Claire J Peet, D. Rowczenio, E. Omoyinmi, C. Papadopoulou, B. R. Mapalo, Michael R. Wood, F. Capon, H. Lachmann
Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti‐interleukin‐1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP. Methods and Results We retrospectively analyzed the medical records of patients with IRP (n=136) and monogenic autoinflammatory diseases (n=1910) attending a national center (London, UK) between 2000 and 2021. We examined 4 genes (MEFV, MVK, NLRP3, TNFRSF1A) by next‐generation sequencing in 128 patients with IRP and compared the frequency of rare deleterious variants to controls obtained from the Genome Aggregation Database. In this cohort of patients with IRP, corticosteroid dependence was common (39/136, 28.7%) and was associated with chronic pain (adjusted odds ratio 2.8 [95% CI, 1.3–6.5], P=0.012). IRP frequently manifested with systemic inflammation (raised C‐reactive protein [121/136, 89.0%] and extrapericardial effusions [68/136, 50.0%]). Pericarditis was observed in all examined monogenic autoinflammatory diseases (0.4%–3.7% of cases). Rare deleterious MEFV variants were more frequent in IRP than in ancestry‐matched controls (allele frequency 9/200 versus 2932/129 200, P=0.040). Conclusions Pericarditis is a feature of interleukin‐1 driven monogenic autoinflammatory diseases and IRP is associated with variants in MEFV, a gene involved in interleukin‐1β processing. We also found that corticosteroid dependence in IRP is associated with chronic noninflammatory pain. Together these data implicate autoinflammation in IRP and support reducing reliance on corticosteroids in its management.
{"title":"Pericarditis and Autoinflammation: A Clinical and Genetic Analysis of Patients With Idiopathic Recurrent Pericarditis and Monogenic Autoinflammatory Diseases at a National Referral Center","authors":"Claire J Peet, D. Rowczenio, E. Omoyinmi, C. Papadopoulou, B. R. Mapalo, Michael R. Wood, F. Capon, H. Lachmann","doi":"10.1161/JAHA.121.024931","DOIUrl":"https://doi.org/10.1161/JAHA.121.024931","url":null,"abstract":"Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti‐interleukin‐1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP. Methods and Results We retrospectively analyzed the medical records of patients with IRP (n=136) and monogenic autoinflammatory diseases (n=1910) attending a national center (London, UK) between 2000 and 2021. We examined 4 genes (MEFV, MVK, NLRP3, TNFRSF1A) by next‐generation sequencing in 128 patients with IRP and compared the frequency of rare deleterious variants to controls obtained from the Genome Aggregation Database. In this cohort of patients with IRP, corticosteroid dependence was common (39/136, 28.7%) and was associated with chronic pain (adjusted odds ratio 2.8 [95% CI, 1.3–6.5], P=0.012). IRP frequently manifested with systemic inflammation (raised C‐reactive protein [121/136, 89.0%] and extrapericardial effusions [68/136, 50.0%]). Pericarditis was observed in all examined monogenic autoinflammatory diseases (0.4%–3.7% of cases). Rare deleterious MEFV variants were more frequent in IRP than in ancestry‐matched controls (allele frequency 9/200 versus 2932/129 200, P=0.040). Conclusions Pericarditis is a feature of interleukin‐1 driven monogenic autoinflammatory diseases and IRP is associated with variants in MEFV, a gene involved in interleukin‐1β processing. We also found that corticosteroid dependence in IRP is associated with chronic noninflammatory pain. Together these data implicate autoinflammation in IRP and support reducing reliance on corticosteroids in its management.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75565095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Kwon, Seung Hun Lee, Jeong Hoon Yang, K. Choi, T. Park, J. Lee, Y. Song, J. Hahn, Seung‐Hyuk Choi, C. Ahn, Y. Ko, C. Yu, W. Jang, Hyun-Joong Kim, S. Kwon, J. Jeong, Sang-Don Park, Sungsoo Cho, J. Bae, H. Gwon
