Topic: Journal Club Selection

Abstract
<div><h4>Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.</h4><i>Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E</i><br /><b>Aims</b><br />Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.<br /><b>Methods and results</b><br />An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.<br /><b>Conclusion</b><br />Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 20 Jan 2023; epub ahead of print</small></div>
Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E
Eur Heart J: 20 Jan 2023; epub ahead of print | PMID: 36660854
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>The Safety of Inpatient Health Care.</h4><i>Bates DW, Levine DM, Salmasian H, Syrowatka A, ... Reynolds ME, Mort E</i><br /><b>Background</b><br />Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted.<br /><b>Methods</b><br />We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events.<br /><b>Results</b><br />In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%).<br /><b>Conclusions</b><br />Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 12 Jan 2023; 388:142-153</small></div>
Bates DW, Levine DM, Salmasian H, Syrowatka A, ... Reynolds ME, Mort E
N Engl J Med: 12 Jan 2023; 388:142-153 | PMID: 36630622
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Diagnosis of cardiac sarcoidosis in patients presenting with cardiac arrest or life-threatening arrhythmias.</h4><i>Hatipoglu S, Gardezi SKM, Azzu A, Baksi J, ... Pennell DJ, Mohiaddin R</i><br /><b>Objective</b><br />Cardiac sarcoidosis (CS) may present with cardiac arrest or life-threatening arrhythmias. There are limited data on this subgroup of patients with CS. Advanced imaging including cardiovascular magnetic resonance (CMR) and cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) are used for diagnosis. This study aimed to describe advanced imaging patterns suggestive of CS among patients presenting with cardiac arrest or life-threatening arrhythmias.<br /><b>Methods</b><br />An imaging database of a CS referral centre (Royal Brompton Hospital, London) was screened for patients presenting with cardiac arrest or life-threatening arrhythmias and having imaging features of suspected CS. Patients diagnosed with definite or probable/possible CS were included.<br /><b>Results</b><br />Study population included 60 patients (median age 49 years) with male predominance (76.7%). The left ventricle was usually non-dilated with mildly reduced ejection fraction (53.4±14.8%). CMR studies showed extensive late gadolinium enhancement (LGE) with 5 (4-8) myocardial segments per patient affected; the right ventricular (RV) side of the septum (28/45) and basal anteroseptum (28/45) were most frequently involved. Myocardial inflammation by FDG-PET was detected in 45 out of 58 patients vs 11 out of 33 patients with oedema imaging available on CMR. When PET was treated as reference to detect myocardial inflammation, CMR oedema imaging was 33.3% sensitive and 77% specific.<br /><b>Conclusions</b><br />In patients with CS presenting with cardiac arrest or life-threatening arrhythmias, LGE was located in areas where the cardiac conduction system travels (basal anteroseptal wall and RV side of the septum). While CMR was the imaging technique that raised possibility of cardiac scarring, oedema imaging had low sensitivity to detect myocardial inflammation compared with FDG-PET.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Jan 2023; epub ahead of print</small></div>
Hatipoglu S, Gardezi SKM, Azzu A, Baksi J, ... Pennell DJ, Mohiaddin R
Heart: 10 Jan 2023; epub ahead of print | PMID: 36627181
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Biventricular Noncompaction Cardiomyopathy in a Patient Presenting With a New Cerebrovascular Event.</h4><i>Madnawat H, Atallah I, Ahmad A, Harjai K</i><br /><AbstractText>Noncompaction (NC) cardiomyopathy (NCCM) is a rare, genetically heterogeneous cardiomyopathy (CM) caused by failure to compact the intertrabecular recesses of the myocardium. This condition usually affects the apical segment of the left ventricle, yet there are noted basal segment, biventricular, and right ventricular predominant cases. NCCM is largely diagnosed in the pediatric population; however, there is increasing recognition in older patients with heart failure and stroke and patients with arrhythmias. Treatment focuses on symptomatic management of heart failure, anticoagulation, and implantable cardiac defibrillators.</AbstractText><br /><br />Copyright © 2022 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 06 Jan 2023; 190:110-112</small></div>
