Topic: General Cardiology

Abstract

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

Son MBF, Murray N, Friedman K, Young CC, ... Randolph AG, Overcoming COVID-19 Investigators
Background
The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy.
Methods
We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2.
Results
A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis.
Conclusions
Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 30 Jun 2021; 385:23-34
Son MBF, Murray N, Friedman K, Young CC, ... Randolph AG, Overcoming COVID-19 Investigators
N Engl J Med: 30 Jun 2021; 385:23-34 | PMID: 34133855
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Abstract

Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes.

Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, ... Branch K, AMPLITUDE-O Trial Investigators
Background
Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain.
Methods
In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium-glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes).
Results
A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P = 0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo.
Conclusions
In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo. (Funded by Sanofi; AMPLITUDE-O ClinicalTrials.gov number, NCT03496298.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 27 Jun 2021; epub ahead of print
Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, ... Branch K, AMPLITUDE-O Trial Investigators
N Engl J Med: 27 Jun 2021; epub ahead of print | PMID: 34215025
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Abstract

Eight-year outcomes for patients with aortic valve stenosis at low surgical risk randomized to transcatheter vs. surgical aortic valve replacement.

Jørgensen TH, Thyregod HGH, Ihlemann N, Nissen H, ... Olsen PS, Søndergaard L
Aims
The aims of the study were to compare clinical outcomes and valve durability after 8 years of follow-up in patients with symptomatic severe aortic valve stenosis at low surgical risk treated with either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).
Methods and results
In the NOTION trial, patients with symptomatic severe aortic valve stenosis were randomized to TAVI or SAVR. Clinical status, echocardiography, structural valve deterioration, and failure were assessed using standardized definitions. In total, 280 patients were randomized to TAVI (n = 145) or SAVR (n = 135). Baseline characteristics were similar, including mean age of 79.1 ± 4.8 years and a mean STS score of 3.0 ± 1.7%. At 8-year follow-up, the estimated risk of the composite outcome of all-cause mortality, stroke, or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P = 0.94). The estimated risks for all-cause mortality (51.8% vs. 52.6%; P = 0.90), stroke (8.3% vs. 9.1%; P = 0.90), or myocardial infarction (6.2% vs. 3.8%; P = 0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P = 0.0017), whereas the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P = 0.61).
Conclusions
In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk for all-cause mortality, stroke, or myocardial infarction, as well as the risk of bioprosthetic valve failure after 8 years of follow-up.
Clinical trial registration
URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 27 Jun 2021; epub ahead of print
Jørgensen TH, Thyregod HGH, Ihlemann N, Nissen H, ... Olsen PS, Søndergaard L
Eur Heart J: 27 Jun 2021; epub ahead of print | PMID: 34179981
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Abstract

Accelerometer-derived physical activity and risk of atrial fibrillation.

Khurshid S, Weng LC, Al-Alusi MA, Halford JL, ... McManus DD, Lubitz SA
Aims
Physical activity may be an important modifiable risk factor for atrial fibrillation (AF), but associations have been variable and generally based on self-reported activity.
Methods and results
We analysed 93 669 participants of the UK Biobank prospective cohort study without prevalent AF who wore a wrist-based accelerometer for 1 week. We categorized whether measured activity met the standard recommendations of the European Society of Cardiology, American Heart Association, and World Health Organization [moderate-to-vigorous physical activity (MVPA) ≥150 min/week]. We tested associations between guideline-adherent activity and incident AF (primary) and stroke (secondary) using Cox proportional hazards models adjusted for age, sex, and each component of the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) risk score. We also assessed correlation between accelerometer-derived and self-reported activity. The mean age was 62 ± 8 years and 57% were women. Over a median of 5.2 years, 2338 incident AF events occurred. In multivariable adjusted models, guideline-adherent activity was associated with lower risks of AF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75-0.89; incidence 3.5/1000 person-years, 95% CI 3.3-3.8 vs. 6.5/1000 person-years, 95% CI 6.1-6.8] and stroke (HR 0.76, 95% CI 0.64-0.90; incidence 1.0/1000 person-years, 95% CI 0.9-1.1 vs. 1.8/1000 person-years, 95% CI 1.6-2.0). Correlation between accelerometer-derived and self-reported MVPA was weak (Spearman r = 0.16, 95% CI 0.16-0.17). Self-reported activity was not associated with incident AF or stroke.
Conclusions
Greater accelerometer-derived physical activity is associated with lower risks of AF and stroke. Future preventive efforts to reduce AF risk may be most effective when targeting adherence to objective activity thresholds.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 30 Jun 2021; 42:2472-2483
Khurshid S, Weng LC, Al-Alusi MA, Halford JL, ... McManus DD, Lubitz SA
Eur Heart J: 30 Jun 2021; 42:2472-2483 | PMID: 34037209
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Abstract

Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes.

Filippatos G, Bakris GL, Pitt B, Agarwal R, ... Anker SD, FIDELIO-DKD Investigators
Background
Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models.
Objectives
This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study.
Methods
Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF.
Results
Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively).
Conclusions
In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2021; 78:142-152
Filippatos G, Bakris GL, Pitt B, Agarwal R, ... Anker SD, FIDELIO-DKD Investigators
J Am Coll Cardiol: 12 Jul 2021; 78:142-152 | PMID: 34015478
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Abstract

HIV infection is associated with thoracic and abdominal aortic aneurysms: a prospective matched cohort study.

Høgh J, Pham MHC, Knudsen AD, Thudium RF, ... Kofoed KF, Nielsen SD
Aims
Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH.
Methods and results
PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47-60) and 52 (48-61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P < 0.001). PLWH had a significantly higher prevalence of ascending aortic aneurysms and infrarenal aortic aneurysms. In an adjusted model, HIV was independently associated with aortic aneurysms (adjusted odds ratio; 4.51 [95% confidence interval 2.56-8.08], P < 0.001). Within PLWH, obesity and hepatitis B co-infection were associated with aortic aneurysms.
Conclusion
PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 07 Jul 2021; epub ahead of print
Høgh J, Pham MHC, Knudsen AD, Thudium RF, ... Kofoed KF, Nielsen SD
Eur Heart J: 07 Jul 2021; epub ahead of print | PMID: 34240121
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Abstract

Predictors, time course, and outcomes of persistence patterns in oral anticoagulation for non-valvular atrial fibrillation: a Dutch Nationwide Cohort Study.

Toorop MMA, Chen Q, Tichelaar VYIG, Cannegieter SC, Lijfering WM
Aims 
Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients.
Methods and results 
DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA2DS2-VASc score of ≥2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA2DS2-VASc score ≥2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs.
Conclusion 
At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 15 Jul 2021; epub ahead of print
Toorop MMA, Chen Q, Tichelaar VYIG, Cannegieter SC, Lijfering WM
Eur Heart J: 15 Jul 2021; epub ahead of print | PMID: 34269375
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Abstract

Impact of Optimal Medical Therapy on 10-Year Mortality After Coronary Revascularization.

Kawashima H, Serruys PW, Ono M, Hara H, ... Onuma Y, SYNTAX Extended Survival Investigators
Background
The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial.
Objectives
The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG.
Methods
This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality.
Results
In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without.
Conclusions
In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:27-38
Kawashima H, Serruys PW, Ono M, Hara H, ... Onuma Y, SYNTAX Extended Survival Investigators
J Am Coll Cardiol: 05 Jul 2021; 78:27-38 | PMID: 34210411
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Abstract

Immediate post-procedural functional assessment of percutaneous coronary intervention: current evidence and future directions.

Ding D, Huang J, Westra J, Cohen DJ, ... Tu S, Wijns W
Percutaneous coronary intervention (PCI) guided by coronary physiology provides symptomatic benefit and improves patient outcomes. Nevertheless, over one-fourth of patients still experience recurrent angina or major adverse cardiac events following the index procedure. Coronary angiography, the current workhorse for evaluating PCI efficacy, has limited ability to identify suboptimal PCI results. Accumulating evidence supports the usefulness of immediate post-procedural functional assessment. This review discusses the incidence and possible mechanisms behind a suboptimal physiology immediately after PCI. Furthermore, we summarize the current evidence base supporting the usefulness of immediate post-PCI functional assessment for evaluating PCI effectiveness, guiding PCI optimization, and predicting clinical outcomes. Multiple observational studies and post hoc analyses of datasets from randomized trials demonstrated that higher post-PCI functional results are associated with better clinical outcomes as well as a reduced rate of residual angina and repeat revascularization. As such, post-PCI functional assessment is anticipated to impact patient management, secondary prevention, and resource utilization. Pre-PCI physiological guidance has been shown to improve clinical outcomes and reduce health care costs. Whether similar benefits can be achieved using post-PCI physiological assessment requires evaluation in randomized clinical outcome trials.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 14 Jul 2021; 42:2695-2707
Ding D, Huang J, Westra J, Cohen DJ, ... Tu S, Wijns W
Eur Heart J: 14 Jul 2021; 42:2695-2707 | PMID: 33822922
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Abstract

The Coronary Artery Risk Development In Young Adults (CARDIA) Study: JACC Focus Seminar 8/8.

Lloyd-Jones DM, Lewis CE, Schreiner PJ, Shikany JM, Sidney S, Reis JP
The CARDIA (Coronary Artery Risk Development in Young Adults) study began in 1985 to 1986 with enrollment of 5,115 Black or White men and women ages 18 to 30 years from 4 US communities. Over 35 years, CARDIA has contributed fundamentally to our understanding of the contemporary epidemiology and life course of cardiovascular health and disease, as well as pulmonary, renal, neurological, and other manifestations of aging. CARDIA has established associations between the neighborhood environment and the evolution of lifestyle behaviors with biological risk factors, subclinical disease, and early clinical events. CARDIA has also identified the nature and major determinants of Black-White differences in the development of cardiovascular risk. CARDIA will continue to be a unique resource for understanding determinants, mechanisms, and outcomes of cardiovascular health and disease across the life course, leveraging ongoing pan-omics work from genomics to metabolomics that will define mechanistic pathways involved in cardiometabolic aging.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:260-277
Lloyd-Jones DM, Lewis CE, Schreiner PJ, Shikany JM, Sidney S, Reis JP
J Am Coll Cardiol: 19 Jul 2021; 78:260-277 | PMID: 34266580
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Abstract

Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial.

Curzen N, Nicholas Z, Stuart B, Wilding S, ... Hlatky MA, FORECAST Investigators
Aims 
Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care.
Methods and results 
Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months; secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized patients were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01).
Conclusion 
A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 15 Jul 2021; epub ahead of print
Curzen N, Nicholas Z, Stuart B, Wilding S, ... Hlatky MA, FORECAST Investigators
Eur Heart J: 15 Jul 2021; epub ahead of print | PMID: 34269376
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Abstract

Oral fluoroquinolones and risk of aortic or mitral regurgitation: a nationwide nested case-control study.

Strange JE, Holt A, Blanche P, Gislason G, ... Køber L, Rasmussen PV
Aims
Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated.
Methods and results
Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95-1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95-1.23 for cDDD >10 compared with cDDD 1-5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions.
Conclusions
In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 09 Jul 2021; epub ahead of print
Strange JE, Holt A, Blanche P, Gislason G, ... Køber L, Rasmussen PV
Eur Heart J: 09 Jul 2021; epub ahead of print | PMID: 34245252
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Abstract

Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

Völz S, Redfors B, Angerås O, Ioanes D, ... Jeppsson A, Omerovic E
Aims 
To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease.
Methods and results 
We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41-0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17-1.38, Ptrend < 0.001).
Conclusion 
In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 14 Jul 2021; 42:2657-2664
Völz S, Redfors B, Angerås O, Ioanes D, ... Jeppsson A, Omerovic E
Eur Heart J: 14 Jul 2021; 42:2657-2664 | PMID: 34023903
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Abstract

Association of the combined effects of air pollution and changes in physical activity with cardiovascular disease in young adults.

Kim SR, Choi S, Kim K, Chang J, ... Kim KH, Park SM
Aims
Little is known about the trade-off between the health benefits of physical activity (PA) and the potential harmful effects of increased exposure to air pollution during outdoor PA. We examined the association of the combined effects of air pollution and changes in PA with cardiovascular disease (CVD) in young adults.
Methods and results
This nationwide cohort study included 1 469 972 young adults aged 20-39 years. Air pollution exposure was estimated by the annual average cumulative level of particulate matter (PM). PA was calculated as minutes of metabolic equivalent tasks per week (MET-min/week) based on two consecutive health examinations from 2009 to 2012. Compared with the participants exposed to low-to-moderate levels of PM2.5 or PM10 who continuously engaged in ≥1000 MET-min/week of PA, those who decreased their PA from ≥1000 MET-min/week to 1-499 MET-min/week [PM10 adjusted hazard ratio (aHR) 1.22; 95% confidence interval (CI) 1.00-1.48] and to 0 MET-min/week (physically inactive; PM10 aHR 1.38; 95% CI 1.07-1.78) had an increased risk of CVD (P for trend <0.01). Among participants exposed to high levels of PM2.5 or PM10, the risk of CVD was elevated with an increase in PA above 1000 MET-min/week.
Conclusion
Reducing PA may lead to subsequent elevation of CVD risk in young adults exposed to low-to-moderate levels of PM2.5 or PM10, whereas a large increase in PA in a high-pollution environment may adversely affect cardiovascular health.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 30 Jun 2021; 42:2487-2497
Kim SR, Choi S, Kim K, Chang J, ... Kim KH, Park SM
Eur Heart J: 30 Jun 2021; 42:2487-2497 | PMID: 33780974
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Impact:
Abstract

SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe.

SCORE2 working group and ESC Cardiovascular risk collaboration
Aims
The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe.
Methods and results 
We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low-risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries.
Conclusion 
SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 30 Jun 2021; 42:2439-2454
SCORE2 working group and ESC Cardiovascular risk collaboration
Eur Heart J: 30 Jun 2021; 42:2439-2454 | PMID: 34120177
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Impact:
Abstract

SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions.

SCORE2-OP working group and ESC Cardiovascular risk collaboration
Aims 
The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.
Methods and results 
Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.
Conclusions 
The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 30 Jun 2021; 42:2455-2467
SCORE2-OP working group and ESC Cardiovascular risk collaboration
Eur Heart J: 30 Jun 2021; 42:2455-2467 | PMID: 34120185
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Impact:
Abstract

Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease.

Eikelboom JW, Bhatt DL, Fox KAA, Bosch J, ... Shestakovska O, Yusuf S
Background
The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).
Objectives
The aim of this work was to report the effects of the combination on overall and cause-specific mortality.
Methods
The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes.
Results
During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months.
Conclusions
The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:14-23
Eikelboom JW, Bhatt DL, Fox KAA, Bosch J, ... Shestakovska O, Yusuf S
J Am Coll Cardiol: 05 Jul 2021; 78:14-23 | PMID: 34210409
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Impact:
Abstract

Transition to adulthood and transfer to adult care of adolescents with congenital heart disease: a global consensus statement of the ESC Association of Cardiovascular Nursing and Allied Professions (ACNAP), the ESC Working Group on Adult Congenital Heart Disease (WG ACHD), the Association for European Paediatric and Congenital Cardiology (AEPC), the Pan-African Society of Cardiology (PASCAR), the Asia-Pacific Pediatric Cardiac Society (APPCS), the Inter-American Society of Cardiology (IASC), the Cardiac Society of Australia and New Zealand (CSANZ), the International Society for Adult Congenital Heart Disease (ISACHD), the World Heart Federation (WHF), the European Congenital Heart Disease Organisation (ECHDO), and the Global Alliance for Rheumatic and Congenital Hearts (Global ARCH).