Background Several studies have shown that obesity is associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the “obesity paradox,” reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in patients with CS. Methods and Results A total of 1227 patients with CS from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) registry in Korea were analyzed. The study population was classified into obese and nonobese groups according to Asian Pacific criteria (BMI ≥25.0 kg/m2 for obese). The clinical impact of obesity on in‐hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. The in‐hospital mortality rate was significantly lower in obese men than nonobese men (34.2% versus 24.1%, respectively; P=0.004), while the difference was not significant in women (37.3% versus 35.8%, respectively; P=0.884). As a continuous variable, higher BMI showed a protective effect in men; conversely, BMI was not associated with clinical outcomes in women. Compared with patients with normal weight, obesity was associated with a decreased risk of in‐hospital death in men (multivariable‐adjusted odds ratio [OR], 0.63; CI, 0.43–0.92 [P=0.016]), but not in women (multivariable‐adjusted OR, 0.94; 95% CI, 0.55–1.61 [P=0.828]). The interaction P value for the association between BMI and sex was 0.023. Conclusions The obesity paradox exists and apparently occurs in men among patients with CS. The differential effect of BMI on in‐hospital mortality was observed according to sex. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.
{"title":"Impact of the Obesity Paradox Between Sexes on In‐Hospital Mortality in Cardiogenic Shock: A Retrospective Cohort Study","authors":"W. Kwon, Seung Hun Lee, Jeong Hoon Yang, K. Choi, T. Park, J. Lee, Y. Song, J. Hahn, Seung‐Hyuk Choi, C. Ahn, Y. Ko, C. Yu, W. Jang, Hyun-Joong Kim, S. Kwon, J. Jeong, Sang-Don Park, Sungsoo Cho, J. Bae, H. Gwon","doi":"10.1161/JAHA.121.024143","DOIUrl":"https://doi.org/10.1161/JAHA.121.024143","url":null,"abstract":"Background Several studies have shown that obesity is associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the “obesity paradox,” reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in patients with CS. Methods and Results A total of 1227 patients with CS from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) registry in Korea were analyzed. The study population was classified into obese and nonobese groups according to Asian Pacific criteria (BMI ≥25.0 kg/m2 for obese). The clinical impact of obesity on in‐hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. The in‐hospital mortality rate was significantly lower in obese men than nonobese men (34.2% versus 24.1%, respectively; P=0.004), while the difference was not significant in women (37.3% versus 35.8%, respectively; P=0.884). As a continuous variable, higher BMI showed a protective effect in men; conversely, BMI was not associated with clinical outcomes in women. Compared with patients with normal weight, obesity was associated with a decreased risk of in‐hospital death in men (multivariable‐adjusted odds ratio [OR], 0.63; CI, 0.43–0.92 [P=0.016]), but not in women (multivariable‐adjusted OR, 0.94; 95% CI, 0.55–1.61 [P=0.828]). The interaction P value for the association between BMI and sex was 0.023. Conclusions The obesity paradox exists and apparently occurs in men among patients with CS. The differential effect of BMI on in‐hospital mortality was observed according to sex. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76286474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this issue of the Journal of the American Heart Association (JAHA), Peet1 challenges the current concept of idiopathic recurrent pericarditis (IRP). Indeed, “idiopathic” means “arising spontaneously or from an obscure or unknown cause,” which implies that the pathophysiology is not established, and the treatment should remain empirical. In 2 words, behind this learned word, we hide our ignorance.
