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Amiloidose , Ecocardiografia Transesofagiana , Cardioversão Elétrica , Humanos , Ecocardiografia Transesofagiana/métodos , Masculino , Cardioversão Elétrica/métodos , Amiloidose/diagnóstico por imagem , Amiloidose/terapia , Feminino , Idoso , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Pessoa de Meia-Idade , Fibrilação Atrial/terapia , Fibrilação Atrial/diagnóstico por imagemRESUMO
BACKGROUND: Quantitative technetium-99m-pyrophosphate cardiac single photon emission computed tomography (99mTc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99mTc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function. METHODS: This prospective longitudinal cohort study investigated changes in 99mTc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVmax, SUVmean), cardiac amyloid activity (CAA; SUVmean*LV activity volume), and percent injected dose (%ID) (mean activity concentration*LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test. RESULTS: Following therapy, visual grade decreased significantly (p=0.003). Several quantitative 99mTc-PYP metrics also decreased significantly: SUVmax (median -0.75, p=0.011), CAA (median -406.6, p<0.001), and %ID (median -0.45, p<0.001). Serum transthyretin levels improved (median +6.5 mg/dL, p=0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable. CONCLUSION: Favorable changes in 99mTc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, while echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than amyloid burden regression. Further investigation is needed to understand the implications of these findings.
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Cardiac amyloidosis includes a group of protein-misfolding diseases characterized by fibril accumulation within the extracellular space of the myocardium and cardiac dysfunction. Cardiac amyloidosis has high mortality. Emerging radionuclide techniques have helped us to better understand disease pathogenesis, prognostication, and treatment response in cardiac amyloidosis. PURPOSE OF REVIEW: To review recent advances in molecular imaging of cardiac amyloidosis using amyloid PET radiotracers. RECENT FINDINGS: Multiple single center studies have shown that amyloid PET radiotracers allow definitive diagnosis and quantification of cardiac amyloid burden. These amyloid targeting tracers may provide means to improve early disease detection, risk stratification and treatment monitoring. Amyloid PET imaging may inform definitive imaging-based diagnosis for therapeutic decisions, risk stratification, and treatment monitoring. More research in unselected cohorts of patients with suspected cardiac amyloidosis is needed to optimize the clinical implementation of amyloid PET imaging.
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Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95-98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8-11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96-2.48) for IFN-based therapy, 4.27% (95% CI 2.93-6.2) for DAA and 0.89% (95% CI 0.4-1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment.
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BACKGROUND: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor outcomes. OBJECTIVES: The authors' objectives were to detect early myocardial alterations, to analyze longitudinal changes with therapy, and to predict major adverse cardiac events (MACE) in participants with AL amyloidosis using cardiac magnetic resonance imaging (MRI). METHODS: Recently diagnosed participants were prospectively enrolled. AL amyloidosis with and without cardiomyopathy (AL-CMP, AL-non-CMP) were defined based on abnormal cardiac biomarkers and wall thickness. MRI was performed at baseline, 6 months in all participants, and 12 months in participants with AL-CMP. MACE were defined as all-cause death, heart failure hospitalization, and cardiac transplantation. Mayo stage was based on troponin T, N-terminal pro-B-type natriuretic peptide, and difference in free light chains. RESULTS: This study included 80 participants (median age 62 years, 58% men). Extracellular volume (ECV) was abnormal (>32%) in all participants with AL-CMP and in 47% of those with AL-non-CMP. ECV tended to increase at 6 months (median +2%; AL-CMP P = 0.120; AL-non-CMP P = 0.018) and returned to baseline values at 12 months in participants with AL-CMP. Global longitudinal strain (GLS) improved at 6 months (median -0.6%; P = 0.048) and 12 months (median -1.2%; P < 0.001) in participants with AL-CMP. ECV and GLS were strongly associated with MACE (P < 0.001) and improved the prognostic value when added to Mayo stage (P ≤ 0.002). No participant with ECV ≤32% had MACE, while 74% of those with ECV >48% had MACE. CONCLUSIONS: In patients with systemic AL amyloidosis, ECV detects subclinical myocardial alterations. With therapy, ECV tends to increase at 6 months and returns to values unchanged from baseline at 12 months, whereas GLS improves at 6 and 12 months in participants with AL-CMP. ECV and GLS offer additional prognostic performance over Mayo stage. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).
