4D Flow Cardiac MR in Primary Mitral Regurgitation.

BACKGROUND: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. PURPOSE: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. STUDY TYPE: Prospective, single-center, two arm, interventional vs. nonintervention observational study. POPULATION: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW). FIELD STRENGTH/SEQUENCE: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). ASSESSMENT: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). STATISTICAL TESTS: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. RESULTS: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). DATA CONCLUSION: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Comprehensive Neonatal Cardiac, Feed and Wrap, Non-contrast, Non-sedated, Free-breathing Compressed Sensing 4D Flow MRI Assessment.

BACKGROUND: Cardiac MRI is an important imaging tool in congenital cardiac disease, but its use has been limited in the neonatal population as general anesthesia has been needed for breath-holding. Technological advances in four-dimensional (4D) flow MRI have now made nonsedated free-breathing acquisition protocols a viable clinical option, but the method requires prospective validation in neonates. PURPOSE: To test the feasibility of compressed sensing (CS) 4D flow MRI in the neonatal population and to compare with standard previously validated two-dimensional (2D) phase-contrast (PC) flow MRI. STUDY TYPE: Prospective, cohort, image quality. POPULATION: A total of 14 healthy neonates (median [range] age: 2.5 [0-80] days; 8 male). FIELD STRENGTH AND SEQUENCE: Noncontrast 2D cine gradient echo sequence with through-plane velocity encoding (PC) sequence and compressed sensing (CS) three-dimensional (3D), time-resolved, cine phase-contrast MRI with 3D velocity-encoding (4D flow MRI) at 3 T. ASSESSMENT: Aortic 2D PC, and aortic, pulmonary trunk and superior vena cava CS 4D flow MRI were acquired using the feed and wrap technique (nonsedated) and quantified using commercially available software. Aortic flow and peak velocity were compared between methods. Internal consistency of 4D flow MRI was determined by comparing mean forward flow of the main pulmonary artery (MPA) vs. the sum of left and right pulmonary artery flows (LPA and RPA) and by comparing mean ascending aorta forward flow (AAo) vs. the sum of superior vena cava (SVC) and descending aorta flows (DAo). STATISTICAL TESTS: Flow and peak-velocity comparisons were assessed using paired t-tests, with P < 0.05 considered significant, and Bland-Altman analysis. Interobserver and intraobserver agreement and internal consistency were analyzed by intraclass correlation co-efficient (ICC). RESULTS: There was no statistically significant difference between ascending aortic forward flow between 2D PC and CS 4D Flow MRI (P = 0.26) with a bias of 0.11 mL (-0.59 to 0.82 mL) nor peak velocity (P = 0.11), with a bias of -5 cm/sec and (-26 to 16 cm/sec). There was excellent interobserver and intraobserver agreement for each vessel (interobserver ICC: AAo 1.00; DAo 0.94, SVC 0.90, MPA 0.99, RPA 0.98, LPA 0.96; intraobserver ICC: AAo 1.00; DAo 0.99, SVC 0.98, MPA 1.00, RPA 1.00, LPA 0.99). Internal consistency measures showed excellent agreement for both mean forward flow of main pulmonary artery vs. the sum of left and right pulmonary arteries (ICC: 0.95) and mean ascending aorta forward flow vs. the sum of superior vena cava and descending aorta flows (ICC: 1.00). CONCLUSION: Sedation-free neonatal feed and wrap MRI is well tolerated and feasible. CS 4D flow MRI quantification is similar to validated 2D PC free-breathing imaging with excellent interobserver and intraobserver agreement. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Acute vasodilator response testing in the adult Fontan circulation using non-invasive 4D Flow MRI: a proof-of-principle study.

