Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.3685
A Collado, R Humoud, E Kontidou, J Swaich, J Yang, A Mahdi, J Tengbom, Z Zhou, J Pernow
Background Recently, we have demonstrated that red blood cells (RBCs) from individuals with type 2 diabetes (T2D-RBCs) induce endothelial dysfunction. However, the mechanism by which RBCs communicate with the vessel is unknown. Extracellular vesicles (EVs) are actively secreted by practically all cell types, including RBCs, and represent a novel mechanism of intercellular communication. However, the involvement of EVs from RBC in the development of endothelial dysfunction remains to be elucidated. Purpose This study was designed to test the hypothesis that EVs are key players in the communication and the transfer of signalling between RBCs and the vascular endothelium to induce endothelial dysfunction in T2D. Methods RBCs from T2D patients and age-matched healthy controls (H-RBCs) were incubated for 18h with Krebs-Henseleit buffer (20% haematocrit) for EV release. RBC-derived EVs in the conditioned medium were isolated using a membrane affinity column. The EVs were co-incubated with mouse aortae to evaluate endothelium-dependent relaxation and with endothelial cells for expression analysis. The uptake of the EVs by endothelial cells and their content of arginase-1 were determined. The functional involvement of arginase was investigated using pharmacological interventions and expression analyses. All animal experiments were performed according to the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and human procedures according to the declaration of Helsinki with approval by the Swedish Ethical Review Authority. Results The uptake of EVs derived from T2D-RBCs by endothelial cells was 2-fold greater than that of EVs from H-RBCs (Fig. 1A-B). Inhibiting the uptake of EVs derived from T2D-RBCs by the addition of heparin during the co-incubation rescued the endothelial function (Fig. 1C). Arginase-1 was detected in RBC-derived EVs (Fig. 2A). Arginase-1 mRNA and protein levels were increased in endothelial cells following co-incubation with EVs derived from T2D-RBCs (Fig. 2B-D). Additionally, the increase in arginase-1 protein induced by EVs derived from T2D-RBCs in endothelial cells was observed also following mRNA silencing for arginase-1 (Fig. 2E-F). Finally, mouse aortae co-incubated with EVs derived from T2D-RBCs in the presence or absence of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid significantly attenuated the impairment in endothelial function induced by EVs derived from T2D-RBCs (Fig. 2G). Conclusion Increased uptake of RBC-derived EVs by the endothelial cells is an important feature of the endothelial dysfunction induced by these EVs in T2D. In addition, these EVs carry arginase-1 protein to induce endothelial dysfunction. The mechanism underlying the increased uptake of EVs in target cells is of importance to identify in future studies, as it could lead to new treatment strategies.
{"title":"Increased endothelial cell uptake of erythrocyte-derived extracellular vesicles carrying arginase-1 induces endothelial dysfunction in type 2 diabetes","authors":"A Collado, R Humoud, E Kontidou, J Swaich, J Yang, A Mahdi, J Tengbom, Z Zhou, J Pernow","doi":"10.1093/eurheartj/ehae666.3685","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.3685","url":null,"abstract":"Background Recently, we have demonstrated that red blood cells (RBCs) from individuals with type 2 diabetes (T2D-RBCs) induce endothelial dysfunction. However, the mechanism by which RBCs communicate with the vessel is unknown. Extracellular vesicles (EVs) are actively secreted by practically all cell types, including RBCs, and represent a novel mechanism of intercellular communication. However, the involvement of EVs from RBC in the development of endothelial dysfunction remains to be elucidated. Purpose This study was designed to test the hypothesis that EVs are key players in the communication and the transfer of signalling between RBCs and the vascular endothelium to induce endothelial dysfunction in T2D. Methods RBCs from T2D patients and age-matched healthy controls (H-RBCs) were incubated for 18h with Krebs-Henseleit buffer (20% haematocrit) for EV