Successful Pediatric Heart Transplantation from a Deceased Donor with SARS-Cov-2 Infection: A Case Report.

We report the case of a 3-year-old who was highly sensitized and received cardiac transplantation from a donor in the acute phase of SARS-CoV-2 infection. Despite maximal immunosuppression owing to a positive cross-match and desensitization protocol, the patient's course was favorable.

Fetal Doppler in monochorionic pregnancies complicated by twin-to-twin transfusion syndrome and selective in utero growth restriction.

BACKGROUND: Monochorionic (MC) twin pregnancies may be complicated by placental pathologies that impact fetal cardiac function, such as twin-twin transfusion syndrome (TTTS) and selective intrauterine growth-restriction (sIUGR). In the TTTS, the unbalanced blood flow through placental anastomoses lead a recipient volume overload, hypertension and hypertrophic cardiomyopathy and the donor twin experiences hypovolemia and hypertension due to increased placental resistance and poor renal perfusion. When MC pregnancies were complicated by sIUGR, the increase of placental resistances lead to complex fetal compensatory mechanisms with redistribution of cardiac output to vital organs. Increased placental vascular resistances, hypoxia and hemodynamic compensation mechanisms lead to higher pre and/or afterload for both ventricles, right cardiac failure and eventually left cardiac failure observed just before fetal death. OBJECTIVES: The purpose of this study was to describe the anomalies of umbilical, ductal and aortic isthmic Doppler as well as left and right myocardial performance index (MPI) across various clinical phenotypes of MC twin pregnancies, uncomplicated or complicated by TTTS or sIUGR, in order to help differentiating these conditions and to improve the understanding of TTTS and sIUGR pathophysiology. STUDY DESIGN: Aortic isthmic systolic index (ISI), umbilical artery pulsatility index (UAPI), ductus venosus pulsatility index (DVPI), and MPI were studied in uncomplicated MC twins (control group) and cases of sIUGR or TTTS. RESULTS: The measurements were obtained in 113 pregnancies (24 uncomplicated, 22 sIUGR, 51 TTTS). In comparison with controls, the sIUGR smaller twin sets had lower ISI and higher UAPI, and the larger twin had higher ISI. The TTTS donor and recipient had lower ISI, higher UAPI and DVPI. Compared to the co-twin, the ISI values were lower in the sIUGR smaller twin and the TTTS donor had lower ISI and MPI. Comparing TTTS and sIUGR, the recipient had higher DVPI and MPI than the sIUGR larger twin. CONCLUSIONS: The Doppler anomalies observed in the smaller twin reflected increased placental blood flow resistance, presumably due to abnormal feto-fetal transfusion in TTTS and to unequal placental sharing in sIUGR. Early hemodynamic changes suggestive of cardiac overload in the recipient twin may help to differentiate TTTS and sIUGR.

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments.

INTRODUCTION: Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. METHODS: A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices. RESULTS: Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid ( P =0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S' wave amplitudes were lower in HR than in SR and HR+DEX groups ( P =0.028, P =0.048, and P =0.005, respectively). The LV lateral E' in diastolic function was lower in the HR than in SR and HR+DEX groups ( P =0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups ( P =0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements. CONCLUSIONS: This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.

Navigation guidance for ventricular septal defect closure in heart phantoms.

PURPOSE: Transesophageal echocardiography (TEE) is the preferred imaging modality in a hybrid procedure used to close ventricular septal defects (VSDs). However, the limited field of view of TEE hinders the maneuvering of surgical instruments inside the beating heart. This study evaluates the accuracy of a method that aims to support navigation guidance in the hybrid procedure. METHODS: A cardiologist maneuvered a needle to puncture the patient's heart and to access a VSD, guided by information displayed in a virtual environment. The information displayed included a model of the patient's heart and a virtual needle that reproduced the position and orientation of the real needle in real time. The physical and the virtual worlds were calibrated with a landmark registration and an iterative closest point algorithms, using an electromagnetic measurement system (EMS). For experiments, we developed a setup that included heart phantoms representing the patient's heart. RESULTS: Experimental results from two pediatric cases studied suggested that the information provided for guidance was accurate enough when the landmark registration algorithm was fed with coordinates of seven points clearly identified on the surfaces of the physical and virtual hearts. Indeed, with a registration error of 2.28 mm RMS, it was possible to successfully access two VSDs (6.2 mm and 6.3 mm in diameter) in all the attempts with a needle (5 attempts) and a guidewire (7 attempts). CONCLUSION: We found that information provided in a virtual environment facilitates guidance in the hybrid procedure for VSD closure. A clear identification of anatomical details in the heart surfaces is key to the accuracy of the procedure.

