Combined Atrial Volume is Associated with Significant Atrial Arrhythmias in Total Cavopulmonary Connection Fontan Patients.

Atrial arrhythmias are a common late manifestation after Fontan palliation and are known to contribute to significant morbidity and mortality. Atrial volume by cardiac magnetic resonance imaging has been increasingly used in patients with congenital heart disease with no reports in those with Fontan palliation. In acquired heart disease, left atrial volume has been shown to be a strong predictor of outcomes of sustained atrial arrhythmias, including recurrence of atrial fibrillation. We hypothesized that combined atrial volume (CAV) in patients with total cavopulmonary connection (TCPC) Fontan palliation may be associated with increased risk of significant atrial arrhythmias (SAA). This is a single center retrospective case-control study. Cases were defined as patients with TCPC Fontan palliation ≥ 18 years of age, with SAA requiring intervention. Only those with advanced imaging for 3D rendering between 2013 and 2022 were included. CAV was analyzed from a 3-dimensional (3D) data set, including both the left and right atria, excluding the Fontan baffle. Seventeen TCPC Fontan case patients and 17 control patients were included. There was no difference in age between the two groups. There was no difference between gender, type of Fontan palliation, atrio-ventricular valve regurgitation, or combined ventricular function between the two groups. CAV was higher in SAA group compared to controls, and all control patients had indexed CAV ≤ 80 mL/kg. This is the first data suggesting CAV is associated with SAA in TCPC Fontan patients. Indexed CAV ≥ 80 mL/kg may be a valuable marker for SAA risk.

Mitral Valve Replacement in Pediatrics Using an Extracellular Matrix Cylinder Valve: A Case Series.

Mitral valve replacement (MVR) in children under 2 years is associated with significant morbidity and mortality. Decellularized porcine intestinal submucosa is a commercially available formulation of an extracellular matrix (ECM) with an indication for cardiac tissue repair. The present study reports our experience using ECM cylinder valves in patients for MVR. A retrospective review of patients under 2 years who underwent ECM custom-made cylinder mitral valve (ECM-MV) replacement was performed. Clinical, demographic, operative and post-operative follow-up data, including serial echocardiographic data are presented. Eight patients (age 5.6 ± 1.6 months; weight: 6.0 ± 1.1 kg) were identified who underwent ECM-MVR. There was one in-hospital death and no major neurological events. Six patients underwent replacement of their cylinder valve with either a Melody valve inside the ECM-MVR (n = 3), a mechanical valve (n = 2), or a decellularized bovine pericardial cylinder valve (n = 1). The mean time to replacement surgery was 8.4 ± 2.6 months after ECM-MV. The indications for replacement of ECM-MV included mitral stenosis/regurgitation (n = 4) or dehiscence (n = 2). One remaining patient is 24 months from ECM-MV, with trivial regurgitation and no stenosis. Mitral valve creation using ECM is an option for MVR in pediatrics, avoiding anticoagulation, and provides a suitable construct for later placement of a Melody valve, extending surgical and non-surgical options. However, the durability of the native ECM-MV in the mitral position is concerning considering the high re-intervention rate in a relatively short time period. Further studies are needed to determine the longer-term outcomes of this valve in this complex patient population.

Echocardiographic diagnosis of atrial flutter in a neonate.

A pregnant female presented at 37 weeks of gestation in labor. The fetus was noted to be tachycardic on fetal monitor. Postnatally, the male neonate was still noted to be tachycardic with heart rates in the low 200 bpm range. EKG was consistent with tachycardia, but rhythm diagnosis was not definitively made. Echocardiogram with M-mode analysis clearly demonstrated 2:1 atrial to ventricular contraction pattern consistent with atrial flutter. The neonate was subsequently transferred to a tertiary pediatric hospital where the diagnosis of atrial flutter was confirmed.

Three-Dimensional Reconstruction of Intracardiac Anatomy Using CTA and Surgical Planning for Double Outlet Right Ventricle: Early Experience at a Tertiary Care Congenital Heart Center.

BACKGROUND: Although transthoracic echocardiography (TTE) routinely establishes the diagnosis of double outlet right ventricle (DORV), it can be suboptimal for depicting exact ventricular septal defect (VSD) position, especially with respect to the outflow tracts. Advanced imaging with computed tomography angiography (CTA) can help visualize structures and relationships not easily seen by echo. Using computer-aided design, we have the ability to create three-dimensional (3D) models of the intracardiac anatomy, which can be helpful for better depicting the overall anatomy to assist surgical planning. METHODS: Patients with a diagnosis of DORV were retrospectively reviewed at our institution from October 2013 to April 2015. Patients who preoperatively underwent both TTE and CTA with 3D reconstruction of the intracardiac anatomy were included. Computed tomography angiography findings with 3D intracardiac model creation were compared to the surgical findings. RESULTS: Twenty-five patients underwent surgical repair of DORV during the study period. Five patients had CTA with 3D reconstruction, in addition to the standard TTE images, and were included in the study. In all five cases, CTA with 3D reconstruction of the intracardiac anatomy accurately depicted the VSD position relative to important adjacent structures, including the outflow tracts. CONCLUSION: Three-dimensional reconstruction of the intracardiac anatomy using CTA data can provide accurate data for presurgical planning of DORV repair and has the potential for being especially useful in patients for whom intracardiac anatomy and VSD position cannot be well seen by TTE. A larger prospective analysis is warranted to help validate this approach.