release. RBC-derived EVs in the conditioned medium were isolated using a membrane affinity column. The EVs were co-incubated with mouse aortae to evaluate endothelium-dependent relaxation and with endothelial cells for expression analysis. The uptake of the EVs by endothelial cells and their content of arginase-1 were determined. The functional involvement of arginase was investigated using pharmacological interventions and expression analyses. All animal experiments were performed according to the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and human procedures according to the declaration of Helsinki with approval by the Swedish Ethical Review Authority. Results The uptake of EVs derived from T2D-RBCs by endothelial cells was 2-fold greater than that of EVs from H-RBCs (Fig. 1A-B). Inhibiting the uptake of EVs derived from T2D-RBCs by the addition of heparin during the co-incubation rescued the endothelial function (Fig. 1C). Arginase-1 was detected in RBC-derived EVs (Fig. 2A). Arginase-1 mRNA and protein levels were increased in endothelial cells following co-incubation with EVs derived from T2D-RBCs (Fig. 2B-D). Additionally, the increase in arginase-1 protein induced by EVs derived from T2D-RBCs in endothelial cells was observed also following mRNA silencing for arginase-1 (Fig. 2E-F). Finally, mouse aortae co-incubated with EVs derived from T2D-RBCs in the presence or absence of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid significantly attenuated the impairment in endothelial function induced by EVs derived from T2D-RBCs (Fig. 2G). Conclusion Increased uptake of RBC-derived EVs by the endothelial cells is an important feature of the endothelial dysfunction induced by these EVs in T2D. In addition, these EVs carry arginase-1 protein to induce endothelial dysfunction. The mechanism underlying the increased uptake of EVs in target cells is of importance to identify in future studies, as it could lead to new treatment strategies.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"194 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2303
K Al-Chaer, A Alhakak, N Vinding, J H Butt, S P Johnsen, C R Kruuse, M Schou, C Torp-Pedersen, L Koeber, E Fosboel
Background The ABCD2-score is a validated risk score used to estimate the short-term risk of stroke after transient ischemic attack (TIA). However, "real-world" contemporary data on the long-term risk of stroke after TIA according to ABCD2-score are needed in order to guide preventive strategies. Purpose To determine the long-term risk of stroke after TIA according to modified ABCD2-score (high-risk (≥4 points) versus low-risk (<4 points)). Methods Patients aged ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified in high-risk (≥4 points) and low-risk (<4 points) ABCD2-score group. We utilized a modified ABCD2-score consisting of the following parameters: age ≥60 years, hypertension, clinical features, and diabetes. The 3-year risk of ischemic stroke and all-cause mortality was compared between the high-risk and low-risk group using the Aalen-Johansen and Kaplan-Meier estimator. A cox regression model was also conducted. Results In total, 21,433 patients with first-time TIA were included; 1,281 (6.0%) in the high-risk and 20,152 (94.0%) in the low-risk group. Patients in the high-risk group were older (77.5 years [interquartile range [IQR] 70.8-84.1] versus 70.3 years [IQR 60.1-78.2]), more often females (52.2% versus 46.6%) (p <0.001), more comorbid and received more medication compared with the low-risk group at baseline. The 3-year cumulative incidence of stroke was 6.0% [95% CI: 4.6-7.5] in the high-risk group and 4.2% [95% CI: 3.9-4.5] in the low-risk group, and the unadjusted hazard ratio (HR) was 1.6 (95% CI 1.2 – 2.0) (Figure 1). The cumulative incidence of all-cause mortality within three-years after TIA was 28.9% [95% CI: 26.1-31.7] in the high-risk group and 10.3% [95% CI: 9.9-10.8] in the low-risk group. The unadjusted HR was 3.2 (95% CI 2.8 – 3.6). Conclusions Patients with high-risk ABCD2-scores had an almost two-fold higher associated long-term stroke-rate compared to those with low-risk scores. Trials focusing on preventive measures, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.