Moons P, Bratt EL, De Backer J, Goossens E, ... Yang HL, Thomet C
The vast majority of children with congenital heart disease (CHD) in high-income countries survive into adulthood. Further, paediatric cardiac services have expanded in middle-income countries. Both evolutions have resulted in an increasing number of CHD survivors. Expert care across the life span is necessitated. In adolescence, patients transition from being a dependent child to an independent adult. They are also advised to transfer from paediatrics to adult care. There is no universal consensus regarding how transitional care should be provided and how the transfer should be organized. This is even more challenging in countries with low resources. This consensus document describes issues and practices of transition and transfer of adolescents with CHD, accounting for different possibilities in high-, middle-, and low-income countries. Transitional care ought to be provided to all adolescents with CHD, taking into consideration the available resources. When reaching adulthood, patients ought to be transferred to adult care facilities/providers capable of managing their needs, and systems have to be in place to make sure that continuity of high-quality care is ensured after leaving paediatric cardiology.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 30 Jun 2021; epub ahead of print
Moons P, Bratt EL, De Backer J, Goossens E, ... Yang HL, Thomet C
Eur Heart J: 30 Jun 2021; epub ahead of print | PMID: 34198319
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Abstract

The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial.

Martens P, Dupont M, Dauw J, Nijst P, ... Tang WHW, Mullens W
Aims
Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF) and negatively affects cardiac function and structure. The study the effect of ferric carboxymaltose (FCM) on cardiac reverse remodelling and contractile status in HFrEF.
Methods and results
Symptomatic HFrEF patients with iron deficiency and a persistently reduced left ventricular ejection fraction (LVEF <45%) at least 6 months after cardiac resynchronization therapy (CRT) implant were prospectively randomized to FCM or standard of care (SOC) in a double-blind manner. The primary endpoint was the change in LVEF from baseline to 3-month follow-up assessed by three-dimensional echocardiography. Secondary endpoints included the change in left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) from baseline to 3-month follow-up. Cardiac performance was evaluated by the force-frequency relationship as assessed by the slope change of the cardiac contractility index (CCI = systolic blood pressure/LVESV index) at 70, 90, and 110 beats of biventricular pacing. A total of 75 patients were randomized to FCM (n = 37) or SOC (n = 38). At baseline, both treatment groups were well matched including baseline LVEF (34 ± 7 vs. 33 ± 8, P = 0.411). After 3 months, the change in LVEF was significantly higher in the FMC group [+4.22%, 95% confidence interval (CI) +3.05%; +5.38%] than in the SOC group (-0.23%, 95% CI -1.44%; +0.97%; P < 0.001). Similarly, LVESV (-9.72 mL, 95% CI -13.5 mL; -5.93 mL vs. -1.83 mL, 95% CI -5.7 mL; 2.1 mL; P = 0.001), but not LVEDV (P = 0.748), improved in the FCM vs. the SOC group. At baseline, both treatment groups demonstrated a negative force-frequency relationship, as defined by a decrease in CCI at higher heart rates (negative slope). FCM resulted in an improvement in the CCI slope during incremental biventricular pacing, with a positive force-frequency relationship at 3 months. Functional status and exercise capacity, as measured by the Kansas City Cardiomyopathy Questionnaire and peak oxygen consumption, were improved by FCM.
Conclusions
Treatment with FCM in HFrEF patients with iron deficiency and persistently reduced LVEF after CRT results in an improvement of cardiac function measured by LVEF, LVESV, and cardiac force-frequency relationship.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 28 Jun 2021; epub ahead of print
Martens P, Dupont M, Dauw J, Nijst P, ... Tang WHW, Mullens W
Eur Heart J: 28 Jun 2021; epub ahead of print | PMID: 34185066
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Impact:
Abstract

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

Becattini C, Maraziti G, Vinson DR, Ng ACC, ... Agnelli G, Jiménez D
Aims
 Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone.
Methods and results
 Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74).
Conclusion
  RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 27 Jun 2021; epub ahead of print
Becattini C, Maraziti G, Vinson DR, Ng ACC, ... Agnelli G, Jiménez D
Eur Heart J: 27 Jun 2021; epub ahead of print | PMID: 34179965
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Abstract

Neuraminidase 1 is a driver of experimental cardiac hypertrophy.

Chen QQ, Ma G, Liu JF, Cai YY, ... Zhang L, Qi LW
Aims 
Despite considerable therapeutic advances, there is still a dearth of evidence on the molecular determinants of cardiac hypertrophy that culminate in heart failure. Neuraminidases are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids. This study sought to characterize the role of neuraminidases in pathological cardiac hypertrophy and identify pharmacological inhibitors targeting mammalian neuraminidases.
Methods and results 
Neuraminidase 1 (NEU1) was highly expressed in hypertrophic hearts of mice and rats, and this elevation was confirmed in patients with hypertrophic cardiomyopathy (n = 7) compared with healthy controls (n = 7). The increased NEU1 was mainly localized in cardiomyocytes by co-localization with cardiac troponin T. Cardiomyocyte-specific NEU1 deficiency alleviated hypertrophic phenotypes in response to transverse aortic constriction or isoproterenol hydrochloride infusion, while NEU1 overexpression exacerbated the development of cardiac hypertrophy. Mechanistically, co-immunoprecipitation coupled with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated that NEU1 translocated into the nucleus and interacted with GATA4, leading to Foetal gene (Nppa and Nppb) expression. Virtual screening and experimental validation identified a novel compound C-09 from millions of compounds that showed favourable binding affinity to human NEU1 (KD = 0.38 μM) and effectively prevented the development of cardiac remodelling in cellular and animal models. Interestingly, anti-influenza drugs zanamivir and oseltamivir effectively inhibited mammalian NEU1 and showed new indications of cardio-protection.
Conclusions 
This work identifies NEU1 as a critical driver of cardiac hypertrophy and inhibition of NEU1 opens up an entirely new field of treatment for cardiovascular diseases.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 27 Jun 2021; epub ahead of print
Chen QQ, Ma G, Liu JF, Cai YY, ... Zhang L, Qi LW
Eur Heart J: 27 Jun 2021; epub ahead of print | PMID: 34179969
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Impact:
Abstract

De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes.

Shoji S, Kuno T, Fujisaki T, Takagi H, ... Latib A, Kohsaka S
Background
Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent P2Y12 inhibitors has become a cornerstone of acute coronary syndrome (ACS) management. Recent randomized controlled trials (RCTs) have investigated DAPT de-escalation to decrease the risk of bleeding outcomes.
Objectives
The aim of this study was to compare the efficacy and safety outcomes of various DAPT strategies in patients with ACS, including de-escalation from a potent P2Y12 inhibitor to clopidogrel or low-dose prasugrel.
Methods
MEDLINE and EMBASE were searched through January 2021 for RCTs investigating the efficacy and safety of DAPT in patients with ACS, and a network meta-analysis was conducted. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding.
Results
Our search identified 15 eligible RCTs, including 55,798 patients with ACS. De-escalation therapy was associated with reduced risk of primary bleeding outcomes (HR: 0.48 [95% CI: 0.30-0.77] vs clopidogrel; HR: 0.32 [95% CI: 0.20-0.52] vs ticagrelor; HR: 0.36 [95% CI: 0.24-0.55] vs standard-dose prasugrel; and HR: 0.40 [95% CI: 0.22-0.75] vs low-dose prasugrel) without negatively affecting primary efficacy outcomes. There were no significant differences in ischemic or bleeding outcomes between de-escalation to clopidogrel or low-dose prasugrel.
Conclusions
Compared with other established uses of DAPT, de-escalation was the most effective strategy for ACS treatment, resulting in fewer bleeding events without increasing ischemic events.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Jul 2021; epub ahead of print
Shoji S, Kuno T, Fujisaki T, Takagi H, ... Latib A, Kohsaka S
J Am Coll Cardiol: 08 Jul 2021; epub ahead of print | PMID: 34275697
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Impact:
Abstract

Persisting burden and challenges of rheumatic heart disease.

Marijon E, Mocumbi A, Narayanan K, Jouven X, Celermajer DS
Rheumatic heart disease (RHD) is the result of episodes of acute rheumatic fever with valvular (and other cardiac) damage caused by an abnormal immune response to group A streptococcal infections, usually during childhood and adolescence. As a result of improved living conditions and the introduction of penicillin, RHD was almost eradicated in the developed world by the 1980s. However, being a disease of poverty, its burden remains disproportionately high in the developing world, despite being a fundamentally preventable disease. Rheumatic heart disease generates relatively little attention from the medical and science communities, in contrast to other common infectious problems (such as malaria, HIV, tuberculosis), despite the major cardiovascular morbidity/mortality burden imposed by RHD. This relative neglect and paucity of funding have probably contributed to limited fundamental medical advances in this field for over 50 years. Given the importance of prevention before the onset of major valvular damage, the main challenges for RHD prevention are improving social circumstances, early diagnosis, and effective delivery of antibiotic prophylaxis. Early identification through ultrasound of silent, subclinical rheumatic valve lesions could provide an opportunity for early intervention. Simple echocardiographic diagnostic criteria and appropriately trained personnel can be valuable aids in large-scale public health efforts. In addition, a better understanding of the immunogenic determinants of the disease may provide potential routes to vaccine development and other novel therapies.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 14 Jul 2021; epub ahead of print
Marijon E, Mocumbi A, Narayanan K, Jouven X, Celermajer DS
Eur Heart J: 14 Jul 2021; epub ahead of print | PMID: 34263296
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Impact:
Abstract

Enhanced Assessment of Perioperative Mortality Risk in Adults With Congenital Heart Disease.

Constantine A, Costola G, Bianchi P, Chessa M, ... Ranucci M, Dimopoulos K
Background
In-hospital mortality is a rare, yet feared complication following cardiac surgery in adult congenital heart disease (ACHD). A risk score, developed and validated in ACHD, can be helpful to optimize risk assessment.
Objectives
The purpose of this study was to assess the performance of EuroSCORE II components and procedure-related Adult Congenital Heart Surgery (ACHS) score, identify additional risk factors, and develop a novel risk score for predicting in-hospital mortality after ACHD surgery.
Methods
We assessed perioperative survival in patients aged >16 years undergoing congenital heart surgery in a large tertiary center between 2003 and 2019. A risk variable-derived PEACH (PErioperative ACHd) score was calculated for each patient. Internal and external validation of the model was undertaken, including testing in a validation cohort of patients operated in a second European ACHD center.
Results
The development cohort comprised 1,782 procedures performed during the study period. Re-sternotomy was undertaken in 897 (50.3%). There were 31 (1.7%) in-hospital deaths. The PEACH score showed excellent discrimination ability (area under the curve [AUC]: 0.88; 95% CI: 0.83-0.94), and performed better than the ACHS score in our population (ACHS AUC: 0.69; 95% CI: 0.6-0.78; P = 0.0003). A simple 3-tiered risk stratification was formed: PEACH score 0 (in-hospital mortality 0.2%), 1-2 (3.6%), and ≥3 (17.2%). In a validation cohort of 975 procedures, the PEACH score retained its discriminative ability (AUC: 0.75; 95% CI: 0.72-0.77) and was well calibrated (Hosmer-Lemeshow chi-square goodness-of-fit P = 0.55). There was agreement in expected and observed perioperative mortality between cohorts.
Conclusions
The PEACH score is a simple, novel perioperative risk score developed and validated specifically for ACHD patients undergoing cardiac surgery.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:234-242
Constantine A, Costola G, Bianchi P, Chessa M, ... Ranucci M, Dimopoulos K
J Am Coll Cardiol: 19 Jul 2021; 78:234-242 | PMID: 34266577
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Impact:
Abstract

Lack of specialist care is associated with increased morbidity and mortality in adult congenital heart disease: a population-based study.

Diller GP, Orwat S, Lammers AE, Radke RM, ... Kaleschke G, Baumgartner H
Aims
The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population.
Methods and results
Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up.
Conclusion
Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 15 Jul 2021; epub ahead of print
Diller GP, Orwat S, Lammers AE, Radke RM, ... Kaleschke G, Baumgartner H
Eur Heart J: 15 Jul 2021; epub ahead of print | PMID: 34269382
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Impact:
Abstract

A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial.

Lansky AJ, Makkar R, Nazif T, Messé S, ... Baumbach A, Moses J
Aims 
The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR).
Methods and results 
This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls.
Conclusion 
REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 14 Jul 2021; 42:2670-2679
Lansky AJ, Makkar R, Nazif T, Messé S, ... Baumbach A, Moses J
Eur Heart J: 14 Jul 2021; 42:2670-2679 | PMID: 34000004
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Impact:
Abstract

Emergency department management of patients with adult congenital heart disease: a consensus paper from the ESC Working Group on Adult Congenital Heart Disease, the European Society for Emergency Medicine (EUSEM), the European Association for Cardio-Thoracic Surgery (EACTS), and the Association for Acute Cardiovascular Care (ACVC).

Chessa M, Brida M, Gatzoulis MA, Diller GP, ... Gallego P, Tutarel O
Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 07 Jul 2021; 42:2527-2535
Chessa M, Brida M, Gatzoulis MA, Diller GP, ... Gallego P, Tutarel O
Eur Heart J: 07 Jul 2021; 42:2527-2535 | PMID: 34021343
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Impact:
Abstract

Impact of sex on the management and outcome of aortic stenosis patients.

Bienjonetti-Boudreau D, Fleury MA, Voisine M, Paquin A, ... Salaun E, Clavel MA
Objective
The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity.
Introduction
Sex differences in the management and outcome of AS are poorly understood.
Methods
Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded.
Results
Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14-3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82-0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63-1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71-2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19-3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73-0.95]; P = 0.009).
Conclusion
In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 14 Jul 2021; 42:2683-2691
Bienjonetti-Boudreau D, Fleury MA, Voisine M, Paquin A, ... Salaun E, Clavel MA
Eur Heart J: 14 Jul 2021; 42:2683-2691 | PMID: 34023890
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Abstract

Prognostically relevant periprocedural myocardial injury and infarction associated with percutaneous coronary interventions: a Consensus Document of the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Bulluck H, Paradies V, Barbato E, Baumbach A, ... Thygesen K, Hausenloy DJ
A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant \'major\' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 14 Jul 2021; 42:2630-2642
Bulluck H, Paradies V, Barbato E, Baumbach A, ... Thygesen K, Hausenloy DJ
Eur Heart J: 14 Jul 2021; 42:2630-2642 | PMID: 34059914
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Abstract

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

Fiolet ATL, Opstal TSJ, Mosterd A, Eikelboom JW, ... Tijssen JGP, Cornel JH
Aims
Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE).
Methods and results
We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060).
Conclusion
Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 20 Jul 2021; 42:2765-2775
Fiolet ATL, Opstal TSJ, Mosterd A, Eikelboom JW, ... Tijssen JGP, Cornel JH
Eur Heart J: 20 Jul 2021; 42:2765-2775 | PMID: 33769515
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Abstract

Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy.

Aboyans V, Bauersachs R, Mazzolai L, Brodmann M, ... Schlager O, De Carlo M
The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient\'s ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 18 Jul 2021; epub ahead of print
Aboyans V, Bauersachs R, Mazzolai L, Brodmann M, ... Schlager O, De Carlo M
Eur Heart J: 18 Jul 2021; epub ahead of print | PMID: 34279602
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Abstract

The heart of the ageing endurance athlete: the role of chronic coronary stress.

