Background: Arterial tortuosity is emerging as an imaging marker of adverse events in aortopathy,... more Background: Arterial tortuosity is emerging as an imaging marker of adverse events in aortopathy, but quantification has focused on patients with Marfan and Loeys-Dietz syndromes. Our objective was to characterize vertebral artery tortuosity among a variety of aortopathy phenotypes and genotypes. Methods: We performed a retrospective analysis of patients ≤50 years old with at least one of the following: aortic dilation or dissection, bicuspid aortic valve (BAV), or a genotype associated with aortopathy. Patients included were either enrolled in GenTAC or were cared for at our institution, and had undergone a magnetic resonance or computed tomography angiogram that included the vertebral arteries. The disease-causing gene mutation was available for a subset of the patients. The vertebral artery tortuosity index (VTI) was utilized to quantify tortuosity, and was compared among phenotypes and genotypes. Increased tortuosity was defined as ≥2SD above the mean VTI of previously reported ...
Background: Data regarding racial and ethnic differences in incidence and survival in pediatric c... more Background: Data regarding racial and ethnic differences in incidence and survival in pediatric cardiac arrest are unknown. In large cities, universal tracking of cardiac arrest is limited by multiple response centers fielding calls. This study was performed in Houston, one of the largest and most ethnically diverse cities in the US. Every 911 call in the city is tracked by a single operations center, providing a unique opportunity to conduct a population based study. Objective: We aimed to examine race and ethnic differences in incidence and survival rates among pediatric cardiac arrests utilizing a non-sampled population in a large metropolitan area. Methods: We performed a retrospective review of all 911 emergency response records involving non-traumatic pediatric cardiac arrests <18 years between 2002-2017. Race and ethnicity data among patients with cardiac arrests were compared to Houston population census data. Results: There were 598 (57% males) pediatric cardiac arrests at median age of 10 mo (IQR 2 mo - 6 yrs). Infants <2 yrs accounted for 60% of cases, 2-5 yrs (14%), 6-10 yrs (15%) and 11-17 yrs (11%). Overall, non-Hispanic black children comprised a significantly larger proportion of those with cardiac arrest than would be expected given population distribution (Figure). When evaluating these differences by age, the largest discrepancy was among infants, where odds of arrest in non-Hispanic black or Hispanic was 2.3 (95%CI 1.2-4.4) and 2.9 (95% CI 1.4-5.8) compared to white children. Overall survival was poor (9%) and did not differ by race/ethnicity, sex, bystander CPR, or time from 911 call to emergency personnel arrival. The only variable associated with greater survival was witnessed arrest (OR 2.2, 95%CI 1.2-4.0). Conclusions: There are racial differences in cardiac arrest in Houston based on age. Identifying reasons for these differences may provide insights into environmental or genetic risk factors associated with pediatric cardiac arrests.
Background The cardiovascular findings noted in both Williams syndrome (WS) and non-Williams (NW... more Background The cardiovascular findings noted in both Williams syndrome (WS) and non-Williams (NW) supravalvar aortic stenosis (SVAS) are most often mediated by abnormal or deficient elastin (ELN). Branch pulmonary artery stenosis (BPAS) is the next most common lesion after SVAS. The prevalence, interventions for, and outcomes of BPAS in WS and NW SVAS has not been well-described. Aim Describe and compare BPAS intervention and outcomes in patients with WS and NW SVAS. Subjects and Methods We included all patients at our institution with either WS or SVAS with negative testing for WS from 2003-2020.Patients with Alagille syndrome, Turner …
Purpose: Two “borderline” left heart phenotypes are evident in the fetus: 1) severe aortic stenos... more Purpose: Two “borderline” left heart phenotypes are evident in the fetus: 1) severe aortic stenosis (AS), which is associated with a globular left ventricle (LV), systolic LV dysfunction, and LV growth arrest, and 2) left heart hypoplasia (LHH) which is associated with a “long, skinny” LV, laminar flow across hypoplastic mitral and aortic valves, and arch hypoplasia. Both phenotypes may be counseled for possible single ventricle palliation. We aimed to compare the rates of aortic valve annulus size and Z-score change over gestation by phenotype. We hypothesized that the …