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BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS: A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS: SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.
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Antivirais , Hepatite C Crônica , Cirrose Hepática , Resposta Viral Sustentada , Humanos , Hepatite C Crônica/tratamento farmacológico , Suíça/epidemiologia , Masculino , Feminino , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Hepacivirus/genética , Falha de Tratamento , Genótipo , Carcinoma Hepatocelular , Neoplasias Hepáticas , AdultoRESUMO
Cardiac amyloidosis (CA) is caused by the misfolding, accumulation and aggregation of proteins into large fibrils in the extracellular compartment of the myocardium, leading to restrictive cardiomyopathy, heart failure and death. The major forms are transthyretin (ATTR) CA and light-chain (AL) CA, based on the respective precursor protein. Each of them requires early diagnosis for a timely treatment initiation that will improve patient outcomes. For this, radionuclide imaging is essentially used as single-photon emission computed tomography (SPECT) with bone-avid radiotracers or as positron emission tomography (PET) with amyloid-binding radiotracers. Both offer unprecedented specificity for the diagnostic of CA. SPECT has even revolutionized the diagnosis of ATTR-CA by making it non-invasive. Indeed, SPECT has now entered the standard diagnostic pathway to CA and has led to earlier diagnosis of the disease. SPECT also modified the epidemiology of ATTR-CA, highlighting that the disease is much more frequent than previously believed, and showing that ATTR-CA plays a substantial role in HFpEF and aortic stenosis, particularly among elderly patients. In parallel, amyloid-binding radiotracers for PET have accumulated a substantial amount of evidence, but are not approved for clinical use in CA yet. Further studies are needed to refine acquisition protocols and validate results in broader populations. Unlike bone-avid SPECT radiotracers, PET radiotracers have been specifically created to bind to amyloid fibrils. Thus, PET is the only imaging method that is truly specific for amyloid deposits and very sensitive to any amyloid type. Indeed, PET can not only detect ATTR-CA, but also AL-CA and rare hereditary forms. For both SPECT and PET, advances in quantitation of myocardial uptake have generated more granular and reproducible findings, paving the way for progress in earlier diagnosis, risk stratification and therapeutic response monitoring. Encouraging findings have shown that SPECT and PET are sensitive to early CA when other diagnostic methods are negative. Both radionuclide imaging techniques can predict adverse outcomes, but more evidence is needed to determine how to use them in conjunction with usual prognostic staging scores. Studies on follow-up imaging after therapy suggested that SPECT and PET can capture myocardial changes in CA, but again, more data are needed to meaningfully interpret such changes. Based on all these promising results, radionuclide imaging has the potential to further impact the landscape of CA in diagnosis, prognosis and follow-up, but also to substantially contribute to the assessment of novel therapies that will improve the lives of patients with CA.
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Amiloidose , Humanos , Amiloidose/diagnóstico por imagem , Cintilografia/métodosRESUMO
BACKGROUND: Positron emission tomography/computed tomography (PET/CT) with 18F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known. OBJECTIVES: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes. METHODS: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. RESULTS: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage. CONCLUSIONS: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.
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Compostos de Anilina , Etilenoglicóis , Amiloidose de Cadeia Leve de Imunoglobulina , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Compostos Radiofarmacêuticos/administração & dosagem , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Prognóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/sangue , Fatores de Risco , Função Ventricular Esquerda , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/metabolismo , Fatores de Tempo , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Biomarcadores/sangue , Transplante de Coração/efeitos adversos , Medição de Risco , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Cardiomiopatias/mortalidade , Cadeias Leves de Imunoglobulina/metabolismoRESUMO
Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood. Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis. Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass. Results: Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21â ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden. Conclusions: In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.
