Differential Requirement of DICER1 Activity during Development of Mitral and Tricuspid Valves

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. We specifically inactivated Dicer1 in the endocardium during cardiogenesis, and unexpectedly found that Dicer1-deletion caused congenital mitral valve stenosis and regurgitation, while it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA Sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. Our study thus reveals miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

Biventricular non-compaction cardiomyopathy and tricuspid hypoplasia in a novel non-POU domain-containing octamer-binding gene variant

A maternally inherited novel pathogenic non-POU domain-containing octamer-binding gene variant c.767G>T, p.R256I [NM_001145408], manifested in a male infant as dilated cardiomyopathy with severe left ventricular dysfunction and dilation, biventricular non-compaction, tricuspid hypoplasia, and hydrocephaly. To the best of our knowledge, no previous non-POU domain-containing octamer-binding gene variants with biventricular non-compaction have been associated with tricuspid valve hypoplasia. Hence, this case introduces a new pathogenic variant observed in the non-POU domain-containing octamer-binding gene and adds to the range of cardiac phenotypes identified in non-POU domain-containing octamer-binding gene variants.

A case of early thrombosis following a percutaneous tricuspid valve in valve implantation managed by thrombolysis

Bioprosthetic valve thrombosis is a growing recognized entity, especially with the increasing use of the valve in vale procedures and the advent of new detection technologies (e.g., 4D CT and 4D echocardiography). However, the optimal management strategy in the acute context is not established. This paper presents a case of early thrombosis following the percutaneous tricuspid valve in vale procedure that was successfully managed with thrombolysis.

Dual Atrial Rhythms: A Case Report Of An Unusual Cause Of Pacemaker Syndrome

Background Atrial dissociation (AD) is described as the existence of two simultaneous electrically isolated atrial rhythms. Theoretically, detection of dual atrial rhythms with a sufficiently high rate by pacemaker can lead to automatic mode switching and associated pacemaker syndrome. Such a clinical observation has not been reported before in the literature. Case Summary An 87-year-old female with Ebstein’s anomaly status post tricuspid valve annuloplasty and tricuspid valve replacement and a dual chamber pacemaker presented with congestive heart failure one week after undergoing atrial lead revision. Interrogation of her dual chamber pacemaker revealed two atrial rhythms: sinus or atrial-paced rhythm and electrically isolated atrial tachycardia (AT). Sensing of both atrial rhythms by the pacemaker led to automatic mode switching, which manifested as ventricular paced rhythm with retrograde P waves on electrocardiogram (ECG). Adjusting the atrial lead sensitivity to a level higher than the sensing amplitude of AT restored atrial paced and ventricular sensed rhythm, which resulted in resolution of heart failure symptoms. Discussion Regardless of the cause of AD, there must be electrical insulation between the two rhythms for their independent coexistence in the atria. AD can lead to pacemaker syndrome from automatic mode switching. If the sensing amplitude during sinus rhythm is significantly larger than that of AT, adjusting the atrial lead sensitivity would solve the issue, as in the present case. Otherwise, atrial lead revision, pharmacotherapy or AT ablation should be considered.

Impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in patients with Ebstein anomaly and tricuspid valve dysplasia

Objectives: To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia. Methods: Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed. Results: Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows. Conclusions: All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.

A Comparison of the Electrophysiological and Anatomic Characteristics of Pacing Different Branches of the Left Bundle Conduction System

Introduction: Left bundle branch pacing (LBBP) is a rapidly growing conduction system pacing technique. However, little is known regarding the electrophysiological characteristics of different types of LBBP. We aimed to evaluate the electrophysiological characteristics and anatomic lead location with pacing different branches of the left bundle branch.Methods: Consecutive bradycardia patients with successful LBBP were enrolled and classified into groups according to the paced electrocardiogram and the lead location. Electrocardiogram, pacing properties, vectorcardiogram, and lead tip location were analyzed.Results: Ninety-one patients were enrolled, including 48 with the left bundle trunk pacing (LBTP) and 43 with the left bundle fascicular pacing (LBFP). The paced QRS duration in the LBTP group was significantly shorter than that in the LBFP group (108.1 ± 9.9 vs. 112.9 ± 11.2 ms, p = 0.03), with a more rightward QRS transition zone (p = 0.01). The paced QRS area in the LBTP group was similar to that during intrinsic rhythm (35.1 ± 15.8 vs. 34.7 ± 16.6 μVs, p = 0.98), whereas in the LBFP group, the paced QRS area was significantly larger compared to intrinsic rhythm (43.4 ± 15.8 vs. 35.7 ± 18.0 μVs, p = 0.01). The lead tip site for LBTP was located in a small fan-shaped area with the tricuspid valve annulus summit as the origin, whereas fascicular pacing sites were more likely in a larger and more distal area.Conclusions: Pacing the proximal left bundle main trunk produced better electrical synchrony compared with pacing the distal left bundle fascicles. A visualization technique can facilitate achieving LBTP.