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BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.
Sujet(s)
Acides gras omega-3 , Hémorragie , Essais contrôlés randomisés comme sujet , Humains , Acides gras omega-3/effets indésirables , Acides gras omega-3/administration et posologie , Acides gras omega-3/usage thérapeutique , Hémorragie/induit chimiquement , Hémorragie/épidémiologie , Appréciation des risques , Facteurs de risque , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologieRÉSUMÉ
BACKGROUND: Gender-based differences in clinical outcomes of patients undergoing fractional flow reserved (FFR) guided coronary revascularization is well documented. This study aimed to compare resting full-cycle ratio (RFR) values between men and women and whether this translated into difference in clinical outcomes in patients who underwent RFR-guided coronary revascularization. METHODS: This was a retrospective single-centre study of consecutive patients who underwent RFR-guided revascularization for coronary lesions with intermediate degree of stenosis. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), unplanned revascularization, and unstable angina requiring hospital admission at one year. RESULTS: In 373 consecutive patients (510 lesions, 26% women) there was no statistically significant difference in RFR value between men and women (0.90 ± 10 versus 0.90 ± 11, P = 0.95). There was no statistically significant difference between men and women in the primary endpoint, even after adjustment to the imbalance between the two groups [3.7% vs. 3.0%; HR 1.43, 95% CI (0.46 to 4.43), P = 0.54]; or its individual components of death (1.1% vs 0.8%, P = 0.76), MI (1.9% vs 0.8%, P = 0.38) or unplanned revascularization, including unstable angina admissions (2.6% vs 2.3%, P = 0.82). The comparable clinical outcomes were consistent across all different subgroups, including clinical presentation, diabetes status, left ventricle systolic function, kidney function, and the interrogated coronary artery. CONCLUSION: Our study suggests no significant gender-based difference in the value of RFR or 1-year clinical outcomes in patients undergoing resting physiology guided coronary revascularization.
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Fraction du flux de réserve coronaire , Humains , Mâle , Femelle , Études rétrospectives , Adulte d'âge moyen , Sujet âgé , Fraction du flux de réserve coronaire/physiologie , Revascularisation myocardique/méthodes , Facteurs sexuels , Intervention coronarienne percutanée/méthodes , Sténose coronarienne/chirurgie , Sténose coronarienne/physiopathologie , Sténose coronarienne/imagerie diagnostique , Études de suivi , Caractères sexuels , Coronarographie , Résultat thérapeutiqueRÉSUMÉ
Optimal myocardial reperfusion during primary percutaneous coronary intervention (pPCI) is increasingly recognized to be beyond restoring epicardial coronary flow. Both invasive and non-invasive tools have highlighted the limitation of using this metric, and more efforts are focused towards achieving optimal reperfusion at the level of the microcirculation. Recent data highlighted the close relationship between thrombus burden and impaired microcirculation in patients presenting with ST-segment elevation myocardial infarction (STEMI). Moreover, distal embolization was an independent predictor of mortality in patients with STEMI. Likewise, the development of no-reflow phenomenon has been directly linked with worse clinical outcomes. Adjunctive thrombus aspiration during pPCI is intuitively intended to remove atherothrombotic material to mitigate the risk of distal embolization and the no-reflow phenomenon (NRP). However, prior trials on the use of thrombectomy during pPCI did not support its routine use, with comparable clinical endpoints to patients who underwent PCI alone. This article aims to review the existing literature highlighting the limitation on the use of thrombectomy and provide future insights into trials investigating the role of thrombectomy in contemporary pPCI.
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Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI.
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BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.