Parry-Williams G, Gati S, Sharma S
Moderate physical exercise is associated with an irrefutable reduction in cardiac morbidity and mortality. The current guidelines recommend at least 150 min of moderate exercise or 75 min of vigorous exercise per week. Endurance athletes perform exercise at a level that is 10- to 20-fold greater than these recommendations. These athletes reveal several structural and functional cardiac adaptations including increased cardiac size, enhanced ventricular filling, and augmentation of stroke volume even at the highest heart rates. The long-term effects of endurance exercise on the heart are unknown. Endurance exercise is associated with a transient increase in serum concentrations of biomarkers of cardiac damage and ventricular dysfunction which improves within 72 h. Over the past decade, there have been emerging studies reporting attenuated mortality benefit amongst individuals who perform the highest volume of exercise. Studies in lifelong male athletes aged above 40 years old show a higher prevalence of high coronary artery calcium scores (>300 Agatston units), a higher coronary plaque burden, and myocardial fibrosis compatible with subclinical myocardial infarction compared with relatively sedentary healthy controls, raising speculation that lifelong intense exercise imposes chronic coronary stress on the heart. This review article will provide a critical analysis of the existing data.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 20 Jul 2021; 42:2737-2744
Parry-Williams G, Gati S, Sharma S
Eur Heart J: 20 Jul 2021; 42:2737-2744 | PMID: 33748860
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Abstract

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

Quispe R, Martin SS, Michos ED, Lamba I, ... Jones SR, Elshazly MB
Aims
Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.
Methods and results
We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.35). Similar results were shown when examining discordance across clinical cutpoints.
Conclusions
In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 18 Jul 2021; epub ahead of print
Quispe R, Martin SS, Michos ED, Lamba I, ... Jones SR, Elshazly MB
Eur Heart J: 18 Jul 2021; epub ahead of print | PMID: 34293083
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Abstract

European Heart Journal quality standards.

Alfonso F, Torp-Pedersen C, Carter RE, Crea F
The aim of the European Heart Journal (EHJ) is to attract innovative, methodologically sound, and clinically relevant research manuscripts able to change clinical practice and/or substantially advance knowledge on cardiovascular diseases. As the reference journal in cardiovascular medicine, the EHJ is committed to publishing only the best cardiovascular science adhering to the highest ethical principles. EHJ uses highly rigorous peer-review, critical statistical review and the highest quality editorial process, to ensure the novelty, accuracy, quality, and relevance of all accepted manuscripts with the aim of inspiring the clinical practice of EHJ readers and reducing the global burden of cardiovascular diseases. This review article summarizes the quality standards pursued by the EHJ to fulfill its mission.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 20 Jul 2021; 42:2729-2736
Alfonso F, Torp-Pedersen C, Carter RE, Crea F
Eur Heart J: 20 Jul 2021; 42:2729-2736 | PMID: 34289494
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Abstract

Mechanical Complications of Acute Myocardial Infarction: A Scientific Statement From the American Heart Association.

Damluji AA, van Diepen S, Katz JN, Menon V, ... American Heart Association Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing
Over the past few decades, advances in pharmacological, catheter-based, and surgical reperfusion have improved outcomes for patients with acute myocardial infarctions. However, patients with large infarcts or those who do not receive timely revascularization remain at risk for mechanical complications of acute myocardial infarction. The most commonly encountered mechanical complications are acute mitral regurgitation secondary to papillary muscle rupture, ventricular septal defect, pseudoaneurysm, and free wall rupture; each complication is associated with a significant risk of morbidity, mortality, and hospital resource utilization. The care for patients with mechanical complications is complex and requires a multidisciplinary collaboration for prompt recognition, diagnosis, hemodynamic stabilization, and decision support to assist patients and families in the selection of definitive therapies or palliation. However, because of the relatively small number of high-quality studies that exist to guide clinical practice, there is significant variability in care that mainly depends on local expertise and available resources.



Circulation: 12 Jul 2021; 144:e16-e35
Damluji AA, van Diepen S, Katz JN, Menon V, ... American Heart Association Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing
Circulation: 12 Jul 2021; 144:e16-e35 | PMID: 34126755
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Abstract

Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS.

Lambrakis K, Papendick C, French JK, Quinn S, ... Cullen LA, Chew DP
Background
High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol.
Methods
We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals.
Results
Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%]; P=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%]; P=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95-1.83]; P=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05-2.46]; P=0.030).
Conclusions
Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.



Circulation: 12 Jul 2021; 144:113-125
Lambrakis K, Papendick C, French JK, Quinn S, ... Cullen LA, Chew DP
Circulation: 12 Jul 2021; 144:113-125 | PMID: 33998255
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Abstract

Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: PATHWAY-A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy.

Wells A, Reeves D, Capobianco L, Heal C, ... Doherty P, Fisher P
Background
Depression and anxiety in cardiovascular disease are significant, contributing to poor prognosis. Unfortunately, current psychological treatments offer mixed, usually small improvements in these symptoms. The present trial tested for the first time the effects of group metacognitive therapy (MCT; 6 sessions) on anxiety and depressive symptoms when delivered alongside cardiac rehabilitation (CR).
Methods
A total of 332 CR patients recruited from 5 National Health Service Trusts across the North-West of England were randomly allocated to MCT+CR (n=163, 49.1%) or usual CR alone (n=169, 50.9%). Randomization was 1:1 via minimization balancing arms on sex and Hospital Anxiety and Depression Scale scores within hospital site. The primary outcome was Hospital Anxiety and Depression Scale total after treatment (4-month follow-up). Secondary outcomes were individual Hospital Anxiety and Depression Scales, traumatic stress symptoms, and psychological mechanisms including metacognitive beliefs and repetitive negative thinking. Analysis was intention to treat.
Results
The adjusted group difference on the primary outcome, Hospital Anxiety and Depression Scale total score at 4 months, significantly favored the MCT+CR arm (-3.24 [95% CI, -4.67 to -1.81], P<0.001; standardized effect size, 0.52 [95% CI, 0.291 to 0.750]). The significant difference was maintained at 12 months (-2.19 [95% CI, -3.72 to -0.66], P=0.005; standardized effect size, 0.33 [95% CI, 0.101 to 0.568]). The intervention improved outcomes significantly for both depression and anxiety symptoms when assessed separately compared with usual care. Sensitivity analysis using multiple imputation of missing values supported these findings. Most secondary outcomes favored MCT+CR, with medium to high effect sizes for psychological mechanisms of metacognitive beliefs and repetitive negative thinking. No adverse treatment-related events were reported.
Conclusions
Group MCT+CR significantly improved depression and anxiety compared with usual care and led to greater reductions in unhelpful metacognitions and repetitive negative thinking. Most gains remained significant at 12 months. Study strengths include a large sample, a theory-based intervention, use of longer-term follow-up, broad inclusion criteria, and involvement of a trials unit. Limitations include no control for additional contact as part of MCT to estimate nonspecific effects, and the trial was not intended to assess cardiac outcomes. Nonetheless, results demonstrated that addition of the MCT intervention had broad and significant beneficial effects on mental health symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ISRCTN74643496.



Circulation: 05 Jul 2021; 144:23-33
Wells A, Reeves D, Capobianco L, Heal C, ... Doherty P, Fisher P
Circulation: 05 Jul 2021; 144:23-33 | PMID: 34148379
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Abstract

Assessing and Addressing Cardiovascular Health in People Who Are Transgender and Gender Diverse: A Scientific Statement From the American Heart Association.

Streed CG, Beach LB, Caceres BA, Dowshen NL, ... American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; and Stroke Council
There is growing evidence that people who are transgender and gender diverse (TGD) are impacted by disparities across a variety of cardiovascular risk factors compared with their peers who are cisgender. Prior literature has characterized disparities in cardiovascular morbidity and mortality as a result of a higher prevalence of health risk behaviors. Mounting research has revealed that cardiovascular risk factors at the individual level likely do not fully account for increased risk in cardiovascular health disparities among people who are TGD. Excess cardiovascular morbidity and mortality is hypothesized to be driven in part by psychosocial stressors across the lifespan at multiple levels, including structural violence (eg, discrimination, affordable housing, access to health care). This American Heart Association scientific statement reviews the existing literature on the cardiovascular health of people who are TGD. When applicable, the effects of gender-affirming hormone use on individual cardiovascular risk factors are also reviewed. Informed by a conceptual model building on minority stress theory, this statement identifies research gaps and provides suggestions for improving cardiovascular research and clinical care for people who are TGD, including the role of resilience-promoting factors. Advancing the cardiovascular health of people who are TGD requires a multifaceted approach that integrates best practices into research, health promotion, and cardiovascular care for this understudied population.



Circulation: 07 Jul 2021:CIR0000000000001003; epub ahead of print
Streed CG, Beach LB, Caceres BA, Dowshen NL, ... American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; and Stroke Council
Circulation: 07 Jul 2021:CIR0000000000001003; epub ahead of print | PMID: 34235936
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Abstract

Incorporating SGLT2i and GLP-1RA for Cardiovascular and Kidney Disease Risk Reduction: Call for Action to the Cardiology Community.

Nelson AJ, Pagidipati NJ, Aroda VR, Cavender MA, ... McGuire DK, Granger CB
Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.



Circulation: 05 Jul 2021; 144:74-84
Nelson AJ, Pagidipati NJ, Aroda VR, Cavender MA, ... McGuire DK, Granger CB
Circulation: 05 Jul 2021; 144:74-84 | PMID: 34228476
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Abstract

Evidence-Based Practices in the Cardiac Catheterization Laboratory: A Scientific Statement From the American Heart Association.

Bangalore S, Barsness GW, Dangas GD, Kern MJ, ... American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Lifestyle and Cardiometabolic Health
Cardiac catheterization procedures have rapidly evolved and expanded in scope and techniques over the past few decades. However, although some practices have emerged based on evidence, many traditions have persisted based on beliefs and theoretical concerns. The aim of this review is to highlight common preprocedure, intraprocedure, and postprocedure catheterization laboratory practices where evidence has accumulated over the past few decades to support or discount traditionally held practices.



Circulation: 29 Jun 2021:CIR0000000000000996; epub ahead of print
Bangalore S, Barsness GW, Dangas GD, Kern MJ, ... American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Lifestyle and Cardiometabolic Health
Circulation: 29 Jun 2021:CIR0000000000000996; epub ahead of print | PMID: 34187171
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Impact:
Abstract

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

Takahashi K, Serruys PW, Gao C, Ono M, ... Holmes DR, SYNTAX Extended Survival Study Investigators
Background
Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG).
Methods
The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR.
Results
IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43]).
Conclusions
IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.



Circulation: 12 Jul 2021; 144:96-109
Takahashi K, Serruys PW, Gao C, Ono M, ... Holmes DR, SYNTAX Extended Survival Study Investigators
Circulation: 12 Jul 2021; 144:96-109 | PMID: 34011163
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Impact:
Abstract

International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational Observational CLARIFY Study.

Mesnier J, Ducrocq G, Danchin N, Ferrari R, ... Steg PG, CLARIFY Investigators
Background: Although angina is common in patients with stable coronary artery disease (CAD), limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization.
Methods:
Using data from 32 691 patients with stable CAD from the prospective observational CLARIFY registry, anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis.
Results:
Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0-4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.12-1.55 for persistence of angina; adjusted HR 1.37, 95% CI 1.11-1.70 for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted HR 0.97, 95% CI 0.82-1.15). Conclusions: Angina affects almost one-quarter of patients with stable CAD but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, while persistence or occurrence was associated with worse outcomes. As most patients with angina are likely to experience resolution of symptoms, and as there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable CAD. Clinical Trial Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.




Circulation: 14 Jul 2021; epub ahead of print
Mesnier J, Ducrocq G, Danchin N, Ferrari R, ... Steg PG, CLARIFY Investigators
Circulation: 14 Jul 2021; epub ahead of print | PMID: 34261331
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Impact:
Abstract

Composite Metric for Benchmarking Site Performance in Transcatheter Aortic Valve Replacement: Results From the STS/ACC TVT Registry.

Desai ND, O\'Brien SM, Cohen DJ, Carroll J, ... Badhwar V, Bavaria JE
Background
Transcatheter aortic valve replacement (TAVR) is a transformative therapy for aortic stenosis. Despite rapid improvements in technology and techniques, serious complications remain relatively common and are not well described by single outcome measures. The purpose of this study was to determine whether there is site-level variation in TAVR outcomes in the United States using a novel 30-day composite measure.
Methods
We performed a retrospective cohort study using data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry to develop a novel ranked composite performance measure that incorporates mortality and serious complications. The selection and rank order of the complications for the composite was determined by their adjusted association with 1-year outcomes. Sites with risk-adjusted outcomes significantly more or less frequent than the national average based on a 95% probability interval were classified as performing worse or better than expected.
Results
The development cohort consisted of 52 561 patients who underwent TAVR between January 1, 2015, and December 31, 2017. Based on associations with 1-year risk-adjusted mortality and health status, we identified 4 periprocedural complications to include in the composite risk model in addition to mortality. Ranked empirically according to severity, these included stroke, major, life-threatening or disabling bleeding, stage III acute kidney injury, and moderate or severe perivalvular regurgitation. Based on these ranked outcomes, we found that there was significant site-level variation in quality of care in TAVR in the United States. Overall, better than expected site performance was observed in 25/301 (8%) sites, performance as expected was observed in 242/301 sites (80%), and worse than expected performance was observed in 34/301 (11%) sites. Thirty-day mortality; stroke; major, life-threatening, or disabling bleeding; and moderate or severe perivalvular leak were each substantially more common in sites with worse than expected performance as compared with other sites. There was good aggregate reliability of the model.
Conclusions
There are substantial variations in the quality of TAVR care received in the United States and 11% of sites were identified as providing care below the average level of performance. Further study is necessary to determine structural, process-related, and technical factors associated with high- and low-performing sites.



Circulation: 19 Jul 2021; 144:186-194
Desai ND, O'Brien SM, Cohen DJ, Carroll J, ... Badhwar V, Bavaria JE
Circulation: 19 Jul 2021; 144:186-194 | PMID: 33947202
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Abstract

Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction.

Docherty KF, Campbell RT, Brooksbank KJM, Dreisbach JG, ... Petrie MC, McMurray JJV
Background
Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.
Methods
We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.
Results
From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m2 (95% CI, -4.9 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.
Conclusions
In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.



Circulation: 19 Jul 2021; 144:199-209
Docherty KF, Campbell RT, Brooksbank KJM, Dreisbach JG, ... Petrie MC, McMurray JJV
Circulation: 19 Jul 2021; 144:199-209 | PMID: 33983794
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Abstract

Effects of Experimental Sleep Restriction on Ambulatory and Sleep Blood Pressure in Healthy Young Adults: A Randomized Crossover Study.