BACKGROUND: Pulmonary vasodilator therapy in Fontan patients can improve exercise tolerance. We aimed to assess the potential for non-invasive testing of acute vasodilator response using four-dimensional (D) flow MRI during oxygen inhalation. MATERIALS AND METHODS: Six patients with well-functioning Fontan circulations were prospectively recruited and underwent cardiac MRI. Ventricular anatomical imaging and 4D Flow MRI were acquired at baseline and during inhalation of oxygen. Data were compared with six age-matched healthy volunteers with 4D Flow MRI scans acquired at baseline. RESULTS: All six patients tolerated the MRI scan well. The dominant ventricle had a left ventricular morphology in all cases. On 4D Flow MRI assessment, two patients (Patients 2 and 6) showed improved cardiac filling with improved preload during oxygen administration, increased mitral inflow, increased maximum E-wave kinetic energy, and decreased systolic peak kinetic energy. Patient 1 showed improved preload only. Patient 5 showed no change, and patient 3 had equivocal results. Patient 4, however, showed a decrease in preload and cardiac filling/function with oxygen. DISCUSSION: Using oxygen as a pulmonary vasodilator to assess increased pulmonary venous return as a marker for positive acute vasodilator response would provide pre-treatment assessment in a more physiological state - the awake patient. This proof-of-concept study showed that it is well tolerated and has shown changes in some stable patients with a Fontan circulation.

Three-dimensional quantification of circulation using finite-element methods in four-dimensional flow MR data of the thoracic aorta.

PURPOSE: Three-dimensional (3D) quantification of circulation using a Finite Elements methodology. METHODS: We validate our 3D method using an in-silico arch model, for different mesh resolutions, image resolution and noise levels, and we compared this with a currently used 2D method. Finally, we evaluated the application of our methodology in 4D Flow MRI data of ascending aorta of six healthy volunteers, and six bicuspid aortic valve (BAV) patients, three with right and three with left handed flow, at peak systole. The in-vivo data was compared using a Mann-Whitney U-test between volunteers and patients (right and left handed flow). RESULTS: The robustness of our method throughout different image resolutions and noise levels showed subestimation of circulation less than 45 cm2 /s in comparison with the 55cm2 /s generated by the current 2D method. The circulation (mean ± SD) of the healthy volunteer group was 13.83 ± 28.78 cm2 /s, in BAV patients with right-handed flow 724.37 ± 317.53 cm2 /s, and BAV patients with left-handed flow -480.99 ± 387.29 cm2 /s. There were significant differences between healthy volunteers and BAV patients groups (P-value < .01), and also between BAV patients with a right-handed or left-handed helical flow and healthy volunteers (P-value < .01). CONCLUSION: We propose a novel 3D formulation to estimate the circulation in the thoracic aorta, which can be used to assess the differences between normal and diseased hemodynamic from 4D-Flow MRI data. This method also can correctly differentiate between the visually seen right- and left-handed helical flow, which suggests that this approach may have high clinical sensitivity, but requires confirmation in longitudinal studies with a large cohort.

Four-Dimensional Flow Magnetic Resonance Imaging in the Assessment of Blood Flow in the Heart and Great Vessels: A Systematic Review.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) allows multidirectional quantification of blood flow in the heart and great vessels. Comparability of the technique to the current reference standards of flow assessment-two-dimensional (2D) flow MRI and Doppler echocardiography-varies in the literature. Image acquisition parameters likely impact upon the accuracy and reproducibility of 4D flow MRI. We therefore sought to review the current literature on 4D flow MRI in the heart and great vessels, in comparison to 2D flow MRI, Doppler echocardiography, and invasive catheterization. Using a predefined search strategy and inclusion and exclusion criteria, the databases EMBASE and Medline were searched in January 2021 for peer-reviewed research articles comparing cardiac 4D flow MRI to 2D flow MRI, Doppler echocardiography and/or invasive catheterization. The data from all relevant articles were assimilated and analyzed using Mann-Whitney U and chi χ2 test. Forty-four manuscripts met the eligibility criteria and were included in the review. The review showed agreement of 4D flow MRI to the reference standard methods of flow assessment, particular in the measurement of peak velocity and stroke volume in 55% of manuscripts. The use of valve tracking significantly improves agreement between 4D flow MRI and the reference modalities (79% matching with the use of valve tracking vs. 50% without, P = 0.04). This review highlights that the impact of acquisition parameters on 4D flow MRI accuracy is multifactorial. It is therefore important that each center conducts its own quality assurance prior to using 4D flow MRI for clinical decision-making. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Rationale and clinical applications of 4D flow cardiovascular magnetic resonance in assessment of valvular heart disease: a comprehensive review.

