Outflow Tract Research Articles

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.

P072 VALIDATION OF A NOVEL METHOD FOR NONINVASIVE ESTIMATION OF CARDIAC OUTPUT USING BRACHIAL OSCILLOMETRIC BLOOD PRESSURE MEASUREMENTS IN PATIENTS WITH VARIOUS CLINICAL CONDITIONS

Background and Objective: Estimating cardiac output (CO) and other hemodynamic parameters from blood pressure (BP) measurements could aid in selecting appropriate antihypertensive treatments in clinical settings. Our research group has developed a non-invasive method to estimate CO based on total arterial compliance (Ct). However, its validity in populations with various cardio-metabolic chronic diseases remains uncertain. The objective of this study is to assess the validity of our CO estimation method across different patient with varied clinical conditions. Methods: A cross-sectional study was conducted involving 217 adult patients who underwent ambulatory transthoracic Doppler echocardiograms, irrespective of valvular or cardiac pathology, or medication use, provided they had normal aortic valvular anatomy. Stroke volume was calculated as the product of the cross-sectional area of the aortic annulus and the average velocity of the left ventricular outflow tract. Simultaneously, oscillometric BP measurements were obtained. Subsequently, the CO values obtained via Doppler echocardiography and those estimated based on Ct were compared to determine validity. Ct was estimated as: Ct/BSA= 38/PPth + 4/5 × Td/T - 3/7, where BSA denotes body surface area, Td signifies diastolic time, T represents the cardiac period, and PPth refers to the theoretical pulse pressure. Results: Of the participants, 49.7% were men, with an average age of 54.0±14.0 years. Among them, three had a history of acute myocardial infarction, one had a pacemaker, nineteen were diabetic, and one hundred thirty-six were hypertensive. CO by echocardiography averaged 4.9±1.0 L/min, ranging from 2.0 to 8.5 L/min. The agreement of CO between the new method and Doppler echocardiography was good. Bland-Altman plots showed that the differences between the methods were randomly distributed along the mean difference line (Figure). Conclusions: The novel method for noninvasive estimation of CO based on Ct with brachial oscillometric BP measurements in patients with various clinical conditions is deemed valid. Its implementation in clinical practice has the potential to transform patient assessment.

ENDOVASCULAR ANGIOPLASTY FOR REPEATED REVASCULARIZATION OF THE ARTERIAL BED IN PATIENTS WITH RECURRENT CHRONIC ARTERIAL INSUFFICIENCY

Aim. To improve the results of repeated reconstruction of the great vessels in case of relapse of chronic arterial insufficiency by differentiated use of popliteal tibial autovenous bypass grafting and endovascular angioplasty for revascularization of the arteries of the leg. Materials and methods. The long-term results of surgical treatment of 522 patients were examined, including 353 patients with bilateral atherosclerotic occlusion of the aortic-femoral zone and 159 patients with unilateral occlusion of the ileo-femoral segment. At the primary surgical intervention, 98 patients were diagnosed with chronic arterial insufficiency (CAI) of stage II B, in 228 – CAI of stage III, in 196 – chronic critical ischemia of the lower extremities, stage III – IV. In the long-term postoperative period, 146 (27.97 %) late complications were diagnosed, of which 78 (56.1 %) had a relapse of chronic arterial insufficiency. In 36 patients, CAI stage II B was established, and in 42 – CAI stage III. Patients were re-operated in the period of 5.4 ± 1.9 years after primary revascularization. All men were 64.4 ± 3.1 years old. Results. The multilevel atherosclerotic lesions of the reconstructed arterial bed, cicatricial changes after the initial surgical intervention, progressive atherosclerotic lesions of the outflow tract required multi-story shunting operations. The success of shunting surgery depends on sufficient revascularization of the outflow paths – the arterial bed of the ankle segment. Revascularization of the distal arterial bed was achieved using popliteal-tibial autovenous bypass grafting (19 cases) and endovascular angioplasty (30 observations). To reduce peripheral vascular resistance and increase the volume of the peripheral vascular bed in 19 (63.3%) cases, endovascular balloon angioplasty of two tibial arteries was performed simultaneously. The postoperative period in 10 (12.8%) patients was complicated by the development of thrombosis of the reconstruction segment. In 7 cases, thrombosis of the reconstruction segment was eliminated. The using of popliteal-tibial autogenous bypass grafting and endovascular angioplasty during revascularization of the ankle segment provided satisfactory results in repeated reconstructive operations in 87.2 % of cases. Conclusions. For the revascularization of the lower leg arteries, the use of popliteal autovenous shunting and endovascular angioplasty provides 87.2% satisfactory results in repeated reconstructive operations for chronic arterial insufficiency relapse.

