Topic: General Cardiology

Abstract

Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation.

Wallentin L, Lindbäck J, Eriksson N, Hijazi Z, ... Oldgren J, Siegbahn A
Aims
The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability.
Methods and results
Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level.
Conclusions
Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.

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

Eur Heart J: 26 Sep 2020; epub ahead of print
Wallentin L, Lindbäck J, Eriksson N, Hijazi Z, ... Oldgren J, Siegbahn A
Eur Heart J: 26 Sep 2020; epub ahead of print | PMID: 32984892
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Abstract

Dapagliflozin in Patients with Chronic Kidney Disease.

Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, ... Wheeler DC,
Background
Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.
Methods
We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.
Results
The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.
Conclusions
Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 23 Sep 2020; epub ahead of print
Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, ... Wheeler DC,
N Engl J Med: 23 Sep 2020; epub ahead of print | PMID: 32970396
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Abstract

Less dementia after catheter ablation for atrial fibrillation: a nationwide cohort study.

Kim D, Yang PS, Sung JH, Jang E, ... Lip GYH, Joung B
Aims
Accumulating evidence shows that atrial fibrillation (AF) is associated with an increased risk of dementia. Catheter ablation for AF prolongs the duration of sinus rhythm, thereby improving the quality of life. We investigated the association of catheter ablation for AF with the occurrence of dementia.
Methods and results
Using the Korean National Health Insurance Service database, among 194 928 adults with AF treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between 1 January 2005 and 31 December 2015, we studied 9119 patients undergoing ablation and 17 978 patients managed with medical therapy. The time-at-risk was counted from the first medical therapy, and ablation was analysed as a time-varying exposure. Propensity score-matching was used to correct for differences between the groups. During a median follow-up of 52 months, compared with patients with medical therapy, ablated patients showed lower incidence and risk of overall dementia (8.1 and 5.6 per 1000 person-years, respectively; hazard ratio 0.73, 95% confidence interval 0.58-0.93). The associations between ablation and dementia risk were consistently observed after additionally censoring for incident stroke (hazard ratio 0.76, 95% confidence interval 0.61-0.95) and more pronounced in cases of ablation success whereas no significant differences observed in cases of ablation failure. Ablation was associated with lower risks of dementia subtypes including Alzheimer\'s disease and vascular dementia.
Conclusion
In this nationwide cohort of AF patients treated with catheter ablation or medical therapy, ablation was associated with decreased dementia risk. This relationship was evident after censoring for stroke and adjusting for clinical confounders.

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

Eur Heart J: 05 Oct 2020; epub ahead of print
Kim D, Yang PS, Sung JH, Jang E, ... Lip GYH, Joung B
Eur Heart J: 05 Oct 2020; epub ahead of print | PMID: 33022705
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Abstract

Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk.

Domanski MJ, Tian X, Wu CO, Reis JP, ... Lloyd-Jones DM, Fuster V
Background
Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.
Objectives
Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.
Methods
This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.
Results
During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).
Conclusions
Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Sep 2020; 76:1507-1516
Domanski MJ, Tian X, Wu CO, Reis JP, ... Lloyd-Jones DM, Fuster V
J Am Coll Cardiol: 28 Sep 2020; 76:1507-1516 | PMID: 32972526
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Abstract

Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study.

Basso C, Leone O, Rizzo S, De Gaspari M, ... Maleszewski JJ, Stone JR
Aims
Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described.
Methods and results
In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.
Conclusions
In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases. Other forms of myocardial injury are also present in these patients. The macrophage infiltration may reflect underlying diseases rather than COVID-19.

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

Eur Heart J: 23 Sep 2020; epub ahead of print
Basso C, Leone O, Rizzo S, De Gaspari M, ... Maleszewski JJ, Stone JR
Eur Heart J: 23 Sep 2020; epub ahead of print | PMID: 32968776
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Abstract

Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.

Dreyfus J, Flagiello M, Bazire B, Eggenspieler F, ... Obadia JF, Messika-Zeitoun D
Aims
The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation.
Methods and results
Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88].
Conclusion
Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.