Background: A recent multi-center study of perinatal outcome in fetuses with Ebstein anomaly or t... more Background: A recent multi-center study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD) found that 1/3rd of live-born patients (pts) died prior to hospital discharge. The purpose of this study was to explore differences in postnatal management and the relationship to outcome. Methods: This 23-center, retrospective study included 243 fetuses with EA/TVD from 2005 to 2011. Neonatal procedure (NP) was defined as surgery or interventional catheterization (cath) prior to discharge. Associations between postnatal management and outcome at discharge were explored. Results: Of 176 live-born pts, 7 received comfort care only, 11 died <24 hrs of life, and 4 had insufficient data. Among 154 remaining pts, 38 (25%) did not survive to discharge. Pts who required ECMO at any point (n=18) had 83% mortality. More than half of pts (54%) did not have an NP, 34% had surgery, 8% had interventional cath, and 4% had both. The median age at 1st NP was 6 days (quartiles: 1-11). Survival did not differ between pts who had an NP and those who did not (70% vs. 80%; p=0.19) or between pts who had surgery and those who did not (68% vs. 80%; p=0.09). However, mortality differed by NP performed and whether pulmonary regurgitation, an indicator of high risk, was present prenatally (Figure). No pts with a right ventricular exclusion (RVE) died. Of 49 surviving neonates with ≥1 procedure, 28 (57%) were palliated with a shunt or RVE and 21 (43%) had a biventricular circulation. Thus, in total, 86 of 154 live-born pts (56%) survived with a biventricular circulation: 65 with medical management only and 21 with ≥1 NP. Conclusion: Among live-born pts diagnosed with EA/TVD in utero, a variety of postnatal management strategies were employed with overall poor outcomes. If surgery beyond PDA ligation is necessary, then RVE or other palliative procedure may need to be considered. A prospective, multi-center study utilizing a management algorithm would help elucidate the optimal strategy.
Introduction: Chromosomal microarray (CMA) testing for children with hypoplastic left heart syndr... more Introduction: Chromosomal microarray (CMA) testing for children with hypoplastic left heart syndrome (HLHS) has become common. While CMA-identified known genetic syndromes are often associated with increased mortality, the prognostic significance of variants of unknown significance (VUS) remains unknown. We sought to determine the spectrum, prevalence, and prognostic significance of CMA-associated VUSs in children with HLHS. Hypothesis: VUSs in HLHS are not associated with increased mortality compared to those with no copy number variation detected on CMA. Methods: Neonates with HLHS at our institution that underwent CMA testing prior to staged surgical palliation from June 2008 to December 2016 were reviewed. CMA results were abstracted and genome mapping conducted and compared against ostensibly healthy CNV (DGV genome browser). The primary outcome was death or cardiac transplant. Secondary endpoints were tracheostomy, feeding tube, requiring cardiopulmonary resuscitation or extracorporeal membrane oxyg...
Background: Dysfunctional intracellular Ca2+ handling has been implicated in adverse cardiac remo... more Background: Dysfunctional intracellular Ca2+ handling has been implicated in adverse cardiac remodeling leading to hypertrophy and failure. Recent evidence has linked mutations in the Ca2+ handling protein Junctophilin-2 (JPH2) with the development of hypertrophic cardiomyopathy (HCM). However, the mechanism remains unknown. Objective: To use advanced in vivo imaging modalities in conjunction with biochemical techniques to determine the mechanism of hypertrophic remodeling in a murine model hosting a novel JPH2 mutation. Methods and Results: 1. Pseudo-knockin (PKI) Mice: transgenic mice with the JPH2-A399S mutation (or WT JPH2) containing inducible shJPH2 were dosed with tamoxifen to knock down the combined levels of JPH2 to near WT expression. 2. MRI: A399S and WT PKI controls were imaged at 2 months post injection at which time body weight was similar for mutants (29.8±.81g) and controls (31.8±1.29g). Intragate (Bruker) was used to obtain FLASH cine images and EKG-gated tagged images were obtained to determine strain. MRI post-processing and measurements were performed using Amira and Diagnosoft software. A399S PKI mice exhibited significantly increased left ventricular mass (2.96±.21g/kg; n=4) compared to controls (2.27±.08g/kg; n=3) and max diastolic septal thickness (1.39±.05mm; n=9 versus 0.97±.00mm; n=4; P<0.01). Mutants trended toward decreased septal strain (-8.97±1.04; n=4) compared to the control (-10.28; n=1) indicative of reduced regional contractility 3. Biochemistry: stress markers were measured by qPCR. Average BNP was increased over 3 fold. Larger sample size is needed to reach significance. Western blot showed no significant change (p=.78) in phosphorylated Ca2+/calmodulin-dependent protein kinase II, which is often activated by aberrant Ca2+ signaling. Conclusions: Our data show that the JPH2-A399S mutation leads to septal hypertrophy in PKI mice. This suggests that defects in JPH2 are sufficient to induce pathological cardiac remodeling. Despite the role of JPH2 in Ca2+ handling, this form of hypertrophy does not appear to be mediated by traditional Ca2+ signaling. Further studies will focus on alternative Ca2+-dependent pathways to elucidate the molecular mechanisms of these hypertrophic changes.
