Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia.

BACKGROUND: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. METHODS: Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). RESULTS: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002-1.017], P=0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. CONCLUSIONS: LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.

Semi-Quantitative [18F]FDG-PET/CT ROC-Analysis-Based Cut-Offs for Aortitis Definition in Giant Cell Arteritis.

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p < 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging.

Early structural valve deterioration of Mitroflow aortic bioprosthesis: mode, incidence, and impact on outcome in a large cohort of patients.

BACKGROUND: Structural valve deterioration (SVD) is a major flaw of bioprostheses. Early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, mode, and impact of SVD on outcome in a large series of Mitroflow aortic valve replacement. METHODS AND RESULTS: Six hundred seventeen consecutive patients (aged 76.1±6.3 years) underwent aortic valve replacement with a Mitroflow prosthesis (models 12A/LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), with stenosis as the main mode (n=36). Mean delay to SVD was only 3.8±1.4 years, and 5-year SVD-free survival was 91.6% (95% confidence interval [CI], 88.7-94.7) for the whole cohort and 79.8% (95% CI, 71.2-89.4) and 94.0% (95% CI, 90.3-97.8) for 19- and 21-mm sizes, respectively. Among the 39 patients with SVD, 13 patients (33%) had an accelerated SVD once the mean gradient exceeded 30 mm Hg. Valve-related death was 46.2% in this SVD subgroup. Five-year overall survival was 69.6% (95% CI, 65.7-73.9). In multivariable analysis, SVD was the strongest correlate of overall mortality (hazard ratio=7.7; 95% CI, 4.4-13.6). CONCLUSIONS: Early SVD is frequent in Mitroflow bioprosthesis (models 12A/LX), especially for small sizes (19 and 21 mm), and reduces overall survival. An unpredictable accelerated pattern of SVD constitutes a life-threatening condition. In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent reoperation should be discussed in patients with severe SVD even though they are still asymptomatic.

Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via Dispersion.

Wave scattering provides profound insight into the structure of matter. Typically, the ability to sense microstructure is determined by the ratio of scatterer size to probing wavelength. Here, we address the question of whether macroscopic waves can report back the presence and distribution of microscopic scatterers despite several orders of magnitude difference in scale between wavelength and scatterer size. In our analysis, monosized hard scatterers 5 µm in radius are immersed in lossless gelatin phantoms to investigate the effect of multiple reflections on the propagation of shear waves with millimeter wavelength. Steady-state monochromatic waves are imaged in situ via magnetic resonance imaging, enabling quantification of the phase velocity at a voxel size big enough to contain thousands of individual scatterers, but small enough to resolve the wavelength. We show in theory, experiments, and simulations that the resulting coherent superposition of multiple reflections gives rise to power-law dispersion at the macroscopic scale if the scatterer distribution exhibits apparent fractality over an effective length scale that is comparable to the probing wavelength. Since apparent fractality is naturally present in any random medium, microstructure can thereby leave its fingerprint on the macroscopically quantifiable power-law exponent. Our results are generic to wave phenomena and carry great potential for sensing microstructure that exhibits intrinsic fractality, such as, for instance, vasculature.

Intratendinous injection of platelet-rich plasma under US guidance to treat tendinopathy: a long-term pilot study.

PURPOSE: To assess the potential therapeutic effect of intratendinous injection of platelet-rich plasma (PRP) under ultrasound (US) guidance to treat tendon tears and tendinosis in a pilot study with long-term follow-up. MATERIALS AND METHODS: The study included 408 consecutive patients referred for treatment by PRP injection of tendinopathy in the upper (medial and lateral epicondylar tendons) and the lower (patellar, Achilles, hamstring and adductor longus, and peroneal tendons) limb who received a single intratendinous injection of PRP under US guidance. Clinical and US data were retrospectively collected for each anatomic compartment for upper and lower limbs before treatment (baseline) and 6 weeks after treatment. Late clinical data without US were collected until 32 months after the procedure (mean, 20.2 months). The McNemar test and regression model were used to compare clinical and US data. RESULTS: QuickDASH score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and residual US size of lesions were significantly lower after intratendinous injection of PRP under US guidance at 6 weeks and during long-term follow-up compared with baseline (P < .001 in upper and lower limb) independent of age, gender, and type of tendinopathy (P > .29). No clinical complication was reported during follow-up. CONCLUSIONS: Intratendinous injection of PRP under US guidance appears to allow rapid tendon healing and is well tolerated.

Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke.

AIMS: Given the impact of vascular injuries and oedema on brain damage caused during stroke, vascular protection represents a major medical need. We hypothesized that angiopoietin-like 4 (ANGPTL4), a regulator of endothelial barrier integrity, might exert a protective effect during ischaemic stroke. METHODS AND RESULTS: Using a murine transient ischaemic stroke model, treatment with recombinant ANGPTL4 led to significantly decreased infarct size and improved behaviour. Quantitative characteristics of the vascular network (density and branchpoints) were preserved in ANGPTL4-treated mice. Integrity of tight and adherens junctions was also quantified and ANGPTL4-treated mice displayed increased VE-cadherin and claudin-5-positive areas. Brain oedema was thus significantly decreased in ANGPTL4-treated mice. In accordance, vascular damage and infarct severity were increased in angptl4-deficient mice thus providing genetic evidence that ANGPTL4 preserves brain tissue from ischaemia-induced alterations. Altogether, these data show that ANGPTL4 protects not only the global vascular network, but also interendothelial junctions and controls both deleterious inflammatory response and oedema. Mechanistically, ANGPTL4 counteracted VEGF signalling and thereby diminished Src-signalling downstream from VEGFR2. This led to decreased VEGFR2-VE-cadherin complex disruption, increased stability of junctions and thus increased endothelial cell barrier integrity of the cerebral microcirculation. In addition, ANGPTL4 prevented neuronal loss in the ischaemic area. CONCLUSION: These results, therefore, show ANGPTL4 counteracts the loss of vascular integrity in ischaemic stroke, by restricting Src kinase signalling downstream from VEGFR2. ANGPTL4 treatment thus reduces oedema, infarct size, neuronal loss, and improves mice behaviour. These results suggest that ANGPTL4 constitutes a relevant target for vasculoprotection and cerebral protection during stroke.

Evaluation of the Contrast Enhancement Performance of Gadopiclenol for Magnetic Resonance Angiography in Healthy Rabbits and Pigs.

OBJECTIVES: Unexpected accumulations of gadolinium in various organs were reported after the administration of gadolinium-based contrast agents, making desirable to reduce the dose while maintaining equivalent diagnostic performance. The aim of this study was to evaluate the contrast enhancement performance of high relaxivity gadopiclenol compared with gadoterate meglumine in abdominal contrast-enhanced magnetic resonance angiography (CE-MRA). MATERIALS AND METHODS: In a first study in healthy rabbits, axial 3D gradient echo sequences were applied at 4.7 T to study arterial enhancement as a function of gadopiclenol dose (0.025, 0.05, 0.075, and 0.1 mmol Gd/kg) or gadoterate meglumine at 0.1 mmol Gd/kg (n = 5-6/group). The increase in signal-to-noise ratio (ΔSNR) in the aorta at the first pass was measured and compared. In a second, crossover study in 6 healthy pigs, abdominal CE-MRA sequences were acquired at 3 T with gadopiclenol at 0.05 mmol Gd/kg or gadoterate meglumine at 0.1 mmol Gd/kg at a 1-week interval. Quantitatively on the maximum intensity projection (MIP) images, the mean MIP SNR within the aorta of both groups was compared. Qualitatively, a blinded comparison of the angiograms was performed by an experienced radiologist to determine the preferred contrast agent. RESULTS: In the rabbit, ∆SNR is linearly correlated with the gadopiclenol dose (P = 0.0010). Compared with gadoterate meglumine 0.1 mmol Gd/kg, an increase in the ∆SNR is observed after 0.05, 0.075, and 0.1 mmol Gd/kg of gadopiclenol (+63% P = 0.0731, +78% P = 0.0081, and +72% P = 0.0773, respectively), whereas at 0.025 mmol Gd/kg, ∆SNR is in the same range as with gadoterate meglumine 0.1 mmol Gd/kg (+15% P > 0.9999). In pigs, contrast enhancement after gadopiclenol at 0.05 mmol/kg is +22% superior to MIP SNR after gadoterate meglumine at 0.1 mmol Gd/kg (P = 0.3095). Qualitatively, a preference was shown for gadopiclenol images (3/6) over the gadoterate meglumine examinations (1/6), with no preference being shown for the remainder (2/6). CONCLUSIONS: First-pass CE-MRA is feasible with gadopiclenol at 0.05 mmol Gd/kg with at least the same arterial signal enhancement and image quality as gadoterate meglumine at 0.1 mmol Gd/kg.

