death; 92% treatment vs. 91% control. Total volume allogeneic red blood cell transfusion (allogeneic blood transfusion ABT) up to 24 hours postoperatively was significantly less in the treatment group,
p
< .0001. Incidence of HAI or mortality was not increased in patients receiving cell saver blood reinfusion >6 to ≤24 hours post collection. Treatment subjects received significantly less volume of ABT. Considering the risks of ABT, these findings support cell saver blood reinfusion up to 24 hours post collection.
Fontan palliation depends on low pulmonary vascular resistance in order to maintain pulmonary blood flow and adequate oxygenation. This physiology results in higher central venous pressures with ...limited renal perfusion pressure and cardiac output. Positive pressure ventilation with mechanical ventilation increases intrathoracic pressure and raises central venous pressure and can further limit pulmonary and renal perfusion. Fluid removal with intermittent hemodialysis can be challenging in Fontan patients and can cause intolerable hypotension, however the increased abdominal filling pressures during peritoneal dialysis dwells can exacerbate systemic venous hypertension seen in Fontan patients and threaten adequate pulmonary blood flow and cardiac output. Successful transition to peritoneal dialysis in a chronically ventilated patient with hypoplastic left heart syndrome, end-stage renal disease and Fontan physiology has not been described. We present details outlining the successful transition across multiple modalities of renal replacement therapy to assist other teams faced with similar challenges in chronically ventilated Fontan patients with end-stage renal disease.
The first patients to undergo a successful arterial switch operation (ASO) for d-transposition of the great arteries (D-TGA) are now entering their fourth decade of life. Past studies of ASO ...survivors’ exercise function have yielded conflicting results. We therefore undertook this study to describe the current function of ASO survivors, to identify factors related to inferior exercise performance and to determine whether their exercise function tends to deteriorate over time. A retrospective cohort study was designed examining all patients with D-TGA after the ASO who underwent comprehensive cardiopulmonary exercise testing (CPET). Patients with palliative surgery prior to ASO, ventricular hypoplasia or severe valvar dysfunction were excluded from the study. Data from CPETs in which the peak respiratory exchange ratio was <1.09 were also excluded. We identified 113 patients who met entry criteria and had 186 CPX at our institution between 1/2002 and 1/2013; 41 patients had at least 2 qualifying CPX. Mean age at the time of the initial test was 17 ± 1 year. Peak oxygen consumption (VO2) averaged 84 ± 2 % predicted. Peak VO2 was lower among patients with repaired ventricular septal defects (82 ± 4 vs. 86 ± 3 % predicted;
p
< 0.05) and among patients with ≥ moderate right-sided obstructive lesions (77 ± 5 vs. 87 ± 3 % predicted;
p
< 0.05). Surgery prior to 1991 was also associated with a lower peak VO2 (81 ± 3 vs. 87 ± 3 % predicted;
p
< 0.01). The mean % predicted peak heart rate was 92 ± 1 %, with no significant difference between any of the subgroups. Non-diagnostic exercise-induced STT changes developed in 10 patients (12 studies). In the subgroup with at least 2 exercise tests, the annual decline in % predicted peak VO2 was quite slow (−0.3 % points/year;
p
< 0.01 vs. expected normal age-related decline). The exercise capacity of ASO survivors is well preserved and is only mildly reduced compared to normal subjects. Moreover, there is only a slight deterioration in exercise capacity over time. VSD repair, residual right-sided obstructive lesions, and earlier surgical era are associated with worse exercise performance. Peak heart rate was preserved with no significant change in follow up testing.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aortic stenosis has been reported to manifest a slow rate of progression in mild disease, with a greater likelihood of progression in patients with moderate-severe disease. The natural history of the ...Doppler-estimated maximum gradient (DEMG) in patients after balloon aortic valvuloplasty (BAVP) has not previously been studied on a large scale.
A retrospective review was performed of 360 patients from 1984 to 2012 with aortic stenosis, providing a total of 2059 echocardiograms both before and after BAVP. Patients were excluded if they had an intervention within the first 30 days of life. The relationships between the aortic stenosis DEMG and several predictors (age at initial study, body surface area, valve morphology, and initial DEMG) were explored using linear mixed effect models. Patients with a unicommissural aortic valve had a significantly higher rate of progression compared with those with a bicommissural aortic valve (0.81 and 0.45 mm Hg/year;
<0.001). The median rate of progression in the post-BAVP group was significantly lower than the median pre-BAVP rate of progression (n=34; pre-BAVP 3.97 1.69-8.7 mm Hg/year; post-BAVP 0.40 -1.80 to 3.88 mm Hg/year;
<0.008). When adjusted for body surface area, there was no significant increase in the DEMG (-0.03 mm Hg/m
per year;
<0.001).
There is a statistically significant increase in the DEMG over time in patients with aortic stenosis. After balloon dilation, the DEMG rate of change is reduced compared with that pre-dilation. Given the effect of body surface area on DEMG progression, more frequent observation should be made during periods of rapid somatic growth.
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