Characterization of blood-mimicking fluids for echocardiography imaging of ventricular septal defects.

PURPOSE: Ventricular septal defects (VSD) are congenital heart malformations and, in severe cases, they require complex interventions under echocardiography guidance. Heart phantoms can be helpful to train and to understand the complex hemodynamics of VSD. The goal of this study was to characterize the best blood mimicking fluids in such heart phantoms for modelling the hemodynamics of VSD patients using echocardiography. METHODS: Four fluid compositions were considered. Distilled water was used as a baseline, while the other three fluids were developed based on physical properties of human blood, such as the viscosity and the refractive index. Three bi-ventricular heart phantoms of three different pediatric patients with complex VSD were designed from preoperative CT imaging. Custom molds were printed in 3-D and the anatomical structure was casted in polyvinyl alcohol cryogel. The VSD in each heart phantom were observed using echocardiography and color Doppler imaging was used for the hemodynamic study. RESULTS: Heart phantoms with blood mimicking fluids of 30% glycerol and 27% glycerol, 10% sodium iodide were found to be anatomically realistic under echocardiography imaging. Hemodynamic parameters such as the pressure gradient and the volume of the shunt were characterized using color Doppler imaging. CONCLUSION: Proper composition of blood mimicking fluids are important for improving the realism in echocardiographic heart phantoms and they contribute to better understand the complex hemodynamic of VSD under echocardiography.

Pulmonary hypertension associated with vein of Galen malformation. Fetal cardiac hemodynamic findings and physiological considerations.

The management of newborns with vein of Galen aneurysmal malformation (VGAM) is clinically challenging for neonatologists and cardiologists. Hemodynamic profiles in four fetuses diagnosed with VGAM who subsequently developed neonatal cardiac failure and pulmonary hypertension were studied using two-dimensional and Doppler echocardiography. All four had an increased cardiothoracic ratio due to right ventricular dilatation on antenatal ultrasound. Doppler studies of the aortic isthmus were abnormal with retrograde flow starting in mid systole and throughout diastole. Left and right ventricular outputs were significantly increased. Net pulmonary flow was highly abnormal with a flow rate almost four times higher than normal. After a short period of clinical stability, all neonates developed cardiac failure and pulmonary hypertension. This article reviews VGAM pathophysiology and the potential relationship between pulmonary hypertension and VGAM, supporting early post-natal treatment of pulmonary hypertension and right ventricular failure.

Outcome of Antibody-Mediated Fetal Heart Disease With Standardized Anti-Inflammatory Transplacental Treatment.

Background Transplacental fetal treatment of immune-mediated fetal heart disease, including third-degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first-degree/second-degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a ß-agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1-year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate <90 beats per minute (odds ratio [OR], 258.4; 95% CI, 11.5-5798.9; P<0.001), endocardial fibroelastosis (OR, 28.9; 95% CI, 1.6-521.7; P<0.001), fetal hydrops (OR, 25.5; 95% CI, 4.4-145.3; P<0.001), ventricular dysfunction (OR, 7.6; 95% CI, 1.5-39.4; P=0.03), and a ventricular rate <45 beats per minute (OR, 12.9; 95% CI, 1.75-95.8; P=0.034). At a median follow-up of 5.9 years, 85 of 100 neonatal survivors were paced, and 1 required a heart transplant for dilated cardiomyopathy. Cotreatment with intravenous immune globulin was used in 16 of 22 fetuses with diagnoses other than AVB III. Neonatal and 1-year survival rates of this cohort were 100% and 95%, respectively. At a median age of 3.1 years, 5 of 21 children were paced, and all had normal ventricular function. Conclusions Our findings reveal a low risk of perinatal mortality and postnatal cardiomyopathy in fetuses that received transplacental dexamethasone±other treatment from the time of a new diagnosis of immune-mediated heart disease.

Design of heart phantoms for ultrasound imaging of ventricular septal defects.