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Recent European Association of Urology (EAU) guidelines and a clinical prediction rule developed by Van Nieuwkoop et al. suggest simple criteria for performing radiological imaging for patients with a febrile urinary tract infection (UTI). We analysed the records of patients with a UTI from four hospitals in Switzerland. Of 107 UTI patients, 58% underwent imaging and 69% (95%CI: 59-77%) and 64% (95%CI: 54-73%) of them were adequately managed according to Van Nieuwkoop's clinical rule and EAU guidelines, respectively. However, only 47% (95%CI: 33-61%) and 57% (95%CI: 44-69%) of the imaging performed would have been recommended according to their respective rules. Clinically significant imaging findings were associated with a history of urolithiasis (OR = 11.8; 95%CI: 3.0-46.5), gross haematuria (OR = 5.9; 95%CI: 1.6-22.1) and known urogenital anomalies (OR = 5.7; 95%CI: 1.8-18.2). Moreover, six of 16 (38%) patients with a clinically relevant abnormality displayed none of the criteria requiring imaging according to Van Nieuwkoop's rule or EAU guidelines. Thus, adherence to imaging guidelines was suboptimal, especially when imaging was not recommended. However, additional factors associated with clinically significant findings suggest the need for a new, efficient clinical prediction rule.
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AIMS: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation). METHODS AND RESULTS: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography. 18F-florbetapir PET/CT identified RV amyloid in 63% of those with and 40% of those without cardiac involvement by conventional criteria. RV amyloid burden correlated with RV ejection fraction (EF), RV free wall longitudinal strain (FWLS), RV wall thickness, RV mass index, N-terminal pro-brain natriuretic peptide, troponin T, LV amyloid, and lung amyloid (each P < 0.001). In multivariable analysis, RV amyloid burden, but not LV or lung amyloid burden, predicted RV dysfunction (EF P = 0.014; FWLS P < 0.001). During a median follow-up of 28 months, RV amyloid burden predicted MACE (P < 0.001). CONCLUSION: This study shows for the first time that 18F-florbetapir PET/CT identifies early RV amyloid in systemic AL amyloidosis prior to alterations in RV structure and function. Increasing RV amyloid on 18F-florbetapir PET/CT is associated with worse RV structure and function, predicts RV dysfunction, and predicts MACE. These results imply a central role for RV amyloid in the pathogenesis of RV dysfunction.
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Compostos de Anilina , Etilenoglicóis , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Disfunção Ventricular Direita , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Disfunção Ventricular Direita/diagnóstico por imagem , Idoso , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Compostos Radiofarmacêuticos , Ventrículos do Coração/diagnóstico por imagemRESUMO
The origin of face or language influences infants' perceptual processing and social learning behavior. However, it remains unclear how infants' social learning behavior is affected when both information are provided simultaneously. Hence, the current study investigated whether and how infants' social learning in terms of gaze following is influenced by face race and language origin of an interaction partner in an uncertain situation. Our sample consisted of 91 Caucasian infants from German speaking families. They were divided into 2 age groups: Younger infants were 5- to 8-month-old (n = 46) and the older infants 11- to 20-month-old (n = 45). We used a modified online version of the gaze following paradigm by Xiao and colleagues by varying face race (Caucasian, and Asian faces) and language (German and French) of a female actor. We recorded infants looking behavior via webcam and coded it offline. Our results revealed that older but not younger infants were biased to follow the gaze of own-race adults speaking their native language. Our findings show that older infants are clearly influenced by adults' ethnicity and language in social learning situations of uncertainty.
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Aprendizado Social , Fala , Lactente , Adulto , Humanos , Feminino , Incerteza , Aprendizagem , IdiomaRESUMO
Aims: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor prognosis. Using myocardial characteristics on magnetic resonance imaging (MRI), this study aimed to detect early myocardial alterations, to analyze temporal changes with plasma cell therapy, and to predict risk of major adverse cardiac events (MACE) in AL amyloidosis. Methods and Results: Participants with recently diagnosed AL amyloidosis were prospectively enrolled. Presence of AL cardiomyopathy (AL-CMP vs. AL-non-CMP) was determined by abnormal cardiac biomarkers. MRI was performed at baseline and 6 months, with 12-month imaging in AL-CMP cohort. MACE was defined as all-cause death, heart failure hospitalization, or cardiac transplantation. Mayo AL stage was based on troponin T, NT-proBNP, and difference in free light chains. The study cohort included 80 participants (median age 62 years, 58% males). Median left ventricular extracellular volume (ECV) was significantly higher in AL-CMP (53% vs. 30%, p<0.001). ECV was abnormal (>32%) in all AL-CMP and in 47% of AL-non-CMP. ECV tended to increase at 6 months and decreased significantly from 6 to 12 months in AL-CMP (median -3%, p=0.011). ECV was strongly associated with MACE (p<0.001), and improved MACE prediction when added to Mayo AL stage (p=0.002). ECV≤32% identified a cohort without MACE, while ECV>48% identified a cohort with 74% MACE. Conclusions: In AL amyloidosis, ECV detects subclinical cardiomyopathy. ECV tends to increase from baseline to 6 months and decreases significantly from 6 and 12 months of plasma cell therapy in AL-CMP. ECV provides excellent risk stratification and offers additional prognostic performance over Mayo AL stage.