Covassin N, Bukartyk J, Singh P, Calvin AD, St Louis EK, Somers VK
Although insufficient sleep is associated with increased cardiovascular risk, evidence of a causal relationship is lacking. We investigated the effects of prolonged sleep restriction on 24-hour ambulatory blood pressure (BP) and other cardiovascular measures in 20 healthy young participants (aged 23.4±4.8 years, 9 females), who underwent a randomized, controlled, crossover, 16-day inpatient study consisting of 4 days of acclimation, 9 days of sleep restriction (4 hours of sleep/night) or control sleep (9 hours), and 3 days of recovery. Subjects consumed a weight maintenance diet with controlled nutrient composition throughout. A 24-hour BP (primary outcome) and cardiovascular biomarkers were measured repeatedly. Polysomnographic monitoring was continuous. Comparing sleep restriction versus control sleep, 24-hour mean BP was higher (adjusted mean difference, day 12: 2.1 mm Hg [95% CI, 0.6-3.6], corrected P=0.016), endothelial function was attenuated (P<0.001), and plasma norepinephrine increased (P=0.011). Despite increased deep sleep, BP was elevated while asleep during sleep restriction and recovery. Post hoc analysis revealed that 24-hour BP, wakefulness, and sleep BP increased during experimental and recovery phases of sleep restriction only in women, in whom 24-hour and sleep systolic BP increased by 8.0 (5.1-10.8) and 11.3 (5.9-16.7) mm Hg, respectively (both P<0.001). Shortened sleep causes persistent elevation in 24-hour and sleep-time BP. Pressor effects are evident despite closely controlled food intake and weight, suggesting that they are primarily driven by the shortened sleep duration. BP increases are especially striking and sustained in women, possibly suggesting lack of adaptation to sleep loss and thus greater vulnerability to its adverse cardiovascular effects.



Hypertension: 11 Jul 2021:HYPERTENSIONAHA12117622; epub ahead of print
Covassin N, Bukartyk J, Singh P, Calvin AD, St Louis EK, Somers VK
Hypertension: 11 Jul 2021:HYPERTENSIONAHA12117622; epub ahead of print | PMID: 34247512
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Abstract

Left Atrioventricular Coupling Index as a Prognostic Marker of Cardiovascular Events: The MESA Study.

Pezel T, Venkatesh BA, De Vasconcellos HD, Kato Y, ... Bluemke DA, Lima JAC
Both left atrial and left ventricular functional parameters influence the prognosis of patients with cardiovascular diseases. This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) in a population without history of cardiovascular diseases at baseline. Participants of the Multi-Ethnic Study of Atherosclerosis who underwent a baseline cardiovascular magnetic resonance study were analyzed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Cox proportional hazard models were used to evaluate the association between LACI and atrial fibrillation, heart failure, coronary heart disease death, and hard cardiovascular disease defined by myocardial infarction, resuscitated cardiac arrest, fatal and nonfatal stroke, or coronary heart disease death. Among the 4124 participants (61.5±10.1 years, 47.4% men), 1074 cardiovascular events were observed (mean follow-up, 13.0±3.2 years). Greater LACI was independently associated with atrial fibrillation (hazard ratio, 1.86 [95% CI, 1.69-2.04]), heart failure (hazard ratio, 1.50 [95% CI, 1.38-1.62]), hard cardiovascular disease (1.23 [95% CI, 1.13-1.34]), and coronary heart disease death (hazard ratio, 1.29 [95% CI, 1.15-1.45]; all P<0.0001). After adjustment for traditional cardiovascular risk factors, LACI showed significant improvement in model discrimination and reclassification compared with currently used standard models to predict outcomes. LACI is a strong predictor for the incidence of heart failure, atrial fibrillation, hard cardiovascular disease, and coronary heart disease death. LACI has incremental prognostic value to predict cardiovascular events over traditional risk factors and better discrimination and reclassification power compared with individual left atrial or left ventricular parameters.



Hypertension: 05 Jul 2021:HYPERTENSIONAHA12117339; epub ahead of print
Pezel T, Venkatesh BA, De Vasconcellos HD, Kato Y, ... Bluemke DA, Lima JAC
Hypertension: 05 Jul 2021:HYPERTENSIONAHA12117339; epub ahead of print | PMID: 34225471
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Impact:
Abstract

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation : A Population-Based Cohort Study.

Dawwas GK, Dietrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD
Background
Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited.
Objective
To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF.
Design
New-user retrospective propensity score-matched cohort study.
Setting
U.S.-based commercial health care database from 1 January 2010 to 30 June 2019.
Participants
Adults with valvular AF who were newly prescribed DOACs or warfarin.
Measurements
The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
Results
Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]).
Limitation
Relatively short follow-up; inability to ascertain disease severity.
Conclusion
In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF.
Primary funding source
None.



Ann Intern Med: 29 Jun 2021; 174:910-919
Dawwas GK, Dietrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD
Ann Intern Med: 29 Jun 2021; 174:910-919 | PMID: 33780291
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Impact:
Abstract

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study.

Kim DH, Pawar A, Gagne JJ, Bessette LG, ... Glynn RJ, Schneeweiss S
Background
The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear.
Objective
To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels.
Design
1:1 propensity score-matched analysis of Medicare data, 2010 to 2017.
Setting
Community.
Patients
Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin.
Measurements
Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index.
Results
In the dabigatran-warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively.
Limitations
Residual confounding and lack of clinical frailty assessment.
Conclusion
For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients.
Primary funding source
National Institute on Aging.



Ann Intern Med: 19 Jul 2021; epub ahead of print
Kim DH, Pawar A, Gagne JJ, Bessette LG, ... Glynn RJ, Schneeweiss S
Ann Intern Med: 19 Jul 2021; epub ahead of print | PMID: 34280330
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Impact:
Abstract

High spatial endothelial shear stress gradient independently predicts site of acute coronary plaque rupture and erosion.

Thondapu V, Mamon C, Poon EKW, Kurihara O, ... Barlis P, Jang IK
Aims
To investigate local haemodynamics in the setting of acute coronary plaque rupture and erosion.
Methods and results
Intracoronary optical coherence tomography performed in 37 patients with acute coronary syndromes caused by plaque rupture (n = 19) or plaque erosion (n = 18) was used for three-dimensional reconstruction and computational fluid dynamics simulation. Endothelial shear stress (ESS), spatial ESS gradient (ESSG), and oscillatory shear index (OSI) were compared between plaque rupture and erosion through mixed-effects logistic regression. Lipid, calcium, macrophages, layered plaque, and cholesterol crystals were also analysed. By multivariable analysis, only high ESSG [odds ratio (OR) 5.29, 95% confidence interval (CI) 2.57-10.89, P < 0.001], lipid (OR 12.98, 95% CI 6.57-25.67, P < 0.001), and layered plaque (OR 3.17, 95% CI 1.82-5.50, P < 0.001) were independently associated with plaque rupture. High ESSG (OR 13.28, 95% CI 6.88-25.64, P < 0.001), ESS (OR 2.70, 95% CI 1.34-5.42, P = 0.005), and OSI (OR 2.18, 95% CI 1.33-3.54, P = 0.002) independently associated with plaque erosion. ESSG was higher at rupture sites than erosion sites [median (interquartile range): 5.78 (2.47-21.15) vs. 2.62 (1.44-6.18) Pa/mm, P = 0.009], OSI was higher at erosion sites than rupture sites [1.04 × 10-2 (2.3 × 10-3-4.74 × 10-2) vs. 1.29 × 10-3 (9.39 × 10-5-3.0 × 10-2), P < 0.001], but ESS was similar (P = 0.29).
Conclusions
High ESSG is independently associated with plaque rupture while high ESSG, ESS, and OSI associate with plaque erosion. While ESSG is higher at rupture sites than erosion sites, OSI is higher at erosion sites and ESS was similar. These results suggest that ESSG and OSI may play critical roles in acute plaque rupture and erosion, respectively.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Cardiovasc Res: 06 Jul 2021; 117:1974-1985
Thondapu V, Mamon C, Poon EKW, Kurihara O, ... Barlis P, Jang IK
Cardiovasc Res: 06 Jul 2021; 117:1974-1985 | PMID: 32832991
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Impact:
Abstract

Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention.

Venetsanos D, Träff E, Erlinge D, Hagström E, ... Jernberg T, Alfredsson J
Objective
The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.
Methods
In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.
Results
We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.
Conclusion
In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Jun 2021; 107:1145-1151
Venetsanos D, Träff E, Erlinge D, Hagström E, ... Jernberg T, Alfredsson J
Heart: 29 Jun 2021; 107:1145-1151 | PMID: 33712510
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Impact:
Abstract

Early invasive versus non-invasive assessment in patients with suspected non-ST-elevation acute coronary syndrome.

Kite TA, Ladwiniec A, Arnold JR, McCann GP, Moss AJ
Non-ST-elevation acute coronary syndrome (NSTE-ACS) comprises a broad spectrum of disease ranging from unstable angina to myocardial infarction. International guidelines recommend a routine invasive strategy for managing patients with NSTE-ACS at high to very high-risk, supported by evidence of improved composite ischaemic outcomes as compared with a selective invasive strategy. However, accurate diagnosis of NSTE-ACS in the acute setting is challenging due to the spectrum of non-coronary disease that can manifest with similar symptoms. Heterogeneous clinical presentations and limited uptake of risk prediction tools can confound physician decision-making regarding the use and timing of invasive coronary angiography (ICA). Large proportions of patients with suspected NSTE-ACS do not require revascularisation but may unnecessarily undergo ICA with its attendant risks and associated costs. Advances in coronary CT angiography and cardiac MRI have prompted evaluation of whether non-invasive strategies may improve patient selection, or whether tailored approaches are better suited to specific subgroups. Future directions include (1) better understanding of risk stratification as a guide to investigation and therapy in suspected NSTE-ACS, (2) randomised clinical trials of non-invasive imaging versus standard of care approaches prior to ICA and (3) defining the optimal timing of very early ICA in high-risk NSTE-ACS.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Jul 2021; epub ahead of print
Kite TA, Ladwiniec A, Arnold JR, McCann GP, Moss AJ
Heart: 06 Jul 2021; epub ahead of print | PMID: 34234006
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Impact:
Abstract

Trends in the pharmacological management of atrial fibrillation in UK general practice 2008-2018.

Phillips K, Subramanian A, Thomas GN, Khan N, ... Fabritz L, Adderley NJ
Objective
The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018.
Methods
Eleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure.
Results
Between 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%).
Conclusions
There has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Jul 2021; epub ahead of print
Phillips K, Subramanian A, Thomas GN, Khan N, ... Fabritz L, Adderley NJ
Heart: 04 Jul 2021; epub ahead of print | PMID: 34226195
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Impact:
Abstract

Associations of atrial fibrillation with renal function decline in patients with chronic kidney disease.

Chen TH, Chu YC, Ou SM, Tarng DC
Background
Chronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.
Methods
In a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).
Results
After propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.
Conclusions
In patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Jun 2021; epub ahead of print
Chen TH, Chu YC, Ou SM, Tarng DC
Heart: 29 Jun 2021; epub ahead of print | PMID: 34193464
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Impact:
Abstract

Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease.

Theuerle JD, Al-Fiadh AH, Amirul Islam FM, Patel SK, ... Wong TY, Farouque O
Aims
Endothelial dysfunction is a precursor to the development of symptomatic atherosclerosis. Retinal microvascular reactivity to flicker light stimulation is a marker of endothelial function and can be quantified in vivo. We sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE).
Methods and results
In a single-centre prospective observational study, patients with coronary artery disease (CAD) or cardiovascular risk factors underwent dynamic retinal vessel assessment in response to flicker light stimulation and were followed up for MACE. Retinal microvascular endothelial dysfunction was quantified by measuring maximum flicker light-induced retinal arteriolar dilatation (FI-RAD) and flicker light-induced retinal venular dilatation (FI-RVD). In total, 252 patients underwent dynamic retinal vessel assessment and 242 (96%) had long-term follow-up. Of the 242 patients, 88 (36%) developed MACE over a median period of 8.6 years (interquartile range 6.0-9.1). After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE [odds ratio (OR) 5.21; 95% confidence interval (CI) 1.78-15.28]. Patients with lower FI-RAD were also more likely to die (OR 2.09; 95% CI 1.00-4.40, per standard deviation decrease in FI-RAD). In Kaplan-Meier analysis, patients with FI-RAD responses below the cohort median of 1.4% exhibited reduced MACE-free survival (55.5 vs. 71.5%; log-rank P = 0.004). FI-RVD was not predictive of MACE.
Conclusion
Retinal arteriolar endothelial dysfunction is an independent predictor of MACE in patients with CAD or cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Cardiovasc Res: 06 Jul 2021; 117:1949-1957
Theuerle JD, Al-Fiadh AH, Amirul Islam FM, Patel SK, ... Wong TY, Farouque O
Cardiovasc Res: 06 Jul 2021; 117:1949-1957 | PMID: 32750111
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Impact:
Abstract

Risk for cardiovascular events following \'microsize\' versus usual myocardial infarctions.

Almarzooq ZI, Colantonio LD, Okin PM, Richman JS, ... Bryan J, Safford MM
Background
Microsize myocardial infarction (MI) is a recently described phenomenon that meets rigorous criteria for MI with very low peak troponin elevations. We aim to compare the risk for cardiovascular events and mortality following microsize versus usual MIs.
Methods and results
Prospective cohort analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a history of coronary heart disease (CHD) who had an incident MI between 2003 and 2015. Incident MIs were classified as microsize MI (peak troponin <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Participants were followed for a composite of cardiovascular events that included recurrent MI, coronary revascularisation, fatal CHD and heart failure, and all-cause mortality. Overall, 1024 participants with an incident MI were included in the analysis (328 with microsize MI and 696 with usual MI). Participants with microsize MI were more likely to be older and black. The multivariable-adjusted adjustment HR for cardiovascular events among participants with microsize versus usual MI after a median follow-up of 1.7 years was 1.11 (95% CI 0.86 to 1.44). The multivariable-adjusted HR for all-cause mortality after 28 days from incident MI among participants with microsize versus usual MI after a median follow-up of 3.6 years was 1.09 (95% CI 0.81 to 1.45).
Conclusion
Microsize MIs have a prognostic value for future cardiovascular events and mortality comparable to usual MIs. These findings should encourage clinicians to initiate secondary prevention strategies in patients with microsize MI until this emerging clinical entity is better understood.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Jun 2021; 107:1152-1159
Almarzooq ZI, Colantonio LD, Okin PM, Richman JS, ... Bryan J, Safford MM
Heart: 29 Jun 2021; 107:1152-1159 | PMID: 33246926
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Impact:
Abstract

Survival and risk of recurrence of takotsubo syndrome.

Lau C, Chiu S, Nayak R, Lin B, Lee MS
Objective
The goal of this study is to evaluate the long-term outcomes of patients with takotsubo syndrome and assess factors associated with death or recurrence.
Methods
This is a retrospective population-based cohort study of consecutive patients who presented to an integrated health system in Southern California with takotsubo syndrome between 2006 and 2016. Medical records were manually reviewed to confirm diagnosis and to identify predisposing factors, medication treatment and long-term outcomes. Factors associated with death or recurrent takotsubo syndrome were tested using Cox regression models.
Results
Between 2006 and 2016, there were 519 patients with a confirmed diagnosis of takotsubo syndrome. Patients were followed for 5.2 years (IQR 3.0-7.2). During the follow-up period, 39 (7.5%) had recurrent takotsubo syndrome and 84 (16.2%) died. In multivariate modelling, factors associated with higher risk of recurrence or death were age (HR 1.56 per 10-year increase, 95% CI 1.29 to 1.87), male sex (HR 2.52, 95% CI 1.38 to 4.60), diabetes (HR 1.6, 95% CI 1.06 to 2.43), pulmonary disease (HR 2.0, 95% CI 1.37 to 2.91) and chronic kidney disease (HR 1.58, 95% CI 1.01 to 2.47). Treatment with beta-blockers were associated with lower risk of recurrence or death (HR 0.46, 95% CI 0.29 to 0.72). No association was observed between treatment with ACE inhibitors or angiotensin-receptor blockers and recurrence or death (HR 0.92, 95% CI 0.59 to 1.42).
Conclusions
Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Jun 2021; 107:1160-1166
Lau C, Chiu S, Nayak R, Lin B, Lee MS
Heart: 29 Jun 2021; 107:1160-1166 | PMID: 33419884
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Impact:
Abstract

Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings.