Madnawat H, Atallah I, Ahmad A, Harjai K
Am J Cardiol: 06 Jan 2023; 190:110-112 | PMID: 36621285
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese.</h4><i>Yin L, Mei J, Dong J, Qu X, Jiang Y</i><br /><b>Objectives</b><br />High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function.<br /><b>Methods</b><br />Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging.<br /><b>Results</b><br />The average age of the participants was 55.70 ± 11.30 years old. The mean urinary sodium of the participants was 172.01 ± 80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling.<br /><b>Conclusions</b><br />Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.<br /><br />Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.<br /><br /><small>J Hypertens: 01 Jan 2023; 41:159-170</small></div>
Yin L, Mei J, Dong J, Qu X, Jiang Y
J Hypertens: 01 Jan 2023; 41:159-170 | PMID: 36453659
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.</h4><i>Choi YJ, Kim HK, Hwang IC, Park CS, ... Cho GY, Kim YJ</i><br /><b>Objective</b><br />To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model.<br /><b>Methods</b><br />This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (<b>≥</b>60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death.<br /><b>Results</b><br />During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death.<br /><b>Conclusions</b><br />Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.<br /><br />© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 29 Dec 2022; epub ahead of print</small></div>
Choi YJ, Kim HK, Hwang IC, Park CS, ... Cho GY, Kim YJ
Heart: 29 Dec 2022; epub ahead of print | PMID: 36581445
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age.</h4><i>Dellborg M, Giang KW, Eriksson P, Liden H, ... Rosengren A, Mandalenakis Z</i><br /><b>Background</b><br />The survival of children with congenital heart disease has increased substantially over the past decades, with 97% currently reaching adulthood. The total effect of advanced treatment on future mortality and morbidity in adult survivors with congenital heart disease (CHD) is less well described.<br /><b>Methods</b><br />We used data from the Swedish National Inpatient, Outpatient, and Cause of Death Register to identify patients with CHD who were born between 1950 and 1999 and were alive at 18 years of age. Ten controls identified from the Total Population Register were matched for year of birth and sex and with each patient with CHD. Follow-up was from 1968 and 18 years of age until death or at the end of the study (2017). Survival percentage with 95% CI for all-cause mortality were performed with Kaplan-Meier survival function. Cox proportional hazard regression models with hazard ratios (HRs) and 95% CI were used to estimate the risk of all-cause mortality.<br /><b>Results</b><br />We included 37 278 patients with adult CHD (ACHD) and 412 799 controls. Mean follow-up was 19.2 years (±13.6). Altogether, 1937 patients with ACHD (5.2%) and 6690 controls (1.6%) died, a death rate of 2.73 per 1000 person-years and 0.84 per 1000 person years, respectively. Mortality was 3.2 times higher (95% CI, 3.0-3.4; <i>P</i><0.001) among patients with ACHD compared with matched controls. Up to the maximum of 50 years of follow-up, >75% of patients with ACHD were still alive. Mortality was highest among patients with conotruncal defects (HR, 10.13 [95% CI, 8.78-11.69]), but also significantly higher for the more benign lesions, with the lowest risk in patients with atrial septal defects (HR, 1.36 [95% CI, 1.19-1.55]). At least 75% of patients with ACHD alive at 18 years of age lived past middle age and became sexagenerians.<br /><b>Conclusions</b><br />In this large, nationwide, register-based cohort study of patients with ACHD surviving to 18 years of age, the risk of mortality up to 68 years of age was >3 times higher compared with matched controls without ACHD. Despite this, at least 75% of patients with CHD alive at 18 years of age lived past middle age and became sexagenerians. A notable risk decline in the mortality for patients with ACHD was noted for those born after 1975.<br /><br /><br /><br /><small>Circulation: 26 Dec 2022; epub ahead of print</small></div>
Dellborg M, Giang KW, Eriksson P, Liden H, ... Rosengren A, Mandalenakis Z
Circulation: 26 Dec 2022; epub ahead of print | PMID: 36571845