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Background: Myocardial immunoglobulin light-chain (AL) amyloid deposits trigger heart failure, cardiomyocyte stretch and myocardial injury, leading to adverse cardiac outcomes. Positron emission tomography/computed tomography (PET/CT) with 18 F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden, but its prognostic value is not known. Therefore, we aimed to evaluate the prognostic value of LV amyloid burden quantified by 18 F-florbetapir PET/CT and to identify mechanistic pathways mediating its association with outcomes. Methods: Eighty-one participants with newly-diagnosed systemic AL amyloidosis were prospectively enrolled and underwent 18 F-florbetapir PET/CT. LV amyloid burden was quantified using 18 F-florbetapir LV percent injected dose (%ID). Mayo AL stage was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and difference between involved and uninvolved free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. Results: Among participants (median age 61 years, 57% males), 36% experienced MACE. Incidence of MACE increased across tertiles of LV amyloid burden from 7% to 63% (p<0.001). LV amyloid burden was significantly associated with MACE in univariable analysis (hazard ratio 1.45, 95% confidence interval 1.15-1.82, p=0.002). However, this association became non-significant in multivariable analyses adjusted for Mayo AL stage. Mediation analysis showed that the association between 18 F-florbetapir LV %ID and MACE was primarily mediated by NT-proBNP (p<0.001), a marker of cardiomyocyte stretch and component of Mayo AL stage. Conclusion: In this first study to link cardiac 18 F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by LV %ID predicted MACE in AL amyloidosis. But this effect was not independent of Mayo AL stage. LV amyloid burden was associated with MACE primarily via NT-pro-BNP, a marker of cardiomyocyte stretch and component of Mayo AL stage. These findings provide novel insights into the mechanism through which myocardial AL amyloid leads to MACE. Clinical Perspective: In systemic light-chain (AL) amyloidosis, cardiac involvement is the key determinant of adverse outcomes. Usually, prognosis is based on the Mayo AL stage, determined by troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the difference between involved and uninvolved immunoglobulin free light chain levels (dFLC). Cardiac amyloid burden is not considered in this staging. In the present study, we used the amyloid-specific radiotracer 18 F-florbetapir to quantify left ventricular (LV) amyloid burden in 81 participants with newly-diagnosed AL amyloidosis and evaluated its prognostic value on major adverse outcomes (MACE: all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months). We found that higher LV amyloid burden by 18 F-florbetapir positron emission tomography/computed tomography (PET/CT) was strongly associated with MACE. However, this association became non-significant after adjustment for the Mayo AL stage. Mediation analysis offered novel pathophysiological insights, implying that LV amyloid burden leads to MACE predominantly through cardiomyocyte stretch and light chain toxicity (by NT-proBNP), rather than through myocardial injury (by troponin T), also considering the severity of plasma cell dyscrasia (by dFLC). This mediation by NT-proBNP may explain why the association with outcomes was non-significant with adjustment for Mayo AL stage. Together, these results establish quantitative 18 F-florbetapir PET/CT as a valid method to predict adverse outcomes in AL amyloidosis. These results support the use of 18 F-florbetapir PET/CT to measure the effects of novel fibril-depleting therapies, in addition to plasma cell therapy, to improve outcomes in systemic AL amyloidosis.
