Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology. AIM: To redefine the phenotypic spectrum of HFpEF. METHODS: The PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio). The study proposes prospective investigations in patients during a 1-day hospital stay: physical examination; electrocardiogram; performance-based tests; blood samples; cardiac magnetic resonance imaging; transthoracic echocardiography (rest and low-level exercise); myocardial shear wave elastography; chest computed tomography; and non-invasive measurement of arterial stiffness. Dyspnoea, depression, general health and quality of life will be assessed by dedicated questionnaires. A biobank will be established. After the hospital stay, patients are asked to wear a connected garment (with digital sensors) to collect electrocardiography, pulmonary and activity variables in real-life conditions (for up to 14 days). Data will be centralized for machine-learning-based analyses, with the aim of reclassifying HFpEF into more distinct subgroups, improving understanding of the disease mechanisms and identifying new biological pathways and molecular targets. The study will also serve as a platform to enable the development of innovative technologies and strategies for the diagnosis and stratification of patients with HFpEF. CONCLUSIONS: PACIFIC-PRESERVED is a prospective multicentre phenomapping study, using novel analytical techniques, which will provide a unique data resource to better define HFpEF and identify new clinically meaningful subgroups of patients.

Extracorporeal membrane oxygenation (ECMO) during aplasia: A bridge towards myopericarditis recovery after autologous hematopoietic stem cell transplant for systemic sclerosis and recent Coronarovirus disease (COVID-19) vaccination.

Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.

Morphological and dynamic analysis of the normal aortic valve with 4D computed tomography.

OBJECTIVES: To evaluate the precise dimensions of the normal aortic root, especially the true aortic annulus, during the cardiac cycle using an innovative reconstruction method based on multiphase cardiac computed tomography and to assess the feasibility and the reproducibility of this method for aortic root analysis. METHODS: Between January 2019 and June 2021, 30 optimal consecutive ECG-gated multiphase cardiac computed tomography of patients with normal tricuspid aortic valve were analysed using an in-house software. Aortic annulus border was pinpointed on 9 reconstructed planes and the 3D coordinates of the 18 consecutive points were interpolated into a 3D curve using a cubic spline. Three additional planes were generated at the level of the left ventricular outflow tract, the level of the Valsalva sinus and the level of the sinotubular junction. This procedure was repeated for all the 10 temporal phases of the RR interval. RESULTS: The aortic annulus mean 3D and 2D areas were 7.67 ± 1.51 and 5.16 ± 1.40 cm2, respectively. The mean 2D diameter was 2.51 ± 0.23 cm. The mean global area expansion was 11.8 ± 3.5% and the mean perimeter expansion of 7.1 ± 2.6%. During the cardiac cycle, the left ventricle outflow tract expands, reaching its maximum surface at the end of diastole, followed by the aortic annulus, the Valsalva sinuses and the sinotubular junction. The aorta changes from a clover-shaped cone during diastole to more cylindrical shape during systole. Compared to the 3D measurements, the analysis of the virtual basal ring significantly underestimates the annulus area, perimeter, and mean diameter. CONCLUSIONS: 4D morphometric analysis enables to have a precise and reproducible evaluation of the aortic annulus. The aortic annulus and root are deformable structures that undergo a unique expansion sequence during the cardiac cycle which should be considered for procedural planning.

Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation.

BACKGROUND: Functional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA). OBJECTIVES: To compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size. MATERIALS AND METHODS: Forty-one prospectively enrolled patients (16.8 to 35.8 years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AAD), and AA and LV elastance (AAE, LVE). RESULTS: bSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5 ± 13.8 vs 106.1 ± 12.0, p < 0.001), cDBP (72.5 ± 6.9 vs 67.1 ± 9.4, p = 0.002), cPP (44.0 ± 12.1 vs 39.1 ± 8.9, p = 0.003) and not related to aortic size. AAD were decreased in ASO patients vs controls (4.70 ± 2.72 vs 6.69 ± 2.16, p < 0.001). LV mass was correlated with bSBP, cSBP, cPP (ρ = 0.48; p < 0.001), while concentric LV remodeling was correlated with AAE (ρ = 0.60, p < 0.001) and LVE (ρ = 0.32, p = 0.04), but not with distensibility. CONCLUSION: Even without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.