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Massively Hypertrophied Right-Sided Heart with Hypoplastic Left-Sided Heart in a Neonate (A Rare Type of Hypertrophic Cardiomyopathy).</h4><i>Roberts WC, Chinta S, Guileyardo JM</i><br /><AbstractText>Described herein is a newborn boy with likely right-sided hypertrophic cardiomyopathy (HC), who survived for 18 hours after birth. At necropsy, he had a severely thickened right ventricular free wall, ventricular septum, right atrial wall and a hypoplastic left-sided heart. There was a large fossa ovale type atrial septal defect and also a patent ductus arteriosus. During peak systole, the right ventricular outflow tract was obstructed, and its contents were pushed into the thick-walled right atrium, then rapidly into the thin-walled left atrium via a large fossa ovale atrial septal defect. The contents were then pushed into the thin-walled left ventricle and finally into the small ascending aorta and into the lungs via a large patent ductus arteriosus. We were unable to find a similar published case.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 15 Dec 2022; epub ahead of print</small></div>
Roberts WC, Chinta S, Guileyardo JM
Am J Cardiol: 15 Dec 2022; epub ahead of print | PMID: 36528398
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.</h4><i>Ishani A, Cushman WC, Leatherman SM, Lew RA, ... Ferguson RE, Diuretic Comparison Project Writing Group</i><br /><b>Background</b><br />Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.<br /><b>Methods</b><br />In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.<br /><b>Results</b><br />A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).<br /><b>Conclusions</b><br />In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).<br /><br />Copyright © 2022 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 14 Dec 2022; epub ahead of print</small></div>
Ishani A, Cushman WC, Leatherman SM, Lew RA, ... Ferguson RE, Diuretic Comparison Project Writing Group
N Engl J Med: 14 Dec 2022; epub ahead of print | PMID: 36516076
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation: JACC State-of-the-Art Review.</h4><i>Farhan S, Silbiger JJ, Halperin JL, Zhang L, ... Sharma S, Lerakis S</i><br /><AbstractText>The conventional view holds that functional mitral regurgitation (MR) is caused by restriction of leaflet motion resulting from displacement of the papillary muscle-bearing segments of the left ventricle. In the past decade, evidence has accrued suggesting functional MR can also be caused by left atrial enlargement. This underrecognized cause of secondary MR-atrial functional MR (AF-MR)-is mechanistically linked to annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering. AF-MR has been described in patients with atrial fibrillation and heart failure with preserved ejection fraction. Preliminary data suggest rhythm control may decrease MR severity in patients with atrial fibrillation. Additionally, several studies have reported reductions in MR and symptomatic improvement with restrictive annuloplasty and transcatheter edge-to-edge repair. This review discusses the pathophysiology, echocardiographic diagnosis, and treatment of AF-MR. AF-tricuspid regurgitation is also discussed.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Dec 2022; 80:2314-2330</small></div>
Farhan S, Silbiger JJ, Halperin JL, Zhang L, ... Sharma S, Lerakis S
J Am Coll Cardiol: 13 Dec 2022; 80:2314-2330 | PMID: 36480974
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Cardiopulmonary Exercise Testing in Athletes With Hypertrophic Cardiomyopathy.</h4><i>Newman DB, Garmany R, Contreras AM, Bos JM, ... Ommen SR, Ackerman MJ</i><br /><AbstractText>Patients with hypertrophic cardiomyopathy (HCM) have historically been restricted from athletic participation because of the perceived risk of sudden cardiac death. More contemporary research has highlighted the relative safety of competitive athletics with HCM. However, lack of published data on reference values for cardiopulmonary exercise testing (CPET) complicates clinical management and counseling on sports participation in the individual athlete. We conducted a single-center, retrospective cohort study to investigate CPET in athletes with HCM and clinical characteristics associated with objective measures of aerobic capacity. We identified 58 athletes with HCM (74% male, mean age 18 ± 3 years, mean left ventricular (LV) wall thickness 20 ± 7 mm). LV outflow tract obstruction was present in 22 (38%). A total of 15 (26%) athletes were taking a β blocker (BB), but only 4 (7%) reported exertional symptoms. Overall, exercise capacity was mildly reduced, with a peak myocardial oxygen consumption (peak VO<sub>2</sub>) of 37.9 ml/min/kg (83% of predicted peak VO<sub>2</sub>). Both