Cardiac biomarker profiles in dogs with naturally occurring precapillary pulmonary hypertension

Introduction/ObjectivesThis study evaluated circulating amino-terminal pro-B-type natriuretic peptide (NT-proBNP), amino-terminal pro-A-type natriuretic peptide (NT-proANP), and cardiac troponin I (cTnI) concentrations in dogs with precapillary pulmonary hypertension (Pre-PH) and control dogs with respiratory clinical signs but no Pre-PH. AnimalsTwenty-six dogs (17 affected, and 9 controls) were involved in the study. Materials and MethodsThis was a sub-study of a large prospective single-center observational study. Dogs underwent blood sample collection, physical examination, and echocardiographic evaluation. Pre-PH was diagnosed when a calculated right ventricular-to-right atrial pressure gradient (RV:RA PG) measuring ≥40 mmHg was identified echocardiographically, barring right ventricular outflow obstruction and/or left-sided cardiac disease. ResultsTwo, nine, and six dogs had mild, moderate, and severe Pre-PH, respectively. Plasma concentrations of NT-proBNP, NT-proANP, and cTnI were significantly higher in the affected group than in the control group (P=0.020, P=0.009, P=0.011, respectively). There was a positive correlation between RV:RA PG and NT-proBNP (r = 0.52), NT-proANP (r = 0.54), and cTnI (r = 0.67) concentrations. DiscussionPre-PH should be included in the differential diagnosis list of elevated cardiac biomarker concentrations in dogs with respiratory signs. Study LimitationsStrict selection criteria reduced group sizes. There were rare missing data points. The diagnosis of Pre-PH was obtained from Doppler echocardiographic RV:RA PG. The disease process causing Pre-PH was not evaluated histopathologically. ConclusionsCirculating cardiac biomarker concentrations are increased in dogs with Pre-PH and there is a positive correlation between RV:RA PG and NT-proBNP, NT-proANP, and cTnI concentrations.

Rupture of a calcified right ventricle to pulmonary artery homograft by balloon dilation– emergency rescue by venus P-Valve

BackgroundPercutaneous pulmonary valve implantation (PPVI) is a recognized alternative treatment to surgery for patients with dysfunctional right ventricular outflow tracts. Patient selection is essential to avoid serious complications from attempted treatment, such as rupture or dissection, especially of the calcified outflow tracts. We describe a case with an unexpected rupture of a calcified homograft valve and main pulmonary artery, which was treated successfully by emergency implantation of a self-expanding Venus P-Valve (Venus MedTech, Hangzhou, China) without the need for pre-stenting with a covered stent.Case detailsA 13-year-old boy had two previous operations of tetralogy of Fallot, one a total repair and the other a homograft valved conduit for pulmonary regurgitation. He presented with dyspnea and severe right ventricular outflow tract obstruction (RVOTO) and had a calcified outflow tract and main pulmonary artery. In the catheter laboratory, a non-compliant balloon dilation resulted in a contained rupture of the conduit. The patient remained hemodynamically stable, and the rupture was treated with a self-expandable Venus P-Valve without the need for a covered stent combined with a balloon-expandable valve or a further surgical procedure.DiscussionPreprocedural evaluation with an inflating balloon is necessary to examine tissue compliance and determine suitability for PPVI. However, this condition is accompanied by a risk of conduit rupture. Risk factors of this complication are calcification and homograft use. These ruptures are mostly controlled with a prophylactic or therapeutic covered stent, with a low rate of requiring surgery. However, there are severe ruptures which lead to hemothorax and death. In the available literature, there was no similar reported case of conduit rupture, which a self-expandable Pulmonary valve stent has managed. It seems that fibrosis and collagen tissue around the heart, formed after open surgeries, can contribute to the control of bleeding in these cases.Conclusion (clinical Learning Point)The suitability of patients for the PPVI procedure should be examined more carefully, specifically patients with homograft and calcification in their conduit. Furthermore, conduit rupture might be manageable with self-expandable artificial pulmonary valves, specifically in previously operated patients, and the applicability of this hypothesis is worth examining in future research.