Description of the Two-Dimensional Layer-Specific Strain Echocardiography Phenotype of Arrhythmogenic Left Ventricular Cardiomyopathy.

BACKGROUND: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is characterized by fibrofatty myocardial replacement demonstrated on cardiac magnetic resonance by late gadolinium enhancement (LGE) mainly involving the subepicardium. The aims of this study were to describe the layer-specific strain (LSS) echocardiography phenotype of ALVC and to compare it with LGE features. METHODS: All consecutive ALVC pathogenic genetic variant carriers and noncarrier relatives were separated into four prespecified groups (overt ALVC [group 1], isolated LGE [group 2], pathogenic genetic variant carrier without ALVC phenotype [group 3], and no genetic variant carrier [group 4]) and studied accordingly using cardiac magnetic resonance and LSS echocardiography. RESULTS: Eighty-five individuals were included. Endocardial global longitudinal strain (GLS)-epicardial GLS (GLSepi) gradient was altered predominantly in group 1, illustrating transmural strain alteration in overt ALVC (3.8 ± 1.1 in group 1, 4.3 ± 2.2 in group 2, 5.2 ± 1.2 in group 3, and 5.4 ± 1.6 in group 4; P = .0017), whereas GLSepi was impaired predominantly in group 2 (endocardial GLS and GLSepi were 15.0 ± 4.1% and 11.2 ± 3.3%, respectively, in group 1; 20.5 ± 2.8% and 16.2 ± 5.5% in group 2; 23.4 ± 3.3% and 18.2 ± 2.7% in group 3; and 24.6 ± 2.8% and 19.2 ± 1.9% in group 4; P < .0001 for all). GLSepi was able to detect subepicardial LGE in genetic variant carriers without overt ALVC with an area under curve of 0.84 (95% CI, 0.73-0.95). However, segmental epicardial and endocardial strain behaved similarly and showed comparable diagnostic values for segmental LGE detection (areas under the curve, 0.72; [95% CI, 0.69-0.76] and 0.73 [95% CI, 0.70-0.76], respectively, P = .40). CONCLUSIONS: LSS alteration in ALVC progresses from the epicardium to the endocardium along with disease severity. Irrespective of LSS analysis, which did not provide incremental diagnostic value for the detection and localization of LGE, strain echocardiography was shown to be a potential surrogate marker of LGE, including in apparently healthy individuals with isolated LV fibrosis.

Calcification of surgical aortic bioprostheses and its impact on clinical outcome.

AIMS: Aortic valve calcification (AVC) of surgical valve bioprostheses (BP) has been poorly explored. We aimed to evaluate in-vivo and ex-vivo BP AVC and its prognosis value. METHODS AND RESULTS: Between 2011 and 2019, AVC was assessed using in-vivo computed tomography (CT) in 361 patients who had undergone surgical valve replacement 6.4±4.3 years earlier. Ex-vivo CT scans were performed for 37 explanted BP. The in-vivo CT scans were interpretable for 342 patients (19 patients [5.2%], were excluded). These patients were 77.2±9.1 years old and 64.3% were male. Mean in-vivo AVC was 307±500 Agatston unit (AU). The AVC was 562±570 AU for the 183 (53.5%) patients with structural valve degeneration (SVD) and 13±43 AU for those without SVD (p<0.0001). In-vivo and ex-vivo AVC were strongly correlated (r=0.88, p<0.0001). An in-vivo AVC>100 AU (n=147, 43%) had a specificity of 96% for diagnosing Stage 2-3 SVD (area under the curve=0.92). Patients with AVC>100 AU had a worse outcome compared with those with AVC≤100 AU (n=195). In multivariable analysis, AVC was a predictor of overall mortality (hazard ratio [HR] and 95% confidence interval=1.16[1.04-1.29]; p=0.006), cardiovascular mortality (HR=1.22[1.04-1.43]; p=0.013), cardiovascular events (HR=1.28 [1.16-1.41]; p<0.0001), and re-intervention (HR=1.15 [1.06-1.25]; p<0.0001). After adjustment for Stage 2-3 SVD diagnosis, AVC remained a predictor of overall mortality (HR=1.20 [1.04-1.39]; p=0.015) and cardiovascular events (HR=1.25 [1.09-1.43]; p=0.001). CONCLUSION: CT scan is a reliable tool to assess BP leaflet calcification. An AVC>100 AU is tightly associated with SVD and it is a strong predictor of overall mortality and cardiovascular events.

Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Cardiac diffusion-weighted MR imaging in recent, subacute, and chronic myocardial infarction: a pilot study.

PURPOSE: To investigate the clinical feasibility of diffusion-weighted imaging (DWI) to detect recent myocardial infarction (MI) and to differentiate it from subacute and chronic MI, with late-gadolinium enhancement (LGE) sequence as reference. Furthermore, to measure variation of the myocardial apparent diffusion coefficient (ADC) according to the age of MI. MATERIALS AND METHODS: Seventy-four MI patients were separated in 3 groups. Group A included 34 recent (< 8 days) MI patients; group B, 22 subacute (9-90 days) MI patients; group C, 18 chronic (> 90 days) MI patients; a fourth group (group D) included 24 controls. DWI and LGE images were acquired on a 1.5T system. DWI and LGE matched images were assessed visually by two blinded observers for hyperintense areas in corresponding segments. RESULTS: Qualitative assessment of DWI compared with LGE images yielded a sensitivity of 97% and a specificity of 61%/14% to differentiate recent from chronic/subacute MI, respectively. The absolute ADCs (recent 0.00632 ± 0.00037 mm(2) /s, subacute 0.00639 ± 0.00035 mm(2) /s, chronic 0.00743 ± 0.00056 mm(2) /s, remote or normal 0.00895 ± 0.00019 mm(2) /s) and relative ADCs were significantly different between groups (P < 0.001) except between recent and subacute MIs. CONCLUSION: DWI is a sensitive technique to diagnose recent MI. DWI MR sequences could help differentiate recent from chronic MI. From these preliminary results, one should expect DWI to be used in the triage of emergency patients with atypical chest pain, to clarify if an MI is present or not in just a few minutes.

Efficacy of intra-tendinous injection of platelet-rich plasma in treating tendinosis: comprehensive assessment of a rat model.

OBJECTIVES: To assess the potential of intra-tendinous injection of platelet rich plasma (PRP) to treat tendinosis (T+) in a rat model of patellar and Achilles T+, and evaluate its local toxicity. METHODS: Thirty rats (120 patellar and Achilles tendons) were used. We induced T+ into 80 tendons (patellar = 40, Achilles = 40) by injecting collagenase at day 0 under ultrasound (US) guidance. Clinical examination and US at day 3, followed by US-guided intra-tendinous injection of either PRP (PRPT+, n = 40) or physiological serum (ST+, n = 40, control). Follow-up was at days 6, 13, 18 and 25 using clinical, US and histological evaluation. To study PRP toxicity, we injected PRP into 40 normal tendons (PRPT-) and compared with 40 untreated normal tendons (T-). RESULTS: All PRPT+ showed better joint mobilisation compared with ST+ at day 6 (P = 0.005), day 13 (P = 0.02), day 18 (P = 0.003) and day 25 (P = 0.01). Similar results were found regarding US and histology, with smaller collagen fibre diameters (day 6, P = 0.003, day 25, P ≤ 0.004), less disorganisation and fewer neovessels (day 6, P = 0.003, day 25, P = 0.0003) in PRPT+ compared with ST+. Comparison between PRPT- and T- showed no PRP toxicity (P = 0.18). CONCLUSIONS: Our study suggests that mono-injection of PRP in T+ improves tendon healing, with no local toxicity. KEY POINTS: • We assessed the potential of platelet rich plasma (PRP) to treat tendinosis. • We treated patellar and Achilles tendinosis in a rat model. • We evaluated clinical, imaging and histological data. • Intra-tendinous PRP injection could be useful in the treatment of tendinosis.