Automatic thoracic aorta calcium quantification using deep learning in non-contrast ECG-gated CT images.

Thoracic aorta calcium (TAC) can be assessed from cardiac computed tomography (CT) studies to improve cardiovascular risk prediction. The aim of this study was to develop a fully automatic system to detect TAC and to evaluate its performance for classifying the patients into four TAC risk categories. The method started by segmenting the thoracic aorta, combining three UNets trained with axial, sagittal and coronal CT images. Afterwards, the surrounding lesion candidates were classified using three combined convolutional neural networks (CNNs) trained with orthogonal patches. Image datasets included 1190 non-enhanced ECG-gated cardiac CT studies from a cohort of cardiovascular patients (age 57 ± 9 years, 80% men, 65% TAC > 0). In the test set (N = 119), the combination of UNets was able to successfully segment the thoracic aorta with a mean volume difference of 0.3 ± 11.7 ml (<6%) and a median Dice coefficient of 0.947. The combined CNNs accurately classified the lesion candidates and 87% of the patients (N = 104) were accurately placed in their corresponding risk categories (Kappa = 0.826, ICC = 0.9915). TAC measurement can be estimated automatically from cardiac CT images using UNets to isolate the thoracic aorta and CNNs to classify calcified lesions.

Association of Impaired Left Ventricular Mitral Filling from 4D Flow Cardiac MRI and Prognosis of Hypertrophic Cardiomyopathy.

Purpose To investigate whether the peak early filling rate normalized to the filling volume (PEFR/FV) estimated from four-dimensional (4D) flow cardiac MRI may be used to assess impaired left ventricular (LV) filling and predict clinical outcomes in individuals with hypertrophic cardiomyopathy (HCM). Materials and Methods Cardiac MRI with a 4D flow sequence and late gadolinium enhancement (LGE), as well as echocardiography, was performed in 88 individuals: 44 participants with HCM from a French prospective registry (ClinicalTrials.gov; NCT01091480) and 44 healthy volunteers matched for age and sex. In participants with HCM, a composite primary end point was assessed at follow-up, including unexplained syncope, new-onset atrial fibrillation, hospitalization for congestive heart failure, ischemic stroke, sustained ventricular arrhythmia, septal reduction therapy, and cardiac death. A Cox proportional hazard model was used to analyze associations with the primary end point. Results PEFR/FV was significantly lower in the HCM group (mean age, 51.8 years ± 18.5 [SD]; 29 male participants) compared with healthy volunteers (mean, 3.35 sec-1 ± 0.99 [0.90-5.20] vs 4.42 sec-1 ± 1.68 [2.74-11.86]; P < .001) and correlated with both B-type natriuretic peptide (BNP) level (r = -0.31; P < .001) and the ratio of pulsed Doppler early transmitral inflow to Doppler tissue imaging annulus velocities (E/E'; r = -0.54; P < .001). At a median follow-up of 2.3 years (IQR, 1.7-3.3 years), the primary end point occurred in 14 (32%) participants. A PEFR/FV of 2.61 sec-1 or less was significantly associated with occurrence of the primary end point (hazard ratio, 9.46 [95% CI: 2.61, 45.17; P < .001] to 15.21 [95% CI: 3.51, 80.22; P < .001]), independently of age, BNP level, E/E', LGE extent, and LV and left atrial strain according to successive bivariate models. Conclusion In HCM, LV filling evaluated with 4D flow cardiac MRI correlated with Doppler and biologic indexes of diastolic dysfunction and predicted clinical outcomes. Keywords: Diastolic Function, Left Ventricular Filling, Hypertrophic Cardiomyopathy, Cardiac MRI, 4D Flow Sequence Clinical trial registration no. NCT01091480 Supplemental material is available for this article. © RSNA, 2024.

Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. METHODS: We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). RESULTS: Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. CONCLUSION: Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

Deep Learning-Based Analysis of Aortic Morphology From Three-Dimensional MRI.