{"title":"High ABCD2-score after transient ischemic attack is associated with a two-fold higher stroke-rate during long-term follow-up","authors":"K Al-Chaer, A Alhakak, N Vinding, J H Butt, S P Johnsen, C R Kruuse, M Schou, C Torp-Pedersen, L Koeber, E Fosboel","doi":"10.1093/eurheartj/ehae666.2303","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2303","url":null,"abstract":"Background The ABCD2-score is a validated risk score used to estimate the short-term risk of stroke after transient ischemic attack (TIA). However, \"real-world\" contemporary data on the long-term risk of stroke after TIA according to ABCD2-score are needed in order to guide preventive strategies. Purpose To determine the long-term risk of stroke after TIA according to modified ABCD2-score (high-risk (≥4 points) versus low-risk (&lt;4 points)). Methods Patients aged ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified in high-risk (≥4 points) and low-risk (&lt;4 points) ABCD2-score group. We utilized a modified ABCD2-score consisting of the following parameters: age ≥60 years, hypertension, clinical features, and diabetes. The 3-year risk of ischemic stroke and all-cause mortality was compared between the high-risk and low-risk group using the Aalen-Johansen and Kaplan-Meier estimator. A cox regression model was also conducted. Results In total, 21,433 patients with first-time TIA were included; 1,281 (6.0%) in the high-risk and 20,152 (94.0%) in the low-risk group. Patients in the high-risk group were older (77.5 years [interquartile range [IQR] 70.8-84.1] versus 70.3 years [IQR 60.1-78.2]), more often females (52.2% versus 46.6%) (p &lt;0.001), more comorbid and received more medication compared with the low-risk group at baseline. The 3-year cumulative incidence of stroke was 6.0% [95% CI: 4.6-7.5] in the high-risk group and 4.2% [95% CI: 3.9-4.5] in the low-risk group, and the unadjusted hazard ratio (HR) was 1.6 (95% CI 1.2 – 2.0) (Figure 1). The cumulative incidence of all-cause mortality within three-years after TIA was 28.9% [95% CI: 26.1-31.7] in the high-risk group and 10.3% [95% CI: 9.9-10.8] in the low-risk group. The unadjusted HR was 3.2 (95% CI 2.8 – 3.6). Conclusions Patients with high-risk ABCD2-scores had an almost two-fold higher associated long-term stroke-rate compared to those with low-risk scores. Trials focusing on preventive measures, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"18 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2054
Z Ashkir, A Abd Samat, L Finnigan, M A Ahktar, N Beyhoff, R Sarwar, E Wicks, O Rider, L Valkovic, M Mahmod, H Watkins, S Neubauer, B Raman
Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p<0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.
{"title":"Impaired myocardial energetics in both sarcomere positive and negative HCM are linked to arrhythmic risk","authors":"Z Ashkir, A Abd Samat, L Finnigan, M A Ahktar, N Beyhoff, R Sarwar, E Wicks, O Rider, L Valkovic, M Mahmod, H Watkins, S Neubauer, B Raman","doi":"10.1093/eurheartj/ehae666.2054","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2054","url":null,"abstract":"Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p&lt;0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"63 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2070
H Malkonen, J Lehtonen, P Poyhonen, V Uusitalo, M I Mayranpaa, M Kupari
Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (<25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p<0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p<0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is <1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing
{"title":"Endomyocardial biopsy in the diagnosis of cardiac sarcoidosis","authors":"H Malkonen, J Lehtonen, P Poyhonen, V Uusitalo, M I Mayranpaa, M Kupari","doi":"10.1093/eurheartj/ehae666.2070","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2070","url":null,"abstract":"Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (&lt;25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p&lt;0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p&lt;0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is &lt;1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing ","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"82 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2077
J Raak-Tarkiainen, J Lehtonen
Background Cardiac sarcoidosis (CS) is characterized by inflammatory myocardial disease, often leading to conduction disturbances, ventricular tachycardias, and heart failure. While factors like initial symptoms, LVEF, and troponin levels are known prognostic indicators, the impact of CS on health-related quality of life (HRQoL) is not well-understood. Additionally, limited data exists on the predictive value of FDG-PET in CS. Purpose This study aimed to assess HRQoL in CS patients and investigate its prognostic relevance concerning cardiac events. Methods Patients diagnosed with CS completed the RAND-36 general health-related questionnaire, covering eight dimensions. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry. Follow-up data on cardiac events, including life-threatening ventricular tachyarrhythmias (VT/VF), heart transplant, left ventricular assist device (LVAD) implantation, pericardial tamponade, or death, were collected over 36 months. Results Of the 240 CS patients surveyed, 179 (75%) were female, with a median age of 56 [IQR 48 – 64]. CS patients reported significantly lower RAND-36 scores across all dimensions compared to the general Finnish population. Over the 3-year follow-up, 38 (16%) patients experienced cardiac-related adverse events, including VT/VF (26 cases), deaths (8 cases), heart transplants (2 cases), LVAD implantation (1 case), and pericardial tamponade (1 case). We divided CS patients into those without adverse event (N=202) and with adverse events (N=38). Interestingly, in four dimensions of PF 70.0 [50.0-90.0] vs 60.0 [33.8-80.0], p=0.019, RP 50.0 [0.0-100.0] vs 0.00 [0-56.3], p=0.002, MH 76.0 [59.0-88.0] vs 66.0 [51.0-84.0], p=0.036, and SF 75.0 [50-100] vs 62.5 [37.5-78.1], p=0.037 were significantly lower scores in the event group. Univariate Cox regression analysis (Table 1) revealed that physical functioning (PF) and role-physical (RP) dimensions, along with certain clinical factors, such as younger age, higher NYHA classification, elevated proBNP levels, lower hemoglobin levels, and the main manifestation of the disease as ventricular tachyarrhythmia, independently predicted adverse cardiac events. In the multivariate analysis, lower role-physical scores and younger age remained independent prognostic factors for adverse cardiac events. Conclusions Patients with CS demonstrated lower HRQoL compared to the general Finnish population. This study enhances our understanding of prognosis in CS and underscores the predictive value of HRQoL in identifying future adverse cardiac events, highlighting its relevance in the clinical management of these patients.