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BACKGROUND: Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. 124I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins. Its ability to quantify cardiac amyloid has not yet been investigated. OBJECTIVES: The objectives of this pilot study were to quantify myocardial 124I-evuzamitide uptake and to compare its diagnostic value to 18F-florbetapir in participants with amyloid CMP and control subjects. METHODS: This study included 46 participants: 12 with light-chain (AL) CMP, 12 with wild-type transthyretin (ATTRwt) CMP, 2 with hereditary amyloidosis, and 20 control subjects. All amyloidosis participants underwent positron emission tomography/computed tomography with 124I-evuzamitide and 18F-florbetapir. Control subjects underwent 124I-evuzamitide (n = 10) or 18F-florbetapir (n = 8) positron emission tomography/computed tomography. Left ventricular percent injected dose (LV% ID) was measured as mean activity concentration × myocardial volume/injected activity. High LV %ID was defined using Youden's index. RESULTS: In CMP participants, median age was 74 years and 92% were men. 124I-evuzamitide LV %ID differed across groups: median AL-CMP 1.48 (IQR: 1.12-1.89), ATTRwt-CMP 2.12 (IQR: 1.66-2.47), and control subjects 0.00 (IQR: 0.00-0.01; overall P < 0.001). High LV %ID perfectly discriminated CMP from control subjects. Discrimination performance was similar for 18F-florbetapir LV %ID. Notably, for ATTRwt-CMP, LV %ID was higher with 124I-evuzamitide than 18F-florbetapir (P = 0.002). 124I-evuzamitide LV %ID was correlated with interventricular septum thickness (Spearman's ρ = 0.78) and LV global longitudinal strain (ρ = 0.54) from echocardiography, and with LV mass index (ρ = 0.82) and extracellular volume (ρ = 0.51) from cardiac magnetic resonance. CONCLUSIONS: 124I-evuzamitide demonstrates uptake by cardiac amyloid and accurately discriminates amyloid CMP from control subjects. In AL-CMP, discrimination performance is similar to 18F-florbetapir. In ATTRwt-CMP, performance may be better with 124I-evuzamitide. Moderate-to-strong correlations of 124I-evuzamitide uptake with cardiac structural and functional metrics suggest valid amyloid quantification. Hence, 124I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid.
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Amiloidose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Humanos , Idoso , Feminino , Projetos Piloto , Valor Preditivo dos Testes , Amiloide , Proteínas Amiloidogênicas/metabolismoRESUMO
BACKGROUND: Little is known about the gatekeeper performance of coronary artery calcium score (CACS) before myocardial perfusion positron emission tomography (PET), compared with updated pre-test probabilities from American and European guidelines (pre-test-AHA/ACC, pre-test-ESC). METHODS: We enrolled participants without known coronary artery disease undergoing CACS and Rubidium-82 PET. Abnormal perfusion was defined as summed stress score ≥ 4. Using Bayes' formula, pre-test probabilities and CACS were combined into post-test probabilities. RESULTS: We included 2050 participants (54% male, mean age 64.6 years) with median CACS 62 (IQR 0-380), pre-test-ESC 17% (11-26), pre-test-AHA/ACC 27% (16-44), and abnormal perfusion in 437 participants (21%). To predict abnormal perfusion, area under the curve of CACS was 0.81, pre-test-AHA/ACC 0.68, pre-test-ESC 0.69, post-test-AHA/ACC 0.80, and post-test-ESC 0.81 (P < 0.001 for CACS vs. each pre-test, and each post-test vs. pre-test). CACS = 0 had 97% negative predictive value (NPV), pre-test-AHA/ACC ≤ 5% 100%, pre-test-ESC ≤ 5% 98%, post-test-AHA/ACC ≤ 5% 98%, and post-test-ESC ≤ 5% 96%. Among participants, 26% had CACS = 0, 2% pre-test-AHA/ACC ≤ 5%, 7% pre-test-ESC ≤ 5%, 23% post-test-AHA/ACC ≤ 5%, and 33% post-test-ESC ≤ 5% (all P < 0.001). CONCLUSIONS: CACS and post-test probabilities are excellent predictors of abnormal perfusion and can rule it out with very high NPV in a substantial proportion of participants. CACS and post-test probabilities may be used as gatekeepers before advanced imaging. Coronary artery calcium score (CACS) predicted abnormal perfusion (SSS ≥ 4) in myocardial positron emission tomography (PET) better than pre-test probabilities of coronary artery disease (CAD), while pre-test-AHA/ACC and pre-test-ESC performed similarly (left). Using Bayes' formula, pre-test-AHA/ACC or pre-test-ESC were combined with CACS into post-test probabilities (middle). This calculation reclassified a substantial proportion of participants to low probability of CAD (0-5%), not needing further imaging, as shown for AHA/ACC probabilities (2% with pre-test-AHA/ACC to 23% with post-test-AHA/ACC, P < 0.001, right). Very few participants with abnormal perfusion were classified under pre-test or post-test probabilities 0-5%, or under CACS 0. AUC: area under the curve. Pre-test-AHA/ACC: Pre-test probability of the American Heart Association/American College of Cardiology. Post-test-AHA/ACC: Post-test probability combining pre-test-AHA/ACC and CACS. Pre-test-ESC: Pre-test probability of the European Society of Cardiology. SSS: Summed stress score.