Journal of Cardiovascular Electrophysiology, Jan 22, 2016
In pediatric patients with pacemakers implanted for atrioventricular block (AVB), nonsustained ve... more In pediatric patients with pacemakers implanted for atrioventricular block (AVB), nonsustained ventricular tachycardia (NSVT) detected during routine surveillance is a finding of unknown significance. We sought to describe the incidence of NSVT and determine if there was an association between NSVT and adverse outcomes in these patients. This is a single-center retrospective study of 136 patients (1971-2013) with pacemakers implanted for advanced and complete AVB. structural heart disease, diagnoses of myocarditis, cardiomyopathy or channelopathy preceding AVB diagnosis, and sustained or polymorphic ventricular tachycardia (VT) as the first occurring arrhythmia after pacemaker implant. During median follow-up of 11.6 years (IQR 4.3 years, 17 years), 14 (10%) patients had NSVT. There were 6 (4.4%) deaths. Overall, Kaplan-Meier 20-year survival from time of implant was 93%. By univariate analysis, earlier mortality was associated with NSVT (P = 0.010), sustained left ventricular (LV) dysfunction (P = 0.004), maternal autoantibodies (P = 0.017), and acquired AVB (P = 0.049). By multivariate analysis, earlier mortality was associated with NSVT (HR: 5.39 [95% CI: 1.02-28.41]; P = 0.047) and sustained LV dysfunction (HR: 10.24 [95% CI: 1.83-57.32]; P = 0.008). In children with pacemakers implanted for AVB, NSVT is not uncommon and may be associated with increased mortality. Persistent LV dysfunction may also be a potential factor associated with death. Closer follow-up should be considered in patients with these findings. Large, multicenter studies should be considered to confirm these findings and identify risk stratification methods for this unique patient population.
Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but... more Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10‐year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow‐up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P =0.026). Right ventricular dysfunction independently predicted overall morta...
World Journal for Pediatric and Congenital Heart Surgery, 2021
We present a case of fulminant myocarditis in a preterm neonate born to a SARS-CoV-2-infected mot... more We present a case of fulminant myocarditis in a preterm neonate born to a SARS-CoV-2-infected mother with COVID-19 disease. Despite complete separation after birth, cardiogenic decompensation initiated on day of life 7. Although the neonate tested negative for SARS-CoV-2, enterovirus viremia accompanied cardiac dysfunction, multiorgan failure, and neonatal death within 36 hours.
Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or ... more Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live‐born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23‐center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live‐born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live‐born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricu...
Loeys‐Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal,... more Loeys‐Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal, craniofacial, and cutaneous manifestations is caused by mutations in one of six genes (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3). Until recently, all reported cases of LDS have been attributed to heterozygous pathogenic variants in these genes. Here, we report the first case of Loeys‐Dietz syndrome due to SMAD3 biallelic likely pathogenic variants in a 15‐year‐old male with classic Loeys‐Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. To our knowledge, this represents the first reported case of biallelic SMAD3‐related Loeys‐Dietz syndrome and the third case in the literature of biallelic LDS, indicating that there are multiple genetic modes of inheritance underlying this disorder.