{"title":"Idiopathic Recurrent Pericarditis: Not Really So Idiopathic?","authors":"F. Roubille, C. Delmas, C. Roubille","doi":"10.1161/JAHA.122.026218","DOIUrl":"https://doi.org/10.1161/JAHA.122.026218","url":null,"abstract":"In this issue of the Journal of the American Heart Association (JAHA), Peet1 challenges the current concept of idiopathic recurrent pericarditis (IRP). Indeed, “idiopathic” means “arising spontaneously or from an obscure or unknown cause,” which implies that the pathophysiology is not established, and the treatment should remain empirical. In 2 words, behind this learned word, we hide our ignorance.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77826930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aino-Maija Vuorinen, J. Lehtonen, S. Pakarinen, M. Holmström, S. Kivistö, T. Kaasalainen
Background Some myocardial diseases, such as cardiac sarcoidosis, predispose to complete atrioventricular block. The European Society of Cardiology Guidelines on cardiac pacing in 2021 recommend myocardial disease screening in patients with conduction disorder requiring pacemaker with multimodality imaging, including cardiac magnetic resonance (CMR) imaging. The ability of CMR imaging to detect myocardial disease in patients with a temporary pacing wire is not well documented. Methods and Results Our myocardial disease screening protocol is based on using an active fixation pacing lead connected to a reusable extracorporeal pacing generator (temporary permanent pacemaker) as a bridge to a permanent pacemaker. From 2011 to 2019, we identified 17 patients from our CMR database who underwent CMR imaging with a temporary permanent pacemaker for atrioventricular block. We analyzed their clinical presentations, CMR data, and pacemaker therapy. All CMRs were performed without adverse events. Pacing leads induced minor artifacts to the septal myocardial segments. The extent of late gadolinium enhancement in CMR imaging was used to screen patients for the presence of myocardial disease. Patients with evidence of late gadolinium enhancement underwent endomyocardial biopsy. If considered clinically indicated, also 18‐F‐fluorodeoxyglucose positron emission tomography and extracardiac tissue biopsy were performed if sarcoidosis was suspected. Eventually, 8 of 17 patients (47.1%) were diagnosed with histologically confirmed granulomatous inflammatory cardiac disease. Importantly, only 1 had a previously diagnosed extracardiac sarcoidosis at the time of presentation with high‐degree atrioventricular block. Conclusions CMR imaging with temporary permanent pacemaker protocol is an effective and safe early screening tool for myocardial disease in patients presenting with atrioventricular block requiring immediate, continuous pacing for bradycardia.
{"title":"Cardiac Magnetic Resonance Imaging–Based Screening for Cardiac Sarcoidosis in Patients With Atrioventricular Block Requiring Temporary Pacing","authors":"Aino-Maija Vuorinen, J. Lehtonen, S. Pakarinen, M. Holmström, S. Kivistö, T. Kaasalainen","doi":"10.1161/JAHA.121.024257","DOIUrl":"https://doi.org/10.1161/JAHA.121.024257","url":null,"abstract":"Background Some myocardial diseases, such as cardiac sarcoidosis, predispose to complete atrioventricular block. The European Society of Cardiology Guidelines on cardiac pacing in 2021 recommend myocardial disease screening in patients with conduction disorder requiring pacemaker with multimodality imaging, including cardiac magnetic resonance (CMR) imaging. The ability of CMR imaging to detect myocardial disease in patients with a temporary pacing wire is not well documented. Methods and Results Our myocardial disease screening protocol is based on using an active fixation pacing lead connected to a reusable extracorporeal pacing generator (temporary permanent pacemaker) as a bridge to a permanent pacemaker. From 2011 to 2019, we identified 17 patients from our CMR database who underwent CMR imaging with a temporary permanent pacemaker for atrioventricular block. We analyzed their clinical presentations, CMR data, and pacemaker therapy. All CMRs were performed without adverse events. Pacing leads induced minor artifacts to the septal myocardial segments. The extent of late gadolinium enhancement in CMR imaging was used to screen patients for the presence of myocardial disease. Patients with evidence of late gadolinium enhancement underwent endomyocardial biopsy. If considered clinically indicated, also 18‐F‐fluorodeoxyglucose positron emission tomography and extracardiac tissue biopsy were performed if sarcoidosis was suspected. Eventually, 8 of 17 patients (47.1%) were diagnosed with histologically confirmed granulomatous inflammatory cardiac disease. Importantly, only 1 had a previously diagnosed extracardiac sarcoidosis at the time of presentation with high‐degree atrioventricular block. Conclusions CMR imaging with temporary permanent pacemaker protocol is an effective and safe early screening tool for myocardial disease in patients presenting with atrioventricular block requiring immediate, continuous pacing for bradycardia.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91370540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The synthetic opioid methadone has long been recognized to cause not only QT prolongation on ECG but also a predilection for torsade de pointes.1,2 Despite the limited distribution of the drug in comparison to other opioids, methadone use has been inordinately implicated in sudden death from ventricular arrhythmia.3 However, the full mechanistic scope of why this drug is arrhythmogenic has been unresolved.
