Long-Term Aortic Valve Function in Patients With or Without Surgical Treatment for Discrete Subaortic Stenosis.

The purpose of this study was to evaluate the long-term function of the aortic valve in patients with discrete subaortic stenosis (DSS), and its prognostic implications. 34 patients with the diagnosis of isolated DSS were treated at our pediatric heart center between 1992 and 2019. Demographic, echocardiographic and surgical data were analyzed. 26 patients had surgery to remove the subaortic membrane. The primary endpoint of this study was a change in the aortic valve function, secondary outcomes included functional class, aortic valve replacement, and reoperation due to recurrence of DSS. The mean post-operative follow-up time was 7.07 years (1-22.5). At the time of the most recent follow up, in the surgical group 11 patients (46%) had echocardiographic evidence of deterioration in their aortic valve insufficiency (AI) (p < 0.002). The deterioration was associated with a pre-operative left ventricular outflow tract (LVOT) gradient greater than 49 mmHg (p < 0.022). 8 patients with DSS were followed for a mean of 12.9 years (6.8-21.3), without meeting the criteria for surgical intervention, none showed any change in the aortic valve function during follow-up time. DSS resection may not prevent worsening of aortic valve insufficiency over time. Patients with stable AI and low LVOT gradient may not require surgery. Given these findings, it may be appropriate to carefully follow patients with new onset AI and low LVOT gradient, delaying surgical intervention.

Immune-Mediated Fetal Complete Atrioventricular Block: Can Dexamethasone Therapy Revert the Process?

BACKGROUND: Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation.

BACKGROUND: Truncus arteriosus (TA) accounts for ~1% of congenital heart defects. The aetiology of isolated TA is largely unknown but when occurring as part of a syndrome, it is mostly associated with chromosome 22q11 deletion. Vice versa, the most common congenital heart defects associated with chromosome 22q11 deletion are conotruncal malformations. In this study we investigated the cause of multiple conotruncal malformations accompanied by athymia in a consanguineous family. METHODS AND RESULTS: Whole exome analysis revealed a homozygous deleterious mutation in the NKX2-6 gene. CONCLUSIONS: NKX2-6 encodes a homeobox-containing protein which is expressed in mouse embryo at E8.0-E9.5 at the caudal pharyngeal arches and the outflow tract. A single missense mutation was previously implicated in the aetiology of familial isolated TA; however, null mice are entirely normal. The clear phenotype associated with a homozygous deleterious mutation in the present report, falls well within the spectrum of the cardiac defects seen in DiGeorge syndrome, is in agreement with NKX2-6 downstream location in the TBX1 signalling pathway and confirms NKX2-6 role in human cardiogenesis.

Two Novel Homozygous Desmoplakin Mutations in Carvajal Syndrome.

BACKGROUND: Mutations in various desmosomal proteins were shown to cause inherited forms of cardiomyopathy. Carvajal syndrome (Online Mendelian Inheritance in Man [OMIM] 605676) is characterized by the association of dilated cardiomyopathy, striate palmoplantar keratoderma, and woolly hair. It is caused by homozygous as well as heterozygous mutations in DSP, which encodes the desmosomal plaque protein desmoplakin. An overlapping cardiocutaneous phenotype was also described with homozygous mutations in genes encoding two other desmosomal proteins; plakoglobin (Naxos disease; OMIM 601214) and desmocollin-2 (OMIM 610476). METHODS: We performed clinical and molecular workups in two consanguineous Arab Palestinian families manifesting an autosomal recessive pattern of inheritance of the above mentioned clinical findings. Whole exome sequencing was employed in the search for the causing mutation. RESULTS: Affected family members suffered from biventricular involvement and arrhythmogenic right ventricular dysplasia based on echocardiography and magnetic resonance imaging. One patient who underwent implantation of an implantable cardioverter-defibrillator (ICD) is still alive at the age of 59 years. Whole exome sequencing revealed two novel homozygous mutations in DSP, each affecting one family. CONCLUSIONS: The association of woolly hair with palmoplantar keratoderma in a child should lead to a cardiac workup in the search for those at increased risk for sudden cardiac death. Early diagnosis and ICD implantation may be lifesaving. Whole exome sequencing should be utilized for rapid genetic analysis since the cardiocutaneous phenotype may result from mutations in one of several genes.

Intracardiac echogenic foci have no hemodynamic significance in the fetus.

Intracardiac echogenic foci (ECFs), probably representing microcalcifications of the papillary muscles, are a common finding in fetal ultrasonic screening examinations. Their significance is unclear, and their value as markers for chromosomal anomalies is debatable. It also is unknown whether ECFs predict abnormal cardiac performance. This prospective study analyzed and compared the systolic and diastolic properties of the heart in 28 fetuses with ECFs and 70 fetuses without ECFs using both conventional and novel myocardial deformation methods. The findings suggest that left-sided ECFs do not predict depressed left- or right-side systolic or diastolic properties in the fetus. A longitudinal study that would follow ECF fetuses into their childhood is warranted to confirm the findings of this study.

Surgical Treatment of Palestinian Patients With Congenital Heart Disease in a Medical Center in Israel: Challenges and Outcome.