Iliou A, Mikros E, Karaman I, Elliott F, ... Tzoulaki I, Elliott P
Metabolomics, the comprehensive measurement of low-molecular-weight molecules in biological fluids used for metabolic phenotyping, has emerged as a promising tool to better understand pathways underlying cardiovascular disease (CVD) and to improve cardiovascular risk stratification. Here, we present the main methodologies for metabolic phenotyping, the methodological steps to analyse these data in epidemiological settings and the associated challenges. We discuss evidence from epidemiological studies linking metabolites to coronary heart disease and stroke. These studies indicate the systemic nature of CVD and identify associated metabolic pathways such as gut microbial cometabolism, branched-chain amino acids, glycerophospholipid and cholesterol metabolism, as well as activation of inflammatory processes. Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation. The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established. As sample sizes with high-dimensional molecular data increase in epidemiological settings, integration of metabolomic data across studies and platforms with other molecular data will lead to new understanding of the metabolic processes underlying CVD and contribute to identification of potentially novel preventive and pharmacological targets. Metabolic phenotyping offers a powerful tool in the characterisation of the molecular signatures of CVD, paving the way to new mechanistic understanding and therapies, as well as improving risk prediction of CVD patients. However, there are still challenges to face in order to contribute to clinically important improvements in CVD.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 29 Jun 2021; 107:1123-1129
Iliou A, Mikros E, Karaman I, Elliott F, ... Tzoulaki I, Elliott P
Heart: 29 Jun 2021; 107:1123-1129 | PMID: 33608305
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Impact:
Abstract

Relative survival after aortic valve surgery in patients with bicuspid aortic valves.

Glaser N, Jackson V, Eriksson P, Sartipy U, Franco-Cereceda A
Objectives
The objective of this cohort study was to analyse long-term relative survival in patients with bicuspid aortic valve (BAV) who underwent aortic valve surgery.
Methods
We studied 865 patients with BAVs who participated in three prospective cohort studies of elective, open-heart, aortic valve surgery at the Karolinska University Hospital, Stockholm, Sweden, between 2007 and 2020. The expected survival for the age, sex and calendar year-matched general Swedish population was obtained from the Human Mortality Database. The Ederer II method was used to calculate relative survival, which was used as an estimate of cause-specific survival.
Results
No differences were found in the observed versus expected survival at 1, 5, 10 or 12 years: 99%, 94%, 83% and 76% vs 99%, 93%, 84% and 80%, respectively. The relative survival at 1, 5, 10 and 12 years was 100% (95% CI 99% to 100%), 101% (95% CI 99% to 103%), 99% (95% CI 95% to 103%) and 95% (95% CI 87% to 102%), respectively. The relative survival at the end of follow-up tended to be lower for women than men (86% vs 95%). The mean follow-up was 6.3 years (maximum 13.3 years).
Conclusions
The survival of patients with BAV following aortic valve surgery was excellent and similar to that of the general population. Our results suggest that the timing of surgery according to current guidelines is correct and provide robust long-term survival rates, as well as important information about the natural history of BAV in patients following aortic valve surgery.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 29 Jun 2021; 107:1167-1172
Glaser N, Jackson V, Eriksson P, Sartipy U, Franco-Cereceda A
Heart: 29 Jun 2021; 107:1167-1172 | PMID: 33622679
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Impact:
Abstract

Aspirin versus P2Y inhibitors with anticoagulation therapy for atrial fibrillation.

Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Objective
Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy.
Methods
We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician\'s discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.
Results
A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456).
Conclusions
There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase.
Trial registration number
UMIN000016612; NCT02642419.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 13 Jul 2021; epub ahead of print
Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Heart: 13 Jul 2021; epub ahead of print | PMID: 34261738
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Impact:
Abstract

Adverse cardiac mechanics and incident coronary heart disease in the Cardiovascular Health Study.

Massera D, Hu M, Delaney JA, Bartz TM, ... Kizer JR, Shah SJ
Objectives
Speckle-tracking echocardiography enables detection of abnormalities in cardiac mechanics with higher sensitivity than conventional measures of left ventricular (LV) dysfunction and may provide insight into the pathogenesis of coronary heart disease (CHD). We investigated the relationship of LV longitudinal strain, LV early diastolic strain rate (SR) and left atrial (LA) reservoir strain with long-term CHD incidence in community-dwelling older adults.
Methods
The association of all three strain measures with incidence of non-fatal and fatal CHD (primary outcome of revascularisation, non-fatal and fatal myocardial infarction) was examined in the population-based Cardiovascular Health Study using multivariable Cox proportional hazards models. Follow-up was truncated at 10 years.
Results
We included 3313 participants (mean (SD) age 72.6 (5.5) years). During a median follow-up of 10.0 (25th-75th percentile 7.7-10.0) years, 439 CHD events occurred. LV longitudinal strain (HR=1.25 per SD decrement, 95% CI 1.09 to 1.43) and LV early diastolic SR (HR=1.31 per SD decrement, 95% CI 1.14 to 1.50) were associated with a significantly greater risk of incident CHD after adjustment for potential confounders. By contrast, LA reservoir strain was not associated with incident CHD (HR=1.06 per SD decrement, 95% CI 0.94 to 1.19). Additional adjustment for biochemical and echocardiographic measures of myocardial stress, dysfunction and remodelling did not meaningfully alter these associations.
Conclusion
We found an association between echocardiographic measures of subclinically altered LV mechanics and incident CHD. These findings inform the underlying biology of subclinical LV dysfunction and CHD. Early detection of asymptomatic myocardial dysfunction may offer an opportunity for prevention and early intervention.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 12 Jul 2021; epub ahead of print
Massera D, Hu M, Delaney JA, Bartz TM, ... Kizer JR, Shah SJ
Heart: 12 Jul 2021; epub ahead of print | PMID: 34257074
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Impact:
Abstract

Coronary Disease Association with ADAMTS7 is due to Protease Activity.

Mizoguchi T, MacDonald BT, Bhandary B, Popp NR, ... Kathiresan S, Ellinor PT
Rationale: Despite contemporary therapy, coronary artery disease (CAD) remains a leading cause of mortality. Genetic variants at ADAMTS7 have been associated with CAD and the loss of ADAMTS7 is protective for atherosclerosis. ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs 7) is a secreted metalloproteinase and complex proteoglycan, yet the mechanism linking ADAMTS7 to CAD risk remains unresolved. Objective: To investigate the role of ADAMTS7 catalytic function in vascular smooth muscle cellular migration and during atherosclerosis.
Methods and results:
We established a new purification strategy for full-length mouse ADAMTS7 and demonstrated the loss of activity in the catalytic mutant form of ADAMTS7. To test if the enzymatic activity of ADAMTS7 mediates atherosclerosis, we generated a catalytically inactive mutant mouse allele and compared it to the Adamts7 knockout. Using two models of atherosclerosis, we found that reducing either ADAMTS7 dosage or catalytic function decreased the burden of atherosclerosis. We demonstrate impaired vascular smooth muscle migration in both Adamts7 catalytic mutant and null cells using a lateral migration wound healing assay. Expression of the wild-type allele rescued the migration phenotype in Adamts7 null cells while expression of the catalytic mutant protein did not. We then characterized a human ADAMTS7 coding variant rs3825807 (Ser214Pro) associated with reduced CAD risk. This variant had a hypomorphic effect on ADAMTS7 secretion and migration of vascular smooth muscle cells (VSMC), findings consistent with our mouse studies. Conclusions: We demonstrated that loss of ADAMTS7 catalytic function protects against atherosclerosis via phenotype switch of VSMCs and that the atherosclerosis protective effects could be mediated by a loss-of-function coding variant associated with CAD risk. In aggregate, we provide compelling evidence that dosage of ADAMTS7 and catalytic function are responsible for the atherosclerotic phenotype, suggesting that the catalytic domain would be an attractive therapeutic target for CAD.




Circ Res: 27 Jun 2021; epub ahead of print
Mizoguchi T, MacDonald BT, Bhandary B, Popp NR, ... Kathiresan S, Ellinor PT
Circ Res: 27 Jun 2021; epub ahead of print | PMID: 34176299
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Impact:
Abstract

Cardiovascular consequences of discontinuing low-dose rivaroxaban in people with chronic coronary or peripheral artery disease.

Dagenais GR, Dyal L, Bosch JJ, Leong DP, ... Yusuf S, Eikelboom JW
Objective
In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.
Methods
Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).
Results
During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.
Conclusion
Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.
Trial registration number
NCT01776424.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Jun 2021; 107:1130-1137
Dagenais GR, Dyal L, Bosch JJ, Leong DP, ... Yusuf S, Eikelboom JW
Heart: 29 Jun 2021; 107:1130-1137 | PMID: 34021038
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Impact:
Abstract

Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest.

Hoiland RL, Ainslie PN, Wellington CL, Cooper J, ... Griesdale D, Sekhon M
Rationale: Secondary brain hypoxia portends significant mortality in ischemic brain diseases, yet our understanding of hypoxic ischemic brain injury (HIBI) pathophysiology in humans remains rudimentary. Objective: To quantify the impact of secondary brain hypoxia on injury to the neurovascular unit in patients with HIBI.
Methods and results:
We conducted a prospective interventional study of invasive neuromonitoring in 18 post-cardiac arrest patients with HIBI. The partial pressures of brain tissue O2 (PbtO2) and intracranial pressure were directly measured via intra-parenchymal micro-catheters. To isolate the cerebrovascular bed, we conducted paired sampling of arterial and jugular venous bulb blood and calculated the trans-cerebral release of biomarkers of neurovascular injury and inflammation in the HIBI patients and 14 healthy volunteers for control comparisons. Ten HIBI patients exhibited secondary brain hypoxia (PbtO2<20mmHg), while eight exhibited brain normoxia (PbtO2≥20mmHg). In the patients with secondary brain hypoxia, we observed active cerebral release of glial fibrillary acidic protein (-161[ -3695 - -75] pg/mL; P=0.0078), neurofilament light chain (-231[-370 - -11] pg/mL; P=0.010), total tau (-32[-310 - -3] pg/mL; P=0.0039), neuron specific enolase (-14890[-148813 - -3311] pg/mL; P=0.0039), and ubiquitin carboxy-terminal hydrolase L1 (-14.7[-37.7 - -4.1] pg/mL; P=0.0059) indicating de novo neuroglial injury. This injury was unrelated to the systemic global ischemic burden or cerebral endothelial injury but rather was associated with cerebral release of interleukin-6 (-10.3[-43.0 - -4.2] pg/mL; P=0.0039). No cerebral release of the aforementioned biomarkers was observed in HIBI patients with brain normoxia or the healthy volunteers. Hyperosmolar therapy in the patients with secondary brain hypoxia reduced the partial pressure of jugular venous O2-to-PbtO2 gradient (39.6[34.1-51.1] vs. 32.0[24.5-39.2] mmHg; P=0.0078) and increased PbtO2 (17.0[9.1-19.7] vs. 20.2[11.9-22.7] mmHg; P=0.039) suggesting improved cerebrovascular-to-parenchymal O2 transport. Conclusions: Secondary brain hypoxia is associated with de novo neuroglial injury and cerebral release of interleukin-6. Mitigating cerebrovascular-to-parenchymal limitations to O2 transport is a promising therapeutic strategy for HIBI patients with secondary brain hypoxia.




Circ Res: 20 Jul 2021; epub ahead of print
Hoiland RL, Ainslie PN, Wellington CL, Cooper J, ... Griesdale D, Sekhon M
Circ Res: 20 Jul 2021; epub ahead of print | PMID: 34287000
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Impact:
Abstract

Cyclic GMP modulating drugs in cardiovascular diseases: Mechanism-based network pharmacology.

Petraina A, Nogales C, Krahn T, Mucke H, ... Hobbs AJ, Schmidt HHHW
Mechanism-based therapy centred on the molecular understanding of disease-causing pathways in a given patient is still the exception rather than the rule in medicine, even in cardiology. However, recent successful drug developments centred around the second messenger cyclic guanosine-3\'-5\'-monophosphate (cGMP), which is regulating a number of cardiovascular disease modulating pathways, are about to provide novel targets for such a personalised cardiovascular therapy. Whether cGMP breakdown is inhibited or cGMP synthesis is stimulated via guanylyl cyclases or their upstream regulators in different cardiovascular disease phenotypes, the outcomes seem to be so far uniformly protective. Thus, a network of cGMP modulating drugs has evolved that act in a mechanism-based, possibly causal manner in a number of cardiac conditions. What remains a challenge is the detection of cGMPopathy endotypes amongst cardiovascular disease phenotypes. Here we review the growing clinical relevance of cGMP and provide a glimpse into the future on how drugs interfering with this pathway may change how we treat and diagnose cardiovascular diseases altogether.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 15 Jul 2021; epub ahead of print
Petraina A, Nogales C, Krahn T, Mucke H, ... Hobbs AJ, Schmidt HHHW
Cardiovasc Res: 15 Jul 2021; epub ahead of print | PMID: 34270705
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Impact:
Abstract

Education on cardiac risk and CPR in cardiology clinic waiting rooms: a randomised clinical trial.

McIntyre D, Thiagalingam A, Klimis H, Von Huben A, Marschner S, Chow CK
Objective
Waiting time is inevitable during cardiovascular (CV) care. This study examines whether waiting room-based CV education could complement CV care.
Methods
A 2:1 randomised clinical trial of patients in waiting rooms of hospital cardiology clinics. Intervention participants received a series of tablet-delivered CV educational videos and were randomised 1:1 to receive another video on cardiopulmonary resuscitation (CPR) or no extra video. Control received usual care. The primary outcome was the proportion of participants reporting high motivation to improve CV risk-modifying behaviours (physical activity, diet and blood pressure monitoring) post-clinic.
Secondary outcomes
clinic satisfaction, CV lifestyle risk factors (RFs) and confidence to perform CPR. Assessors were blinded to treatment allocation.
Results
Among 514 screened, 330 were randomised (n=220 intervention, n=110 control) between December 2018 and March 2020, mean age 53.8 (SD 15.2), 55.2% male. Post-clinic, more intervention participants reported high motivation to improve CV risk-modifying behaviours: 29.6% (64/216) versus 18.7% (20/107), relative risk (RR) 1.63 (95% CI 1.04 to 2.55). Intervention participants reported higher clinic satisfaction RR: 2.19 (95% CI 1.45 to 3.33). Participants that received the CPR video (n=110) reported greater confidence to perform CPR, RR 1.61 (95% CI 1.20 to 2.16). Overall, the proportion of participants reporting optimal CV RFs increased between baseline and 30-day follow-up (16.1% vs 24.8%, OR=2.44 (95% CI 1.38 to 4.49)), but there was no significant between-group difference at 30 days.
Conclusion
CV education delivery in the waiting room is a scalable concept and may be beneficial to CV care. Larger studies could explore its impact on clinical outcomes.
Trial registration number
ANZCTR12618001725257.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 20 Jul 2021; epub ahead of print
McIntyre D, Thiagalingam A, Klimis H, Von Huben A, Marschner S, Chow CK
Heart: 20 Jul 2021; epub ahead of print | PMID: 34290036
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Impact:
Abstract

Testosterone therapy and cardiovascular diseases.