Computational modeling of left ventricular flow using PC-CMR-derived four-dimensional wall motion.

Intracardiac hemodynamics plays a crucial role in the onset and development of cardiac and valvular diseases. Simulations of blood flow in the left ventricle (LV) have provided valuable insight into assessing LV hemodynamics. While fully coupled fluid-solid modelings of the LV remain challenging due to the complex passive-active behavior of the LV wall myocardium, the integration of imaging-driven quantification of structural motion with computational fluid dynamics (CFD) modeling in the LV holds the promise of feasible and clinically translatable characterization of patient-specific LV hemodynamics. In this study, we propose to integrate two magnetic resonance imaging (MRI) modalities with the moving-boundary CFD method to characterize intracardiac LV hemodynamics. Our method uses the standard cine cardiac magnetic resonance (CMR) images to estimate four-dimensional myocardial motion, eliminating the need for involved myocardial material modeling to capture LV wall behavior. In conjunction with CMR, phase contrast-MRI (PC-MRI) was used to measure temporal blood inflow rates at the mitral orifice, serving as an additional boundary condition. Flow patterns, including velocity streamlines, vortex rings, and kinetic energy, were characterized and compared to the available data. Moreover, relationships between LV wall kinematic markers and flow characteristics were determined without myocardial material modeling and using a non-rigid image registration (NRIR) method. The fidelity of the simulation was quantitatively evaluated by validating the flow rate at the aortic outflow tract against respective PC-MRI measures. The proposed methodology offers a novel and feasible toolset that works with standard PC-CMR protocols to improve the clinical assessment of LV characteristics in prognostic studies and surgical planning.

Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock: prognosis and treatment

BackgroundPatients with Takotsubo syndrome (TTS) who develop cardiogenic shock may present with left ventricular outflow tract obstruction (LVOTO). The prognosis and treatment of this population have not been defined in...

Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the H2FPEF score.

The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0-1), intermediate (2-5) and high (6-9) H2FPEF score. The primary combined endpoint was a composite of all-cause death and HF admissions, while the secondary endpoints were all-cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow-up (median 90 months [interquartile range 49-176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event-free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157-2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076-11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133-2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005-1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612-4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908-7.134; p < 0.001) were independently associated with the primary combined endpoint. The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.

Lipomatous hypertrophy of the interatrial septum: A benign cardiac mass.

Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare but benign cardiac tumor that can be found on cardiac imaging such as echocardiogram, or during surgery or an autopsy. Cardiac MRI is the best imaging modality to determine the borders of the tumor and its extension into the intraventricular septum and ventricular free wall. Patients require close monitoring because LHIS may cause right or left outflow tract obstruction or superior vena cava obstruction, requiring cardiac surgical intervention. This article describes a patient with LHIS who underwent cardiac surgery because of her increasing symptomatology.

Evolution of cardiac tissue and flow mechanics in developing Japanese Medaka.

The effects of pressure drop across cardiac valve cushion regions and endocardial wall strain in the early developmental stages of a teleost species heart are poorly understood. In the presented work, we utilize microscale particle image velocimetry (μPIV) flow measurements of developing medaka hearts from 3 to 14 dpf (n = 5 at each dpf) to quantify the pressure field and endocardial wall strain. Peak pressure drop at the atrioventricular canal (ΔPAVC) and outflow tract (ΔPOFT) show a steady increase with fish age progression. Pressure drops when non-dimensionalized with blood viscosity and heart rate at each dpf are comparable with measurements in zebrafish hearts. Retrograde flows captured at these regions display a negative pressure drop. A novel metric, Endocardial Work (EW), is introduced by analyzing the ΔPAVC-strain curves, which is a non-invasive measure of work required for ventricle filling. EW is a metric that can differentiate between the linear heart stage (< 100 Pa-%), cardiac looped chamber stage (< 300 Pa-%), and the fully formed chamber stage (> 300 Pa-%).