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Maladie des artères coronaires , Lithotritie , Calcification vasculaire , Humains , Maladie des artères coronaires/imagerie diagnostique , Maladie des artères coronaires/thérapie , Maladie des artères coronaires/étiologie , Études rétrospectives , Résultat thérapeutique , Calcification vasculaire/imagerie diagnostique , Calcification vasculaire/thérapie , Calcification vasculaire/étiologie , Lithotritie/effets indésirablesRÉSUMÉ
Contemporary randomised trials of percutaneous coronary intervention (PCI) in chronic coronary syndrome (CCS) demonstrate no difference between patients treated with a conservative or invasive strategy with respect to all-cause mortality or myocardial infarction, although trials lack power to test for individual endpoints and long-term follow-up data are needed. Open-label trials consistently show greater improvement in symptoms and quality of life among patients with stable angina treated with PCI. Further studies are awaited to clarify this finding. In patients with severe left ventricular (LV) systolic dysfunction and obstructive coronary artery disease in the Revascularization for Ischemic Ventricular Dysfunction trial, PCI has not been found to improve all-cause mortality, heart failure hospitalisation or recovery of LV function when compared with medical therapy. PCI was, however, performed without additional hazard and so remains a treatment option when there are favourable patient characteristics. The majority of patients reported no angina, and the low burden of angina in many of the randomised PCI trials is a widely cited limitation. Despite contentious evidence, elective PCI for CCS continues to play a significant role in UK clinical practice. While PCI for urgent indications has more than doubled since 2006, the rate of elective PCI remains unchanged. PCI remains an important strategy when symptoms are not well controlled, and we should maximise its value with appropriate patient selection. In this review, we provide a framework to assist in critical interpretation of findings from most recent trials and meta-analysis evidence.
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Angor stable , Maladie des artères coronaires , Infarctus du myocarde , Intervention coronarienne percutanée , Dysfonction ventriculaire gauche , Humains , Angor stable/thérapie , Maladie des artères coronaires/thérapie , Infarctus du myocarde/étiologie , Intervention coronarienne percutanée/effets indésirables , Qualité de vie , Résultat thérapeutique , Dysfonction ventriculaire gauche/étiologieRÉSUMÉ
AIMS: Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. METHODS AND RESULTS: In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. CONCLUSION: Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.
Sujet(s)
Sténose aortique , Bioprothèse , Prothèse valvulaire cardiaque , Mâle , Humains , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Valve aortique/imagerie diagnostique , Valve aortique/chirurgie , Valve aortique/anatomopathologie , Études prospectives , Lipoprotéine (a) , Sténose aortique/imagerie diagnostique , Sténose aortique/chirurgie , Échocardiographie/effets indésirables , Prothèse valvulaire cardiaque/effets indésirables , Bioprothèse/effets indésirablesRÉSUMÉ
BACKGROUND: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). METHODS: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. RESULTS: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001). CONCLUSIONS: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276.
Sujet(s)
Maladie de la valve aortique/physiopathologie , Prothèse valvulaire cardiaque/normes , Remplacement valvulaire aortique par cathéter/méthodes , Sujet âgé , Sujet âgé de 80 ans ou plus , Études de cohortes , Études transversales , Évolution de la maladie , Femelle , Humains , MâleRÉSUMÉ
BACKGROUND: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. METHODS: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. RESULTS: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. CONCLUSIONS: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.
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Alendronate/usage thérapeutique , Sténose aortique/imagerie diagnostique , Sténose aortique/traitement médicamenteux , Agents de maintien de la densité osseuse/usage thérapeutique , Dénosumab/usage thérapeutique , Évolution de la maladie , Sujet âgé , Sujet âgé de 80 ans ou plus , Sténose aortique/métabolisme , Méthode en double aveugle , Femelle , Humains , Mâle , Adulte d'âge moyen , Tomographie par émission de positons couplée à la tomodensitométrie , Résultat thérapeutique , Calcification vasculaire/imagerie diagnostique , Calcification vasculaire/traitement médicamenteux , Calcification vasculaire/métabolismeRÉSUMÉ
OBJECTIVES: Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. METHODS: This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. RESULTS: Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). CONCLUSIONS: Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.