{"title":"Health-related quality of life and prognosis in cardiac sarcoidosis","authors":"J Raak-Tarkiainen, J Lehtonen","doi":"10.1093/eurheartj/ehae666.2077","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2077","url":null,"abstract":"Background Cardiac sarcoidosis (CS) is characterized by inflammatory myocardial disease, often leading to conduction disturbances, ventricular tachycardias, and heart failure. While factors like initial symptoms, LVEF, and troponin levels are known prognostic indicators, the impact of CS on health-related quality of life (HRQoL) is not well-understood. Additionally, limited data exists on the predictive value of FDG-PET in CS. Purpose This study aimed to assess HRQoL in CS patients and investigate its prognostic relevance concerning cardiac events. Methods Patients diagnosed with CS completed the RAND-36 general health-related questionnaire, covering eight dimensions. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry. Follow-up data on cardiac events, including life-threatening ventricular tachyarrhythmias (VT/VF), heart transplant, left ventricular assist device (LVAD) implantation, pericardial tamponade, or death, were collected over 36 months. Results Of the 240 CS patients surveyed, 179 (75%) were female, with a median age of 56 [IQR 48 – 64]. CS patients reported significantly lower RAND-36 scores across all dimensions compared to the general Finnish population. Over the 3-year follow-up, 38 (16%) patients experienced cardiac-related adverse events, including VT/VF (26 cases), deaths (8 cases), heart transplants (2 cases), LVAD implantation (1 case), and pericardial tamponade (1 case). We divided CS patients into those without adverse event (N=202) and with adverse events (N=38). Interestingly, in four dimensions of PF 70.0 [50.0-90.0] vs 60.0 [33.8-80.0], p=0.019, RP 50.0 [0.0-100.0] vs 0.00 [0-56.3], p=0.002, MH 76.0 [59.0-88.0] vs 66.0 [51.0-84.0], p=0.036, and SF 75.0 [50-100] vs 62.5 [37.5-78.1], p=0.037 were significantly lower scores in the event group. Univariate Cox regression analysis (Table 1) revealed that physical functioning (PF) and role-physical (RP) dimensions, along with certain clinical factors, such as younger age, higher NYHA classification, elevated proBNP levels, lower hemoglobin levels, and the main manifestation of the disease as ventricular tachyarrhythmia, independently predicted adverse cardiac events. In the multivariate analysis, lower role-physical scores and younger age remained independent prognostic factors for adverse cardiac events. Conclusions Patients with CS demonstrated lower HRQoL compared to the general Finnish population. This study enhances our understanding of prognosis in CS and underscores the predictive value of HRQoL in identifying future adverse cardiac events, highlighting its relevance in the clinical management of these patients.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"237 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2093
M Mueller, A Brand, I Mattig, S Spethmann, D Messroghli, K Hahn, U Landmesser, B Heidecker
Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values <0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages
{"title":"Prognostic staging system correctly identifies high risk groups in cardiac transthyretin amyloidosis treated with tafamidis","authors":"M Mueller, A Brand, I Mattig, S Spethmann, D Messroghli, K Hahn, U Landmesser, B Heidecker","doi":"10.1093/eurheartj/ehae666.2093","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2093","url":null,"abstract":"Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values &lt;0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"67 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2554
H Takami
Background Blood pressure is one of the criteria for detecting metabolic syndrome in Japan as follows: systolic blood pressure(SBP) ≥ 130mmHg or diastolic blood pressure (DBP) ≥ 85mmHg, and mean arterial pressure(MAP) is related to atherosclerosis of small artery and insulin resistance is the risk facor of it. Recent experts propose that triglyceride-to-glucose (TyG) index and in addition to waist circumference (WC) are alternative method to predict insulin resistance. Methods and Results 27939 individuals under 65 years old who received health check-up were eligible for the present study. MAP is calculated as follow: (SBP - DBP)/3 + (DBP). TyG index is calculated as follow: Ln(triglyceride x glucose/2). TyG-WC index is calculated as follow: (TyG index) x (WC). Mean triglyceride, glucose, TyG index and TyG-WC index were 103.9, 94.2, 9.02 and 733.6, respectively. Receiver operating characteristics (ROC) curve showed the cut-off value of MAP ≥ 96.33mmHg as high blood pressure. Using this cut-off value, ROC curves of TyG index and TyG-WC index for predicting high MAP shows 9.06 (AUC 0.66) and 734.8 (AUC 0.70), respectively. Conclusions TyG index and TyG-WC index as markers of insulin resistance were significantly correlated with MAP. TyG-WC index was better marker of insulin resistance then TyG index and it might be useful for predicting hypertension and metabolic syndrome.