Background: Arterial tortuosity is emerging as an imaging marker of adverse events in aortopathy,... more Background: Arterial tortuosity is emerging as an imaging marker of adverse events in aortopathy, but quantification has focused on patients with Marfan and Loeys-Dietz syndromes. Our objective was to characterize vertebral artery tortuosity among a variety of aortopathy phenotypes and genotypes. Methods: We performed a retrospective analysis of patients ≤50 years old with at least one of the following: aortic dilation or dissection, bicuspid aortic valve (BAV), or a genotype associated with aortopathy. Patients included were either enrolled in GenTAC or were cared for at our institution, and had undergone a magnetic resonance or computed tomography angiogram that included the vertebral arteries. The disease-causing gene mutation was available for a subset of the patients. The vertebral artery tortuosity index (VTI) was utilized to quantify tortuosity, and was compared among phenotypes and genotypes. Increased tortuosity was defined as ≥2SD above the mean VTI of previously reported ...
Background: Data regarding racial and ethnic differences in incidence and survival in pediatric c... more Background: Data regarding racial and ethnic differences in incidence and survival in pediatric cardiac arrest are unknown. In large cities, universal tracking of cardiac arrest is limited by multiple response centers fielding calls. This study was performed in Houston, one of the largest and most ethnically diverse cities in the US. Every 911 call in the city is tracked by a single operations center, providing a unique opportunity to conduct a population based study. Objective: We aimed to examine race and ethnic differences in incidence and survival rates among pediatric cardiac arrests utilizing a non-sampled population in a large metropolitan area. Methods: We performed a retrospective review of all 911 emergency response records involving non-traumatic pediatric cardiac arrests &amp;amp;amp;lt;18 years between 2002-2017. Race and ethnicity data among patients with cardiac arrests were compared to Houston population census data. Results: There were 598 (57% males) pediatric cardiac arrests at median age of 10 mo (IQR 2 mo - 6 yrs). Infants &amp;amp;amp;lt;2 yrs accounted for 60% of cases, 2-5 yrs (14%), 6-10 yrs (15%) and 11-17 yrs (11%). Overall, non-Hispanic black children comprised a significantly larger proportion of those with cardiac arrest than would be expected given population distribution (Figure). When evaluating these differences by age, the largest discrepancy was among infants, where odds of arrest in non-Hispanic black or Hispanic was 2.3 (95%CI 1.2-4.4) and 2.9 (95% CI 1.4-5.8) compared to white children. Overall survival was poor (9%) and did not differ by race/ethnicity, sex, bystander CPR, or time from 911 call to emergency personnel arrival. The only variable associated with greater survival was witnessed arrest (OR 2.2, 95%CI 1.2-4.0). Conclusions: There are racial differences in cardiac arrest in Houston based on age. Identifying reasons for these differences may provide insights into environmental or genetic risk factors associated with pediatric cardiac arrests.
Background The cardiovascular findings noted in both Williams syndrome (WS) and non-Williams (NW... more Background The cardiovascular findings noted in both Williams syndrome (WS) and non-Williams (NW) supravalvar aortic stenosis (SVAS) are most often mediated by abnormal or deficient elastin (ELN). Branch pulmonary artery stenosis (BPAS) is the next most common lesion after SVAS. The prevalence, interventions for, and outcomes of BPAS in WS and NW SVAS has not been well-described. Aim Describe and compare BPAS intervention and outcomes in patients with WS and NW SVAS. Subjects and Methods We included all patients at our institution with either WS or SVAS with negative testing for WS from 2003-2020.Patients with Alagille syndrome, Turner …
Purpose: Two “borderline” left heart phenotypes are evident in the fetus: 1) severe aortic stenos... more Purpose: Two “borderline” left heart phenotypes are evident in the fetus: 1) severe aortic stenosis (AS), which is associated with a globular left ventricle (LV), systolic LV dysfunction, and LV growth arrest, and 2) left heart hypoplasia (LHH) which is associated with a “long, skinny” LV, laminar flow across hypoplastic mitral and aortic valves, and arch hypoplasia. Both phenotypes may be counseled for possible single ventricle palliation. We aimed to compare the rates of aortic valve annulus size and Z-score change over gestation by phenotype. We hypothesized that the …
