A Comparison of Perinatal Circulatory Transition in Critical Right and Left Heart Obstructive Lesions.

BACKGROUND: During perinatal transition in hypoplastic left heart syndrome (HLHS) reduced systemic (Qs) and cerebral blood flow and increased pulmonary flow (Qp) is observed, contributing to hemodynamic instability. In the current study, we explored whether similar or discordant perinatal changes occur in critical pulmonary outflow obstruction (POFO), when compared to HLHS and healthy controls. METHODS: Echocardiography was prospectively performed at 36-39 gestational weeks and then serially from 6-96 hours after birth prior to cardiac intervention. The combined cardiac output (CCO) superior vena cava (SVC), Qs and Qp flow-rates, and resistance indices (RI) in middle cerebral artery (MCA), celiac and superior mesenteric arterial were compared between the three groups. RESULTS: In fetal POFO (n=19) and HLHS (n=31), CCO was comparable to controls (n=21) due to elevated stroke volume, but CCO in POFO was lower compared to HLHS (p<0.01). Compared to controls, POFO CCO was lower at 6 hours post-delivery, but comparable at 24-96 hours. In contrast, from 6-96 hours the HLHS group had higher CCO than POFO and controls. Compared to controls, both POFO and HLHS neonates had lower Qs and SVC flow (POFO 24 hours (p<0.001), HLHS 6-hour Qs and 6-24-hour SVC flow). Compared to controls, Qp was increased in POFO at 48-96 hours (p< 0.05) and in HLHS at all time points (P<0.001). Compared to fetal MCARI, postnatal MCARI was acutely higher in both POFO and HLHS, whereas, in controls, it tended to decrease postnatally. Celiac artery RI and superior mesenteric artery pulsatility index were higher in POFO and HLHS from 6 to 48 hours versus controls. CONCLUSION: POFO and HLHS demonstrate divergent acute hemodynamic changes in the early neonatal period with early decreased CCO in POFO and increased CCO in HLHS. Both demonstrate early compromise in Qs and SVC (cerebral flow) and ongoing altered splanchnic flow.

Prenatal Diagnosis of Isolated Right Ventricular Non-Compaction Cardiomyopathy with an MYH7 Likely Pathogenic Variant.

Background: Noncompaction of ventricular myocardium is a cardiomyopathy that typically involves the left ventricle or both ventricles; it has often been associated with mutations in genes encoding sarcomere proteins. Little is known about isolated right ventricular noncompaction, as only a few cases have been reported. Case Report: A 30 year old G2P1 woman experienced a spontaneous fetal loss at 19 weeks and 4 days. An ultrasound examination at 19 weeks showed right ventricular and tricuspid valve abnormalities, ascites, and early hydrops. At autopsy, the right ventricular chamber was dilated with numerous prominent trabeculations and deep intrabecular recesses as well as a dysplastic tricuspid valve. Histologic examination confirmed isolated right ventricular noncompaction. Whole exome sequencing showed a likely pathogenic variant in the MYH7 gene. Conclusions: This appears to be the first report of isolated right ventricular noncompaction associated with a gene mutation as well as the first diagnosis in a fetus.

The Perinatal Transition and Early Neonatal Period in Hypoplastic Left Heart Syndrome Is Associated With Reduced Systemic and Cerebral Perfusion.