Concomitant Dynamic, Fixed Left Ventricular Outflow Tract Obstruction and Mitral Regurgitation: A Triple Jet to Decipher

Concomitant Dynamic, Fixed Left Ventricular Outflow Tract Obstruction and Mitral Regurgitation: A Triple Jet to Decipher

Comparison Between Heart Failure Without Left Ventricular Systolic Dysfunction and Progression to End-Stage in Hypertrophic Cardiomyopathy.

The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated. This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD. In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Integrated prenatal and postnatal management for neonates with transposition of the great arteries: thirteen-year experience at a single center

BackgroundTransposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates.MethodsA total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals.ResultsThe population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO.ConclusionEarlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

A novel functional index, aortic-valve-coefficient, for assessing aortic-stenosis in patients undergoing TAVR: A prospective-pilot study

BackgroundEvaluating the severity of aortic stenosis (AS) can be challenging, particularly in patients with low-gradient (LG, Δp < 40 mmHg) AS. Objective: This study aims to improve the accuracy of assessing severity of AS using a novel functional index- Aortic Valve Coefficient (AVC). The AVC is defined as ratio of mean transvalvular pressure-drop (Δp) to the proximal dynamic pressure (1/2 × blood density × VLVOT2; VLVOT: left ventricular outflow tract peak velocity). Hypothesis: AVC, developed from fundamental fluid dynamic principles, is a better index for accessing AS severity as it incorporates square of VLVOT and downstream pressure recovery. MethodsThis pilot prospective study enrolled 47 patients undergoing TAVR for AS. Using cardiac-catheterization-measured Δp and echocardiography-Doppler-derived VLVOT, AVC was evaluated. Pre- and post-TAVR pressure-velocity measurements were obtained, resulting in a dataset with 78 data points, including 32 data points specifically linked to LG AS. Linear regression analysis was performed to correlate AVC with Δp, VLVOT and aortic-valve-area. Welch 2-sample t-test was carried out to compare the means of AVC against aortic-valve-area. ResultsModerate correlation (r = 0.85) was observed between AVC and aortic-valve-area indicating AVC could be a prospective index. However, correlation decreased (r = 0.75) in LG AS patients, indicating increased discordancy. Comparing AVC and aortic-valve-area in LG AS patients with left ventricular ejection fraction (LVEF) < 50 % and LVEF ≥50 %, t-test showed that AVC values are significantly different (p < 0.05) as compared to aortic-valve-area (p = 0.48). ConclusionAVC, a novel index, has the potential to improve assessment of AS severity and clinical decision making for treating patients with AS. Condensed abstractComplex hemodynamics, such as paradoxical “low-flow low-gradient (LG)” Aortic stenosis (AS) can be difficult to diagnose. Currently, mean transvalvular pressure-drop and flow-derived aortic-valve-area assess AS severity. Aortic valve coefficient (AVC) is a novel index which combines both pressure-drop and flow measurements to assess the severity of AS. A total of 47 patients (72 data points) were studied undergoing TAVR. In LG AS patients, t-test comparing left ventricular ejection fraction (LVEF) < 50 % and LVEF ≥50 % showed that AVC are significantly different (p < 0.05) as compared to aortic-valve-area (p = 0.48). Therefore, AVC could be a better index.

Revolutionizing Bladder Health: Artificial-Intelligence-Powered Automatic Measurement of Bladder Volume Using Two-Dimensional Ultrasound.

