Phase I, open label safety and feasibility trial of autologous cord blood (CB) stem cells (CBSC) therapy via a novel blood cardioplegia-based intracoronary infusion technique during the Norwood ...procedure in neonates with antenatal diagnosis of hypoplastic left heart syndrome (HLHS). CBSC therapy may support early cardiac remodelling with enhancement of RV function during the critical interstage period.
Clinical grade CB mononucleated cells (CBMNC) were processed to NetCord-FACT International Standards. To maximise yield, CBSC were not isolated from CBMNC. CBMNC were stored at 4°C (no cryopreservation) for use within 3 days and delivered after each cardioplegia dose (4x15mL).
Of 16 patients with antenatal diagnosis, 13 were recruited, 3 were not treated due to placental abruption (n=1) or conditions delaying the Norwood >4 days (n=2) and 10 patients received 644.9±134x106 CBMNC, representing 1.5±1.1x106 (CD34+) CBSC. Interstage mortality was 30% (day 7, 25, 62). Of 36 serious adverse events (53% linked to 3 deaths), none were related to CBMNC therapy. Cardiac magnetic resonance imaging before Stage 2 (n=5) found RV mass index comparable to an exact-matched historical cohort (n=22), while RV ejection fraction was 66.2±4.5% and indexed stroke volume was 47.4±6.2mL/m2 versus 53.5±11.6% and 37.2±10.3mL/m2, respectively. All 7 survivors completed Stage 2 and are alive with normal RV function (≤mild (n=6), moderate (n=1) tricuspid regurgitation).
This trial demonstrated that autologous CBMNC, delivered in large numbers without prior cryopreservation, via a novel intracoronary infusion technique at cardioplegic arrest during Norwood palliation on day 2-3 of life is feasible and safe.
Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 ...are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant, were observed across all reported families. Additionally, we observed similarity to the human phenotype of short stature and skeletal anomalies in a heterozygous Bmp2-knockout mouse model, suggesting that haploinsufficiency of BMP2 could be the primary phenotypic determinant in individuals with predicted truncating variants and deletions encompassing BMP2. These findings demonstrate the important role of BMP2 in human craniofacial, skeletal, and cardiac development and confirm that individuals heterozygous for BMP2 truncating sequence variants or deletions display a consistent distinct phenotype characterized by short stature and skeletal and cardiac anomalies without neurological deficits.
Stenosis or diffuse hypoplasia of central pulmonary arteries (PA) is common in patients with single ventricle physiology, often requiring surgical patching. Such repairs are prone to failure, ...particularly with low pressure venous flow (bidirectional cavopulmonary connection or Fontan). We describe our experience of disconnection of central PA and selective systemic-PA shunt to the hypoplastic vessel. Single ventricle patients (n = 12) with diffuse left pulmonary artery (LPA) hypoplasia (LPA:right pulmonary artery diameter <0.7) underwent PA disconnection (ligation clip) and selective arterial shunt to the LPA. Patients with ≤mild atrioventricular valve regurgitation, and no more than mild systolic dysfunction on echocardiogram were considered. Following systemic-LPA shunt, patients were reassessed by cardiac catheterization prior to further surgery, with follow-up catheterization later performed and description of changes observed. Increased volume loading was well tolerated with no greater than mild atrioventricular valve regurgitation and preserved systolic function (normal or mildly reduced). Selective arterial shunting increased the caliber of the LPA from 4.1 mm (1.2–5.6) to 6.5 mm (1.7–11.9) and this increase was preserved post-Fontan (6.7 mm 1.3–8.0) (median range). Ventricular end diastolic pressure increased with arterial shunting but resolved after shunt takedown and Fontan completion (median +3 and −4 mm Hg respectively). Post-Fontan hospital length of stay was not prolonged (median 11 days, range 7–14). No deaths occurred. In univentricular hearts and PA hypoplasia, selective systemic-PA shunting physiologically increases the caliber of the distal vessels. In selected patients this can be done safely with maintenance of PA growth and resolution of the elevated end diastolic pressure with Fontan completion.
Intra-annular mitral valve replacement in neonates and infants Brizard, Christian P., MD, MS; d'Udekem, Yves, MD, PhD, FRACS; Eastaugh, Lucas J., MBBS, FRACP, FCSANZ ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
2015, January 2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
149, Številka:
1
Journal Article
Background Assessment of diastolic function has not been described after repair of total anomalous pulmonary venous drainage (TAPVD), but studies of exercise capacity demonstrate impaired performance ...in this population despite normal systolic function. We postulated that diastolic impairment might contribute to this finding. Methods We analyzed echocardiographic variables from 28 patients with repaired TAPVD and compared these with data from 32 healthy controls (normals) and 21 subjects with repaired transposition of the great arteries (TGA). Results Left ventricular (LV) end-diastolic volumes were smaller in the TAPVD group (median, 50 mL/m2 compared with a median of 64 mL/m2 in TGA and 67 mL/m2 in normals; P < .001 in each case). LV diastolic function in the TAPVD group was impaired. Mitral early to late ratio was increased (median, 2.7 in TAPVD compared with a median of 1.9 in TGA P = .047 and 2.1 in normals P = .021). LV isovolumic relaxation time was reduced (median, 50 milliseconds in TAPVD compared with a median of 70 milliseconds in both TGA and normals; P < .001 in each case). Late diastolic and systolic tissue Doppler velocities were lower and the E/e′ ratio was higher in the TAPVD group. Conclusions Patients with repaired TAPVD are usually regarded as having excellent outcomes, but the finding of LV diastolic dysfunction in this population warrants more careful follow-up. We postulate that the diastolic impairment in these patients is the result of relative unloading of the LV during early cardiac development. These findings may also have implications in considering therapeutic approaches for hypoplastic ventricles in attempting to achieve biventricular repair.