BACKGROUND: Accurate evaluation of valvular pathology is crucial in the timing of surgical intervention. Whilst transthoracic echocardiography is widely available and routinely used in the assessment of valvular heart disease, it is bound by several limitations. Although cardiovascular magnetic resonance (CMR) imaging can overcome many of the challenges encountered by echocardiography, it also has a number of limitations. MAIN TEXT: 4D Flow CMR is a novel technique, which allows time-resolved, 3-dimensional imaging. It enables visualisation and direct quantification of flow and peak velocities of all valves simultaneously in one simple acquisition, without any geometric assumptions. It also has the unique ability to measure advanced haemodynamic parameters such as turbulent kinetic energy, viscous energy loss rate and wall shear stress, which may add further diagnostic and prognostic information. Although 4D Flow CMR acquisition can take 5-10 min, emerging acceleration techniques can significantly reduce scan times, making 4D Flow CMR applicable in contemporary clinical practice. CONCLUSION: 4D Flow CMR is an emerging CMR technique, which has the potential to become the new reference-standard method for the evaluation of valvular lesions. In this review, we describe the clinical applications, advantages and disadvantages of 4D Flow CMR in the assessment of valvular heart disease.

Le Cœur en Sabot: shape associations with adverse events in repaired tetralogy of Fallot.

BACKGROUND: Maladaptive remodelling mechanisms occur in patients with repaired tetralogy of Fallot (rToF) resulting in a cycle of metabolic and structural changes. Biventricular shape analysis may indicate mechanisms associated with adverse events independent of pulmonary regurgitant volume index (PRVI). We aimed to determine novel remodelling patterns associated with adverse events in patients with rToF using shape and function analysis. METHODS: Biventricular shape and function were studied in 192 patients with rToF (median time from TOF repair to baseline evaluation 13.5 years). Linear discriminant analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events. Adverse events included death, arrhythmias, and cardiac arrest with median follow-up of 10 years. RESULTS: LDA and PCA showed that shape characteristics pertaining to adverse events included a more circular left ventricle (LV) (decreased eccentricity), dilated (increased sphericity) LV base, increased right ventricular (RV) apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.77). PRVI did not add value, and shape changes associated with increased PRVI were not predictive of adverse outcomes. CONCLUSION: Pathological remodelling patterns in patients with rToF are significantly associated with adverse events, independent of PRVI. Mechanisms related to incident events include LV basal dilation with a reduced RV apical ejection fraction.

Differential flow improvements after valve replacements in bicuspid aortic valve disease: a cardiovascular magnetic resonance assessment.