{"title":"Arrhythmogenesis and Prolonged Repolarization From Synthetic Opioids: Finally Sorted?","authors":"L. Eckhardt","doi":"10.1161/JAHA.122.025778","DOIUrl":"https://doi.org/10.1161/JAHA.122.025778","url":null,"abstract":"The synthetic opioid methadone has long been recognized to cause not only QT prolongation on ECG but also a predilection for torsade de pointes.1,2 Despite the limited distribution of the drug in comparison to other opioids, methadone use has been inordinately implicated in sudden death from ventricular arrhythmia.3 However, the full mechanistic scope of why this drug is arrhythmogenic has been unresolved.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88308538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
nlike conduction disease in elderly patients, advanced atrioventricular block in young and middle-aged patients is predominantly attributable to causes other than degenerative conduction disease and coronary artery disease. 1 Frequent causes of advanced atrioventricular block in young people include cardiac sarcoidosis, 2– 4 giant cell myocarditis, 2 genetic cardiomyopathies 5 caused by mutations in LMNA , 6 SCN5A , 7 and EMD , 8 and Lyme carditis in places where Lyme disease is endemic. 9 tachyarrhythmia, follow-
{"title":"Managing Patients With Advanced Atrioventricular Block: The Essential Role of Cardiovascular Magnetic Resonance Imaging for Timely and Accurate Diagnosis","authors":"L. von Wald, C. Shenoy","doi":"10.1161/JAHA.122.026199","DOIUrl":"https://doi.org/10.1161/JAHA.122.026199","url":null,"abstract":"nlike conduction disease in elderly patients, advanced atrioventricular block in young and middle-aged patients is predominantly attributable to causes other than degenerative conduction disease and coronary artery disease. 1 Frequent causes of advanced atrioventricular block in young people include cardiac sarcoidosis, 2– 4 giant cell myocarditis, 2 genetic cardiomyopathies 5 caused by mutations in LMNA , 6 SCN5A , 7 and EMD , 8 and Lyme carditis in places where Lyme disease is endemic. 9 tachyarrhythmia, follow-","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85544397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nataraja Sarna Vaitinadin, Mingjian Shi, C. Shaffer, E. Farber-Eger, B. Lowery, V. Agrawal, D. Gupta, D. Roden, Q. Wells, J. Mosley
Background Early (grade 1) cardiac left ventricular diastolic dysfunction (G1DD) increases the risk for heart failure with preserved ejection fraction and may improve with aggressive risk factor modification. Type 2 diabetes, obesity, hypertension, and coronary heart disease are associated with increased incidence of diastolic dysfunction. The genetic drivers of G1DD are not defined. Methods and Results We curated genotyped European ancestry G1DD cases (n=668) and controls with normal diastolic function (n=1772) from Vanderbilt’s biobank. G1DD status was explored through (1) an additive model genome‐wide association study, (2) shared polygenic risk through logistic regression, and (3) instrumental variable analysis using 2‐sample Mendelian randomization (the inverse‐variance weighted method, Mendelian randomization‐Egger, and median) to determine potential modifiable risk factors. There were no common single nucleotide polymorphisms significantly associated with G1DD status. A polygenic risk score for BMI was significantly associated with increased G1DD risk (odds ratio [OR], 1.20 for 1‐SD increase in BMI [95% CI, 1.08–1.32]; P=0.0003). The association was confirmed by the inverse‐variance weighted method (OR, 1.89 [95% CI, 1.37–2.61]). Among the candidate mediators for BMI, only fasting glucose was significantly associated with G1DD status by the inverse‐variance weighted method (OR, 4.14 for 1‐SD increase in fasting glucose [95% CI, 1.55–11.02]; P=0.005). Multivariable Mendelian randomization showed a modest attenuation of the BMI association (OR, 1.84 [95% CI, 1.35–2.52]) when adjusting for fasting glucose. Conclusions These data suggest that a genetic predisposition to elevated BMI increases the risk for G1DD. Part of this effect may be mediated through altered glucose homeostasis.