LV outflow tract obstruction and BB use were associated with reduced exercise capacity. Limited peak heart rate was more common in athletes taking BB (47% vs 9%, p = 0.002). At a mean 5.6 years follow-up, 5 patients underwent myectomy (9%), and 8 (14%) received an implantable cardioverter defibrillator (ICD) for primary prevention. One individual with massive LV hypertrophy experienced recurrent ICD shocks for ventricular fibrillation and underwent myectomy 7 years after initial evaluation and was no longer participating in sports. There were no deaths over the follow-up period. In conclusion, the prognostic role of CPET remains unclear in athletes with HCM. Mildly reduced exercise capacity was common; however, reduced peak VO<sub>2</sub> did not correlate with symptom status or clinical outcomes. A significant proportion went on to require myectomy and/or ICD, thus highlighting the need for close follow-up. These data provide some initial insight into the clinical evaluation of \"real world\" athletes with HCM; however, further study is warranted to help guide shared decision-making, return-to-play discussions, and the potential long-term safety of competitive athletic participation.</AbstractText><br /><br />Copyright © 2022 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 09 Dec 2022; 189:49-55</small></div>
Newman DB, Garmany R, Contreras AM, Bos JM, ... Ommen SR, Ackerman MJ
Am J Cardiol: 09 Dec 2022; 189:49-55 | PMID: 36508762
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.</h4><i>Costa F, Montalto C, Branca M, Hong SJ, ... Mehran R, Valgimigli M</i><br /><b>Aims</b><br />The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients.<br /><b>Methods and results</b><br />A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation.<br /><b>Conclusion</b><br />In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.<br /><b>Study registration</b><br />PROSPERO registration number CRD42021284004.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
Costa F, Montalto C, Branca M, Hong SJ, ... Mehran R, Valgimigli M
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477292
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Translational opportunities of single-cell biology in atherosclerosis.</h4><i>de Winther MPJ, Bäck M, Evans P, Gomez D, ... Bochaton-Piallat ML, Monaco C</i><br /><AbstractText>The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
de Winther MPJ, Bäck M, Evans P, Gomez D, ... Bochaton-Piallat ML, Monaco C
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36478058
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Prevention of cardiorenal damage: importance of albuminuria.</h4><i>Ruilope LM, Ortiz A, Lucia A, Miranda B, ... Ruiz-Hurtado G, Pitt B</i><br /><AbstractText>Chronic kidney disease (CKD) is projected to become a leading global cause of death by 2040, and its early detection is critical for effective and timely management. The current definition of CKD identifies only advanced stages, when kidney injury has already destroyed >50% of functioning kidney mass as reflected by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or a urinary albumin/creatinine ratio >six-fold higher than physiological levels (i.e. > 30 mg/g). An elevated urinary albumin-excretion rate is a known early predictor of future cardiovascular events. There is thus a \'blind spot\' in the detection of CKD, when kidney injury is present but is undetectable by current diagnostic criteria, and no intervention is made before renal and cardiovascular damage occurs. The present review discusses the CKD \'blind spot\' concept and how it may facilitate a holistic approach to CKD and cardiovascular disease prevention and implement the call for albuminuria screening implicit in current guidelines. Cardiorenal risk associated with albuminuria in the high-normal range, novel genetic and biochemical markers of elevated cardiorenal risk, and the role of heart and kidney protective drugs evaluated in recent clinical trials are also discussed. As albuminuria is a major risk factor for cardiovascular and renal disease, starting from levels not yet considered in the definition of CKD, the implementation of opportunistic or systematic albuminuria screening and therapy, possibly complemented with novel early biomarkers, has the potential to improve cardiorenal outcomes and mitigate the dismal 2040 projections for CKD and related cardiovascular burden.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
Ruilope LM, Ortiz A, Lucia A, Miranda B, ... Ruiz-Hurtado G, Pitt B
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477861