{"title":"Relationship between triglyceride-to-glucose index in addition to waist circumference as a marker of insulin resistance and mean arterial pressure","authors":"H Takami","doi":"10.1093/eurheartj/ehae666.2554","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.2554","url":null,"abstract":"Background Blood pressure is one of the criteria for detecting metabolic syndrome in Japan as follows: systolic blood pressure(SBP) ≥ 130mmHg or diastolic blood pressure (DBP) ≥ 85mmHg, and mean arterial pressure(MAP) is related to atherosclerosis of small artery and insulin resistance is the risk facor of it. Recent experts propose that triglyceride-to-glucose (TyG) index and in addition to waist circumference (WC) are alternative method to predict insulin resistance. Methods and Results 27939 individuals under 65 years old who received health check-up were eligible for the present study. MAP is calculated as follow: (SBP - DBP)/3 + (DBP). TyG index is calculated as follow: Ln(triglyceride x glucose/2). TyG-WC index is calculated as follow: (TyG index) x (WC). Mean triglyceride, glucose, TyG index and TyG-WC index were 103.9, 94.2, 9.02 and 733.6, respectively. Receiver operating characteristics (ROC) curve showed the cut-off value of MAP ≥ 96.33mmHg as high blood pressure. Using this cut-off value, ROC curves of TyG index and TyG-WC index for predicting high MAP shows 9.06 (AUC 0.66) and 734.8 (AUC 0.70), respectively. Conclusions TyG index and TyG-WC index as markers of insulin resistance were significantly correlated with MAP. TyG-WC index was better marker of insulin resistance then TyG index and it might be useful for predicting hypertension and metabolic syndrome.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"3 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.3377
T Pettersen, D Ferrel-Yui, D Candelaria, M M A Cruz, G L M Ghisi, M Hagen, C Hanson, T M Norekval, R Gallagher
Background The use of wearable activity trackers has been found to significantly improve health profile and cardiorespiratory fitness, as well as to reinforce positive health behaviours in patients participating in cardiac rehabilitation (CR) programs. However, clinicians’ perceptions of activity trackers and their use in clinical practice have not been widely explored. Purpose To describe perceptions, attitudes, and behaviours of CR clinicians towards the use and usefulness of activity trackers in CR programs, and identify barriers and enablers associated with their personal and clinical use. Methods Descriptive cross-sectional survey. Data were collected using Research Electronic Data Capture (REDCap) from April to December 2023. Clinicians working in CR programs were recruited in each country via social media, email and digital flyers, group chats and author networks. A purpose-built 44-item digital survey comprising four sections was constructed: (1) socio-demographic details, (2) personal and professional use of activity trackers, (3) perspectives on the use of activity trackers for CR, and (4) perceptions of factors affecting the use of activity trackers in CR. Results In total, 199 clinicians from Australia (n=44), Brazil (n=102) and Canada (n=53) responded to the survey. Most were women (74%), physiotherapists (37%), working at a metropolitan hospital (55%), with a median age of 35 years (range 22-71). The majority found activity trackers helpful for patients with goal setting and monitoring exercise (89%) and promoting patient engagement and autonomy beyond structured, supervised CR (75%). Activity trackers were also perceived to be useful in engaging patients in their own health (94%), improving patient-provider communication (73%), boosting patient adherence with directed exercise (87%), and improving patient’s understanding of their own health conditions (79%). Furthermore, activity trackers were perceived to enable a more personalised care (69%), increase accessibility to CR (45%) and be time- and cost-effective for CR programs (49%). Sixty percent were motivated to use activity trackers and 69% recommended the use of trackers to their patients. On the other hand, the use of activity trackers was reported to be related to dependence (44%) and excessive obsession of one’s own health (55%); 50% reported a lack of relevant policies on activity trackers for clinical use in their respective institutions and limited funding for purchasing activity trackers by health services (78%). Only 30% reported that there was support from leadership and/or peers for the use of activity trackers. Conclusion In general, clinicians held positive attitudes towards the use of activity trackers in CR. However, a lack of relevant policies, funding and support from leadership are important barriers to the adoption and use of activity trackers in CR programs. Development of guidelines for the use of activity trackers in clinical practice is warranted.