PURPOSE: Ventricular septal defects (VSDs) are common congenital heart malformations. Echocardiography used during VSD hybrid cardiac procedures requires extensive training for image acquisition and interpretation. Cardiac surgery simulators with heart phantoms have shown usefulness for such training, but they are limited in visualization and characterization of complex VSD. This study explores a new method to build patient-specific heart phantoms with VSD, with proper tissue echogenicity for ultrasound imaging. METHODS: Heart phantoms were designed from preoperative imaging of three patients with complex VSDs. Each whole heart phantom, including atrial and ventricular septums, was obtained by manual segmentation and by surface reconstruction, then by molding and by casting in different materials. Heart phantoms in silicone and polyvinyl alcohol cryogel (PVA-C) were considered, and they were reconstructed in 3-D using 2-D freehand ultrasound imaging. RESULTS: An electromagnetic measurement system was used to measure the mean VSD diameters from the heart phantoms. Errors were evaluated below 1.0 mm for mean VSD diameters between 6.2 and 7.5 mm. CONCLUSION: Patient-specific heart phantoms promise for representing complex heart malformations such as VSDs. PVA-C showed better tissue echogenicity than silicone for VSDs visualization and characterization.

Genetic factors in treatment-related cardiovascular complications in survivors of childhood acute lymphoblastic leukemia.

Aim: Cardiovascular disease represents one of the main causes of secondary morbidity and mortality in patients with childhood cancer. Patients & methods: To further address this issue, we analyzed cardiovascular complications in relation to common and rare genetic variants derived through whole-exome sequencing from childhood acute lymphoblastic leukemia survivors (PETALE cohort). Results: Significant associations were detected among common variants in the TTN gene, left ventricular ejection fraction (p ≤ 0.0005), and fractional shortening (p ≤ 0.001). Rare variants enrichment in the NOS1, ABCG2 and NOD2 was observed in relation to left ventricular ejection fraction, and in NOD2 and ZNF267 genes in relation to fractional shortening. Following stratification according to risk groups, the modulatory effect of rare variants was additionally found in the CBR1, ABCC5 and AKR1C3 genes. None of the associations was replicated in St-Jude Lifetime Cohort Study. Conclusion: Further studies are needed to confirm whether the described genetic markers may be useful in identifying patients at increased risk of these complications.

Supravalvular and Valvular Pulmonary Stenosis: Predictive Features and Responsiveness to Percutaneous Dilation.

Supravalvular pulmonary stenosis (SVPS) is considered a rare form of pulmonary stenosis (PS) and represents both a diagnostic and therapeutic challenge. There currently exist no reliable echocardiographic criteria to accurately predict the supravalvular form. The aims of the study were to describe the response to treatment of the different PS presentations and to outline the diagnostic capacity of echocardiogram to differentiate the SVPS from valvular PS (VPS). This retrospective study included 106 patients who underwent percutaneous angioplasty between 2006 and 2017. Interventional outcomes of patients with SVPS were compared to those of patients with VPS. Diagnosis of VPS vs. SVPS by echocardiogram was compared to diagnosis obtained by angiogram. Echocardiogram yielded a sensitivity of 56%, a specificity of 82.5%, a positive predictive value of 50%, and a negative predictive value of 85.7%. Patients with SVPS had a significantly smaller pulmonary artery to pulmonary valve (PA:PV) ratio. At 6-12 months of follow-up, the VPS group had a mean right ventricular to pulmonary artery (RV-PA) gradient of 21.68 ± 19.85 mmHg compared to 45.27 ± 24.58 mmHg in the SVPS group. Patients with SVPS had a higher rate of reintervention than patients with VPS (32% vs. 6.2%, p < 0.001). There was no difference in major complications between groups, whereas VPS patients had a higher proportion of pulmonary insufficiency. Percutaneous angioplasty for PS is less effective in patients with a supravalvular component. A better understanding of the underlying histopathology of different PS subtypes could lead to development of different techniques to improve outcomes, with fewer reinterventions, in this population.

Effect of Fenestration on Fontan Procedure Outcomes: A Meta-Analysis and Review.