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Enhanced Mitochondrial Calcium Uptake Suppresses Atrial Fibrillation Associated With Metabolic Syndrome.</h4><i>Fossier L, Panel M, Butruille L, Colombani S, ... Montaigne D, Fauconnier J</i><br /><b>Background</b><br />Patients with metabolic syndrome (MetS) have an increased risk of atrial fibrillation (AF). Impaired Ca<sup>2+</sup> homeostasis and mitochondrial dysfunction have emerged as an arrhythmogenic substrate in both patients and animal models of MetS. Whether impaired mitochondrial Ca<sup>2+</sup> handling underlies AF associated with MetS remains poorly explored.<br /><b>Objectives</b><br />The aim of this study was to determine the initial mechanisms related to AF susceptibility and mitochondrial dysfunction encountered in metabolic cardiomyopathy.<br /><b>Methods</b><br />A total of 161 mice and 34 patients were studied. Mitochondrial Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) were investigated in right atrial tissue of patients with (n = 18) or without (n = 16) MetS and of C57Bl/6J mice fed with a high-fat sucrose diet (HFS) for 2 (n = 42) or 12 (n = 39) weeks. Susceptibility to AF was evaluated in isolated sinoatrial tissue and in vivo in mice.<br /><b>Results</b><br />Increased expression of the MICUs subunits of the MCUC (1.00 ± 0.33 AU vs 1.29 ± 0.23 AU; P = 0.034) was associated with impaired mitochondrial Ca<sup>2+</sup> uptake in patients (168.7 ± 31.3 nmol/min/mg vs 127.3 ± 18.4 nmol/min/mg; P = 0.026) and HFS mice (0.10 ± 0.04 ΔF/F0 × ms<sup>-1</sup> vs 0.06 ± 0.03 ΔF/F0 × ms<sup>-1</sup>; P = 0.0086, and 0.15 ± 0.07 ΔF/F0 × ms<sup>-1</sup> vs 0.046 ± 0.03 ΔF/F0 × ms<sup>-1</sup>; P = 0.0076 in 2- and 12-week HFS mice, respectively). HFS mice elicited a 70% increased susceptibility to AF. The MCUC agonist kaempferol restored MCUC activity in vitro and abolished the occurrence of AF in HFS mice.<br /><b>Conclusions</b><br />Impaired MCUC activity and mitochondrial Ca<sup>2+</sup> homeostasis from the early stage of metabolic cardiomyopathy in mice lead to AF. Given that similar defects in cardiac mitochondrial Ca<sup>2+</sup> handling are present in MetS patients, the modulation of the MCUC activity represents an attractive antiarrhythmic strategy.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Dec 2022; 80:2205-2219</small></div>
Fossier L, Panel M, Butruille L, Colombani S, ... Montaigne D, Fauconnier J
J Am Coll Cardiol: 06 Dec 2022; 80:2205-2219 | PMID: 36456051
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>The response to the COVID-19 pandemic: With hindsight what lessons can we learn?</h4><i>Faghy M, Arena R, Hills AP, Yates J, ... Lavie CJ, Smith A</i><br /><AbstractText>The purpose of this paper is to put forward some evidence-based lessons that can be learned from how to respond to a Pandemic that relate to healthy living behaviours (HLB). A 4-step methodology was followed to conduct a narrative review of the literature and to present a professional practice vignette. The narrative review identified 8 lessons: 1) peer review; 2) historical perspectives; 3) investing in resilience and protection; 4) unintended consequences; 5) protecting physical activity; 6) school closures; 7) mental health; and 8) obesity. As in all probability there will be another Pandemic, it is important that the lessons learned over the last three years in relation to HLB are acted upon. Whilst there will not always be a consensus on what to emphasise, it is important that many evidence-based positions are presented. The authors of this paper recognise that this work is a starting point and that the lessons presented here will need to be revisited as new evidence becomes available.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 05 Dec 2022; epub ahead of print</small></div>
Faghy M, Arena R, Hills AP, Yates J, ... Lavie CJ, Smith A
Prog Cardiovasc Dis: 05 Dec 2022; epub ahead of print | PMID: 36481211