BACKGROUND: The impact of the striking perinatal circulatory changes on blood flow distribution have not to date been well examined in hypoplastic left heart syndrome (HLHS). This study aimed to document perinatal redistribution of cardiac output in HLHS compared with healthy control subjects, to further understand the impact of the perinatal transition on cerebral and systemic blood flow. METHODS: Prospectively recruited HLHS case subjects (n = 31) and healthy control subjects (n = 19) underwent serial echocardiography from late fetal stages to 96 hours after birth. Combined cardiac output (CCO), systemic, pulmonary, cerebrovascular, and splanchnic flow data were compared between neonates with HLHS and control subjects, and the impact of vasoactive support and positive pressure ventilation in HLHS patients was examined. RESULTS: In late gestation, CCO was similar between HLHS and control subjects, whereas middle cerebral artery (MCA) pulsatility index (PI) in HLHS was consistent with low cerebral vascular resistance. In the 96 hours after birth, CCO and pulmonary blood flow progressively increased in HLHS compared with control subjects (P < 0.001), and CCO was further increased in neonates with HLHS receiving vasoactive support (P = 0.01). Neonates with HLHS had reduced systemic and 6-24-hour superior vena cava (SVC) flow compared with control subjects (P < 0.001). Low systemic flow was further suggested by increased MCA and celiac artery PI at 6-48 hours in neonates with HLHS (P < 0.001). Systemic and SVC flow did not differ between those with and without vasoactive support. CONCLUSIONS: We provide quantitative echocardiographic evidence associating impaired cerebral and systemic blood flow with perinatal hemodynamic changes in the preoperative neonate with HLHS.

Fetal Diagnosis is Associated with Improved Perioperative Condition of Neonates Requiring Surgical Intervention for Coarctation.

To define the relative importance of fetal diagnosis and comorbidities in severity of preoperative compromise, outcomes and hospitalization in neonatal coarctation of the aorta (CoA). Retrospective comparison of preoperative condition and postoperative course of neonates prenatally (PreDx n = 48) or postnatally diagnosed (PostDx n = 67) with CoA. Congenital and non-congenital comorbidities were adjusted for. Postnatal diagnosis was associated with preoperative mortality (n = 2), and severe acidosis (lactate > 5 mM or pH < 7.20) on multivariate analysis (OR 4.2 (1.3-14.4, p = 0.02), with extracardiac congenital anomalies also a risk factor (OR 3.2 (1.03-10, p = 0.044). Median age at operation was delayed in the PostDx group (PreDx 6.5 days (IQR 4-9) vs PostDx 10 days (IQR 6-17)). Only comorbid left heart disease and extracardiac congenital anomalies were associated with prolonged total length of hospital stay. Prenatal diagnosis is the major adjustable risk factor affecting preoperative condition in critical CoA but does not reduce length of stay.

Effects of Early Myocardial Postnatal Maturation on Tolerance to Atrial Tachycardia With Altered Loading Conditions: An in vivo Swine Model.

Post-natal maturation of the myocardium starts shortly after birth and could affect how clinicians should provide hemodynamic support during this transition. Our aim was to assess the impact of post-natal maturation on tolerance to tachycardia with altered loading condition in a piglet model. Methods: We report three series of experimentations. Six groups of landrace cross neonatal piglets (NP) (1-3 days) and young piglets (YP) (14-17 days) were assigned to tachycardia (NP, YP), tachycardia and hypervolemia (NPV, YPV) or tachycardia and increased afterload (NPA, YPA) groups (n = 7/group). Under anesthesia, a pressure catheter was placed in the left ventricle and pacing wire in the right atrium. NPV and YPV groups had 60 ml/kg of normal saline infused over 20 min. NPA and YPA had balloon sub-occlusion of the descending aorta. Heart rate was increased by 10 bpm increments to 300 bpm. Left ventricular output was measured by echocardiography. Results: NP maintained left ventricular output throughout the pacing protocol but it decreased in the YP (p < 0.001). With volume loading both NPV and YPV maintained their output with tachycardia. Although increased afterload resulted in reduced output during tachycardia in NPA (p = 0.005), there was no added impact on output in YPA. Interestingly, 4 of 7 NPV had significant desaturation at 300 bpm (baseline 99.7% vs. 300 bpm 87.9%, p = 0.04), associated with a right to left shunt through the patent foramen ovale which resolved immediately on cessation of pacing. Conclusions: Early post-natal maturation is associated with improved myocardial tolerance to increased afterload and poor tolerance of tachycardia, the latter of which may be alleviated by increasing intravascular volume. These data could translate into the development of better strategies to optimize cardiac output at these early development ages.

Prenatal Detection, Comorbidities, and Management of Vascular Rings.