{"title":"Genetic Determinants of Body Mass Index and Fasting Glucose Are Mediators of Grade 1 Diastolic Dysfunction","authors":"Nataraja Sarna Vaitinadin, Mingjian Shi, C. Shaffer, E. Farber-Eger, B. Lowery, V. Agrawal, D. Gupta, D. Roden, Q. Wells, J. Mosley","doi":"10.1161/JAHA.122.025578","DOIUrl":"https://doi.org/10.1161/JAHA.122.025578","url":null,"abstract":"Background Early (grade 1) cardiac left ventricular diastolic dysfunction (G1DD) increases the risk for heart failure with preserved ejection fraction and may improve with aggressive risk factor modification. Type 2 diabetes, obesity, hypertension, and coronary heart disease are associated with increased incidence of diastolic dysfunction. The genetic drivers of G1DD are not defined. Methods and Results We curated genotyped European ancestry G1DD cases (n=668) and controls with normal diastolic function (n=1772) from Vanderbilt’s biobank. G1DD status was explored through (1) an additive model genome‐wide association study, (2) shared polygenic risk through logistic regression, and (3) instrumental variable analysis using 2‐sample Mendelian randomization (the inverse‐variance weighted method, Mendelian randomization‐Egger, and median) to determine potential modifiable risk factors. There were no common single nucleotide polymorphisms significantly associated with G1DD status. A polygenic risk score for BMI was significantly associated with increased G1DD risk (odds ratio [OR], 1.20 for 1‐SD increase in BMI [95% CI, 1.08–1.32]; P=0.0003). The association was confirmed by the inverse‐variance weighted method (OR, 1.89 [95% CI, 1.37–2.61]). Among the candidate mediators for BMI, only fasting glucose was significantly associated with G1DD status by the inverse‐variance weighted method (OR, 4.14 for 1‐SD increase in fasting glucose [95% CI, 1.55–11.02]; P=0.005). Multivariable Mendelian randomization showed a modest attenuation of the BMI association (OR, 1.84 [95% CI, 1.35–2.52]) when adjusting for fasting glucose. Conclusions These data suggest that a genetic predisposition to elevated BMI increases the risk for G1DD. Part of this effect may be mediated through altered glucose homeostasis.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74318231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victor J. Del Brutto, Hans-Christoph Diener, J. Easton, C. Granger, Lisa Cronin, E. Kleine, Claudia Grauer, M. Brueckmann, K. Toyoda, P. Schellinger, P. Lyrer, C. Molina, A. Chutinet, C. Bladin, C. Estol, R. Sacco
Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA2DS2‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
{"title":"Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial","authors":"Victor J. Del Brutto, Hans-Christoph Diener, J. Easton, C. Granger, Lisa Cronin, E. Kleine, Claudia Grauer, M. Brueckmann, K. Toyoda, P. Schellinger, P. Lyrer, C. Molina, A. Chutinet, C. Bladin, C. Estol, R. Sacco","doi":"10.1161/JAHA.121.023545","DOIUrl":"https://doi.org/10.1161/JAHA.121.023545","url":null,"abstract":"Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA2DS2‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72699682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Park, Hyungwoo Kim, Y. S. Joo, J. Park, T. Chang, T. Yoo, S. Park, D. Chae, W. Chung, Yong‐Soo Kim, K. Oh, Shin-Wook Kang, S. Han
Background Whether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean. Conclusions Higher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.