Coronary artery assessment on pre transcatheter aortic valve implantation computed tomography may avoid the need for additional coronary angiography.

PURPOSE: The purpose of this study was to evaluate the percentage of coronary angiography that can be securely avoided by the interpretation of coronary arteries on pre transcatheter aortic valve implantation CT (TAVI-CT), using CT images obtained with deep-learning reconstruction and motion correction algorithms. MATERIAL AND METHOD: All consecutive patients who underwent TAVI-CT and coronary angiography, from December 2021 to July 2022 were screened for inclusion in the study. Patients who had previous coronary artery revascularization or who did not undergo TAVI were excluded. All TAVI-CT examinations were obtained using deep-learning reconstruction and motion correction algorithms. On TAVI-CT examinations, quality and stenosis of coronary artery were analyzed retrospectively. When insufficient image quality and/or when diagnosis or doubt of one significant coronary artery stenosis, patients were considered as having possible coronary artery stenosis. The results of coronary angiography were used as the standard of reference for significant CAS. RESULTS: A total of 206 patients (92 men; mean age, 80.6 years) were included; of these 27/206 (13%) had significant coronary artery stenosis on coronary angiography and were referred for potential revascularization. Sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of TAVI-CT to identify patients requiring coronary artery revascularization was 100% (95% confidence interval [CI]: 87.2-100%), 100% (95% CI: 96.3-100%), 54% (95% CI: 46.6-61.6), 25% (95% CI: 17.0-34.0%) and 60% (95% CI: 53.1-66.9%) respectively. Intra- and inter observer variability was substantial agreement for quality and decision to recommend coronary angiography. Mean reading time was 2 ± 1.2 (standard deviation) min (range: 1-5 min). Overall, TAVI-CT could potentially rule out indication for revascularization for 97 patients (47%). CONCLUSION: Analysis of coronary artery on TAVI-CT using deep-learning reconstruction and motion correction algorithms can potentially safely avoid coronary angiography in 47% of patients.

Prognostic factors in giant cell arteritis associated aortitis with PET/CT and CT angiography at diagnosis.

BACKGROUND: Prognosis data on giant-cell arteritis (GCA)-associated aortitis are scarce and heterogeneous. The aim of this study was to compare the relapses of patients with GCA-associated aortitis according to the presence of aortitis on CT-angiography (CTA) and/or on FDG-PET/CT. METHODS: This multicenter study included GCA patients with aortitis at diagnosis; each case underwent both CTA and FDG-PET/CT at diagnosis. A centralized review of image was performed and identified patients with both CTA and FDG-PET/CT positive for aortitis (Ao-CTA+/PET+); patients with positive FDG-PET/CT but negative CTA for aortitis (Ao-CTA-/PET+), and patients solely positive on CTA. RESULTS: Eighty-two patients were included with 62 (77%) of female sex. Mean age was 67±8 years; 64 patients (78%) were in the Ao-CTA+/PET+ group; 17 (22%) in the Ao-CTA-/PET+ group and 1 had aortitis only on CTA. Overall, 51 (62%) patients had at least one relapse during follow-up: 45/64 (70%) in the Ao-CTA+/PET+ group and 5/17 (29%) in the Ao-CTA-/PET+ group (log rank, p = 0.019). In multivariate analysis, aortitis on CTA (Hazard Ratio 2.90, p = 0.03) was associated with an increased risk of relapse. CONCLUSION: Positivity of both CTA and FDG-PET/CT for GCA-related aortitis was associated with an increased risk of relapse. Aortic wall thickening on CTA was a risk factor of relapse compared with isolated aortic wall FDG uptake.

Long-Term Outcome and Prognosis of Noninfectious Thoracic Aortitis.

BACKGROUND: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known. OBJECTIVES: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis. METHODS: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis. RESULTS: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died. CONCLUSIONS: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures.

Machine Learning-Based Phenogrouping in MVP Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events.

BACKGROUND: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment. OBJECTIVES: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis. METHODS: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429, age 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes. RESULTS: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain <21% and indexed LA volume >42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles. CONCLUSIONS: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse, NCT03884426; Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP], NCT02879825).