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Late outcomes of ST-elevation myocardial infarction treated by pharmaco-invasive or primary percutaneous coronary intervention.</h4><i>Jamal J, Idris H, Faour A, Yang W, ... Lo S, French JK</i><br /><b>Aims</b><br />Pharmaco-invasive percutaneous coronary intervention (PI-PCI) is recommended for patients with ST-elevation myocardial infarction (STEMI)who are unable to undergo timely primary PCI (pPCI). The present study examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI)compared with timely and late pPCI (>120 min from first medical contact).<br /><b>Methods and results</b><br />All patients with STEMI presenting within 12 h of symptom onset, who underwent PCI during their initial hospitalization at Liverpool Hospital (Sydney), from October 2003 to March 2014, were included. Amongst 2091 STEMI patients (80% male), 1077 (52%)underwent pPCI (68% timely, 32% late), and 1014 (48%)received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01. After propensity matching, the adjusted mortality hazard ratio (HR) for timely pPCI compared with scheduled PCI was 0.9 (95% CIs 0.4-2.0) and compared with rescue PCI was 0.5 (95% CIs 0.2-0.9). The adjusted mortality HR for late pPCI, compared with scheduled PCI was 2.2 (95% CIs 1.2-3.1)and compared with rescue PCI, it was 1.5 (95% CIs 0.7-2.0).<br /><b>Conclusion</b><br />Patients who underwent late pPCI had higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 02 Dec 2022; epub ahead of print</small></div>
Jamal J, Idris H, Faour A, Yang W, ... Lo S, French JK
Eur Heart J: 02 Dec 2022; epub ahead of print | PMID: 36459120
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Trial of Deferiprone in Parkinson\'s Disease.</h4><i>Devos D, Labreuche J, Rascol O, Corvol JC, ... Moreau C, FAIRPARK-II Study Group</i><br /><b>Background</b><br />Iron content is increased in the substantia nigra of persons with Parkinson\'s disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson\'s disease, but its effects on disease progression are unclear.<br /><b>Methods</b><br />We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson\'s disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson\'s Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.<br /><b>Results</b><br />A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.<br /><b>Conclusions</b><br />In participants with early Parkinson\'s disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).<br /><br />Copyright © 2022 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 01 Dec 2022; 387:2045-2055</small></div>
Devos D, Labreuche J, Rascol O, Corvol JC, ... Moreau C, FAIRPARK-II Study Group
N Engl J Med: 01 Dec 2022; 387:2045-2055 | PMID: 36449420
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Trial of Training to Reduce Driver Inattention in Teens with ADHD.</h4><i>Epstein JN, Garner AA, Kiefer AW, Peugh J, ... Simon JO, Fisher DL</i><br /><b>Background</b><br />Teens with attention deficit-hyperactivity disorder (ADHD) are at increased risk for motor vehicle collisions. A computerized skills-training program to reduce long glances away from the roadway, a contributor to collision risk, may ameliorate driving risks among teens with ADHD.<br /><b>Methods</b><br />We evaluated a computerized skills-training program designed to reduce long glances (lasting ≥2 seconds) away from the roadway in drivers 16 to 19 years of age with ADHD. Participants were randomly assigned in a 1:1 ratio to undergo either enhanced Focused Concentration and Attention Learning, a program that targets reduction in the number of long glances (intervention) or enhanced conventional driver\'s education (control). The primary outcomes were the number of long glances away from the roadway and the standard deviation of lane position, a measure of lateral movements away from the center of the lane, during two 15-minute simulated drives at baseline and at 1 month and 6 months after training. Secondary outcomes were the rates of long glances and collisions or near-collisions involving abrupt changes in vehicle momentum (g-force event), as assessed with in-vehicle recordings over the 1-year period after training.<br /><b>Results</b><br />During simulated driving after training, participants in the intervention group had a mean of 16.5 long glances per drive at 1 month and 15.7 long glances per drive at 6 months, as compared with 28.0 and 27.0 long glances, respectively, in the control group (incidence rate ratio at 1 month, 0.64; 95% confidence interval [CI], 0.52 to 0.76; P<0.001; incidence rate ratio at 6 months, 0.64; 95% CI, 0.52 to 0.76; P<0.001). The standard deviation of lane position (in feet) was 0.98 SD at 1 month and 0.98 SD at 6 months in the intervention group, as compared with 1.20 SD and 1.20 SD, respectively, in the control group (difference at 1 month, -0.21 SD; 95% CI, -0.29 to -0.13; difference at 6 months, -0.22 SD; 95% CI, -0.31 to -0.13; P<0.001 for interaction for both comparisons). During real-world driving over the year after training, the rate of long glances per g-force event was 18.3% in the intervention group and 23.9% in the control group (relative risk, 0.76; 95% CI, 0.61 to 0.92); the rate of collision or near-collision per g-force event was 3.4% and 5.6%, respectively (relative risk, 0.60, 95% CI, 0.41 to 0.89).