Background: A recent multi-center study of perinatal outcome in fetuses with Ebstein anomaly or t... more Background: A recent multi-center study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD) found that 1/3rd of live-born patients (pts) died prior to hospital discharge. The purpose of this study was to explore differences in postnatal management and the relationship to outcome. Methods: This 23-center, retrospective study included 243 fetuses with EA/TVD from 2005 to 2011. Neonatal procedure (NP) was defined as surgery or interventional catheterization (cath) prior to discharge. Associations between postnatal management and outcome at discharge were explored. Results: Of 176 live-born pts, 7 received comfort care only, 11 died &amp;amp;amp;amp;lt;24 hrs of life, and 4 had insufficient data. Among 154 remaining pts, 38 (25%) did not survive to discharge. Pts who required ECMO at any point (n=18) had 83% mortality. More than half of pts (54%) did not have an NP, 34% had surgery, 8% had interventional cath, and 4% had both. The median age at 1st NP was 6 days (quartiles: 1-11). Survival did not differ between pts who had an NP and those who did not (70% vs. 80%; p=0.19) or between pts who had surgery and those who did not (68% vs. 80%; p=0.09). However, mortality differed by NP performed and whether pulmonary regurgitation, an indicator of high risk, was present prenatally (Figure). No pts with a right ventricular exclusion (RVE) died. Of 49 surviving neonates with ≥1 procedure, 28 (57%) were palliated with a shunt or RVE and 21 (43%) had a biventricular circulation. Thus, in total, 86 of 154 live-born pts (56%) survived with a biventricular circulation: 65 with medical management only and 21 with ≥1 NP. Conclusion: Among live-born pts diagnosed with EA/TVD in utero, a variety of postnatal management strategies were employed with overall poor outcomes. If surgery beyond PDA ligation is necessary, then RVE or other palliative procedure may need to be considered. A prospective, multi-center study utilizing a management algorithm would help elucidate the optimal strategy.
Introduction: Chromosomal microarray (CMA) testing for children with hypoplastic left heart syndr... more Introduction: Chromosomal microarray (CMA) testing for children with hypoplastic left heart syndrome (HLHS) has become common. While CMA-identified known genetic syndromes are often associated with increased mortality, the prognostic significance of variants of unknown significance (VUS) remains unknown. We sought to determine the spectrum, prevalence, and prognostic significance of CMA-associated VUSs in children with HLHS. Hypothesis: VUSs in HLHS are not associated with increased mortality compared to those with no copy number variation detected on CMA. Methods: Neonates with HLHS at our institution that underwent CMA testing prior to staged surgical palliation from June 2008 to December 2016 were reviewed. CMA results were abstracted and genome mapping conducted and compared against ostensibly healthy CNV (DGV genome browser). The primary outcome was death or cardiac transplant. Secondary endpoints were tracheostomy, feeding tube, requiring cardiopulmonary resuscitation or extracorporeal membrane oxyg...
Background: Dysfunctional intracellular Ca2+ handling has been implicated in adverse cardiac remo... more Background: Dysfunctional intracellular Ca2+ handling has been implicated in adverse cardiac remodeling leading to hypertrophy and failure. Recent evidence has linked mutations in the Ca2+ handling protein Junctophilin-2 (JPH2) with the development of hypertrophic cardiomyopathy (HCM). However, the mechanism remains unknown. Objective: To use advanced in vivo imaging modalities in conjunction with biochemical techniques to determine the mechanism of hypertrophic remodeling in a murine model hosting a novel JPH2 mutation. Methods and Results: 1. Pseudo-knockin (PKI) Mice: transgenic mice with the JPH2-A399S mutation (or WT JPH2) containing inducible shJPH2 were dosed with tamoxifen to knock down the combined levels of JPH2 to near WT expression. 2. MRI: A399S and WT PKI controls were imaged at 2 months post injection at which time body weight was similar for mutants (29.8±.81g) and controls (31.8±1.29g). Intragate (Bruker) was used to obtain FLASH cine images and EKG-gated tagged images were obtained to determine strain. MRI post-processing and measurements were performed using Amira and Diagnosoft software. A399S PKI mice exhibited significantly increased left ventricular mass (2.96±.21g/kg; n=4) compared to controls (2.27±.08g/kg; n=3) and max diastolic septal thickness (1.39±.05mm; n=9 versus 0.97±.00mm; n=4; P&amp;amp;amp;lt;0.01). Mutants trended toward decreased septal strain (-8.97±1.04; n=4) compared to the control (-10.28; n=1) indicative of reduced regional contractility 3. Biochemistry: stress markers were measured by qPCR. Average BNP was increased over 3 fold. Larger sample size is needed to reach significance. Western blot showed no significant change (p=.78) in phosphorylated Ca2+/calmodulin-dependent protein kinase II, which is often activated by aberrant Ca2+ signaling. Conclusions: Our data show that the JPH2-A399S mutation leads to septal hypertrophy in PKI mice. This suggests that defects in JPH2 are sufficient to induce pathological cardiac remodeling. Despite the role of JPH2 in Ca2+ handling, this form of hypertrophy does not appear to be mediated by traditional Ca2+ signaling. Further studies will focus on alternative Ca2+-dependent pathways to elucidate the molecular mechanisms of these hypertrophic changes.
