Transannular patch repair of tetralogy of Fallot with or without monocusp valve reconstruction: a meta-analysis

Background Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases. Pulmonary regurgitation is the most common and severe comorbidity after transannular patch (TAP) repair of TOF patients. It has not been confirmed whether a TAP repair with monocusp valve reconstruction would benefit TOF patients in perioperative period compared to those without monocusp valve reconstruction. The purpose of the study is to review and analyze all clinical studies that have compared perioperative outcomes of TOF patients undergoing TAP repair with or without monocusp valve reconstruction and conduct a preferable surgery. Methods Eligible studies were identified by searching the electronic databases. The year of publication of studies was restricted from 2000 till present. The primary outcome was perioperative mortality, and secondary outcomes included cardiopulmonary bypass time, aortic cross-clamp time, ventilation duration, ICU length of stay, hospital length of stay, perioperative right ventricular outflow tract (RVOT) pressure gradient, and moderate or severe pulmonary regurgitation (PR). The meta-analysis and forest plots were drawn using Review Manager 5.3. Statistically significant was considered when p-value ≤ 0.05. Results Eight studies were included which consisted of 8 retrospective cohort study and 2 randomized controlled trial. The 10 studies formed a pool of 526 TOF patients in total, in which are 300 undergoing TAP repair with monocusp valve reconstruction (monocusp group) compared to 226 undergoing TAP repair without monocusp valve reconstruction (non-monocusp group). It demonstrated no significant differences between two groups in perioperative mortality (OR = 0.69, 95% CI 0.20–2.41, p = 0.58). It demonstrated significant differences in perioperative cardiopulmonary bypass time (minute, 95% CI 17.93–28.42, p < 0.00001), mean length of ICU stay (day, 95% CI − 2.11–0.76, p < 0.0001), and the degree of perioperative PR (OR = 0.03, 95% CI 0.010.12, p < 0.00001). Significant differences were not found in other secondary outcomes. Conclusion Transannular patch repair with monocusp valve reconstruction have significant advantages on decreasing length of ICU stay and reducing degree of PR for TOF patients. Large, multicenter, randomized, prospective studies which focuse on perioperative outcomes and postoperative differences based on long-term follow-up between TAP repair with and without monocusp valve reconstruction are needed.

A Case of Isolated Bicuspid Pulmonic Valve and Pulmonary Artery Aneurysm

A 33-year-old woman with a history of thyroid surgery for thyroid cancer and radioactive iodine therapy was referred for echocardiography due to dyspnea on exertion. Transthoracic echocardiography showed normal left ventricular size and function (the ejection fraction = 55%), a prolapsing mitral valve with redundant chordae, mild mitral regurgitation, a tricuspid aortic valve, mild aortic insufficiency, and mild tricuspid regurgitation. The most remarkable echocardiographic findings were moderate right ventricular dilation with mild systolic dysfunction, moderate right atrial dilation, an aneurysmal pulmonary artery (the main pulmonary artery = 47 mm), mild pulmonary stenosis (the peak gradient = 22 mmHg), and severe pulmonary regurgitation (the vena contracta = 6–7 mm and the pressure half time = 105 ms). Transesophageal echocardiography with the use of 3D modalities demonstrated a bicuspid pulmonic valve with doming and poor coaptation of the pulmonic valve leaflets (Figure 1). Additionally, a large patent foramen ovale was visualized in color Doppler (the flap separation = 2 mm and the tunnel length = 11 mm) with bubble passage in agitated saline injection. Bicuspid pulmonic valves constitute a rare finding, and they are most often associated with other congenital heart diseases. Isolated bicuspid pulmonic valves are extremely rare, with an incidence rate of about 0.1% in clinical practice.1 Pulmonary artery aneurysms also comprise a rare abnormality, with an incidence rate of approximately 1 in 14 000 cases in most studies.2 The association between bicuspid pulmonic valves and pulmonary artery aneurysms has been reported, and the pathophysiologic causes of this association include hemodynamic alterations due to bicuspid pulmonic valves and most likely the abnormal migration of neural crest cells.3 The diagnosis of a bicuspid pulmonic valve by 2D imaging is challenging and sometimes impossible. Using 3D echocardiography and reconstruction confers a better assessment of the pulmonic valve morphology and identification of bicuspid pulmonic valves.