Measuring elevated post-void residual volume is important for diagnosing urinary outflow tract obstruction and cauda equina syndrome. Catheter placement is exact but painful, invasive, and may cause infection, whereas an ultrasound is accurate, painless, and safe. The purpose of this single-center study is to evaluate the accuracy of a module for artificial-intelligence (AI)-based fully automated bladder volume (BV) prospective measurement using two-dimensional ultrasound images, as compared with manual measurement by expert sonographers. Pairs of transverse and longitudinal bladder images were obtained from patients evaluated in an urgent care clinic. The scans were prospectively analyzed by the automated module using the prolate ellipsoid method. The same examinations were manually measured by a blinded expert sonographer. The two methods were compared using the Pearson correlation, kappa coefficients, and the Bland-Altman method. A total of 111 pairs of transverse and longitudinal views were included. A very strong correlation was found between the manual BV measurements and the AI-based module with r = 0.97 [95% CI: 0.96-0.98]. The specificity and sensitivity for the diagnosis of an elevated post-void residual volume using a threshold ≥200 mL were 1.00 and 0.82, respectively. An almost-perfect agreement between manual and automated methods was obtained (kappa = 0.85). Perfect reproducibility was found for both inter- and intra-observer agreements. This AI-based module provides an accurate automated measurement of the BV based on ultrasound images. This novel method demonstrates a very strong correlation with the gold standard, making it a potentially valuable decision-support tool for non-experts in acute settings.

Prenatal chromosomal microarray analysis in a large Chinese cohort of fetuses with congenital heart defects: a single center study

Background and objectivesCongenital heart defect (CHD) is one of the most common birth defects. The aim of this cohort study was to evaluate the prevalence of chromosomal abnormalities and the clinical utility of chromosomal microarray analysis (CMA) in fetuses with different types of CHD, aiming to assist genetic counseling and clinical decision-making.MethodsIn this study, 642 fetuses with CHD were enrolled from a single center over a six-year period (2017–2022). Both conventional karyotyping and CMA were performed simultaneously on these fetuses.ResultsThe diagnostic yield of CMA in fetuses with CHD in our study was 15.3% (98/642). Our findings revealed a significant increase in the diagnostic yield of CMA compared to karyotyping in fetuses with CHD. Among CHD subgroups, the diagnostic yields were high in complex CHD (34.9%), conotruncal defects (28.6%), right ventricular outflow tract obstructive defects (RVOTO) (25.9%), atrioventricular septal defects (AVSD) (25.0%) and left ventricular outflow tract obstructive defects (LVOTO) (24.1%), while those in other CHD (10.6%) and septal defects (10.9%) were relatively low. The overall detection rate of clinically significant chromosomal abnormalities was significantly higher in the non-isolated CHD group compared to the isolated CHD group (33.1% vs. 9.9%, P < 0.0001). Interestingly, numerical chromosomal abnormalities were more likely to occur in the non-isolated CHD group than in the isolated CHD group (20.3% vs. 2.0%, P < 0.0001). The rate of termination of pregnancy (TOP)/Still birth in the non-isolated CHD group was significantly higher than that in the isolated CHD group (40.5% vs. 20.6%, P < 0.0001). Compared to the isolated CHD group, the detection rate of clinically significant chromosomal abnormalities was significantly higher in the group of CHD with soft markers (35.6% vs. 9.9%, P < 0.0001) and in the group of CHD with additional structural anomalies (36.1% vs. 9.9%, P < 0.0001).ConclusionsCMA is a reliable and high-resolution technique that should be recommended as the front-line test for prenatal diagnosis of fetuses with CHD. The prevalence of chromosomal abnormalities varies greatly among different subgroups of CHD, and special attention should be given to prenatal non-isolated cases of CHD, especially those accompanied by additional structural anomalies or soft markers.

Right Ventricular Strain With 4-Dimensional Computed Tomography Identifies Pulmonary Hypertension in Adults With Repaired Tetralogy of Fallot.

This study evaluated right ventricular (RV) volume, strain, and morphology using cardiac 4-dimensional computed tomography (4D-CT) to detect pulmonary hypertension (PH) in adults with repaired tetralogy of Fallot (TOF) scheduled for transcatheter pulmonary valve implantation (TPVI). Using cardiac 4D-CT data, we calculated RV strain in 3 different geometries and RV outflow tract (RVOT) mass in 42 patients with repaired TOF. We compared RV strain and RVOT mass between patients with and without PH. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance of these measurements for identifying PH. Four-chamber (4ch) strain was significantly smaller for patients with (n=10) than without (n=32) PH (8.8±1.7% vs. 11.1±2.4%, respectively; P<0.01), whereas RVOT mass was significantly larger in the PH group (12.5±3.5 vs. 9.2±3.2 cm2; P<0.01). ROC analysis of the diagnostic performance revealed that the respective sensitivity and specificity was 70% and 84% (area under the curve [AUC]=0.784) for 4ch strain of 8.8%; 80% and 69% (AUC=0.766) for RVOT mass of 10.7 cm2; and 80% and 81% (AUC=0.844) for a 4ch strain/RVOT mass ratio of 0.97. RVOT mass and 4ch strain obtained from cardiac 4D-CT may be helpful for identifying PH in patients with repaired TOF.