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Sténose aortique/diagnostic , Valve aortique/imagerie diagnostique , Calcinose/diagnostic , Produits de contraste/pharmacologie , Tomodensitométrie multidétecteurs/méthodes , Sujet âgé , Évolution de la maladie , Femelle , Fibrose/diagnostic , Humains , Mâle , Adulte d'âge moyen , Indice de gravité de la maladieRÉSUMÉ
OBJECTIVE: CT quantification of aortic valve calcification (CT-AVC) is useful in the assessment of aortic stenosis severity. Our objective was to assess its ability to track aortic stenosis progression compared with echocardiography. METHODS: Subjects were recruited in two cohorts: (1) a reproducibility cohort where patients underwent repeat CT-AVC or echocardiography within 4 weeks and (2) a disease progression cohort where patients underwent annual CT-AVC and/or echocardiography. Cohen's d-statistic (d) was computed from the ratio of annualised progression and measurement repeatability and used to estimate group sizes required to detect annualised changes in CT-AVC and echocardiography. RESULTS: A total of 33 (age 71±8) and 81 participants (age 72±8) were recruited to the reproducibility and progression cohorts, respectively. Ten CT scans (16%) were excluded from the progression cohort due to non-diagnostic image quality. Scan-rescan reproducibility was excellent for CT-AVC (limits of agreement -12% to 10 %, intraclass correlation (ICC) 0.99), peak velocity (-7% to +17%; ICC 0.92) mean gradient (-25% to 27%, ICC 0.96) and dimensionless index (-11% to +15%; ICC 0.98). Repeat measurements of aortic valve area (AVA) were less reliable (-44% to +28%, ICC 0.85).CT-AVC progressed by 152 (65-375) AU/year. For echocardiography, the median annual change in peak velocity was 0.1 (0.0-0.3) m/s/year, mean gradient 2 (0-4) mm Hg/year and AVA -0.1 (-0.2-0.0) cm2/year. Cohen's d-statistic was more than double for CT-AVC (d=3.12) than each echocardiographic measure (peak velocity d=0.71 ; mean gradient d=0.66; AVA d=0.59, dimensionless index d=1.41). CONCLUSION: CT-AVC is reproducible and demonstrates larger increases over time normalised to measurement repeatability compared with echocardiographic measures.
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Sténose aortique/diagnostic , Valve aortique/imagerie diagnostique , Calcium/métabolisme , Tomodensitométrie multidétecteurs/méthodes , Sujet âgé , Valve aortique/métabolisme , Sténose aortique/métabolisme , Échocardiographie-doppler , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Reproductibilité des résultats , Études rétrospectives , Indice de gravité de la maladieSujet(s)
Sténose aortique , Calcinose , Valve aortique , Femelle , Humains , Mâle , Valeur prédictive des tests , Caractères sexuelsRÉSUMÉ
OBJECTIVES: The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque. BACKGROUND: High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. METHODS: In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18F-fluoride uptake. RESULTS: In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33). CONCLUSIONS: Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303).
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Intervention coronarienne percutanée , Plaque d'athérosclérose , Ticagrélor/usage thérapeutique , Vaisseaux coronaires , Humains , Mâle , Plaque d'athérosclérose/traitement médicamenteux , Antiagrégants plaquettaires , Valeur prédictive des tests , Études prospectives , Tomodensitométrie , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Bioprosthetic aortic valve degeneration is increasingly common, often unheralded, and can have catastrophic consequences. OBJECTIVES: The authors sought to assess whether 18F-fluoride positron emission tomography (PET)-computed tomography (CT) can detect bioprosthetic aortic valve degeneration and predict valve dysfunction. METHODS: Explanted degenerate bioprosthetic valves were examined ex vivo. Patients with bioprosthetic aortic valves were recruited into 2 cohorts with and without prosthetic valve dysfunction and underwent in vivo contrast-enhanced CT angiography, 18F-fluoride PET, and serial echocardiography during 2 years of follow-up. RESULTS: All ex vivo, degenerate bioprosthetic valves displayed 18F-fluoride PET uptake that colocalized with tissue degeneration on histology. In 71 patients without known bioprosthesis dysfunction, 14 had abnormal leaflet pathology on CT, and 24 demonstrated 18F-fluoride PET uptake (target-to-background ratio 1.55 [interquartile range (IQR): 1.44 to 1.88]). Patients with increased 18F-fluoride uptake exhibited more rapid deterioration in valve function compared with those without (annualized change in peak transvalvular velocity 0.30 [IQR: 0.13 to 0.61] vs. 0.01 [IQR: -0.05 to 0.16] ms-1/year; p < 0.001). Indeed 18F-fluoride uptake correlated with deterioration in all the conventional echocardiographic measures of valve function assessed (e.g., change in peak velocity, r = 0.72; p < 0.001). Each of the 10 patients who developed new overt bioprosthesis dysfunction during follow-up had evidence of 18F-fluoride uptake at baseline (target-to-background ratio 1.89 [IQR: 1.46 to 2.59]). On multivariable analysis, 18F-fluoride uptake was the only independent predictor of future bioprosthetic dysfunction. CONCLUSIONS: 18F-fluoride PET-CT identifies subclinical bioprosthetic valve degeneration, providing powerful prediction of subsequent valvular dysfunction and highlighting patients at risk of valve failure. This technique holds major promise in the diagnosis of valvular degeneration and the surveillance of patients with bioprosthetic valves. (18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome [18F-FAABULOUS]; NCT02304276).