Long-Term Outcomes After Melody Transcatheter Pulmonary Valve Replacement in the US Investigational Device Exemption Trial

Background: The Melody valve was developed to extend the useful life of previously implanted right ventricular outflow tract (RVOT) conduits or bioprosthetic pulmonary valves, while preserving RV function and reducing the lifetime burden of surgery for patients with complex congenital heart disease. Methods: Enrollment for the US Investigational Device Exemption study of the Melody valve began in 2007. Extended follow-up was completed in 2020. The primary outcome was freedom from transcatheter pulmonary valve (TPV) dysfunction (freedom from reoperation, reintervention, moderate or severe pulmonary regurgitation, and/or mean RVOT gradient >40 mm Hg). Secondary end points included stent fracture, catheter reintervention, surgical conduit replacement, and death. Results: One hundred seventy-one subjects with RVOT conduit or bioprosthetic pulmonary valve dysfunction were enrolled. One hundred fifty underwent Melody TPV replacement. Median age was 19 years (Q1–Q3: 15–26). Median discharge mean RVOT Doppler gradient was 17 mm Hg (Q1–Q3: 12–22). The 149 patients implanted >24 hours were followed for a median of 8.4 years (Q1–Q3: 5.4–10.1). At 10 years, estimated freedom from mortality was 90%, from reoperation 79%, and from any reintervention 60%. Ten-year freedom from TPV dysfunction was 53% and was significantly shorter in children than in adults. Estimated freedom from TPV-related endocarditis was 81% at 10 years (95% CI, 69%–89%), with an annualized rate of 2.0% per patient-year. Conclusions: Ten-year outcomes from the Melody Investigational Device Exemption trial affirm the benefits of Melody TPV replacement in the lifetime management of patients with RVOT conduits and bioprosthetic pulmonary valves by providing sustained symptomatic and hemodynamic improvement in the majority of patients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00740870.

First experiences with Myval Transcatheter Heart Valve System in the treatment of severe pulmonary regurgitation in native right ventricular outflow tract and conduit dysfunction

The rate of morbidity and mortality related to pulmonary regurgitation and pulmonary stenosis are big concerns after the surgery for CHD. Percutaneous pulmonary valve implantation has been established as a less invasive technique compared to surgery with promising results according to long-term follow-up of the patients. There are only two approved valve options for percutaneous pulmonary valve implantation until now, which are Melody (Medtronic, Minneapolis, Minn, USA) and Sapien (Edwards Lifesciences, Irvine, Ca, USA). Both valves have limitations and do not cover entire patient population. Therefore, the cardiologists need more options to improve outcomes with fewer complications in a such promising area. Herein, we present a case series applying for pulmonary position in conduits and native right ventricular outflow tract of a new transcatheter valve system Myval ® which is designed for transcatheter aortic valve implantation procedures. This is the first patient series in which the use of Myvalv in dysfunctional right ventricular outflow tracts is described, after surgical repair of CHD.

Single-cell RNA sequencing reveals that BMPR2 mutation regulates right ventricular function via ID genes

Mutations in bone morphogenetic protein type II receptor (BMPR2) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). Our study aimed to clarify whether deficient BMPR2 signalling acts through downstream effectors, inhibitors of DNA-binding proteins (IDs), during heart development to contribute to the progress of PAH in CHD patients. To confirm that IDs are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH, we generated Cardiomyocytes (CMs)-specific Id 1/3 knockout mice (Ids cDKO), and 12/25 developed mild PAH with altered haemodynamic indices and pulmonary vascular remodelling. Moreover, we generated ID1 and ID3 double-knockout (IDs KO) human embryonic stem cells that recapitulated the BMPR2 signalling deficiency of CHD-PAH iPSCs. CMs differentiated from induced pluripotent stem cells (iPSCs) derived from CHD-PAH patients with BMPR mutations exhibited dysfunctional cardiac differentiation and reduced Ca2+ transients, as evidenced by confocal microscopy experiments. Smad1/5 phosphorylation and ID1 and ID3 expression were reduced in CHD-PAH iPSCs and in Bmpr2+/– rat right ventricles. Moreover, Ultrasound revealed that 33% of Ids cDKO mice had detectable defects in their ventricular septum and pulmonary regurgitation. CMs isolated from the mouse right ventricles also showed reduced Ca2+ transients and shortened sarcomeres. Single-cell RNA(scRNA)-seq analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type (WT) cells. We found that BMPR2 signals through IDs and USP9X to regulate cardiac differentiation, and the loss of ID1 and ID3 expression contributes to CM dysfunction in CHD-PAH patients with BMPR2 mutations.