Journal of Cardiovascular Electrophysiology, Jan 22, 2016
In pediatric patients with pacemakers implanted for atrioventricular block (AVB), nonsustained ve... more In pediatric patients with pacemakers implanted for atrioventricular block (AVB), nonsustained ventricular tachycardia (NSVT) detected during routine surveillance is a finding of unknown significance. We sought to describe the incidence of NSVT and determine if there was an association between NSVT and adverse outcomes in these patients. This is a single-center retrospective study of 136 patients (1971-2013) with pacemakers implanted for advanced and complete AVB. structural heart disease, diagnoses of myocarditis, cardiomyopathy or channelopathy preceding AVB diagnosis, and sustained or polymorphic ventricular tachycardia (VT) as the first occurring arrhythmia after pacemaker implant. During median follow-up of 11.6 years (IQR 4.3 years, 17 years), 14 (10%) patients had NSVT. There were 6 (4.4%) deaths. Overall, Kaplan-Meier 20-year survival from time of implant was 93%. By univariate analysis, earlier mortality was associated with NSVT (P = 0.010), sustained left ventricular (LV) dysfunction (P = 0.004), maternal autoantibodies (P = 0.017), and acquired AVB (P = 0.049). By multivariate analysis, earlier mortality was associated with NSVT (HR: 5.39 [95% CI: 1.02-28.41]; P = 0.047) and sustained LV dysfunction (HR: 10.24 [95% CI: 1.83-57.32]; P = 0.008). In children with pacemakers implanted for AVB, NSVT is not uncommon and may be associated with increased mortality. Persistent LV dysfunction may also be a potential factor associated with death. Closer follow-up should be considered in patients with these findings. Large, multicenter studies should be considered to confirm these findings and identify risk stratification methods for this unique patient population.
Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but... more Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10‐year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow‐up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P =0.026). Right ventricular dysfunction independently predicted overall morta...
World Journal for Pediatric and Congenital Heart Surgery, 2021
We present a case of fulminant myocarditis in a preterm neonate born to a SARS-CoV-2-infected mot... more We present a case of fulminant myocarditis in a preterm neonate born to a SARS-CoV-2-infected mother with COVID-19 disease. Despite complete separation after birth, cardiogenic decompensation initiated on day of life 7. Although the neonate tested negative for SARS-CoV-2, enterovirus viremia accompanied cardiac dysfunction, multiorgan failure, and neonatal death within 36 hours.
Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or ... more Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live‐born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23‐center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live‐born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live‐born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricu...
Loeys‐Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal,... more Loeys‐Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal, craniofacial, and cutaneous manifestations is caused by mutations in one of six genes (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3). Until recently, all reported cases of LDS have been attributed to heterozygous pathogenic variants in these genes. Here, we report the first case of Loeys‐Dietz syndrome due to SMAD3 biallelic likely pathogenic variants in a 15‐year‐old male with classic Loeys‐Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. To our knowledge, this represents the first reported case of biallelic SMAD3‐related Loeys‐Dietz syndrome and the third case in the literature of biallelic LDS, indicating that there are multiple genetic modes of inheritance underlying this disorder.
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