Cittadini A, Isidori AM, Salzano A
Since it was first synthesised in 1935, testosterone (T) has been viewed as the mythical Fountain of Youth, promising rejuvenation, restoring sexual appetites, growing stronger muscles, and quicker thinking. T is endowed with direct effects on myocardial and vascular structure and function, as well as on risk factors for cardiovascular (CV) disease. Indeed, low serum T levels are a risk factor for diabetes, metabolic syndrome, inflammation, and dyslipidaemia. Moreover, many studies have shown that T deficiency per se is an independent risk factor of CV and all-cause mortality. On this background and due to direct-to-patient marketing by drug companies, we have witnessed to the widespread use of T replacement therapy (TT) without clear indications particularly in late-life onset hypogonadism. The current review will dwell upon current evidence and controversies surrounding the role of T in the pathophysiology of CV diseases, the link between circulating T levels and CV risk, and the use of replacing T as a possible adjuvant treatment in specific CV disorders. Specifically, recent findings suggest that heart failure and type 2 diabetes mellitus represent two potential targets of T therapy once that a state of hypogonadism is diagnosed. However, only if ongoing studies solve the CV safety issue the T orchid may eventually \'bloom\'.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions please email: [email protected]

Cardiovasc Res: 21 Jul 2021; epub ahead of print
Cittadini A, Isidori AM, Salzano A
Cardiovasc Res: 21 Jul 2021; epub ahead of print | PMID: 34293112
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Impact:
Abstract

The Burden of Mental Illness Among Survivors of Critical Care-Risk Factors and Impact on Quality of Life: A Multicenter Prospective Cohort Study.

Teixeira C, Rosa RG, Sganzerla D, Sanchez EC, ... Falavigna M, Friedman G
Background
Survivors of critical care may demonstrate mental health disorders in the months after discharge.
Research question
What are risk factors for mental health disorders after ICU discharge and is there an association between the burden of mental illness and health-related quality of life (HRQoL)?
Study design and methods
Multicenter prospective cohort study that included 579 adult ICU survivors with an ICU stay of > 72 h in 10 ICUs.
Results
The outcomes were anxiety and depression assessed by the Hospital Anxiety and Depression Scale, posttraumatic stress disorder (PTSD) assessed by the Impact Event Scale 6, and HRQoL assessed by the Short Form 12 version 2. The 6-month prevalences of any mental health disorder were 36.2% (the prevalences of anxiety, depression, and PTSD were 24.2%, 20.9%, and 15.4%, respectively). ICU survivors with mental health disorders showed worse HRQoL scores in both physical and mental dimensions than those without. The higher the number of psychiatric syndromes manifested, the worse the mental dimension of HRQoL. Age of < 65 years (P = .009), history of depression (P = .009), anxiety (P = .003) and depression (P = .02) symptoms at ICU discharge, physical dependence (P = .01), and decreased physical functional status (P = .04) at 6 months were associated with anxiety. History of depression (P = .001), depression symptoms at ICU discharge (P < .001), and decreased physical functional status at 6 months (P = .01) were associated with depression. Depression symptoms at ICU discharge (P = .01), physical dependence (P = .01), and decreased physical functional status (P = .02) at 6 months were associated with PTSD.
Interpretation
The network of potential risk factors for mental illness among patients discharged from an ICU is complex and involves multiple factors (age, premorbid mental health, acute emotional stress, and physical impairment after ICU stay). The negative impact of the burden of mental illness on HRQoL among critical care survivors is of concern.

Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 29 Jun 2021; 160:157-164
Teixeira C, Rosa RG, Sganzerla D, Sanchez EC, ... Falavigna M, Friedman G
Chest: 29 Jun 2021; 160:157-164 | PMID: 33640377
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Impact:
Abstract

Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and oral anticoagulants: results from The Swedish Primary Care Cardiovascular Database of Skaraborg.

Bager JE, Hjerpe P, Schiöler L, Bengtsson Boström K, ... Manhem K, Mourtzinis G
Objective
To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs).
Methods
We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130 mmHg as reference.
Results
There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180 mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130 mmHg.
Conclusion
In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180 mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130 mmHg. This suggests that lowering SBP to below 145 mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1670-1677
Bager JE, Hjerpe P, Schiöler L, Bengtsson Boström K, ... Manhem K, Mourtzinis G
J Hypertens: 31 Jul 2021; 39:1670-1677 | PMID: 33710172
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Impact:
Abstract

Impact of Antifibrotic Therapy on Mortality and Acute Exacerbation in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Petnak T, Lertjitbanjong P, Thongprayoon C, Moua T
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone are two antifibrotic medications currently approved for slowing the rate of lung function decline in IPF, but information on treatment effect on mortality and risk of acute exacerbation (AE) remains limited or unknown.
Research question
Does antifibrotic treatment decrease risk of mortality and AE?
Study design and methods
A comprehensive search of several databases, including Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted. Studies were included if they were original articles comparing mortality or AE events in IPF patients with and without antifibrotic treatment. Relative risk (RR) with 95% confident interval (CI) was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and acute exacerbation (AE) risk.
Results
A total of 12,956 patients across 26 studies (8 randomized controlled trials and 18 cohort studies) were included in the meta-analysis. Antifibrotic treatment was associated with decreased risk of all-cause mortality with a pooled RR 0.55 (95% CI, 0.45-0.66) and I2 of 82%. This effect was consistent across additional subgroup analyses, including stratification by study type, risk of bias, duration of follow-up, and antifibrotic subtype. Antifibrotic treatment also reduced the risk of AE, with a pooled RR of 0.63 (95% CI, 0.53-0.76), and I2 of 0%. Effect on AE risk was consistent across subgroup analyses by study type and for nintedanib but not for pirfenidone.
Interpretation
Antifibrotic treatment appears to reduce the risk of all-cause mortality and AE in IPF. Despite greater heterogeneity with pooled analysis, its effect was robust in subgroup analyses by study type, duration of follow-up, and antifibrotic subtype.

Copyright © 2021. Published by Elsevier Inc.

Chest: 30 Jun 2021; epub ahead of print
Petnak T, Lertjitbanjong P, Thongprayoon C, Moua T
Chest: 30 Jun 2021; epub ahead of print | PMID: 34217681
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Impact:
Abstract

An original risk score to predict early major bleeding in acute pulmonary embolism:The Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score.

Chopard R, Piazza G, Falvo N, Ecarnot F, ... Badoz M, Meneveau N
Background
Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management.
Research question
Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding?
Study design and methods
From a multicenter prospective registry including 2,754 patients, we performed post-hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared to that of the VTE-BLEED, RIETE and BACS models.
Results
Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%, 95%CI, 2.39-3.72%): Syncope (+1.5), Anemia defined as hemoglobin <12 g/dL (+2.5), and Renal Dysfunction defined as glomerular filtration rate <60 mL/min (+1 point). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI, 50.29-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53-1.62%) in the low-risk to 8.93% (95% CI, 6.15-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not.
Interpretation
The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

Copyright © 2021. Published by Elsevier Inc.

Chest: 30 Jun 2021; epub ahead of print
Chopard R, Piazza G, Falvo N, Ecarnot F, ... Badoz M, Meneveau N
Chest: 30 Jun 2021; epub ahead of print | PMID: 34217683
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Impact:
Abstract

Local transversal aortic strain is impaired in ascending aorta dilatation.

Cesareo M, Sabia L, Leone D, Avenatti E, ... Vallelonga F, Milan A
Background
Ascending aorta dilatation is found in 13% of hypertensive patients. Little is known about elastic properties of ascending aorta in such patients. Echo-based transverse aortic strain analysis can describe mechanical properties of ascending aorta but has never been applied to patients with ascending aorta dilatation.
Aim
To assess mechanical properties of ascending aorta by transverse aortic strain analysis (as β2-stiffness index) in hypertensive patients with ascending aorta dilatation and association between mechanical properties of ascending aorta and cardiovascular damage.
Methods
A total of 100 hypertensive outpatients underwent transthoracic echocardiography and assessment of pulse wave velocity (PWV). Strain analysis of ascending aorta was performed with echocardiographic speckle-tracking software. Patients were divided in three groups based on ascending aorta diameter: less than 40, 40-45, and at least 45 mm.
Results
Beta-SI increased exponentially with ascending aorta dimensions (P < 0.001). Patients with ascending aorta dilatation had Beta-SI significantly higher than those with normal ascending aorta diameter. A greater proportion of patient with impaired (i.e., elevated) Beta-SI was present in groups with larger ascending aorta (18.2 vs. 48.4 vs. 80%, respectively, P < 0.05). On multivariate logistic regression only impaired Beta-SI predicted ascending aorta dilatation (P < 0.001). Beta-SI was related to cardiovascular damage in terms of left ventricular (LV) mass (LV mass indexed to BSA, P = 0.030) and PWV (P = 0.028). Patients with high Beta-SI had greater LV mass indexed to BSA (117 ± 47 vs. 94 ± 24 g/m2; P = 0.010) and PWV (10.20 ± 2.99 vs. 8.63 ± 1.88 m/s; P = 0.013).
Conclusion
Ascending aorta dilatation is associated with increased local aortic stiffness in hypertensive patients. Strain analysis adds functional information to the mere morphological evaluation of aortic diameter and could be a useful tool to better define cardiovascular risk in this population.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1402-1411
Cesareo M, Sabia L, Leone D, Avenatti E, ... Vallelonga F, Milan A
J Hypertens: 30 Jun 2021; 39:1402-1411 | PMID: 33399306
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Impact:
Abstract

Endothelial function of healthy adults from 20 to 91 years of age: prediction of cardiovascular risk by vasoactive range.

Königstein K, Wagner J, Frei M, Knaier R, ... Hinrichs T, Schmidt-Trucksäss A
Objectives
Brachial arterial low flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) are ultrasound-based biomarkers that emerge into scientific and clinical practice indicating cardiovascular effects of medical and lifestyle-based treatment beyond classical risk factors. This study is the first to provide reference values and to assess the predictive value of L-FMC, FMD and their composite endpoint vasoactive range (VAR) in healthy adults.
Methods
L-FMC, FMD and VAR were measured in 457 nonsmoking adults of 20-91 years without chronic diseases, medication, with normal heart function and very low cardiovascular risk. Sex-specific percentiles were calculated and predictive ability for elevated cardiovascular risk was assessed using receiver-operating characteristic (ROC) curves.
Results
From 20 to 91 years of age, L-FMC increased 86.1 and 105.3%, FMD decreased 63.6 and 47.1% and VAR decreased 58.3 and 55.2% in women and men, respectively. Area under the ROC curves was 0.54 (95% CI = 0.49-0.54) for L-FMC, 0.67 (95% CI = 0.62-0.67) for FMD and 0.72 (95% CI = 0.67-0.72) for VAR (P < 0.001). Discriminatory cut-offs for elevated risk were 0.24% for L-FMC (sensitivity = 0.42, specificity = 0.67), 6.4% for FMD (sensitivity = 0.71, specificity = 0.60) and 6.3% for VAR (sensitivity = 0.62, specificity = 0.73).
Conclusion
This study demonstrates reduced endothelial function with aging in healthy men and women with very low cardiovascular risk. Percentiles crossed cut-offs for elevated cardiovascular risk between 50 and 55 years in men and 70 and 75 years in women, indicating higher risk for cardiovascular disease in men. VAR showed the highest ability to identify individuals with elevated cardiovascular risk, and should be included in the monitoring and treatment of accelerated vascular aging even in healthy individuals.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1361-1369
Königstein K, Wagner J, Frei M, Knaier R, ... Hinrichs T, Schmidt-Trucksäss A
J Hypertens: 30 Jun 2021; 39:1361-1369 | PMID: 33470736
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Impact:
Abstract

Increased pulse wave velocity in patients with an orthostatic blood pressure rise independent of other cardiovascular risk factors.

Nolde JM, Lugo-Gavidia LM, Kannenkeril D, Chan J, ... Kiuchi MG, Schlaich MP
Background
Positional changes in blood pressure (BP) have been shown to have effects on long-term outcomes. Although a BP drop with upright posture is frequently observed, an orthostatic rise in BP can also occur. Here, we aimed to investigate whether the phenotype of orthostatic hypertension is associated with more pronounced vascular hypertension-mediated organ damage (HMOD) and whether this is associated with other cardiovascular risk factors.
Methods
In a cohort of 200 patients referred to our tertiary hypertension clinic, we prospectively assessed unattended seated automated office BP and the response to 1 min of upright posture. The difference in BP after standing up was calculated and pulse wave velocity (PWV) was assessed as a marker of vascular HMOD. Routine clinical cardiovascular risk markers were also assessed. Regression models were used to assess the association between orthostatic BP changes and pulse wave velocity.
Results
Baseline characteristics and clinic cardiovascular risk factors were similar between orthostatic BP response groups. A U-shaped association was evident between PWV and orthostatic BP changes with elevated PWV in patients with either a fall or a rise in BP in response to upright posture. The regression models remained significant after adjusting for other cardiovascular risk factors, including 24 h ambulatory BP.
Conclusion
Both an orthostatic BP drop and rise were associated with elevated PWV. Although standing BP is commonly measured in elderly hypertensive patients to exclude significant orthostatic hypotension, this simple measurement may provide an additional independent risk factor for vascular HMOD at any age.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1352-1360
Nolde JM, Lugo-Gavidia LM, Kannenkeril D, Chan J, ... Kiuchi MG, Schlaich MP
J Hypertens: 30 Jun 2021; 39:1352-1360 | PMID: 33470734
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Impact:
Abstract

The differential impact of aerobic and isometric handgrip exercise on blood pressure variability and central aortic blood pressure.

Seidel M, Pagonas N, Seibert FS, Bauer F, ... Nina B, Westhoff TH
Background
Blood pressure variability and central SBP are independent markers of cardiovascular risk. Data on lifestyle-interventions to reduce these parameters are sparse. The present work reports the differential effects of aerobic vs. isometric handgrip exercise on blood pressure variability and central SBP in a prospective randomized trial.
Methods
Seventy-five hypertensive patients were randomized to one of the following 12-week programs: isometric handgrip training five times weekly; \'Sham-handgrip training\' five times weekly; aerobic exercise training (30 min three to five times/week). Blood pressure variability was assessed by the coefficient of variation in 24-h ambulatory blood pressure monitoring (ABPM). Central SBP was measured noninvasively by the SphygmoCor device (AtCor Medical, Australia).
Results
The aerobic exercise program significantly decreased systolic daytime variability (12.1 ± 2.5 vs. 10.3 ± 2.8, P = 0.04), whereas diastolic daytime blood pressure variability was not significantly altered (P = 0.14). Night-time variability was not significantly affected (P > 0.05). Central SBP was reduced from 145±15 to 134 ± 19 mmHg (P = 0.01). Isometric handgrip and sham-handgrip exercise did not significantly affect blood pressure variability (P > 0.05 each). Isometric exercise tended to reduce central SBP (142 ± 19 to 136 ± 17 mmHg, P = 0.06). ANCOVA revealed significant intergroup differences for the change of daytime SBP and DBP variability (P = 0.048 and 0.047, respectively).
Conclusion
Aerobic exercise reduces blood pressure variability and central SBP. Isometric handgrip exercise does not reduce blood pressure variability but tends to lower central SBP in this hypertensive population.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1269-1273
Seidel M, Pagonas N, Seibert FS, Bauer F, ... Nina B, Westhoff TH
J Hypertens: 30 Jun 2021; 39:1269-1273 | PMID: 33470732
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Impact:
Abstract

Association between the proportions of carbohydrate and fat intake and hypertension risk: findings from the China Health and Nutrition Survey.