BACKGROUND: Many studies investigating fenestration in the context of Fontan procedure have been showing controversial results when it comes to whether this procedure truly improves the Surgical outcomes. The aim of this meta-analysis was to compare the early outcomes of a fenestrated (F) vs a nonfenestrated (NF) Fontan procedure. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for articles measuring the outcomes of an F vs an NF Fontan. RESULTS: A total of 19 studies were selected with a total of 4806 patients (F. 2727; NF. 2079). There was no difference in the risk of Fontan failure between both groups (odds ratio [OR], 0.95 [95% confidence interval [CI], 0.57, 1.56]; P = .83). The F group had a significantly lower need for pleural drainage (OR, 0.59 [95% CI, 0.37, 0.94]; P = .03), a lower pulmonary artery pressure (mean difference, -0.99 mm Hg [95% CI, -1.68, 0.30 mm Hg]; P = .005), and a lower oxygen saturation (mean difference, -3.07% [95% CI, -4.30%, -1.85%]; P < .001) than the NF group. There was no significant difference in the stroke occurrence between the 2 groups (OR, 1.32 [95% CI, 0.40, 4.36]; P = .65). CONCLUSIONS: The Fontan fenestration effectively reduced the pulmonary pressure and the need for prolonged pleural drainage. However, the risks of Fontan failure, early death, and longer hospital stay were not modified.

Left Superior Vena Cava in the Fetus: A Rarely Isolated Anomaly.

The frequency of chromosomal anomalies among fetuses with isolated persistent left superior vena cava (PLSVC) is still debated. The objective of the present study was to assess the prevalence of genetic and morphological anomalies identified in fetuses with PLSVC. We conducted a single-center retrospective study including all fetuses diagnosed with a PLSVC between 2010 and 2017. PLSVC was categorized as isolated or associated according to antenatal diagnosis of associated congenital heart defects, hypoplastic aortic isthmus, abnormal venous/arterial connections, and extracardiac anomalies. Among 229 fetuses diagnosed with PLSVC, 39 cases (17%) were strictly isolated and no syndromic/genetic anomaly or aortic coarctation was diagnosed. Seventy-two fetuses had a cardiovascular defect with a rate of genetic anomalies of 22%, 29 had an extracardiac malformation, and 89 had both an extracardiac and a cardiovascular defect. Among fetuses with abnormal development of the arterial/venous system as the only associated anomaly such as aberrant right subclavian artery or absent ductus venosus, 22% had a genetic anomaly. Overall, sixty-five fetuses or infants had a genetic concern, including 23 aneuploidies, 15 pathogenic micro-deletions/duplications, and 5 variants of unknown significance; 12 patients had VACTERL association, and 12 heterotaxy syndrome. Seven infants had an aortic coarctation diagnosed at birth.In conclusion, a thorough prenatal ultrasound examination is paramount, and the identification of variants of the venous/arterial system in addition to PLSVC should raise suspicion for genetic or morphologic abnormalities. Invasive prenatal diagnosis with array-CGH should be offered when PLSVC is non-isolated, after a detailed ultrasound evaluation in a tertiary center.

Physical Activity and Sedentary Behaviors in Childhood Acute Lymphoblastic Leukemia Survivors.

INTRODUCTION: More than two thirds of survivors have long-term adverse effects, and no study proposes a portrait of physical activity level in childhood acute lymphoblastic leukemia survivors. The aims of this study were to present the cardiorespiratory fitness (CRF) levels of survivors detailed overview sedentary activities portrait. METHODS: A total of 247 childhood acute lymphoblastic leukemia survivors were included in our study. Survivors underwent a cardiopulmonary exercise test on ergocycle and completed physical activity and sedentary questionnaires to assess their leisure physical and sedentary activities and total daily energy expenditure. RESULTS: Up to 67% of survivors (84% below 18 y and 60% 18 y of age or above) did not fulfill the physical activity guidelines. Their CRF was reduced by almost 16% in regard to their predicted maximum oxygen consumption (VO2peak). Almost three quarters of the survivors (70% below 18 y and 76% 18 y of age or above) spent >2 hours/day in leisure sedentary activities. Adult survivors who received high doses of anthracyclines and those who received radiation therapy had decreased odds to spend ≥2 hours/day in sedentary activities. CONCLUSIONS: Our results showed that survivors, especially children, were not active enough and had a reduced CRF. This study highlights the importance of promoting physical activity in survivors, especially because they are exposed to an increased risk of chronic health problems, which could be mitigated by physical activity.