<br /><b>Conclusions</b><br />In teens with ADHD, a specially designed computerized simulated-driving program with feedback to reduce long glances away from the roadway reduced the frequency of long glances and lessened variation in lane position as compared with a control program. During real-world driving in the year after training, the rate of collisions and near-collisions was lower in the intervention group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02848092.).<br /><br />Copyright © 2022 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 01 Dec 2022; 387:2056-2066</small></div>
Epstein JN, Garner AA, Kiefer AW, Peugh J, ... Simon JO, Fisher DL
N Engl J Med: 01 Dec 2022; 387:2056-2066 | PMID: 36449421
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.</h4><i>Neglia D, Liga R, Gimelli A, Podlesnikar T, ... Delgado V, EURECA Investigators </i><br /><b>Background</b><br />The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS).<br /><b>Methods</b><br />Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD).<br /><b>Results</b><br />The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization.<br /><b>Conclusions</b><br />In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 01 Dec 2022; epub ahead of print</small></div>
Neglia D, Liga R, Gimelli A, Podlesnikar T, ... Delgado V, EURECA Investigators
Eur Heart J: 01 Dec 2022; epub ahead of print | PMID: 36452988
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>The association of disparities in neighborhood median household income and mortality in patients admitted to the hospital with atrial fibrillation.</h4><i>Dhore-Patil A, Crawford M, Nedunchezhian S, El Hajjar AH, ... Sidhu G, Marrouche N</i><br /><b>Background</b><br />Lower neighborhood median household income (nMHI) is associated with increased adverse outcomes in patients with atrial fibrillation (AF). However, its effect on mortality is yet unknown.<br /><b>Methods</b><br />Data from the regional United States (U.S.) electronic medical records database, Research Action for Health Network (REACHnet), was extracted for adult patients with AF at Tulane Medical Center over 10 years. Annual nMHI & neighborhood high school graduation (HSG) data was collected from the US Census bureau. Only African Americans (AA) and Caucasians (CC) who had socioeconomic data were included. Low nMHI and low HSG were defined as ≤$25,000 & <90% respectively. High nMHI and HSG were defined as >$50,000 & ≥90% respectively. Primary endpoints were all cause and cardiovascular (CV) mortality. Cox-proportional hazard ratios were used to evaluate the endpoints.<br /><b>Results</b><br />We included 4616 patients diagnosed with AF. During a median follow up of 4.6 years, 434 patients died of which 32.7% patients had CV mortality. There was a stepwise decrease in incidence of both all-cause and CV mortality as nMHI increased. Patients with low nMHI had the greatest risk of all-cause mortality (HR 1.9, C.I. 1.2-3.2, P 0.004). The association between low nMHI and all-cause mortality persisted after adjusting for age, sex, race, HSG and stroke risk factors using CHA<sub>2</sub>DS<sub>2</sub>VASC, delta CHA<sub>2</sub>DS<sub>2</sub>VASC scores and oral anticoagulant use. CV mortality followed a similar trend as all-cause mortality, however, this association was not significant after adjusting for the above variables. Apart from low nMHI, CHA<sub>2</sub>DS<sub>2</sub>VASC delta CHA<sub>2</sub>DS<sub>2</sub>VASC were statistically significant independent predictors of both all-cause and CV mortality.<br /><b>Conclusion</b><br />Low nMHI is an independent risk factor for all cause and CV mortality in AF. Higher burden of co-morbidities is the driving force behind this disparity. Future studies should evaluate the role of educational and therapeutic intervention in these populations to reduce mortality.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 30 Nov 2022; epub ahead of print</small></div>
Dhore-Patil A, Crawford M, Nedunchezhian S, El Hajjar AH, ... Sidhu G, Marrouche N
Prog Cardiovasc Dis: 30 Nov 2022; epub ahead of print | PMID: 36462553