BACKGROUND: Quantification of aortic morphology plays an important role in the evaluation and follow-up assessment of patients with aortic diseases, but often requires labor-intensive and operator-dependent measurements. Automatic solutions would help enhance their quality and reproducibility. PURPOSE: To design a deep learning (DL)-based automated approach for aortic landmarks and lumen detection derived from three-dimensional (3D) MRI. STUDY TYPE: Retrospective. POPULATION: Three hundred ninety-one individuals (female: 47%, age = 51.9 ± 18.4) from three sites, including healthy subjects and patients (hypertension, aortic dilation, Turner syndrome), randomly divided into training/validation/test datasets (N = 236/77/78). Twenty-five subjects were randomly selected and analyzed by three operators with different levels of expertise. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, 3D spoiled gradient-recalled or steady-state free precession sequences. ASSESSMENT: Reinforcement learning and a two-stage network trained using reference landmarks and segmentation from an existing semi-automatic software were used for aortic landmark detection and segmentation from sinotubular junction to coeliac trunk. Aortic segments were defined using the detected landmarks while the aortic centerline was extracted from the segmentation and morphological indices (length, aortic diameter, and volume) were computed for both the reference and the proposed segmentations. STATISTICAL TESTS: Segmentation: Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetrical surface distance (ASSD); landmark detection: Euclidian distance (ED); model robustness: Spearman correlation, Bland-Altman analysis, Kruskal-Wallis test for comparisons between reference and DL-derived aortic indices; inter-observer study: Williams index (WI). A WI 95% confidence interval (CI) lower bound >1 indicates that the method is within the inter-observer variability. A P-value <0.05 was considered statistically significant. RESULTS: DSC was 0.90 ± 0.05, HD was 12.11 ± 7.79 mm, and ASSD was 1.07 ± 0.63 mm. ED was 5.0 ± 6.1 mm. A good agreement was found between all DL-derived and reference aortic indices (r >0.95, mean bias <7%). Our segmentation and landmark detection performances were within the inter-observer variability except the sinotubular junction landmark (CI = 0.96;1.04). DATA CONCLUSION: A DL-based aortic segmentation and anatomical landmark detection approach was developed and applied to 3D MRI data for achieve aortic morphology evaluation. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. OBJECTIVE: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. METHODS: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). RESULTS: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. CONCLUSION: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.

The PACIFIC ontology for heterogeneous data management in cardiology.

With the emergence of health data warehouses and major initiatives to collect and analyze multi-modal and multisource data, data organization becomes central. In the PACIFIC-PRESERVED (PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - Heart Failure with PRESERVED LVEF Study, NCT04189029) study, a data driven research project aiming at redefining and profiling the Heart Failure with preserved Ejection Fraction (HFpEF), an ontology was developed by different data experts in cardiology to enable better data management in a complex study context (multisource, multiformat, multimodality, multipartners). The PACIFIC ontology provides a cardiac data management framework for the phenomapping of patients. It was built upon the BMS-LM (Biomedical Study -Lifecycle Management) core ontology and framework, proposed in a previous work to ensure data organization and provenance throughout the study lifecycle (specification, acquisition, analysis, publication). The BMS-LM design pattern was applied to the PACIFIC multisource variables. In addition, data was structured using a subset of MeSH headings for diseases, technical procedures, or biological processes, and using the Uberon ontology anatomical entities. A total of 1372 variables were organized and enriched with annotations and description from existing ontologies and taxonomies such as LOINC to enable later semantic interoperability. Both, data structuring using the BMS-LM framework, and its mapping with published standards, foster interoperability of multimodal cardiac phenomapping datasets.

Abdominal aortic calcium and geometry in patients with essential hypertension.