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

Eur Heart J: 24 Sep 2020; epub ahead of print
Dreyfus J, Flagiello M, Bazire B, Eggenspieler F, ... Obadia JF, Messika-Zeitoun D
Eur Heart J: 24 Sep 2020; epub ahead of print | PMID: 32974668
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Abstract

Assessing left ventricular systolic function: from ejection fraction to strain analysis.

Halliday BP, Senior R, Pennell DJ

The measurement of left ventricular ejection fraction (LVEF) is a ubiquitous component of imaging studies used to evaluate patients with cardiac conditions and acts as an arbiter for many management decisions. This follows early trials investigating heart failure therapies which used a binary LVEF cut-off to select patients with the worst prognosis, who may gain the most benefit. Forty years on, the cardiac disease landscape has changed. Left ventricular ejection fraction is now a poor indicator of prognosis for many heart failure patients; specifically, for the half of patients with heart failure and truly preserved ejection fraction (HF-PEF). It is also recognized that LVEF may remain normal amongst patients with valvular heart disease who have significant myocardial dysfunction. This emphasizes the importance of the interaction between LVEF and left ventricular geometry. Guidelines based on LVEF may therefore miss a proportion of patients who would benefit from early intervention to prevent further myocardial decompensation and future adverse outcomes. The assessment of myocardial strain, or intrinsic deformation, holds promise to improve these issues. The measurement of global longitudinal strain (GLS) has consistently been shown to improve the risk stratification of patients with heart failure and identify patients with valvular heart disease who have myocardial decompensation despite preserved LVEF and an increased risk of adverse outcomes. To complete the integration of GLS into routine clinical practice, further studies are required to confirm that such approaches improve therapy selection and accordingly, the outcome for patients.

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

Eur Heart J: 24 Sep 2020; epub ahead of print
Halliday BP, Senior R, Pennell DJ
Eur Heart J: 24 Sep 2020; epub ahead of print | PMID: 32974648
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Abstract

Impact of Peri-Procedural Myocardial Infarction on Outcomes After Revascularization.

Hara H, Serruys PW, Takahashi K, Kawashima H, ... Mack MJ,
Background
Numerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist.
Objectives
The purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial.
Methods
PMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression.
Results
PMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these \"enzyme-driven events\" on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year.
Conclusions
The rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Oct 2020; 76:1622-1639
Hara H, Serruys PW, Takahashi K, Kawashima H, ... Mack MJ,
J Am Coll Cardiol: 05 Oct 2020; 76:1622-1639 | PMID: 33004127
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Abstract

Physician Work Hours and the Gender Pay Gap - Evidence from Primary Care.

Ganguli I, Sheridan B, Gray J, Chernew M, Rosenthal MB, Neprash H
Background
The gender gap in physician pay is often attributed in part to women working fewer hours than men, but evidence to date is limited by self-report and a lack of detail regarding clinical revenue and gender differences in practice style.
Methods
Using national all-payer claims and data from electronic health records, we conducted a cross-sectional analysis of 24.4 million primary care office visits in 2017 and performed comparisons between female and male physicians in the same practices. Our primary independent variable was physician gender; outcomes included visit revenue, visit counts, days worked, and observed visit time (interval between the initiation and the termination of a visit). We created multivariable regression models at the year, day, and visit level after adjustment for characteristics of the primary care physicians (PCPs), patients, and types of visit and for practice fixed effects.
Results
In 2017, female PCPs generated 10.9% less revenue from office visits than their male counterparts (-$39,143.2; 95% confidence interval [CI], -53,523.0 to -24,763.4) and conducted 10.8% fewer visits (-330.5 visits; 95% CI, -406.6 to -254.3) over 2.6% fewer clinical days (-5.3 days; 95% CI, -7.7 to -3.0), after adjustment for age, academic degree, specialty, and number of sessions worked per week, yet spent 2.6% more observed time in visits that year than their male counterparts (1201.3 minutes; 95% CI, 184.7 to 2218.0). Per visit, after adjustment for PCP, patient, and visit characteristics, female PCPs generated equal revenue but spent 15.7% more time with a patient (2.4 minutes; 95% CI, 2.1 to 2.6). These results were consistent in subgroup analyses according to the gender and health status of the patients and the type and complexity of the visits.
Conclusions
Female PCPs generated less visit revenue than male colleagues in the same practices owing to a lower volume of visits, yet spent more time in direct patient care per visit, per day, and per year. (Funded in part by the Robert Wood Johnson Foundation.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 30 Sep 2020; 383:1349-1357
Ganguli I, Sheridan B, Gray J, Chernew M, Rosenthal MB, Neprash H
N Engl J Med: 30 Sep 2020; 383:1349-1357 | PMID: 32997909
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Abstract