He D, Sun N, Xiong S, Qiao Y, Ke C, Shen Y
Objective
The aim of this study was to expound the dietary effects of different proportions of carbohydrate and fat on hypertension in the Chinese population.
Methods
We used data derived from the China Health and Nutrition Survey (CHNS) from 1991 to 2011. In total, 10 459 Chinese participants aged over 12 years were included in the final analysis. A multivariable Cox regression was used to calculate the hazard ratio and 95% confidence interval (95% CI) of hypertension in each group, and the medium proportion of carbohydrate and fat (MPCF) diet intake group was used as the reference.
Results
Compared with the participants who consumed an MPCF diet, the individuals who consumed a high-carbohydrate and low-fat (HCLF) diet had a higher risk of developing hypertension (hazard ratio: 1.295, 95% CI: 1.167-1.436), especially the individuals who were young (hazard ratio: 1.422, 95% CI: 1.106-1.828), were living in rural areas (hazard ratio: 1.373, 95% CI: 1.206-1.565) and consumed alcohol (hazard ratio: 1.363, 95% CI: 1.153-1.611). In addition, a low-carbohydrate and high-fat (LCHF) diet was not associated with hypertension (hazard ratio: 0.861, 95% CI: 0.694-1.068). Moreover, these associations were observed at the majority energy intake level.
Conclusion
An HCLF diet was significantly associated with an increased risk of hypertension.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1386-1392
He D, Sun N, Xiong S, Qiao Y, Ke C, Shen Y
J Hypertens: 30 Jun 2021; 39:1386-1392 | PMID: 33534340
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Impact:
Abstract

The aortic-femoral arterial stiffness gradient: an atherosclerosis risk in communities (ARIC) study.

Stone K, Fryer S, Meyer ML, Kucharska-Newton A, ... Tanaka H, Stoner L
Background
The aortic to femoral arterial stiffness gradient (af-SG) may be a novel measure of arterial health and cardiovascular disease (CVD) risk, but its association with CVD risk factors and CVD status, and whether or not they differ from the referent measure, carotid-femoral pulse-wave velocity (cfPWV), is not known.
Method
Accordingly, we compared the associations of the af-SG and cfPWV with (i) age and traditional CVD risk factors and (ii) CVD status. We evaluated 4183 older-aged (75.2 ± 5.0 years) men and women in the community-based Atherosclerosis Risk in Communities (ARIC) Study. cfPWV and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The af-SG was calculated as faPWV divided by cfPWV. Associations of af-SG and cfPWV with age, CVD risk factors (age, BMI, blood pressure, heart rate, glucose and blood lipid levels) and CVD status (hypertension, diabetes, coronary heart disease, heart failure, stroke) were determined using linear and logistic regression analyses.
Results
(i) the af-SG and cfPWV demonstrated comparable associations with age and CVD risk factors, except BMI. (ii) a low af-SG was associated with diabetes, coronary heart disease, heart failure and stroke, whilst a high cfPWV was only associated with diabetes.
Conclusion
Although future studies are necessary to confirm clinical utility, the af-SG is a promising tool that may provide a unique picture of hemodynamic integration and identification of CVD risk when compared with cfPWV.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1370-1377
Stone K, Fryer S, Meyer ML, Kucharska-Newton A, ... Tanaka H, Stoner L
J Hypertens: 30 Jun 2021; 39:1370-1377 | PMID: 33560059
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Impact:
Abstract

Optimal blood pressure levels in different phases of peripheral thrombolysis period in acute ischemic stroke.

He M, Wang H, Tang Y, Cui B, ... Hui R, Wang Y
Background
Dramatic changes of blood pressure (BP) were observed in the peripheral thrombolysis period, however, there is no consensus about BP control targets in the different phases.
Methods
We retrospectively studied a consecutive sample of 510 patients treated with intravenous thrombolysis and followed-up for 3 months. The peripheral thrombolysis period was divided into these phases: Phase 1 (from onset to thrombolysis), Phase 2 (thrombolysis), Phase 3 (from thrombolysis to 24 h after thrombolysis), and Phase 4 (from 24 h to 7 days after thrombolysis). Patients were divided into quintiles according to mean blood pressure in these phases, respectively. Neurological improvement was evaluated using the modified Rankin Scale score at 3-month after thrombolysis.
Results
Lower risk of intracerebral hemorrhage within 7 days was found in lower quintiles of SBP (OR = 0.100, 95% CI 0.011-0.887, P = 0.039 in Phase 1 quintile Q1, OR = 0.110, 95% CI 0.012-0.974, P = 0.047 in Phase 2-3 quintile Q1, and OR, 0.175, 95% CI, 0.035-0.872; P = 0.033 in Phase 4 quintile Q2, respectively). Better neurological improvement was found in SBP quintiles: Q2-Q4 (127.3-155.7 mmHg) in Phase 4 (OR = 3.095, 95% CI 1.524-6.286, P = 0.002 for Q2; OR = 2.697, 95% CI 1.354-5.370, P = 0.005 for Q3; and OR = 2.491, 95% CI 1.263-4.913, P = 0.008 for Q4, respectively). Our results also showed higher average real variability of SBP was negatively associated with better neurological outcome in Phase 1 and Phase 2-3.
Conclusions
Maintaining SBP levels (≤148 mmHg) from admission to the first 24 h after thrombolysis, then keeping SBP levels (127-138 mmHg) would be beneficial.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1453-1461
He M, Wang H, Tang Y, Cui B, ... Hui R, Wang Y
J Hypertens: 30 Jun 2021; 39:1453-1461 | PMID: 33560058
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Impact:
Abstract

Isolated systolic and diastolic hypertension by the 2017 American College of Cardiology/American Heart Association guidelines and risk of cardiovascular disease: a large prospective cohort study.

Li FR, He Y, Yang HL, Liu HM, ... Wang JY, Wu XB
Objective
The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines lowered the hypertension threshold from a SBP/DBP level of at least 140/90 mmHg to at least 130/80 mmHg. The cardiovascular impact of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) under the new definition remains unclear.
Methods
We used data from the UK Biobank study, which is a prospective population-based cohort study. Participants were categorized into five groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension. The primary endpoint for this study was the composite of nonfatal myocardial infarction (MI), nonfatal ischaemic stroke, nonfatal haemorrhagic stroke and cardiovascular disease (CVD) death. We also explored the results for the above-mentioned CVD outcomes separately. Baseline BP measurements were obtained twice after the participant had been at rest for at least 5 min in a seated position.
Results
We included 385 955 participants who were not taking antihypertensive medications, were free of CVD at baseline and had available data on BP measurements. During a median follow-up of 8.1 years, 8959 CVD events were recorded, including 4729 nonfatal MIs, 2287 nonfatal ischaemic strokes, 813 nonfatal haemorrhagic strokes, and 1826 CVD deaths. According to the hypertension threshold of at least 130/80 mmHg by the American College of Cardiology/American Heart Association guidelines, both ISH (hazard ratio 1.39; 95% confidence interval 1.27, 1.15) and IDH (hazard ratio 1.28; 95% confidence interval 1.15, 1.43) were significantly associated with a higher overall CVD risk than normal BP. ISH was associated with most CVD risk, except for ischaemic stroke, while the excess CVD risk associated with IDH appeared to be driven mainly by MI and CVD death. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with significant associations in younger adults (age <60 years) and women and null associations in men and older adults (age ≥60 years).
Conclusion
ISH was associated with the risk of most CVD events, while the association between IDH and CVD risk was mainly driven by MI incidence and CVD death. Further research is needed to identify participants with IDH who have a particular risk for developing CVD.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1594-1601
Li FR, He Y, Yang HL, Liu HM, ... Wang JY, Wu XB
J Hypertens: 31 Jul 2021; 39:1594-1601 | PMID: 33560057
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Impact:
Abstract

Reverse dipping and subclinical cardiac organ damage: a meta-analysis of echocardiographic studies.

Cuspidi C, Tadic M, Sala C, Carugo S, Mancia G, Grassi G
Aim
Available evidence on the association between reverse dipping pattern and subclinical cardiac damage is scanty. We performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue.
Methods
The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from January from the inception up to 31 July 2020. Studies were identified by using MeSH terms and crossing the following search items: \'reverse dipping\', \'nondipping\', \'inverted dipping\', \'ambulatory blood pressure\', \'cardiac damage\', \'hypertensive heart disease\', \'left ventricular mass\', \'left ventricular hypertrophy\', and \'echocardiography\'.
Results
Data from 14 studies including 1429 patients with reverse dipping, 2584 dippers and 3508 nondippers were considered. Left ventricular (LV) mass index and relative wall thickness were greater in reverse dippers than in dippers (SMD: 0.40 ± 0.04 g/m2, P < 0.0001; 0.31 ± 0.07, P < 0.0001) and nondippers (SMD: 0.25 ± 0.04 g/m2, P < 0.0001; 0.21 ± 0.07, P = 0.004). The reverse dipping group had an increased risk of LV hypertrophy compared with dipping (OR = 1.85, CI 1.47-2.32, P < 0.0001) and nondipping group (OR = 1.45, CI 1.19-1.78, P < 0.0001). A significant progressive reduction in the E/A ratio, paralleled by an increase in left atrium diameter occurred from dippers, to nondippers and reverse dippers.
Conclusion
The present meta-analysis provides a novel piece of information about the unfavourable association between the reverse dipping pattern and subclinical cardiac alterations and suggests that the detection of this blood pressure phenotype may identify individuals at increased risk for subclinical organ damage.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1505-1512
Cuspidi C, Tadic M, Sala C, Carugo S, Mancia G, Grassi G
J Hypertens: 31 Jul 2021; 39:1505-1512 | PMID: 33657585
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Impact:
Abstract

Protective effect of controlled blood pressure on risk of dementia in low-risk, grade 1 hypertension.

Lee CJ, Hwang J, Kang CY, Kim HC, ... Kim C, Park S
Objective
High blood pressure (BP) increases the risk of dementia; however, few studies have reported on the risk of dementia in patients with low-risk, early-grade hypertension. We investigated the protective effect of controlled BP on risk of dementia in treated, low-risk, grade 1 hypertensive patients from the entire National Health Insurance Service National Health Examinee cohort.
Methods
We selected grade 1 hypertension (140-159/90-99 mmHg) patients with low risk, diagnosed in 2005-2006. All patients (N = 128 665) were classified into controlled (average BP < 140/90 mmHg during the follow-up) and uncontrolled (average BP ≥ 140/90 mmHg) BP groups and followed up until 2015. The risk of dementia was estimated using Cox proportional hazard model after adjustments for propensity score.
Results
Average BP was 131/81 mmHg in the controlled group (N = 49 408) and 144/87 mmHg in the uncontrolled group (N = 99 257). Overall dementia incidence rates in controlled and uncontrolled groups were 4.9 and 8.1 per 1000 person-year, respectively. The controlled group showed lower risk of overall dementia, Alzheimer\'s disease, and vascular dementia than the uncontrolled group. The controlled group had a low risk of vascular dementia at all ages, especially in the younger group (age <60). The optimal BP level associated with the lowest risk of dementia was 130 to less than 140 mmHg for SBP and 70 to less than 80 mmHg for DBP.
Conclusion
We concluded that among even low-risk and grade 1 hypertension patients, controlled BP significantly reduced the risk of dementia, including Alzheimer\'s disease and vascular dementia.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1662-1669
Lee CJ, Hwang J, Kang CY, Kim HC, ... Kim C, Park S
J Hypertens: 31 Jul 2021; 39:1662-1669 | PMID: 33710170
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Impact:
Abstract

Antihypertensive treatment decrease stroke occurrence: a prospective cohort study.

Zuo Y, Wang A, Wu S, Chen S, ... Li H, He Y
Objective
Among the risk factors of stroke, hypertension was one of the most important and modifiable factors. The current study aimed to assess whether antihypertensive treatment to ideal levels of blood pressure can eliminate stroke risk in a prospective cohort study.
Methods
The Kailuan study was a prospective longitudinal cohort study on stroke risk factors and events. We analyzed association of baseline antihypertensive treatment efficacy with the risk of stroke during 11.0-year follow-up, and further evaluated association of newly antihypertensive treatment efficacy at 4-year follow-up with subsequent stroke. Multivariate Cox proportion models were used to calculated hazard ratios and their 95% confidence intervals (CIs) for stroke.
Results
A total of 97 772 participants (median age: 51.65 years) without previous stroke were included. At baseline, 55 518 participants had normotension, 2339 treated and controlled, 32 331 untreated hypertension and 7584 treated but uncontrolled. Compared with normotension, individuals with treated and controlled, untreated hypertension and treated but uncontrolled, had 83, 97 and 162% higher risk of developing total stroke after adjusting for potential stroke risk factors, respectively (hazard ratio 1.83 [95% CI 1.56-2.15], 1.97 [95% CI 1.85-2.11] and 2.62 [95% CI 2.40-2.86]; all P < 0.05). Whereas, normotension at baseline, who were newly normotension with antihypertensives at 4-year follow-up, exhibited no elevated total stroke risk (hazard ratio, 1.41 [95% CI 0.87-2.30]). Similar results existed for stroke subtypes (ischemic stroke and hemorrhagic stroke).
Conclusion
The data suggest that, antihypertensive treatment to normotensive individuals can reduce stroke risk in a short time.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1652-1661
Zuo Y, Wang A, Wu S, Chen S, ... Li H, He Y
J Hypertens: 31 Jul 2021; 39:1652-1661 | PMID: 33710169
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Impact:
Abstract

Low admission blood pressure as a marker of poor 1-year survival in patients with revascularized critical limb ischemia.

Yannoutsos A, Lin F, Billuart O, Buronfosse A, ... Lazareth I, Priollet P
Objective
To contrast the association between blood pressure (BP) level and antihypertensive medications at hospital admission with 1-year mortality in patients undergoing revascularization for critical limb ischemia (CLI).
Methods
From November 2013 to May 2019, 315 consecutive patients were retrospectively included. A median of seven (IQR 3-13) separate readings were recorded for each patient before revascularization procedure and the average represented patient\'s mean BP. BP-lowering medications, clinical and biological parameters were recorded at baseline. The main outcome was total 1-year mortality.
Results
The cohort included 172 men (55%) and 143 women (45%), with a mean age of 77.9 ± 11.9 years. Treated hypertension was present in 245 (78%) patients; 288 (91%) patients had BP-lowering drug prescriptions (2.1 ± 1.3 medications at baseline). Mean SBP, DBP, mean BP (MBP) and pulse pressure (PP) were 132 ± 18, 70 ± 8, 90 ± 10 and 62 ± 16mmHg. During 1-year follow-up, 80 (25.4%) patients died. In single-pressure multivariate analysis, SBP (hazard ratio 0.97; 95% CI 0.96-0.99; P = 0.005), MBP (hazard ratio 0.96; 95% CI 0.92-0.99; P = 0.01), PP (hazard ratio 0.97; 95% CI 0.95-0.99; P = 0.009), but not DBP, were inversely correlated with 1-year mortality, independently of age, coronary heart disease, left ventricular ejection fraction, brain natriuretic peptide, serum albumin, institutionalized status and antihypertensive drugs. Association between SBP, MBP and PP with 1-year mortality had a quite linear reverse pattern.
Conclusion
Among patients undergoing revascularization for CLI, there is an inverse correlation between admission SBP, MBP and PP with 1-year mortality. BP may represent a modifiable therapeutic target to prevent poor outcome in CLI patients.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1611-1620
Yannoutsos A, Lin F, Billuart O, Buronfosse A, ... Lazareth I, Priollet P
J Hypertens: 31 Jul 2021; 39:1611-1620 | PMID: 33710168
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Impact:
Abstract

Combination blood pressure lowering in the presence or absence of background statin and aspirin therapy: a combined analysis of PROGRESS and ADVANCE Trials.