PURPOSE: Abdominal aorta calcium (AAC) burden and dilatation are associated with an increased risk of mortality. The purpose of this study was to investigate determinants of AAC and abdominal aorta size in patients with essential hypertension. MATERIALS AND METHODS: Patients with uncomplicated essential hypertension who had undergone non-enhanced abdominal CT to rule out secondary hypertension in addition to biological test were recruited between 2010 and 2018. A semi-automatic system was designed to estimate the aortic size (diameter, length, volume) and quantify the AAC from mesenteric artery to bifurcation using the Agatston score. Determinants of aortic size and those related to AAC were searched for using uni- and multivariables analyses. RESULTS: Among 293 randomly selected patients with hypertension (age 52 ± 11 [SD] years) included, 23% had resistant hypertension. Mean abdominal aorta diameter was 20.1 ± 2.1 (SD) mm. Eight (3%) patients had abdominal aorta aneurysm ≥ 30 mm and 58 (20%) had dilated abdominal aorta ≥ 27 mm. Median AAC score was 38 and calcifications were detected in the infra- and supra-renal abdominal aortic portions in 59% and 26% of the patients, respectively. After adjustment for age, male sex and body surface area, abdominal aorta diameter was positively associated with diastolic blood pressure (P = 0.0019). Smoking was the single variable associated with calcified abdominal aorta (P < 0.001) after adjustment for cofactors. In patients with calcifications of abdominal aorta, the score increased with smoking history (P < 0.001), statins treatment (P < 0.01), greater number of anti-hypertensive drugs (P < 0.01), larger abdominal aorta (P < 0.05) and greater systolic blood pressure (P < 0.05). Patients with resistant hypertension had more AAC in the supra-renal abdominal aorta portion than those without resistant hypertension (P < 0.01). CONCLUSION: In patients with essential hypertension, abdominal aorta dilation is related with diastolic blood pressure while AAC is associated with smoking history and resistant hypertension when located to the supra-renal abdominal aorta portion.

Evaluación del tracto de salida del ventrículo derecho mediante resonancia magnética con flujo 4D en pacientes sometidos a recambio valvular pulmonar transcatéter / 4D flow magnetic resonance imaging to assess right ventricular outflow tract in patients undergoing transcatheter pulmonary valve replacement

Introducción y objetivos: La resonancia magnética (RM) con flujo 4D suele utilizarse para evaluar el ventrículo derecho y las arterias pulmonares antes del implante percutáneo de la válvula pulmonar (IPVP). Como el IPVP está limitado por el tamaño del tracto de salida del ventrículo derecho (TSVD), se necesita medirlo con precisión para planificar la intervención. El objetivo del presente estudio es comparar diferentes modalidades de RM con la medición invasiva del TSVD con balón.MétodosEstudio unicéntrico prospectivo de pacientes sometidos a IPVP por insuficiencia pulmonar aislada evaluada mediante RM con flujo 4D, precesión libre en estado estacionario/gradiente eco 3D (3D SSFP/GRE) y angiografía por RM con contraste. La medición con balón se consideró la referencia.ResultadosSe incluyó a 23 adultos (media de edad, 38,4±12,5 años). En 18 pacientes el IPVP fue exitoso. El diámetro medio del TSVD más pequeño fue de 25,4±4,3 mm medido con balón y 25,6±3,8 mm y 21,8±3,6 mm por RM con flujo 4D en sístole y diástole respectivamente. Comparados con los medidos con balón, los diámetros de TSVD se correlacionaron mejor cuando se estimaron mediante RM con flujo 4D sistólico (r=0,89; p<0,001) que mediante RM con flujo 4D diastólico (r=0,71; p<0,001), angiografía por R; 3D con contraste (r=0,73; p<0,001) o 3D SSFP/GRE (r=0,50; p=0,04), y no se correlacionaron de manera significativa cuando se realizaron en 2D en diástole o sístole. La diferencia media entre la RM con flujo 4D sistólico y la medición con balón fue de 0,2 mm (IC95%, –3,5 a 3,9 mm), en tanto que con las otras técnicas fue mayor.ConclusionesAdemás de la cuantificación de la insuficiencia de la válvula pulmonar, la RM con flujo 4D permite una estimación fiable de los diámetros del TSVD, sobre todo en sístole, lo que es fundamental antes de planificar el IPVP. (AU)