ImportanceCOVID-19 mRNA vaccine-associated myocarditis has previously been described; however specific features in the adolescent population are currently not well understood.ObjectiveTo describe ...myocarditis adverse events following immunisation reported following any COVID-19 mRNA vaccines in the adolescent population in Victoria, Australia.DesignStatewide, population-based study.SettingSurveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) is the vaccine-safety service for Victoria, Australia.ParticipantsAll SAEFVIC reports of myocarditis and myopericarditis in 12–17-year-old COVID-19 mRNA vaccinees submitted between 22 February 2021 and 22 February 2022, as well as accompanying diagnostic investigation results where available, were assessed using Brighton Collaboration criteria for diagnostic certainty.ExposuresAny mRNA COVID-19 vaccine.Main outcomes/MmeasureConfirmed myocarditis as per Brighton Collaboration criteria (levels 1–3).ResultsClinical review demonstrated definitive (Brighton level 1) or probable (level 2) diagnoses in 75 cases. Confirmed myocarditis reporting rates were 8.3 per 100 000 doses in this age group. Cases were predominantly male (n=62, 82.7%) and post dose 2 (n=61, 81.3%). Rates peaked in the 16–17-year-old age group and were higher in males than females (17.7 vs 3.9 per 100 000, p=<0.001).The most common presenting symptoms were chest pain, dyspnoea and palpitations. A large majority of cases who had a cardiac MRI had abnormalities (n=33, 91.7%). Females were more likely to have ongoing clinical symptoms at 1-month follow-up (p=0.02).ConclusionAccurate evaluation and confirmation of episodes of COVID-19 mRNA vaccine-associated myocarditis enabled understanding of clinical phenotypes in the adolescent age group. Any potential vaccination and safety surveillance policies needs to consider age and gender differences.
Children with functionally univentricular circulations have chronic volume loading of the systemic ventricle, potentially affecting ventricular function. Medications including angiotensin-converting ...enzyme inhibitors and β-blockers are used to treat ventricular dysfunction, despite limited evidence of their efficacy in this population.
To determine the effects of angiotensin-converting enzyme inhibitors on elevated filling pressures in children with single ventricle physiology.
We performed a single-centre, retrospective review of patients with single ventricle physiology who underwent multiple cardiac catheterisations between 1991 and 2013. Study population comprised of patients who commenced or had optimised dosing of angiotensin-converting enzyme inhibitors between assessments in response to high ventricular filling pressures. Patients undergoing interventions influencing loading conditions between assessments were excluded.
A total of 17 patients were identified, with dominant morphologic right ventricle in eight patients (47.1%). Among them, 11 (64.7%) were pre-Fontan and six (35.3%) were post-Fontan completion. Median inter-assessment interval was 9.4 months (range 7.3-19.1). There was a reduction in end-diastolic pressure from 13 to 10 mmHg (p=0.002), mean pulmonary artery pressure from 16 to 13 mmHg (p=0.049), and mean atrial pressure from 12 to 9 mmHg (p=0.001). There was one cardiac transplant, and there were no patient deaths at median follow-up after 31 months.
We observed a reduction in ventricular end-diastolic pressure, pulmonary artery pressure, and mean atrial pressure following treatment with angiotensin-converting enzyme inhibitors in patients with single ventricle physiology. Our study provides insights into the potential impact of anti-heart failure therapy in single ventricle circulations and calls for larger, controlled studies to assess for a therapeutic response.
We report the case of a 9-year-old girl who developed acute anthracycline-induced cardiotoxicity with severe, refractory congestive heart failure. Rescue treatment with cardiac re-synchronization ...therapy was initiated, resulting in rapid improvement in left ventricular function and clinical status.
Cystic lymphangioma is a rare lesion of the mediastinum. We present a patient with an antenatally detected mediastinal mass that appeared to regress during foetal life and was not demonstrated on ...early postnatal imaging. Acute severe respiratory distress at two months of age precipitated surgery with subsequent diagnosis of lymphangioma.
Background Recent evidence has suggested that haemodynamic information obtained from cardiac catheterisation is not essential in pre-operative assessment of children with hypoplastic left heart ...syndrome (HLHS) undergoing Bidirectional Cavopulmonary Connection (BCPC). Therefore our unit changed to cardiac Magnetic Resonance Imaging (MRI) in 2006. We aimed to compare peri-operative outcomes before and after this change. Methods Children with HLHS who underwent BCPC between 2004 and 2008 were identified. Data were collected regarding pre-operative findings and peri-operative outcomes. Results Forty patients were identified-catheterisation ( n = 21), MRI ( n = 19). Catheterisation patients were older at the time of BCPC (114.9 ± 22.7 days vs. 95.4 ± 11 days: p value 0.002), with no other differences in baseline data. Two patients required cardiopulmonary resuscitation during catheterisation; with no adverse events during MRI. Cardiopulmonary bypass time, ventilation time, inotrope score, and intensive care unit stay were similar. Length of hospital stay and oxygen saturations at discharge were also not significantly different. Conclusions We have demonstrated that post-operative course and outcomes are similar in patients with HLHS who had MRI or catheterisation as their pre-BCPC investigation. Additionally the complementary data provided by echocardiography and MRI safely provides sufficient anatomic and functional information with which to plan the BCPC.
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