Wang N, Harris K, Chalmers J, Harrap S, ... Woodward M, Rodgers A
Objectives
To assess the effects of combination BP lowering on cardiovascular events and mortality in the presence of aspirin and/or statin therapy in a combined analysis of the ADVANCE and PROGRESS trials.
Methods
We conducted an analysis of 14 682 participants allocated combination therapy with perindopril and indapamide or placebo followed up for a mean of 4.2 years. Participants were stratified into four groups defined by background use of medications at baseline: statin, aspirin, both or neither. Linear mixed effect models were used to assess differences in BP and Cox proportional hazard models were used to estimate the risks of major cardiovascular events, all-cause mortality and treatment discontinuation.
Results
At baseline, 14% of patients were on both aspirin and statin, 35% on aspirin, 9% on statins and 42% on neither aspirin/statins. Compared with placebo, combination BP therapy reduced mean SBP by 5.7 mmHg in ADVANCE and 12.1 mmHg in PROGRESS, with no difference (P > 0.447) between patients by baseline use of aspirin/statin. Combination BP therapy reduced the risk of major cardiovascular events (hazard ratio 0.78, 95% CI 0.71-0.86), with no significant difference (P = 0.600) between aspirin/statin subgroups. Rates of treatment discontinuation were similar with combination BP therapy compared with placebo (18.4 versus 18%), with no evidence of difference across the subgroups (P = 0.340).
Conclusion
BP lowering with perindopril and indapamide reduces the risk of major cardiovascular events independent of baseline use of aspirin and/or statins.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1689-1696
Wang N, Harris K, Chalmers J, Harrap S, ... Woodward M, Rodgers A
J Hypertens: 31 Jul 2021; 39:1689-1696 | PMID: 33883461
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Abstract

The association of SBP with mortality in patients with stage 1-4 chronic kidney disease.

Zhuo M, Yang D, Goldfarb-Rumyantzev A, Brown RS
Objectives
Hypertension is a risk factor for chronic kidney disease (CKD) progression and mortality. However, the optimal blood pressure associated with decreased mortality in each stage of CKD remains uncertain.
Methods
In this retrospective cohort study, we included 13 414 individuals with CKD stages 1-4 from NHANES general population datasets from 1999 to 2004 followed to 31 December 2010. Multivariate analysis and Kaplan--Meier curves were used to assess SBP and risk factors associated with overall mortality in each CKD stage.
Results
In these individuals with death rates of 9, 12, 30 and 54% in baseline CKD stages 1 through 4, respectively, SBP less than 100 mmHg was associated with significantly increased mortality adjusted for age, sex and race in stages 2,3,4. After excluding less than 100 mmHg, as a continuous variable, higher SBP is associated with fully adjusted increased mortality risk in those on or not on antihypertensive medication (hazard ratio 1.006, P = 0.0006 and hazard ratio 1.006 per mmHg, P < 0.0001, respectively). In those on antihypertensive medication, SBP less than 100 mmHg or in each 20 mmHg categorical group more than 120 mmHg is associated with an adjusted risk of increased mortality. Increasing age, men, smoking, diabetes and comorbidities are associated with increased mortality risk.
Conclusion
For patients with CKD stages 1-4, the divergence of SBP above or below 100-120 mmHg was found to be associated with higher all-cause mortality, especially in those patients on antihypertensive medication. These findings support the recent guideline of an optimal target goal SBP of 100-120 mmHg in patients with CKD stages 1-4.

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J Hypertens: 05 Jul 2021; epub ahead of print
Zhuo M, Yang D, Goldfarb-Rumyantzev A, Brown RS
J Hypertens: 05 Jul 2021; epub ahead of print | PMID: 34232158
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Abstract

Impact of stroke work on the ability of left ventricular mass to account for pressure effects on function in a community with prevalent systemic flow-dependent hypertension.

Bello H, Woodiwiss AJ, Naran R, Peterson VR, ... Sareli P, Norton GR
Aims
To determine whether the confounding influence of stroke work on left ventricular mass (LVM) limits the ability of LVM to detect hypertensive LV dysfunction in systemic flow-dependent hypertension.
Methods
In a community with prevalent systemic flow-dependent hypertension (n = 709), arterial haemodynamics, LVM and LV function were determined using central arterial pressure, aortic velocity and diameter measurements in the outflow tract, and echocardiography with tissue Doppler imaging.
Results
In multivariate models, stroke work showed markedly stronger relations with LVM index (LVMI) than blood pressure load [central arterial SBP (SBPc), backward wave pressure (Pb), 24-h SBP] (P < 0.0001 for comparisons). In contrast, although SBPc, Pb, and 24-h SBP were inversely associated with myocardial tissue shortening (s\') and lengthening (e\') velocity, stroke work was not. With adjustments for stroke work, positive relationships between SBPc, Pb, or 24-h SBP and LVMI were eliminated (P = 0.20 to P = 0.89), but strong relations between BP and s\', e\' or E/e\' (P = 0.009 to P < 0.0001) remained. In mediation analysis, stroke work fully accounted for BP effects on LVMI, but explained none of the effects of BP on LV function. Hence LVMI accounted for little of the impact of BP load on LV function. Although LVMI beyond stroke work (inappropriate LVM) improved on relations between LVMI and s\', it failed to improve on relations with e\' or E/e\' and contributed little beyond LVMI to the impact of BP on LV function.
Conclusion
In systemic flow-dependent hypertension, the impact of stroke work markedly limits the ability of LVM to account for adverse effects of hypertension on LV function.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 05 Jul 2021; epub ahead of print
Bello H, Woodiwiss AJ, Naran R, Peterson VR, ... Sareli P, Norton GR
J Hypertens: 05 Jul 2021; epub ahead of print | PMID: 34232159
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Abstract

Refining determinants of associations of visit-to-visit blood pressure variability with cardiovascular risk: results from the Action to Control Cardiovascular Risk in Diabetes Trial.

Nuyujukian DS, Zhou JJ, Koska J, Reaven PD
Objectives
As there is uncertainty about the extent to which baseline blood pressure level or cardiovascular risk modifies the relationship between blood pressure variability (BPv) and cardiovascular disease, we comprehensively examined the role of BPv in cardiovascular disease risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial.
Methods
Using data from ACCORD, we examined the relationship of BPv with development of the primary CVD outcome, major coronary heart disease (CHD), and total stroke using time-dependent Cox proportional hazards models.
Results
BPv was associated with the primary CVD outcome and major CHD but not stroke. The positive association with the primary CVD outcome and major CHD was more pronounced in low and high strata of baseline SBP (<120 and >140 mmHg) and DBP (<70 and >80 mmHg). The effect of BPv on CVD and CHD was more pronounced in those with both prior CVD history and low blood pressure. Dips, not elevations, in blood pressure appeared to drive these associations. The relationships were generally not attenuated by adjustment for mean blood pressure, medication adherence, or baseline comorbidities. A sensitivity analysis using CVD events from the long-term posttrial follow-up (ACCORDION) was consistent with the results from ACCORD.
Conclusion
In ACCORD, the effect of BPv on adverse cardiovascular (but not cerebrovascular) outcomes is modified by baseline blood pressure and prior CVD. Recognizing these more nuanced relationships may help improve risk stratification and blood pressure management decisions as well as provide insight into potential underlying mechanisms.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 05 Jul 2021; epub ahead of print
Nuyujukian DS, Zhou JJ, Koska J, Reaven PD
J Hypertens: 05 Jul 2021; epub ahead of print | PMID: 34232160
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Abstract

Urinary sodium and potassium excretions in young adulthood and blood pressure by middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Hisamatsu T, Lloyd-Jones DM, Colangelo LA, Liu K
Objective
Data are sparse regarding the impact of sodium and potassium intakes on serial blood pressure (BP) levels during long-term follow-up.
Methods
Among 1007 Coronary Artery Risk Development in Young Adults participants (mean age, 30.2 years; 53% blacks; 57% women) who had at least two 24-h urine samples collected at year 5 (Y5) examination, we assessed associations of urinary sodium and potassium excretions with BP trends and incident hypertension in the subsequent 25 years. Participants were classified by sex-specific medians for averaged 24-h urinary excretions: lower sodium and higher potassium (Na-Lo-K-Hi); higher sodium and lower potassium (Na-Hi-K-Lo); and others.
Results
In the adjusted generalized estimating equation model, SBP and DBP greatly increased in the Na-Hi-K-Lo group (n = 185) compared with the Na-Lo-K-Hi group (n = 185), with statistically significant BP differences at Y20, Y25, and Y30 (mean SBP, 3.93, 4.94, and 4.88 mmHg, respectively; and mean DBP, 4.70, 4.95, and 4.59 mmHg, respectively). During 25-year follow-up, among 926 participants without prevalent hypertension by Y5, 381 (41.1%) developed hypertension. In the adjusted Cox proportional hazards model, the Na-Hi-K-Lo group had hazard ratio (95% confidence interval), 1.45 (1.00-2.10) for incident hypertension compared with the Na-Lo-K-Hi group. The association with incident hypertension was predominant in blacks and white women (race--sex interaction, P = 0.03). Sodium-to-potassium ratio and sodium excretion were positively, whereas potassium excretion was inversely, associated with incident hypertension (all P trend <0.05).
Conclusion
Our findings highlight the importance of dietary sodium reduction and higher potassium intake for hypertension prevention among young adults.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 31 Jul 2021; 39:1586-1593
Hisamatsu T, Lloyd-Jones DM, Colangelo LA, Liu K
J Hypertens: 31 Jul 2021; 39:1586-1593 | PMID: 34188003
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Abstract

Cardiovascular outcomes in patients at high cardiovascular risk with previous myocardial infarction or stroke.

Böhm M, Schumacher H, Teo KK, Lonn EM, ... Mann JFE, Mahfoud F
Background
Guidelines recommend to start blood pressure (BP)-lowering drugs also according to cardiovascular risk including history of cardiovascular events. We hypothesized that in patients with a history of myocardial infarction (MI), stroke, both or none of those, the index events predict the next event and have different SBP risk associations to different cardiovascular outcomes.
Design and measurements
In this pooled posthoc, nonprespecified analysis, we assessed outcome data from high-risk patients aged 55 years or older with a history of cardiovascular events or proven cardiovascular disease, randomized to the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease Trial investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months. Associations of mean achieved BP on treatment were investigated on MI, stroke and cardiovascular death. We identified patients with previous MI (N = 13 487), stroke (N = 4985), both (N = 1509) or none (N = 10 956) of these index events. Analyses were done by Cox regression, analysis of variance and Chi2-test. 30 937 patients with complete data were enrolled between 1 December 2001 and 31 July 2003, and followed until 31 July 2008. Data of both trials were pooled as the outcomes were similar.
Results
Patients with MI as index event had a higher risk to experience a second MI [hazard ratio 1.42 (confidence interval (CI) 1.20-1.69), P < 0.0001] compared with patients with no events but no increased risk for a stroke as a next event [hazard ratio 0.95 (CI 0.73-1.23), n.s.]. The risk was roughly doubled when they had both, MI and stroke before [hazard ratio 2.07 (CI 1.58-2.71), P < 0.0001]. Patients with a stroke history had a roughly three-fold higher likelihood to experience a second stroke [hazard ratio 2.89 (CI 2.37-3.53) P < 0.0001] but not MI [hazard ratio 1.07 (CI 0.88-1.32), n.s.]. Both types of index events increased roughly three-fold the risk of a second stroke compared with no previous events. The SBP-risk relationship was not meaningfully altered by the event history. After MI and stroke the risk for subsequent events and cardiovascular death was increased over the whole SBP spectrum. A J-shape relationship between BP and outcome was only observed for cardiovascular death.
Conclusion
Previous MI and previous stroke are associated with increased risk for the same event in the future, independent of achieved SBP. Thus, secondary prevention may also be chosen according to the event history of patients.
Clinical trial registration
http://clinicaltrials.gov. Unique identifier: NCT00153101.

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J Hypertens: 31 Jul 2021; 39:1602-1610
Böhm M, Schumacher H, Teo KK, Lonn EM, ... Mann JFE, Mahfoud F
J Hypertens: 31 Jul 2021; 39:1602-1610 | PMID: 34188004
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Abstract

Within-visit and between-visit intra-individual blood pressure variability in an unselected adult population from rural China.

Fan WG, Wang WY, Meng YX, Sharman JE, ... Campbell NRC, Su H
Objective
To assess the association between the variability of blood pressure (BP) readings within an initial clinic visit, the variability within subsequent visits and the variability between visits over 1 week in a general population.
Methods
This study included 1401 adult residents, who were not taking antihypertensive drugs, having BP measurements at three visits over 1 week. The difference between maximal and minimal BP readings (ΔBP), ΔBP/BPm (the mean BP value in a visit), the standard deviation (SD) and coefficient of variation (coefficient of variation = SD × 100/mean) of three BP values in each visit were used to estimate the within-visit BP variability (BPV). The SD and coefficient of variation of all nine BP readings over the three visits were calculated as SD9 or CV9 to reflect the overall BPV during the study visits. The SD and coefficient of variation on the mean BP values (BPm) of three visits were computed as SD-3 or CV-3, whereas the difference between maximal and minimal BP in three visits was computed as ΔBP-3 to estimate visit-to-visit BPV. The average BP or HR was the mean values of nine BP or HR readings over three visits.
Results
The systolic and diastolic mean BP (SBP and DBP) decreased from the first to the third visit. The ΔBP, SD and coefficient of variation for both SBP and DBP at the first visit were positively and significantly correlated with the corresponding variables computed at the second and third visits, as well as with overall BPV (ΔBP9, SD9 and CV9). A positive correlation was also found between overall BPV and visit-to visit BPV (SD-3, CV-3 and ΔBP9). Multivariate analysis showed: no association between average SBP and systolic coefficient of variation or ΔBP/BPm but a negative association between average DBP and coefficient of variation or ΔBP/BPm for DBP at the first visit, DBP-3 and DBP9. Age was positively correlated with coefficient of variation or ΔBP/BPm for SBP at the first visit, SBP-3 and SBP9, and correlated with coefficient of variation and ΔBP/BPm for DBP only at the first visit.
Conclusion
In a general population, within-visit BPV at an initial visit is associated with within-visit BPV at subsequent visits and with visit-to-visit BPV over three visits within 1 week.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Hypertens: 30 Jun 2021; 39:1346-1351
Fan WG, Wang WY, Meng YX, Sharman JE, ... Campbell NRC, Su H
J Hypertens: 30 Jun 2021; 39:1346-1351 | PMID: 33967241
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Abstract

Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability.

Ikeda S, Shinohara K, Enzan N, Matsushima S, ... Komuro I, Tsutsui H
Background
Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability.
Methods
The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months.
Results
In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45-0.90) and 1.21 (95% CI 0.82-1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results.
Conclusion
Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.

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J Hypertens: 30 Jun 2021; 39:1435-1443
Ikeda S, Shinohara K, Enzan N, Matsushima S, ... Komuro I, Tsutsui H
J Hypertens: 30 Jun 2021; 39:1435-1443 | PMID: 34001809
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