Introduction and objectives: Magnetic resonance imaging (MRI) including 4D flow is used before percutaneous pulmonary valve implantation (PPVI). As PPVI is limited by the size of the right ventricular outflow tract (RVOT), accurate sizing is needed to plan the intervention. The aim of this study was to compare different MRI modalities and invasive angiogram to balloon sizing of RVOT.MethodsSingle-centre prospective study of patients who underwent PPVI for isolated pulmonary regurgitation assessed by 4D flow MRI, 3D steady-state free precession/gradient echo (3D SSFP/GRE) and contrast magnetic resonance angiogram. Balloon sizing was considered as the reference.ResultsA total of 23 adults were included (mean age, 38.4±12.5 years). Eighteen patients underwent successful primary PPVI. The average of the narrowest RVOT diameter was 25.4±4.3mm by balloon sizing. Compared to balloon sizing, RVOT diameters were better correlated when estimated by systolic 4D flow MRI (r=0.89, P<0.001) than by diastolic 4D flow MRI (r=0.71, P<0.001), 3D contrast magnetic resonance angiography (r=0.73; P<.001) and 3D SSFP/GRE (r=0.50; P=.04) and not significantly correlated when estimated by 2D in diastole and systole. The mean difference between systolic 4D flow MRI and balloon sizing was 0.2mm (95%CI, –3.5 to 3.9 mm), whereas it was wider with other techniques.ConclusionsBeyond the quantification of pulmonary valve regurgitation, 4D flow allows accurate estimation of RVOT diameters, especially in systole, which is fundamental before planning PPVI. (AU)

Rationale and design of the direct oral anticoagulants for prevention of left ventricular thrombus after anterior acute myocardial infarction (APERITIF) trial.

BACKGROUND: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. STUDY DESIGN: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. CONCLUSION: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. CLINICALTRIALS: gov Identifier: NCT05077683.

Aortic Stiffness Measured from Either 2D/4D Flow and Cine MRI or Applanation Tonometry in Coronary Artery Disease: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Aortic stiffness can be evaluated by aortic distensibility or pulse wave velocity (PWV) using applanation tonometry, 2D phase contrast (PC) MRI and the emerging 4D flow MRI. However, such MRI tools may reach their technical limitations in populations with cardiovascular disease. Accordingly, this work focuses on the diagnostic value of aortic stiffness evaluated either by applanation tonometry or MRI in high-risk coronary artery disease (CAD) patients. METHODS: 35 patients with a multivessel CAD and a myocardial infarction treated 1 year before were prospectively recruited and compared with 18 controls with equivalent age and sex distribution. Ascending aorta distensibility and aortic arch 2D PWV were estimated along with 4D PWV. Furthermore, applanation tonometry carotid-to-femoral PWV (cf PWV) was recorded immediately after MRI. RESULTS: While no significant changes were found for aortic distensibility; cf PWV, 2D PWV and 4D PWV were significantly higher in CAD patients than controls (12.7 ± 2.9 vs. 9.6 ± 1.1; 11.0 ± 3.4 vs. 8.0 ± 2.05 and 17.3 ± 4.0 vs. 8.7 ± 2.5 m·s-1 respectively, p < 0.001). The receiver operating characteristic (ROC) analysis performed to assess the ability of stiffness indices to separate CAD subjects from controls revealed the highest area under the curve (AUC) for 4D PWV (0.97) with an optimal threshold of 12.9 m·s-1 (sensitivity of 88.6% and specificity of 94.4%). CONCLUSIONS: PWV estimated from 4D flow MRI showed the best diagnostic performances in identifying severe stable CAD patients from age and sex-matched controls, as compared to 2D flow MRI PWV, cf PWV and aortic distensibility.

Acute stress induces long-term metabolic, functional, and structural remodeling of the heart.

Takotsubo cardiomyopathy is a stress-induced cardiovascular disease with symptoms comparable to those of an acute coronary syndrome but without coronary obstruction. Takotsubo was initially considered spontaneously reversible, but epidemiological studies revealed significant long-term morbidity and mortality, the reason for which is unknown. Here, we show in a female rodent model that a single pharmacological challenge creates a stress-induced cardiomyopathy similar to Takotsubo. The acute response involves changes in blood and tissue biomarkers and in cardiac in vivo imaging acquired with ultrasound, magnetic resonance and positron emission tomography. Longitudinal follow up using in vivo imaging, histochemistry, protein and proteomics analyses evidences a continued metabolic reprogramming of the heart towards metabolic malfunction, eventually leading to irreversible damage in cardiac function and structure. The results combat the supposed reversibility of Takotsubo, point to dysregulation of glucose metabolic pathways as a main cause of long-term cardiac disease and support early therapeutic management of Takotsubo.

Value of aortic volumes assessed by automated segmentation of 3D MRI data in patients with thoracic aortic dilatation: A case-control study.