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Doença da Artéria Coronariana , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Cálcio , Teorema de Bayes , Tomografia Computadorizada por Raios X , Tomografia por Emissão de Pósitrons , PerfusãoRESUMO
PURPOSE: The objective of this study was to quantify secondary prevention care by creating a secondary prevention benchmark (2PBM) score for patients undergoing ambulatory cardiac rehabilitation (CR) after acute coronary syndrome (ACS). METHODS: In this observational cohort study, 472 consecutive ACS patients who completed the ambulatory CR program between 2017 and 2019 were included. Benchmarks for secondary prevention medication and clinical and lifestyle targets were predefined and combined in the comprehensive 2PBM score with maximum 10 points. The association of patient characteristics and achievement rates of components and the 2PBM were assessed using multivariable logistic regression analysis. RESULTS: Patients were on average 62 ± 11 yr of age and predominantly male (n = 406; 86%). The types of ACS were ST-elevation myocardial infarction (STEMI) in 241 patients (51%) and non-ST-elevation myocardial infarction in 216 patients (46%). Achievement rates for components of the 2PBM were 71% for medication, 35% for clinical benchmark, and 61% for lifestyle benchmark. Achievement of medication benchmark was associated with younger age (OR = 0.979: 95% CI, 0.959-0.996, P = .021), STEMI (OR = 2.05: 95% CI, 1.35-3.12, P = .001), and clinical benchmark (OR = 1.80: 95% CI, 1.15-2.88, P = .011). Overall ≥8 of 10 points were reached by 77% and complete 2PBM by 16%, which was independently associated with STEMI (OR = 1.79: 95% CI, 1.06-3.08, P = .032). CONCLUSIONS: Benchmarking with 2PBM identifies gaps and achievements in secondary prevention care. ST-elevation myocardial infarction was associated with the highest 2PBM scores, suggesting best secondary prevention care in patients after ST-elevation myocardial infarction.
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Síndrome Coronariana Aguda , Infarto do Miocárdio sem Supradesnível do Segmento ST , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Síndrome Coronariana Aguda/prevenção & controle , Síndrome Coronariana Aguda/complicações , Benchmarking , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Prevenção Secundária , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings. METHODS: Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients. RESULTS: Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively. CONCLUSIONS: ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.
Assuntos
Calcinose , Doença da Artéria Coronariana , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Cálcio , Rubídio , Angiografia Coronária/métodos , Prognóstico , Calcinose/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Valor Preditivo dos TestesRESUMO
AIMS: Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed. METHODS AND RESULTS: Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis. CONCLUSION: At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments. STUDY REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02573532.
Assuntos
Cardiopatias , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Prospectivos , Fatores de Risco , Biomarcadores , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/epidemiologia , Cardiopatias/complicaçõesRESUMO
To prevent the spread of COVID-19, face masks were mandatory in many public spaces around the world. Since faces are the gateway to early social cognition, this raised major concerns about the effect face masks may have on infants' attention to faces as well as on their language and social development. The goal of the present study was to assess how face masks modulate infants' attention to faces over the course of the first year of life. We measured 3, 6, 9, and 12-month-olds' looking behavior using a paired visual preference paradigm under two experimental conditions. First, we tested infants' preference for upright masked or unmasked faces of the same female individual. We found that regardless of age, infants looked equally long at the masked and unmasked faces. Second, we compared infants' attention to an upright masked versus an inverted masked face. Three- and 6-month-olds looked equally long to the masked faces when they were upright or inverted. However, 9- and 12-month-old infants showed a novelty preference for the inverted masked face. Our findings suggest that more experience with faces, including masked faces, leads to efficient adaptations of infants' visual system for processing impoverished social stimuli, such as partially occluded faces.