BACKGROUND: The treatment of congenital heart disease patients in the West Bank and Gaza involves both medical and political challenges. Understanding the difficulties faced in treating the Palestinian population is an important step to improving surgical care, better allocating resources and overcoming the region's unique problems. METHODS: The Hadassah Medical Center congenital heart disease database over the 2011-2017 period was analyzed. There were 872 operations performed in patients with Israeli health insurance and 207 operations in Palestinian patients. Patient characteristics and surgical outcome were compared between the two groups using standard statistical practices. FINDINGS: The Society of Thoracic Surgeons Complexity Scores were significantly higher in the Palestinian patients, p = 0.003 (d = 0.27, 95% CI, 0.12 to 0.42). Israeli neonates had surgery at an average age of 9.5 ±â€¯7.8 days as compared to Palestinian neonates with an average age of 15.7 ±â€¯8.2 days, p < 0.001 (d = 0.78, 95% CI, 0.41 to 1.15), a finding indicative of a possible delay of treatment. Overall in hospital mortality was not significantly different. Late mortality was significantly higher for the Palestinian 5.4% (9/168) compared to Israeli patients 2% (14/698), p = 0.015 (RR = 2.67, 95% CI, 1.18 to 6.07). INTERPRETATION: The findings suggest that Palestinian patients receive later treatment and poorer follow-up care than Israeli patients. Despite the political challenges in the region surgical results are excellent and comparable between the two groups. The challenges described are not unique to congenital heart disease and may affect many medical fields. We believe that extensive collaborations between Israeli and Palestinian physicians may be key to improving the Palestinian medical care. FUNDING: None.

Prevalence of persistent superior vena cava and association with congenital heart anomalies.

A contralateral persistent superior vena cava (PSVC) can occur in a normal child or in association with congenital heart defects (CHDs). Its prevalence has been demonstrated in relatively small cohorts. We aim to assess the frequency of a PSVC in a large cohort of children with and without CHDs. To estimate its significance, we have searched for a PSVC in all children referred for echocardiography in our institution during a 16.5-year period. A group of 17,219 children comprised 8,140 children with a structural heart anomaly and 9,079 children with a structurally normal heart. Association between a PSVC and specific classes of CHD were looked for. A total of 288 children (1.7%) had a PSVC; 0.56% (51 of 9,079) in the normal heart group and 2.9% (237 of 8,140) in the congenital heart anomalies group. Odds ratio for having heart anomaly in the presence of PSVC was 5.2 (95% confidence interval 3.7 to 7.0). A PSVC was above all associated with atrioventricular septal defects, conotruncal malformations, and left-sided defects. The odds ratio of having PSVC in the aforementioned malformations compared with the normal heart group was 23.8, 13.6, and 11.0, respectively. In conclusion, although present in normal subjects, PSVC was more often associated with congenital heart and other anomalies, especially with atrioventricular septal defects, conotruncal malformations, and left-sided defects.

Search for the azygos: a lesson learnt from a case with left superior vena cava, esophageal atresia and tracheo-esophageal fistula.

The azygos vein is of superior importance during the operation for esophageal atresia with tracheo-esophageal fistula (EA; TEF). Its location helps the surgeon to locate the fistula. Newborns with persistent left superior vena cava (LSVC) may have alterations in the location of the azygos, and since LSVC is not uncommon in EAs with fistulae, it is important to locate the azygos during a pre-operative echocardiogram. Foreknowledge of a possible absent azygos may avoid morbidity while trying to locate the fistula. We present a case of a newborn with EA, TEF, and LSVC in which the azygos vein was absent.

Analysis of segmental and global function of the fetal heart using novel automatic functional imaging.

BACKGROUND: Functional assessment of the fetal heart has always been a challenge. Automatic functional imaging (AFI), a novel non-Doppler methodology based on 2-dimensional acoustic markers tracking, measures myocardial deformation regardless of angle of interrogation. Thus, we studied the validity of AFI in segmental and global assessment of myocardial function in the fetus. METHODS: AFI-based myocardial deformation parameters including segmental tissue velocity, strain, and strain rate as well as biventricular global strain and strain rate were measured from raw scan-line data obtained from 28 normal fetuses (20-38, median 28 weeks of gestation). Interobserver and intraobserver variability was analyzed. AFI data were compared with analogous Doppler-derived tissue velocity imaging parameters measured in the same 28 fetuses. RESULTS: AFI was feasible in 94% of the fetuses studied with high reproducibility. AFI-based tissue velocity (3.9 +/- 1 cm/s) was comparable with tissue velocity imaging-based velocity (4 +/- 1.6 cm/s) in the right ventricle and in the left ventricle (AFI velocity 3.3 +/- 0.6 vs tissue velocity imaging 3.1 +/- 0.9 cm/s). Strain rate obtained by these two methods was also similar. Biventricular global strain and strain rate measured 16 +/- 4% and 1.6 +/- .5 seconds(-1), respectively. Tissue velocity increased whereas segmental strain rate decreased throughout gestation. Strain remained unchanged. Global strain rate significantly decreased with gestational age (r = -0.7). CONCLUSION: AFI, a novel non-Doppler methodology, allows fast and accurate quantification of segmental and global myocardial function in the fetus. AFI-based tissue velocity increases with gestational age whereas segmental and the new parameter global strain rate decrease throughout gestation.