PURPOSE: The purpose of this study was to investigate the benefit of aortic volumes compared to diameters or cross-sectional areas on three-dimensional (3D) magnetic resonance imaging (MRI) in discriminating between patients with dilated aorta and matched controls. MATERIALS AND METHODS: Sixty-two patients (47 men and 15 women; median age, 66 years; age range: 33-86 years) with tricuspid aortic valve and ascending thoracic aorta aneurysm (TAV-ATAA) and 43 patients (35 men and 8 women; median age, 51 years; age range: 17-76 years) with bicuspid aortic valve and dilated ascending aorta (BAV) were studied. One group of 54 controls matched for age and sex to patients with TAV-ATAA (39 men and 15 women; median age, 68 years; age range: 33-81 years) and one group of 42 controls matched for age and sex to patients with BAV (34 men and 8 women; median age, 50 years; age range: 17-77 years) were identified. All participants underwent 3D MRI, used for 3D-segmentation for measuring aortic length, maximal diameter, maximal cross-sectional area (CSA) and volume for the ascending aorta. RESULTS: An increase in ascending aorta volume (TAV-ATAA: +107%; BAV: +171% vs. controls; P < 0.001) was found, which was three times greater than the increase in diameter (TAV-ATAA: +29%; BAV: +40% vs. controls; P < 0.001). In differentiating patients with TAV-ATAA from their controls, the indexed ascending aorta volume showed better performances (AUC, 0.935 [95% confidence interval (CI): 0.882-0.989]; accuracy, 88.7% [95% CI: 82.9-94.5]) than indexed ascending aorta length (P < 0.001), indexed ascending aorta maximal diameter (P = 0.003) and indexed ascending aorta maximal CSA (P = 0.03). In differentiating patients with BAV from matched controls, indexed ascending aorta volume showed significantly better performances performance (AUC, 0.908 [95% CI: 0.829-0.987]; accuracy, 88.0% [95% CI: 80.9-95.0]) than indexed ascending aorta length (P = 0.02) and not different from indexed ascending aorta maximal diameter (P = 0.07) or from indexed ascending aorta maximal CSA (P = 0.27) CONCLUSION: Aortic volume measured by 3D-MRI integrates both elongation and luminal dilatation, resulting in greater classification performance than maximal diameter and length in differentiating patients with dilated ascending aorta or aneurysm from controls.

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

OBJECTIVES: Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. METHODS: In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. RESULTS: In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5 mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). CONCLUSIONS: In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. KEY POINTS: • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

4D flow magnetic resonance imaging to assess right ventricular outflow tract in patients undergoing transcatheter pulmonary valve replacement.

INTRODUCTION AND OBJECTIVES: Magnetic resonance imaging (MRI) including 4D flow is used before percutaneous pulmonary valve implantation (PPVI). As PPVI is limited by the size of the right ventricular outflow tract (RVOT), accurate sizing is needed to plan the intervention. The aim of this study was to compare different MRI modalities and invasive angiography to balloon sizing of RVOT. METHODS: Single-center prospective study of patients who underwent PPVI for isolated pulmonary regurgitation assessed by 4D flow MRI, 3D steady-state free precession/gradient echo (3D SSFP/GRE) and contrast magnetic resonance angiography. Balloon sizing was considered as the reference. RESULTS: A total of 23 adults were included (mean age, 38.4±12.5 years). Eighteen patients underwent successful primary PPVI. The average of the narrowest RVOT diameter was 25.4±4.3 mm by balloon sizing. Compared to balloon sizing, RVOT diameters were better correlated when estimated by systolic 4D flow MRI (r=0.89, P<.001) than by diastolic 4D flow MRI (r=0.71, P <.001), 3D contrast magnetic resonance angiography (r=0.73; P <.001) and 3D SSFP/GRE (r=0.50; P=.04) and was not significantly correlated when estimated by 2D in diastole and systole. The mean difference between systolic 4D flow MRI and balloon sizing was 0.2 mm (95%CI, -3.5 to 3.9 mm), whereas it was wider with other techniques. CONCLUSIONS: Beyond the quantification of pulmonary valve regurgitation, 4D flow allows accurate estimation of RVOT diameters, especially in systole, which is fundamental before planning PPVI.