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

BACKGROUND AND PURPOSE: Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). METHODS: We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours. RESULTS: DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024). CONCLUSIONS: DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

Magnetic resonance imaging quantitative T2* mapping to predict the red blood cell content of in vivo thrombi retrieved from patients with large vessel occlusions in acute ischemic stroke.

BACKGROUND AND PURPOSE: Magnetic resonance imaging quantitative T2* mapping has shown reliable identification of thrombus red blood cell content in vitro. The thrombus composition has been in vivo, associated with outcomes after endovascular therapy for acute ischemic stroke. We aim to analyze the red blood cell content of thrombi retrieved from patients with large vessel occlusions in relation to the thrombus-T2* relaxation time in magnetic resonance imaging. MATERIAL AND METHODS: Consecutive acute ischemic stroke patients treated by endovascular therapy were scanned with an magnetic resonance imaging quantitative T2* mapping sequence. Quantitative histologic evaluations of red blood cell content were performed. A linear regression assessed the association between vascular risk factors, comorbidities, antithrombotic drugs intake, baseline National Institutes of Health Stroke Scale (NIHSS), intravenous thrombolysis before endovascular therapy, time between onset and groin puncture, patient's outcome at 3 months, magnetic resonance imaging quantitative T2* mapping results, and the red blood cell content of thrombi. The correlation between the mean thrombus-T2* relaxation time and red blood cell content was assessed by calculating the Pearson correlation coefficient. RESULTS: Among 31 thrombi, 16 were "Fibrin rich" and 15 "red blood cell dominant." The median red blood cell content was 39 (range, 0-90; interquartile range, 37). The median (interquartile range) thrombus-T2* relaxation time was shorter in "red blood cell dominant" thrombi (21, interquartile range 6) than in "Fibrin rich" thrombi (24, interquartile range 7), without significant difference (p = 0.15), as shown in the Box plot. An inverse correlation between thrombus-T2* relaxation time and red blood cell content was found, with a correlation coefficient of -0.41 (95% CI, -0.67 to -0.08, p = 0.02). CONCLUSION: Our study shows that a shorter thrombus-T2* relaxation time is related to a higher red blood cell content within in vivo thrombi.

Apixaban and Valve Thrombosis After Transcatheter Aortic Valve Replacement: The ATLANTIS-4D-CT Randomized Clinical Trial Substudy.

BACKGROUND: Subclinical obstructive valve thrombosis after transcatheter aortic valve replacement (TAVR) is of uncertain frequency and clinical impact. OBJECTIVES: The aim of this study was to determine the effects of apixaban vs standard of care on post-TAVR valve thrombosis detected by 4-dimensional (4D) computed tomography. METHODS: The randomized ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial demonstrated that apixaban 5 mg twice daily was not superior to standard of care (vitamin K antagonists or antiplatelet therapy) after successful TAVR and was associated with similar safety but with more noncardiovascular deaths. Three months after randomization, 4D computed tomography was proposed to all patients to determine the percentage of patients with ≥1 prosthetic valve leaflet with grade 3 or 4 reduced leaflet motion or grade 3 or 4 hypoattenuated leaflet thickening (the primary endpoint) in the intention-to-treat population. RESULTS: Seven hundred sixty-two participants had complete multiphase datasets and were included in the 4D computed tomographic analysis. The primary endpoint occurred in 33 (8.9%) and 51 (13.0%) patients in the apixaban and standard-of-care groups, respectively. It was reduced with apixaban vs antiplatelet therapy (OR: 0.51; 95% CI: 0.30-0.86) but not vs vitamin K antagonists (OR: 1.80; 95% CI: 0.62-5.25) (Pinteraction = 0.037). The composite of death, myocardial infarction, any stroke, or systemic embolism at 1 year occurred in 10.7% (n = 9 of 84) and 7.1% (n = 48 of 178) of patients with and without subclinical valve thrombosis at 90 days, respectively (HR: 1.68; 95% CI: 0.82-3.44). CONCLUSIONS: Apixaban reduced subclinical obstructive valve thrombosis in the majority of patients who underwent TAVR without having an established indication for anticoagulation. This study was not powered for clinical outcomes. (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis [ATLANTIS]; NCT02664649).

The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.