BACKGROUND: Abnormal aortic flow patterns in bicuspid aortic valve disease (BAV) may be partly responsible for the associated aortic dilation. Aortic valve replacement (AVR) may normalize flow patterns and potentially slow the concomitant aortic dilation. We therefore sought to examine differences in flow patterns post AVR. METHODS: Ninety participants underwent 4D flow cardiovascular magnetic resonance: 30 BAV patients with prior AVR (11 mechanical, 10 bioprosthetic, 9 Ross procedure), 30 BAV patients with a native aortic valve and 30 healthy subjects. RESULTS: The majority of subjects with mechanical AVR or Ross showed normal flow pattern (73% and 67% respectively) with near normal rotational flow values (7.2 ± 3.9 and 10.6 ± 10.5 mm2/ms respectively vs 3.8 ± 3.1 mm2/s for healthy subjects; both p > 0.05); and reduced in-plane wall shear stress (0.19 ± 0.13 N/m2 for mechanical AVR vs. 0.40 ± 0.28 N/m2 for native BAV, p < 0.05). In contrast, all subjects with a bioprosthetic AVR had abnormal flow patterns (mainly marked right-handed helical flow), with comparable rotational flow values to native BAV (20.7 ± 8.8 mm2/ms and 26.6 ± 16.6 mm2/ms respectively, p > 0.05), and a similar pattern for wall shear stress. Data before and after AVR (n = 16) supported these findings: mechanical AVR showed a significant reduction in rotational flow (30.4 ± 16.3 → 7.3 ± 4.1 mm2/ms; p < 0.05) and in-plane wall shear stress (0.47 ± 0.20 → 0.20 ± 0.13 N/m2; p < 0.05), whereas these parameters remained similar in the bioprosthetic AVR group. CONCLUSIONS: Abnormal flow patterns in BAV disease tend to normalize after mechanical AVR or Ross procedure, in contrast to the remnant abnormal flow pattern after bioprosthetic AVR. This may in part explain different aortic growth rates post AVR in BAV observed in the literature, but requires confirmation in a prospective study.

Test-retest variability of left ventricular 4D flow cardiovascular magnetic resonance measurements in healthy subjects.

BACKGROUND: Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements. METHODS: Forty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28-57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components' volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components' volume. RESULTS: The dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%-9.2% for the flow components' volume ratio and between 13.5%-17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2-16.1% for the flow components' volume ratio and 16.9-29.0% for the kinetic energy of the flow components. CONCLUSION: LV flow components' volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements.

Aortic 4D flow: quantification of signal-to-noise ratio as a function of field strength and contrast enhancement for 1.5T, 3T, and 7T.

PURPOSE: To investigate for the first time the feasibility of aortic four-dimensional (4D) flow at 7T, both contrast enhanced (CE) and non-CE. To quantify the signal-to-noise ratio (SNR) in aortic 4D flow as a function of field strength and CE with gadobenate dimeglumine (MultiHance). METHODS: Six healthy male volunteers were scanned at 1.5T, 3T, and 7T with both non-CE and CE acquisitions. Temporal SNR was calculated. Flip angle optimization for CE 4D flow was carried out using Bloch simulations that were validated against in vivo measurements. RESULTS: The 7T provided 2.2 times the SNR of 3T while 3T provided 1.7 times the SNR of 1.5T in non-CE acquisitions in the descending aorta. The SNR gains achieved by CE were 1.8-fold at 1.5T, 1.7-fold at 3T, and 1.4-fold at 7T, respectively. CONCLUSION: The 7T provides a new tool to explore aortic 4D flow, yielding higher SNR that can be used to push the boundaries of acceleration and resolution. Field strength and contrast enhancement at all fields provide significant improvements in SNR.

Aortic relative pressure components derived from four-dimensional flow cardiovascular magnetic resonance.

PURPOSE: To describe the assessment of the spatiotemporal distribution of relative aortic pressure quantifying the magnitude of its three major components. METHODS: Nine healthy volunteers and three patients with aortic disease (bicuspid aortic valve, dissection, and Marfan syndrome) underwent 4D-flow CMR. Spatiotemporal pressure maps were computed from the CMR flow fields solving the pressure Poisson equation. The individual components of pressure were separated into time-varying inertial ("transient"), spatially varying inertial ("convective"), and viscous components. RESULTS: Relative aortic pressure is primarily caused by transient effects followed by the convective and small viscous contributions (64.5, 13.6, and 0.3 mmHg/m, respectively, in healthy subjects), although regional analysis revealed prevalent convective effects in specific contexts, e.g., Sinus of Valsalva and aortic arch at instants of peak velocity. Patients showed differences in peak transient values and duration, and localized abrupt convective changes explained by abnormalities in aortic geometry, including the presence of an aneurysm, a pseudo-coarctation, the inlet of a dissection, or by complex flow patterns. CONCLUSION: The evaluation of the three components of relative pressure enables the quantification of mechanistic information for understanding and stratifying aortic disease, with potential future implications for guiding therapy.