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>Lecanemab in Early Alzheimer\'s Disease.</h4><i>van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, ... Kramer LD, Iwatsubo T</i><br /><b>Background</b><br />The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer\'s disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer\'s disease.<br /><b>Methods</b><br />We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer\'s disease (mild cognitive impairment or mild dementia due to Alzheimer\'s disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab (10 mg per kilogram of body weight every 2 weeks) or placebo. The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points were the change in amyloid burden on PET, the score on the 14-item cognitive subscale of the Alzheimer\'s Disease Assessment Scale (ADAS-cog14; range, 0 to 90; higher scores indicate greater impairment), the Alzheimer\'s Disease Composite Score (ADCOMS; range, 0 to 1.97; higher scores indicate greater impairment), and the score on the Alzheimer\'s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0 to 53; lower scores indicate greater impairment).<br /><b>Results</b><br />A total of 1795 participants were enrolled, with 898 assigned to receive lecanemab and 897 to receive placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, -0.45; 95% confidence interval [CI], -0.67 to -0.23; P<0.001). In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo (difference, -59.1 centiloids; 95% CI, -62.6 to -55.6). Other mean differences between the two groups in the change from baseline favoring lecanemab were as follows: for the ADAS-cog14 score, -1.44 (95% CI, -2.27 to -0.61; P<0.001); for the ADCOMS, -0.050 (95% CI, -0.074 to -0.027; P<0.001); and for the ADCS-MCI-ADL score, 2.0 (95% CI, 1.2 to 2.8; P<0.001). Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with edema or effusions in 12.6%.<br /><b>Conclusions</b><br />Lecanemab reduced markers of amyloid in early Alzheimer\'s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer\'s disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455.).<br /><br />Copyright © 2022 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 29 Nov 2022; epub ahead of print</small></div>
van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, ... Kramer LD, Iwatsubo T
N Engl J Med: 29 Nov 2022; epub ahead of print | PMID: 36449413
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract
<div><h4>2-Year Outcomes of Angiographic Quantitative Flow Ratio-Guided Coronary Interventions.</h4><i>Song L, Xu B, Tu S, Guan C, ... Stone GW, FAVOR III China Study Group</i><br /><b>Background</b><br />In the multicenter, randomized, sham-controlled FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, quantitative flow ratio (QFR)-based lesion selection improved 1-year clinical outcomes compared with conventional angiographic guidance for percutaneous coronary intervention (PCI).<br /><b>Objectives</b><br />The purpose of this study was to determine whether the benefits of QFR guidance persist at 2 years, particularly for patients in whom QFR changed the revascularization strategy.<br /><b>Methods</b><br />Eligible patients were randomized to a QFR-guided strategy (PCI performed only if QFR ≤0.80) or a standard angiography-guided strategy. Major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization occurring within 2 years were analyzed in the intention-to-treat population.<br /><b>Results</b><br />Among 3,825 randomized participants, 2-year MACE occurred in 161 of 1,913 (8.5%) patients in the QFR-guided group and in 237 of 1,912 (12.5%) patients in the angiography-guided group (HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), driven by fewer MIs (4.0% vs 6.8%; HR: 0.58; 95% CI: 0.44-0.77; P = 0.0002) and ischemia-driven revascularizations (4.2% vs 5.8%; HR: 0.71; 95% CI: 0.53-0.95; P = 0.02) in the QFR-guided group. Landmark analysis showed consistent results within the first year and between 1-2 years (P<sub>int</sub> = 0.99). Although the 2-year MACE rate was lower in the QFR-guided group in both patients with and without revascularization strategy changes, the extent of outcome improvement was greater (P<sub>int</sub> = 0.009) among those patients in whom the preplanned PCI strategy was modified by QFR.<br /><b>Conclusions</b><br />QFR-guided lesion selection improved 2-year clinical outcomes compared with standard angiography guidance. The benefits were most pronounced among patients in whom QFR assessment altered the planned revascularization strategy. (FAVOR III China Study [The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease] NCT03656848).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Nov 2022; 80:2089-2101</small></div>
Song L, Xu B, Tu S, Guan C, ... Stone GW, FAVOR III China Study Group
J Am Coll Cardiol: 29 Nov 2022; 80:2089-2101 | PMID: 36424680
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.