Durability of Aortic Homografts in Pulmonary Atresia and Major Aortopulmonary Collateral Arteries.

Objectives: It is well-known that right ventricle-to-pulmonary artery homograft conduit durability is worse for smaller conduits and smaller/younger patients. However, there is limited literature on age and conduit-size specific outcomes, or on the role of conduit oversizing. Methods: Patients diagnosed with tetralogy of Fallot and major aortopulmonary collateral arteries undergoing right ventricular outflow tract (RVOT) reconstruction with a valved aortic homograft conduit from November 2001 through March 2023, at our institution were included. Conduits were grouped and evaluated by diameter, diameter Z-score, and patient age at implant. The primary time-related outcome was freedom from RVOT reintervention. Factors associated with freedom from time-related outcomes were assessed with univariable Cox regression analysis. Results: A total of 863 RVOT conduits were implanted in 722 patients. On multivariable analysis, younger age, male sex, Alagille syndrome, smaller diameter of the conduit, and smaller Z-score were associated with shorter freedom from reintervention. Among patients with smaller diameter conduits, larger Z-scores were associated with longer freedom from conduit reintervention (P < .001). Transcatheter interventions were commonly used to extend conduit lifespan across ages and conduit sizes. Conclusions: Larger conduit diameter, older age, and higher conduit Z-score were associated with longer freedom from reintervention in patients undergoing RVOT reconstruction in this cohort. Oversizing of conduits, even beyond a Z-score of 4, is generally appropriate.

Characteristics and Outcomes of Fetal Cardiac Rhabdomyoma With or Without mTOR Inhibitors, a Systematic Review and Meta-Analysis.

To investigate the characteristics and outcomes of fetal cardiac rhabdomyoma with or without prenatal use of mammalian target of rapamycin inhibitor (mTORi). We systematically searched PubMed, Scopus, and Web of Science until June 2023. Studies reporting on pregnancies with fetal cardiac rhabdomyoma were included. A meta-analysis of proportions was conducted only on studies that included three or more cases. A systematic review included 61 studies reporting on 400 fetuses with cardiac rhabdomyoma, of which 52 studies (389 fetuses) had expectant management and 9 studies (11 fetuses) were managed with mTORi. The meta-analysis included 26 studies reporting on 354 fetuses. Prenatally, 14% (95% CI 4-36) had pericardial effusion, 13% (95% CI 6-27) had arrhythmia, 16% (95% CI 7-31) had outflow tract obstruction, and 10% (95% CI 4-21) had hydrops. Fetal demise occurred in 12% (95% CI 5-30). Before delivery, tumor size reduction was noted in 13%, and after birth in 58%. Following birth, 8% (95% CI 3-14) had neonatal death and 9% (95% 4-17) required cardiac surgery. 60% (95% CI 41-79) of cases were diagnosed with tuberous sclerosis. Seizures were reported only in cases with a tuberous sclerosis diagnosis (41/71 infants). For the 9 studies reporting all together on 11 fetuses with tuberous sclerosis receiving prenatal mTORi, they showed improvement in the size of cardiac rhabdomyoma as well as outflow obstruction and none had fetal demise or neonatal death, and none required postnatal cardiac surgery. We report on the natural history of prenatal cardiac rhabdomyoma, including characteristics, progression, and survival. We report 11 fetuses with tuberous sclerosis and cardiac rhabdomyoma receiving prenatal mTORi, showing promising results.

Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis

BackgroundThe congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear.MethodsThe nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers.ResultsThe lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs.ConclusionFindings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.