Fetal Cardiac MRI Using Doppler US Gating: Emerging Technology and Clinical Implications.

Fetal cardiac MRI using Doppler US gating is an emerging technique to support prenatal diagnosis of congenital heart disease and other cardiovascular abnormalities. Analogous to postnatal electrocardiographically gated cardiac MRI, this technique enables directly gated MRI of the fetal heart throughout the cardiac cycle, allowing for immediate data reconstruction and review of image quality. This review outlines the technical principles and challenges of cardiac MRI with Doppler US gating, such as loss of gating signal due to fetal movement. A practical workflow of patient preparation for the use of Doppler US-gated fetal cardiac MRI in clinical routine is provided. Currently applied MRI sequences (ie, cine or four-dimensional flow imaging), with special consideration of technical adaptations to the fetal heart, are summarized. The authors provide a literature review on the clinical benefits of Doppler US-gated fetal cardiac MRI for gaining additional diagnostic information on cardiovascular malformations and fetal hemodynamics. Finally, future perspectives of Doppler US-gated fetal cardiac MRI and further technical developments to reduce acquisition times and eliminate sources of artifacts are discussed. Keywords: MR Fetal, Ultrasound Doppler, Cardiac, Heart, Congenital, Obstetrics, Fetus Supplemental material is available for this article. © RSNA, 2024.

Cardiovascular Imaging, Climate Change, and Environmental Sustainability.

Environmental exposures including poor air quality and extreme temperatures are exacerbated by climate change and are associated with adverse cardiovascular outcomes. Concomitantly, the delivery of health care generates substantial atmospheric greenhouse gas (GHG) emissions contributing to the climate crisis. Therefore, cardiac imaging teams must be aware not only of the adverse cardiovascular health effects of climate change, but also the downstream environmental ramifications of cardiovascular imaging. The purpose of this review is to highlight the impact of climate change on cardiovascular health, discuss the environmental impact of cardiovascular imaging, and describe opportunities to improve environmental sustainability of cardiac MRI, cardiac CT, echocardiography, cardiac nuclear imaging, and invasive cardiovascular imaging. Overarching strategies to improve environmental sustainability in cardiovascular imaging include prioritizing imaging tests with lower GHG emissions when more than one test is appropriate, reducing low-value imaging, and turning equipment off when not in use. Modality-specific opportunities include focused MRI protocols and low-field-strength applications, iodine contrast media recycling programs in cardiac CT, judicious use of US-enhancing agents in echocardiography, improved radiopharmaceutical procurement and waste management in nuclear cardiology, and use of reusable supplies in interventional suites. Finally, future directions and research are highlighted, including life cycle assessments over the lifespan of cardiac imaging equipment and the impact of artificial intelligence tools. Keywords: Heart, Safety, Sustainability, Cardiovascular Imaging Supplemental material is available for this article. © RSNA, 2024.

Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.

Bicuspid Aortic Valve (BAV) is the most common adult congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that early onset complications of BAV (EBAV) are driven by specific impactful genetic variants. We analyzed whole exome sequences (WES) to identify rare coding variants that contribute to BAV disease in 215 EBAV families. Predicted pathogenic variants of causal genes were present in 111 EBAV families (51% of total), including genes that cause BAV (8%) or heritable thoracic aortic disease (HTAD, 17%). After appropriate filtration, we also identified 93 variants in 26 novel genes that are associated with autosomal dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants contribute to early onset complications of BAV disease.

Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.

[Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes]. / Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación.

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in cohorts with late onset sporadic disease (n = 5040). We identified 34 large and rare (< 1:1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 8% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.