Prevention of Long-term Adverse Health Outcomes With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of therapy. A regular practice of physical activity and a good cardiorespiratory fitness have the potential to reduce the risk of chronic disease and improve quality of life. The aim of this study was to evaluate in a cohort of ALL survivors, the association between a good cardiorespiratory fitness or the respect of physical activity guidelines and major long-term health outcomes. METHODS: In total, 247 ALL survivors underwent a cardiopulmonary exercise test, completed a physical activity questionnaire and a battery of clinical examinations. We calculated the odds ratio to obtain the preventive fraction (PF) to evaluate the effects of the cardiorespiratory fitness and physical activity levels on health outcomes (ie, obesity, metabolic health, cardiac health, cognitive health and mood, bone health). RESULTS: Despite their young age, 88% of the participants presented at least one adverse health outcome, and 46% presented ≥3. Their cardiorespiratory fitness was also lower than expected with a median VO2 peak reaching 84% of the predicted value. In the analyses using cardiorespiratory fitness, statistically significant PFs were observed for obesity (0.30), low-high-density lipoprotein-cholesterol (0.21) and depression (0.26). In the physical activity level analyses, statistically significant PFs were observed for obesity, depression, and low bone mineral density, with a PF of 0.55, 0.81, and 0.60, respectively. CONCLUSIONS: Our results indicate that a good cardiorespiratory fitness and physical activity level induced a preventive action for most health outcomes studied and was associated with a lower late adverse effects prevalence in ALL survivors.

Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies.

BACKGROUND: Fetal atrioventricular block (AVB) occurs in 2% to 4% of anti-Ro antibody-positive pregnancies and can develop in <24 h. Only rarely has standard fetal heart rate surveillance detected AVB in time for effective treatment. OBJECTIVES: Outcome of anti-Ro pregnancies was surveilled with twice-daily home fetal heart rate and rhythm monitoring (FHRM) and surveillance echocardiography. METHODS: Anti-Ro pregnant women were recruited from 16 international centers in a prospective observational study. Between 18 and 26 weeks' gestation, mothers checked FHRM twice daily with a commercially available Doppler monitor and underwent weekly or biweekly surveillance fetal echocardiograms. If FHRM was abnormal, a diagnostic echocardiogram was performed. Cardiac cycle length and atrioventricular interval were measured, and cardiac function was assessed on all echocardiograms. After 26 weeks, home FHRM and echocardiograms were discontinued, and mothers were monitored during routine obstetrical visits. Postnatal electrocardiograms were performed. RESULTS: Most mothers (273 of 315, 87%) completed the monitoring protocol, generating 1,752 fetal echocardiograms. Abnormal FHRM was detected in 21 mothers (6.7%) who sought medical attention >12 h (n = 7), 3 to 12 h (n = 9), or <3 h (n = 5) after abnormal FHRM. Eighteen fetuses had benign rhythms, and 3 had second- or third-degree AVB. Treatment of second-degree AVB <12 h after abnormal FHRM restored sinus rhythm. Four fetuses had first-degree AVB diagnosed by echocardiography; none progressed to second-degree AVB. No AVB was missed by home FHRM or developed after FHRM. CONCLUSIONS: Home FHRM confirms the rapid progression of normal rhythm to AVB and can define a window of time for successful therapy. (Prospective Maternal Surveillance of SSA [Sjögren Syndrome A] Positive Pregnancies Using a Hand-held Fetal Heart Rate Monitor; NCT02920346).

Apical Muscular Ventricular Septal Defects: Surgical Strategy Using Three-Dimensional Printed Model.

To evaluate the utility of a three-dimensional printed model (3D-model) for surgical decision planning in a complex case of multiple ventricular septal defect (VSD) (so-called Swiss-cheese septum). A 3 month-old-girl with diagnosis of multiple apical VSDs in the trabecular septum, perimembranous VSD, and atrial septal defect that resulted in congestive heart failure was referred for surgical intervention. Due to inconclusive understanding of the total number, openings and locations of the apical VSDs, there were concerns regarding the best surgical approach. Using computed tomography images, a 3D-model was fabricated by fused deposition modeling of polyurethane filament. The 3D model helped identifying the total number of VSD, their origins and exits as well as the minimum number of septal bands to resect, the optimal patch size and morphology to completely close all VSDs without reducing significantly the RV cavity. The procedure was successfully replicated in the patient by right atrial approach, resulting in good RV cavity size, function and no residual VSDs evaluated by transesophageal echocardiography. Direct evaluation of the 3D printed replica anatomy and surgical simulation may help optimizing surgical approach, patch size and location and therefore it might reduce complications and residual defects.