The 3-vessel and trachea view is now integrated into obstetrical screening and facilitates prenatal detection of vascular rings. We examined trends in prenatal detection, associated cardiac and extracardiac anomalies, and surgical management in this population. We reviewed a population-based cohort of pediatric vascular ring patients diagnosed prenatally and postnatally between 2002 and 2017 in Alberta, Canada. Of 106 cases, 28 (26%) had a prenatal diagnosis. Prenatal detection increased over time: 0/29 from 2002 to 2009, 4/28 (14%) from 2009 to 2011, 7/23 (30%) from 2012 to 2014, and 17/26 (65%) from 2015 to 2017 (p <0.01). The prenatal group more commonly had right aortic arch/left ductus/aberrant left subclavian artery (24/28vs 53/78, p = 0.04) and associated cardiac pathology (18/28vs 33/78, p = 0.05). The rate of genetic anomalies was overall higher than previously reported (34%) and did not differ between groups (11/28vs 25/78, p = 0.48). Those with a prenatal diagnosis were less likely to require cross-sectional imaging (9/28vs 48/78, p <0.01), modifying the vascular ring subtype diagnosis in 2 patients. Surgical intervention was common and did not differ between groups (24/28vs 66/78, p = 0.89). In conclusion, prenatal detection of vascular rings has increased. Despite differences in vascular ring subtype and associated cardiac pathology, the incidence of genetic anomalies and need for surgical intervention is not associated with timing of diagnosis. Genetic counseling should be universally offered. The diagnostic accuracy of echocardiography suggests additional imaging may not be routinely required.

Strain Rate in Children and Young Piglets Mirrors Changes in Contractility and Demonstrates a Force-Frequency Relationship.

BACKGROUND: In adult humans and pig models, strain rate (SR) correlates strongly with invasive measures of contractility but does not demonstrate a force-frequency relationship, which is a fundamental behavior of myocardial contraction. Given the considerable maturational changes of the myocardium from fetal stages to adulthood, extrapolation of adult findings to the young heart may not be appropriate. We sought to evaluate the SR response of the immature heart to increased heart rate (HR) and inotropic stimulation. METHODS: The study consisted of two parts. In part 1, children without obvious structural or functional cardiac abnormalities were evaluated following successful radiofrequency ablation. Echocardiography was performed at baseline HR and then with atrial pacing and isoprenaline infusion titrated to achieve 130% of baseline HR. Left ventricular (LV) speckle tracking-derived SR and tissue Doppler isovolumic acceleration (IVA, a load-independent marker of contractility) were measured. In part 2, young piglets were submitted to atrial pacing at 200, 230, and 260 bpm. Invasive LV dP/dt was assessed, and speckle tracking-derived SR was measured at all stages. Repeated measures analysis of variance was used for comparison with baseline values. RESULTS: In part 1, the LV SR and IVA (septal and lateral) in 23 children (ages 7.8-17.5 years) increased significantly with pacing and isoprenaline infusion (P < .001). In part 2, SR and invasive dP/dt increased significantly with increasing HR in young piglets (1-17 days; P < .01 and P < .001, respectively). Both LV SR and dP/dt plateaued at highest HRs concurrent with the decrease in LV end-diastolic dimension from baseline (73.0% ± 9.9% of the baseline value at 260 bpm; P < .001). CONCLUSIONS: SR in children is augmented with chronotropic and inotropic stimulation and in young infant piglets with chronotropic stimulation; in both children and piglets it has a force-frequency relationship, a behavior that is consistent with a measure of contractility.

Prenatal Diagnosis of the Criss-Cross Heart.