{"title":"Association Between Systolic Blood Pressure Variability and Major Adverse Cardiovascular Events in Korean Patients With Chronic Kidney Disease: Findings From KNOW‐CKD","authors":"C. Park, Hyungwoo Kim, Y. S. Joo, J. Park, T. Chang, T. Yoo, S. Park, D. Chae, W. Chung, Yong‐Soo Kim, K. Oh, Shin-Wook Kang, S. Han","doi":"10.1161/JAHA.122.025513","DOIUrl":"https://doi.org/10.1161/JAHA.122.025513","url":null,"abstract":"Background Whether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean. Conclusions Higher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90564404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Dai, S. Yuan, K. Dou, Rui Zhang, Nan Hu, Jining He, C. Guan, Tongqiang Zou, Z. Qiao, S. Duan, Lihua Xie, Yongfu Yu, Yingmei Zhang, Bo Xu, Junbo Ge
Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre‐PCI focal or diffuse disease patterns combined with post‐PCI quantitative flow ratio (QFR). Methods and Results Pre‐PCI QFR derived pullback pressure gradient (PPG) (QFR‐PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre‐PCI QFR‐PPG and post‐PCI QFR. Vessel‐oriented composite outcome, a composite of vessel‐related ischemia‐driven revascularization, vessel‐related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre‐PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08–3.44; P=0.02) or low post‐PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61–8.87; P=0.001) demonstrated higher vessel‐oriented composite outcome risk after stent implantation. Of note, despite high post‐PCI QFR achieved, vessels with low pre‐PCI QFR‐PPG presented higher risk of vessel‐oriented composite outcome than those with high pre‐PCI QFR‐PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09–3.76; P=0.03) and pre‐PCI QFR‐PPG demonstrated direct prognostic effect not mediated by post‐PCI QFR. Integration of groups classified by pre‐PCI QFR‐PPG and post‐PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C‐index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre‐PCI focal or diffuse disease patterns assessed by QFR‐PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post‐PCI QFR. Integration of both pre‐PCI and post‐PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.
{"title":"Prognostic Implications of Prestent Pullback Pressure Gradient and Poststent Quantitative Flow Ratio in Patients Undergoing Percutaneous Coronary Intervention","authors":"N. Dai, S. Yuan, K. Dou, Rui Zhang, Nan Hu, Jining He, C. Guan, Tongqiang Zou, Z. Qiao, S. Duan, Lihua Xie, Yongfu Yu, Yingmei Zhang, Bo Xu, Junbo Ge","doi":"10.1161/JAHA.121.024903","DOIUrl":"https://doi.org/10.1161/JAHA.121.024903","url":null,"abstract":"Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre‐PCI focal or diffuse disease patterns combined with post‐PCI quantitative flow ratio (QFR). Methods and Results Pre‐PCI QFR derived pullback pressure gradient (PPG) (QFR‐PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre‐PCI QFR‐PPG and post‐PCI QFR. Vessel‐oriented composite outcome, a composite of vessel‐related ischemia‐driven revascularization, vessel‐related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre‐PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08–3.44; P=0.02) or low post‐PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61–8.87; P=0.001) demonstrated higher vessel‐oriented composite outcome risk after stent implantation. Of note, despite high post‐PCI QFR achieved, vessels with low pre‐PCI QFR‐PPG presented higher risk of vessel‐oriented composite outcome than those with high pre‐PCI QFR‐PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09–3.76; P=0.03) and pre‐PCI QFR‐PPG demonstrated direct prognostic effect not mediated by post‐PCI QFR. Integration of groups classified by pre‐PCI QFR‐PPG and post‐PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C‐index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre‐PCI focal or diffuse disease patterns assessed by QFR‐PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post‐PCI QFR. Integration of both pre‐PCI and post‐PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82515475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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