Divergent action potential morphologies reveal nonequilibrium properties of human cardiac Na channels.

OBJECTIVE: Fast inward Na current (I(Na)) carried by the voltage-gated Na channel (Na(V)1.5) is critical for action potential (AP) propagation and the rapid upstroke of the cardiac AP. In addition, a small fraction of Na(V)1.5 channels remains open throughout the plateau of the AP, and this current is termed as late I(Na). In patients with mutant Na(V)1.5-based congenital long Q-T (LQT) syndrome, mutant channels pass more late I(Na) compared to wild-type channels in unaffected patients. Although LQT mutant Na(V)1.5 channels are well studied, there is no careful evaluation of the effects of cardiac APs on early and late current. This is important with the recent documentation of nonequilibrium I(Na). METHODS: We measured AP-stimulated I(Na) through Na(V)1.5 wild-type and two LQT mutant channels (DeltaKPQ and N1325S). Three distinct AP morphologies were used: human embryonic stem cell-derived cardiac myocyte (hES-CM) APs with a relatively slow upstroke and canine endocardial and epicardial ventricular myocytes with rapid upstrokes. RESULTS: All three APs elicited both early and late I(Na). For wild-type Na(V)1.5, the hES-CM AP elicits more early and late I(Na) than either the endocardial or epicardial AP. The mechanism for this difference is that the hES-CM has a relative slow dV/dt(max) that causes a maximal open channel probability. Slower upstroke stimulation also allows greater Na flux through wild-type and N1325S channels, but not the DeltaKPQ mutant. CONCLUSIONS: The inherent gating properties of Na(V)1.5 provide natural tuning of optimal I(Na) density. Slower upstroke velocities can yield more I(Na) and Na flux in some Na(V)1.5 variants.

Mouse strain determines cardiac growth potential.

RATIONALE: The extent of heart disease varies from person to person, suggesting that genetic background is important in pathology. Genetic background is also important when selecting appropriate mouse models to study heart disease. This study examines heart growth as a function of strain, specifically C57BL/6 and DBA/2 mouse strains. OBJECTIVE: In this study, we test the hypothesis that two strains of mice, C57BL/6 and DBA/2, will produce varying degrees of heart growth in both physiological and pathological settings. METHODS AND RESULTS: Differences in heart dimensions are detectable by echocardiography at 8 weeks of age. Percentages of cardiac progenitor cells (c-kit+ cells) and mononucleated cells were found to be in a higher percentage in DBA/2 mice, and more tri- and quad-nucleated cells were in C57BL/6 mice. Cardiomyocyte turnover shows no significant changes in mitotic activity, however, there is more apoptotic activity in DBA/2 mice. Cardiomyocyte cell size increased with age, but increased more in DBA/2 mice, although percentages of nucleated cells remained the same in both strains. Two-week isoproterenol stimulation showed an increase in heart growth in DBA/2 mice, both at cardiomyocyte and whole heart level. In isoproterenol-treated DBA/2 mice, there was also a greater expression level of the hypertrophy marker, ANF, compared to C57BL/6 mice. CONCLUSION: We conclude that the DBA/2 mouse strain has a more immature cardiac phenotype, which correlates to a cardiac protective response to hypertrophy in both physiological and pathological stimulations.

Rem-GTPase regulates cardiac myocyte L-type calcium current.

RATIONALE: The L-type calcium channels (LTCC) are critical for maintaining Ca(2+)-homeostasis. In heterologous expression studies, the RGK-class of Ras-related G-proteins regulates LTCC function; however, the physiological relevance of RGK-LTCC interactions is untested. OBJECTIVE: In this report we test the hypothesis that the RGK protein, Rem, modulates native Ca(2+) current (I(Ca,L)) via LTCC in murine cardiomyocytes. METHODS AND RESULTS: Rem knockout mice (Rem(-/-)) were engineered, and I(Ca,L) and Ca(2+) -handling properties were assessed. Rem(-/-) ventricular cardiomyocytes displayed increased I(Ca,L) density. I(Ca,L) activation was shifted positive on the voltage axis, and ß-adrenergic stimulation normalized this shift compared with wild-type I(Ca,L). Current kinetics, steady-state inactivation, and facilitation was unaffected by Rem(-/-) . Cell shortening was not significantly different. Increased I(Ca,L) density in the absence of frank phenotypic differences motivated us to explore putative compensatory mechanisms. Despite the larger I(Ca,L) density, Rem(-/-) cardiomyocyte Ca(2+) twitch transient amplitude was significantly less than that compared with wild type. Computer simulations and immunoblot analysis suggests that relative dephosphorylation of Rem(-/-) LTCC can account for the paradoxical decrease of Ca(2+) transients. CONCLUSIONS: This is the first demonstration that loss of an RGK protein influences I(Ca,L) in vivo in cardiac myocytes.