We sought to describe the prenatal features and postnatal outcomes of the "criss-cross heart" (CCH) with crossing atrioventricular connections as encountered in 5 cases and to review the literature regarding fetal diagnoses of this lesion. We reviewed the clinical history and fetal echocardiograms of 5 patients with a diagnosis of CCH encountered in our institution from 2010 to 2015. Affected pregnancies were identified through the University of Alberta fetal cardiology database. Fetal and postnatal echocardiograms, prenatal and postnatal clinical records, autopsy, and surgical reports were reviewed. Over the past 5 years, major fetal congenital heart disease was identified in 448 pregnancies in the province of Alberta. Of these, 5 had CCH. All 5 were referred for suspected congenital heart disease, and none had significant extracardiac pathology. Detailed methodical 2-dimensional and color Doppler fetal echocardiography defined the complex diagnoses that were subsequently confirmed postnatally (n = 4) and at fetal autopsy (n = 1). Prenatal diagnosis correctly predicted postnatal presentation and outcomes in 1 with double outlet right ventricle and coarctation, 2 presenting with complete (D) transposition of the great arteries physiology, and 1 presenting as corrected (L) transposition. Three required single ventricle palliation and 1 underwent an arterial switch procedure. In conclusion, detailed evaluation of fetal CCH can result in correct anatomical and pathophysiological diagnoses. It demands a full understanding of the anatomy and pathophysiology to predict accurately the presentation at birth for accurate counseling and planning perinatal management.

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment.

Doppler studies at rest suggest left ventricular (LV) diastolic function rapidly improves from the neonate to infant. Whether this translates to its response to hemodynamic challenges is uncertain. We sought to explore the impact of early LV maturation on its ability to tolerate atrial tachycardia. As tachycardia reduces filling time, we hypothesized that the neonatal LV would be less tolerant of atrial tachycardia. Landrace cross piglets of two age groups (1-3 days; NPs; 14-17 days, YPs; n = 7/group) were instrumented for an atrial pacing protocol (from 200 to 300 beats/min) and assessed by invasive monitoring and echocardiography. NPs maintained their LV output and blood pressure, whereas YPs did not. Although negative dP/dt in NPs at baseline was lower than that of YPs (-1,599 ± 83 vs. -2,470 ± 226 mmHg/s, respectively, P = 0.007), with increasing tachycardia negative dP/dt converged between groups and was not different. Both groups had similar preload reduction during tachycardia; however, NPs maintained shortening fraction while YPs decreased (NPs: 35.4 ± 1.4 vs. 31.8 ± 2.2%, P = 0.35; YPs: 31.4 ± 0.8 vs. 22.9 ± 0.8%, P < 0.001). Contractility measures did not differ between groups. Peak LV twist and untwisting rate also did not differ; however, NPs tended to augment LV twist through increased apical rotation and YPs through increasing basal rotation (P = 0.009). The NPs appear more tolerant of atrial tachycardia than the YPs. They have at least similar diastolic performance, enhanced systolic performance, and different LV twist mechanics, which may contribute to improved tachycardia tolerance of NPs.

Lone atrial fibrillation in the pediatric population.

BACKGROUND: There are few reports of pediatric studies of atrial fibrillation (AF). We sought to describe the clinical characteristics, management strategies, and recurrence rates and to identify predictors of AF recurrence in a contemporary pediatric population. METHODS: A retrospective review was performed of patients ≤ 18 years with lone AF who were seen at 4 pediatric institutions from 1996-2011. Patients with AF in the setting of thyroid disease, ventricular pre-excitation, coexisting congenital heart disease, or a history of cardiac surgery were excluded. Demographics, clinical presentation, investigations, treatment, and follow-up were analyzed. RESULTS: Forty-two patients were diagnosed with a first episode of lone AF, and 4 of these cases were later classified as persistent AF. Thirty-one (74%) were male patients, median age was 15.3 years, and median (interquartile range [IQR]) duration of AF episode was 12 (IQR, 7-24) hours. AF recurred in 39% (15 of 38) of patients. The Kaplan-Meier median time to estimated recurrence was 19 months. By univariate analysis, initial AF episode duration was associated with a higher risk of recurrence (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1-1.02; P = 0.034). Sex, age, family history, size of the left atrium, and history of cardioversion were not associated with recurrence. Recurrence with another supraventricular tachyarrhythmia (SVT) was observed in 6 of 38 (16%) patients, and 12 patients underwent electrophysiology (EP) study, with 6 patients receiving ablation. CONCLUSIONS: Our reported rate of recurrence of 39% is important when counseling pediatric patients and their parents on the expected course and treatment goals.