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Insuffisance aortique , Sténose aortique/chirurgie , Valve aortique , Bioprothèse , Prothèse valvulaire cardiaque , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Complications postopératoires , Défaillance de prothèse/effets indésirables , Sujet âgé , Valve aortique/physiopathologie , Valve aortique/chirurgie , Insuffisance aortique/diagnostic , Insuffisance aortique/étiologie , Sténose aortique/diagnostic , Calcinose/diagnostic , Calcinose/étiologie , Angiographie par tomodensitométrie/méthodes , Échocardiographie/méthodes , Femelle , Fluorodésoxyglucose F18/pharmacologie , Humains , Mâle , Complications postopératoires/diagnostic , Complications postopératoires/étiologie , Valeur prédictive des tests , Pronostic , Radiopharmaceutiques/pharmacologieRÉSUMÉ
OBJECTIVES: This study investigated processes causing leaflet thickening and structural valve degeneration (SVD). BACKGROUND: Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes. METHODS: Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms. RESULTS: THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis. CONCLUSIONS: There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD.
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Valve aortique/anatomopathologie , Valve aortique/chirurgie , Prothèse valvulaire cardiaque , Défaillance de prothèse , Remplacement valvulaire aortique par cathéter/instrumentation , Sujet âgé , Sujet âgé de 80 ans ou plus , Valve aortique/enzymologie , Calcinose/étiologie , Calcinose/anatomopathologie , Ablation de dispositif , Cellules endothéliales/anatomopathologie , Femelle , Fibrose , Humains , Mâle , Matrix metalloproteinase 1/métabolisme , Conception de prothèse , Enregistrements , Études rétrospectives , Thrombose/étiologie , Thrombose/anatomopathologie , Facteurs temps , Remplacement valvulaire aortique par cathéter/effets indésirables , Résultat thérapeutiqueRÉSUMÉ
In the current era of transcatheter device therapy, the prevalence of prosthetic aortic valves and their associated complications is increasing. Echocardiography remains the first-line imaging investigation for the assessment of prosthetic valve complications, however, this often fails to identify the underlying mechanism of prosthesis failure. Recently, cardiac CT has emerged as an imaging technique capable of providing high isotropic spatial resolution of the prosthetic valve and its utility can provide important complementary diagnostic information. In this pictorial review, we present a series of common prosthetic aortic valve complications imaged with cardiac CT and demonstrate how use of this modality can enhance diagnostic accuracy.
Sujet(s)
Sténose aortique/imagerie diagnostique , Sténose aortique/chirurgie , Échocardiographie-doppler/méthodes , Prothèse valvulaire cardiaque/effets indésirables , Tomodensitométrie/méthodes , Remplacement valvulaire aortique par cathéter/effets indésirables , Sujet âgé , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Complications postopératoires/imagerie diagnostique , Défaillance de prothèse , Appréciation des risques , Remplacement valvulaire aortique par cathéter/méthodes , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. METHODS AND RESULTS: Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P=0.010). CONCLUSIONS: Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.
Sujet(s)
Sténose aortique/diagnostic , Valve aortique/imagerie diagnostique , Calcinose/diagnostic , Calcium/métabolisme , Tomodensitométrie multidétecteurs/méthodes , Enregistrements , Sujet âgé , Sujet âgé de 80 ans ou plus , Sténose aortique/étiologie , Sténose aortique/chirurgie , Calcinose/complications , Calcinose/métabolisme , Échocardiographie-doppler , Femelle , Prothèse valvulaire cardiaque , Humains , Mâle , Pronostic , Études prospectives , Indice de gravité de la maladieRÉSUMÉ
Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management.