{"title":"Assessing the use of activity trackers in clinical practice: a survey of cardiac rehabilitation clinicians from Australia, Brazil, and Canada","authors":"T Pettersen, D Ferrel-Yui, D Candelaria, M M A Cruz, G L M Ghisi, M Hagen, C Hanson, T M Norekval, R Gallagher","doi":"10.1093/eurheartj/ehae666.3377","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.3377","url":null,"abstract":"Background The use of wearable activity trackers has been found to significantly improve health profile and cardiorespiratory fitness, as well as to reinforce positive health behaviours in patients participating in cardiac rehabilitation (CR) programs. However, clinicians’ perceptions of activity trackers and their use in clinical practice have not been widely explored. Purpose To describe perceptions, attitudes, and behaviours of CR clinicians towards the use and usefulness of activity trackers in CR programs, and identify barriers and enablers associated with their personal and clinical use. Methods Descriptive cross-sectional survey. Data were collected using Research Electronic Data Capture (REDCap) from April to December 2023. Clinicians working in CR programs were recruited in each country via social media, email and digital flyers, group chats and author networks. A purpose-built 44-item digital survey comprising four sections was constructed: (1) socio-demographic details, (2) personal and professional use of activity trackers, (3) perspectives on the use of activity trackers for CR, and (4) perceptions of factors affecting the use of activity trackers in CR. Results In total, 199 clinicians from Australia (n=44), Brazil (n=102) and Canada (n=53) responded to the survey. Most were women (74%), physiotherapists (37%), working at a metropolitan hospital (55%), with a median age of 35 years (range 22-71). The majority found activity trackers helpful for patients with goal setting and monitoring exercise (89%) and promoting patient engagement and autonomy beyond structured, supervised CR (75%). Activity trackers were also perceived to be useful in engaging patients in their own health (94%), improving patient-provider communication (73%), boosting patient adherence with directed exercise (87%), and improving patient’s understanding of their own health conditions (79%). Furthermore, activity trackers were perceived to enable a more personalised care (69%), increase accessibility to CR (45%) and be time- and cost-effective for CR programs (49%). Sixty percent were motivated to use activity trackers and 69% recommended the use of trackers to their patients. On the other hand, the use of activity trackers was reported to be related to dependence (44%) and excessive obsession of one’s own health (55%); 50% reported a lack of relevant policies on activity trackers for clinical use in their respective institutions and limited funding for purchasing activity trackers by health services (78%). Only 30% reported that there was support from leadership and/or peers for the use of activity trackers. Conclusion In general, clinicians held positive attitudes towards the use of activity trackers in CR. However, a lack of relevant policies, funding and support from leadership are important barriers to the adoption and use of activity trackers in CR programs. Development of guidelines for the use of activity trackers in clinical practice is warranted.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"31 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.1842
A Apostolos, N Ktenopoulos, D D Chlorogiannis, K Konstantinou, O Katsaros, M Drakopoulou, S Tsalamandris, A Karanasos, G Latsios, A Synetos, C Aggeli, V Panoulas, C Tsioufis, K Toutouzas
Background Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, leading frequently to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR to elective procedures. Methods We systematically screened three databases searching for studies comparing urgent versus elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-day stroke, 30-day acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage and 30-day bleedings. Results Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality (RR: 2.53, 95% CI: 1.81 – 3.54), in-hospital mortality (RR: 2.67, 95% CI: 1.94 – 3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28 – 2.85) and AKI (RR: 2.83, 95% CI: 1.93 – 4.14), compared to elective procedure. No differences were observed in the rest secondary endpoints. Conclusions Urgent TAVR was associated with higher in-hospital and 30-day mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.