97 An unusual combination of rare congenital heart defects in a 70 years old lady complaining worsening dyspnea

Methods and results A 70-year-old woman presented to our outpatient clinic complaining of worsening dyspnoea in the last 3 months. She had a medical history of hypertension, diabetes, dyslipidemia, and paroxysmal atrial fibrillation. We performed a comprehensive evaluation starting with a transthoracic echocardiogram that showed a dilatation of right ventricle with normal function, severe pulmonary regurgitation, and moderate tricuspid regurgitation with estimated pulmonary artery systolic pressure of 55 mmHg; the left ventricle had normal dimension and function, with mild aortic and mitral regurgitation, and a subaortic membrane which caused a mild obstruction (maximum gradient 17 mmHg). The cardiac magnetic resonance (CMR) confirmed the enlargement of the right ventricle and of the pulmonary artery trunk (51 mm) and the severity of pulmonary regurgitation (regurgitant fraction of 41%). CMR also clearly showed the VSD just below the subaortic membrane and the left to right shunt with a jet that appeared to proceed straight from the left ventricle through the pulmonary valve (Figure 1A). The estimated Qp/Qs was 1.6 and no intramyocardial late enhancement was present. Pulmonary pressures and pulmonary vascular resistance were normal at the right heart catheterization and the Qp/Qs ratio calculated invasively was 1.45. Considering patient high-risk profile for coronary artery disease, a coronary angiography was also performed showing an abnormal origin of the right coronary artery (RCA) from the mid-portion of the left anterior descending coronary artery (LAD) with two significant stenosis: one involving the bifurcation of RCA and the other the mid-portion of the LAD (Figure 1B). The coronary computed tomography angiography (CCTA) showed a benign course of the RCA anterior to the pulmonary artery towards the auriculoventricular groove (Figure 1C, D). Taking into account all these findings, multidisciplinary heart team decided to perform a cardiac surgery intervention of pulmonary valve and trunk replacement, closure of ventricular septal defect and two coronary bypass grafts on LAD and RCA. Conclusions This case represents a combination of some rare congenital heart abnormalities where multimodality cardiovascular imaging techniques were essential to establish a proper diagnosis and to plan an adequate surgical repair. We hypothesize that the peculiar orientation of the VSD jet may have caused the pulmonary trunk dilatation considering that neither the shunt, nor the pulmonary pressure appear to have been of sufficient magnitude to cause it. Pulmonary ectasia and the damage inflicted by the jet to the cusps of the valve have led to the severe valvular insufficiency. While aortic and tricuspid regurgitation are known to be associated with VSD, to the best of our knowledge this is the first report of pulmonary regurgitation secondary to VSD.

Outcome and right ventricle remodelling after valve replacement for pulmonic stenosis

BackgroundComplications and need for reinterventions are frequent in patients with pulmonary valve stenosis (PVS). Pulmonary regurgitation is common, but no data are available on outcome after pulmonary valve replacement (PVR).MethodsWe performed a retrospective analysis of 215 patients with PVS who underwent surgical valvotomy or balloon valvuloplasty. Incidence and predictors of reinterventions and complications were identified. Right ventricle (RV) remodelling after PVR was also assessed.ResultsAfter a median follow-up of 38.6 (30.9–49.4) years, 93% of the patients were asymptomatic. Thirty-nine patients (18%) had at least one PVR. Associated right ventricular outflow tract (RVOT) intervention and the presence of an associated defect were independent predictors of reintervention (OR: 4.1 (95% CI 1.5 to 10.8) and OR: 3.6 (95% CI 1.9 to 6.9), respectively). Cardiovascular death occurred in 2 patients, and 29 patients (14%) had supraventricular arrhythmia. Older age at the time of first intervention and the presence of an associated defect were independent predictors of complications (OR: 1.0 (95% CI 1.0 to 1.1) and OR: 2.1 (95% CI 1.1 to 4.2), respectively). In 16 patients, cardiac magnetic resonance before and after PVR was available. The optimal cut-off values for RV volume normalisation were 193 mL/m2 for RV end-diastolic volume indexed(sensitivity 80%, specificity 64%) and 100 mL/m2 for RV end-systolic volume indexed(sensitivity 80%, specificity 56%).ConclusionsPrevious RVOT intervention, presence of an associated defect and older age at the time of first repair were predictors of outcome. More data are needed to guide timing of PVR, and extrapolation of tetralogy of Fallot guidelines to this population is unlikely to be appropriate.

Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage

Background: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF.Methods and Results: We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&amp;E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group.Conclusions: A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.

Congenital isolated absence of a single cusp of pulmonary valve

A 25-year-old, previously asymptomatic female, presented to the outpatient clinic with episodic palpitations for past 6 months. She was acyanotic and showed no peripheral stigmata of infective endocarditis. Transthoracic echocardiography revealed dilated right ventricle with severe low-pressure pulmonary regurgitation. A cardiac computed tomography angiography performed for evaluation of pulmonary arterial circulation and intracardiac anatomy revealed isolated absence of posterior pulmonary cusp. The two other (right anterior and left anterior) cusps were normal and covered only part of the valve orifice, resulting in pulmonary insufficiency. The main pulmonary artery showed asymmetric dilatation. No other structural heart defects were noted.