{"title":"Mortality rates in patients undergoing urgent versus elective transcatheter aortic valve replacement: a systematic review and meta-analysis","authors":"A Apostolos, N Ktenopoulos, D D Chlorogiannis, K Konstantinou, O Katsaros, M Drakopoulou, S Tsalamandris, A Karanasos, G Latsios, A Synetos, C Aggeli, V Panoulas, C Tsioufis, K Toutouzas","doi":"10.1093/eurheartj/ehae666.1842","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae666.1842","url":null,"abstract":"Background Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, leading frequently to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR to elective procedures. Methods We systematically screened three databases searching for studies comparing urgent versus elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-day stroke, 30-day acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage and 30-day bleedings. Results Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality (RR: 2.53, 95% CI: 1.81 – 3.54), in-hospital mortality (RR: 2.67, 95% CI: 1.94 – 3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28 – 2.85) and AKI (RR: 2.83, 95% CI: 1.93 – 4.14), compared to elective procedure. No differences were observed in the rest secondary endpoints. Conclusions Urgent TAVR was associated with higher in-hospital and 30-day mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"43 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1093/eurheartj/ehae666.2640
G Mavraganis, G Georgiopoulos, A Kotsogianni, D Delialis, E Aivalioti, N Rachiotis, A Alexandropoulos, A Kalogeropoulos, C Kalogeropoulos, S Tual-Chalot, K Sopova, E Psimmenou, K Stellos, K Stamatelopoulos
Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p<0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p<0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p>0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.
背景 淀粉样蛋白-β (1-40) (Αb1-40)是一种促炎症和促动脉粥样硬化肽，与阿尔茨海默病和血管老化有关，被认为是动脉粥样硬化性心血管疾病 (ASCVD) 和心力衰竭的新兴预后标志物。由于 Ab1-40 的清除率在很大程度上取决于肾功能，而临床数据一直将该肽与肾功能联系在一起，因此我们假设 Ab1-40 循环水平可作为肾功能障碍进展的预测指标。目的 在具有各种 ASCVD 风险的人群中，研究 Ab1-40 水平与肾功能之间潜在的横断面和前瞻性双向关联。方法 在雅典心脏代谢登记处的背景下，对连续招募的患有（n=137）和未患有（n=674）临床明显的 ASCVD 的受试者的数据进行分析，这些受试者同时具有 Ab1-40 血浆水平和 GFR 值（总计 n=811）。Αb1-40通过酶联免疫吸附测定法进行测量，肾功能通过估算肾小球滤过率（GFR）进行评估。在这些受试者中，有 182 人同意在至少 12 个月后接受随访和重新评估，以研究 Ab1-40 水平变化与肾小球滤过率之间的潜在双向联系。结果 与 Ab1-40 水平较低的患者相比，基线时 Ab1-40 水平升高的患者肾功能明显较差，表现为 GFR 值较低 (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001)。Ab1-40 水平升高与基线时的慢性肾脏病（CKD）2 期[几率比（OR）=2.29，95% 置信区间（CI）=1.58-3.31，p<0.001]和 CKD 3 期（OR=3.67，95% CI=2.37-5.70，p<0.001）有关。此外，根据基线与随访期间 GFR 值的变化评估，基线时 Ab1-40 水平的升高与肾功能障碍的加速进展具有前瞻性关联[随访 12 个月期间，Ab1-40 水平较高与较低三分位数的平均调整下降率=-7.20（95% CI=-1.33，-13.07），交互作用 p=0.017]。相反，基线 GFR 值与随访时的 Ab1-40 水平没有前瞻性关联（p>0.05）。结论 在具有广泛 ASCVD 风险的人群中，基线时的高Αb1-40 水平既与基线时的肾功能有关，也与随访时 GFR 恶化速度加快有关，而与基线水平无关。这些发现提示了Ab1-40与肾功能关联的机理背景，值得进一步研究，以明确监测其循环水平作为一种新型生物标志物的临床价值，这种生物标志物可反映肾功能障碍风险的增加。
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