HPV Vaccination and the Risk of Invasive Cervical Cancer.

Lei J, Ploner A, Elfström KM, Wang J, ... Dillner J, Sparén P
Background
The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking.
Methods
We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother\'s country of birth, and maternal disease history.
Results
During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years.
Conclusions
Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 30 Sep 2020; 383:1340-1348
Lei J, Ploner A, Elfström KM, Wang J, ... Dillner J, Sparén P
N Engl J Med: 30 Sep 2020; 383:1340-1348 | PMID: 32997908
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Abstract

Machine Learning Improves Cardiovascular Risk Definition for Young, Asymptomatic Individuals.

Sánchez-Cabo F, Rossello X, Fuster V, Benito F, ... García-Ruiz JM, Lara-Pezzi E
Background
Clinical practice guidelines recommend assessment of subclinical atherosclerosis using imaging techniques in individuals with intermediate atherosclerotic cardiovascular risk according to standard risk prediction tools.
Objectives
The purpose of this study was to develop a machine-learning model based on routine, quantitative, and easily measured variables to predict the presence and extent of subclinical atherosclerosis (SA) in young, asymptomatic individuals. The risk of having SA estimated by this model could be used to refine risk estimation and optimize the use of imaging for risk assessment.
Methods
The Elastic Net (EN) model was built to predict SA extent, defined by a combined metric of the coronary artery calcification score and 2-dimensional vascular ultrasound. The performance of the model for the prediction of SA extension and progression was compared with traditional risk scores of cardiovascular disease (CVD). An external independent cohort was used for validation.
Results
EN-PESA (Progression of Early Subclinical Atherosclerosis) yielded a c-statistic of 0.88 for the prediction of generalized subclinical atherosclerosis. Moreover, EN-PESA was found to be a predictor of 3-year progression independent of the baseline extension of SA. EN-PESA assigned an intermediate to high cardiovascular risk to 40.1% (n = 1,411) of the PESA individuals, a significantly larger number than atherosclerotic CVD (n = 267) and SCORE (Systematic Coronary Risk Evaluation) (n = 507) risk scores. In total, 86.8% of the individuals with an increased risk based on EN-PESA presented signs of SA at baseline or a significant progression of SA over 3 years.
Conclusions
The EN-PESA model uses age, systolic blood pressure, and 10 commonly used blood/urine tests and dietary intake values to identify young, asymptomatic individuals with an increased risk of CVD based on their extension and progression of SA. These individuals are likely to benefit from imaging tests or pharmacological treatment. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Oct 2020; 76:1674-1685
Sánchez-Cabo F, Rossello X, Fuster V, Benito F, ... García-Ruiz JM, Lara-Pezzi E
J Am Coll Cardiol: 05 Oct 2020; 76:1674-1685 | PMID: 33004133
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Abstract

Development and validation of two SCORE-based cardiovascular risk prediction models for Eastern Europe: a multicohort study.

Tillmann T, Läll K, Dukes O, Veronesi G, ... Kivimäki M, Bobak M
Aims
Cardiovascular disease (CVD) risk prediction models are used in Western European countries, but less so in Eastern European countries where rates of CVD can be two to four times higher. We recalibrated the SCORE prediction model for three Eastern European countries and evaluated the impact of adding seven behavioural and psychosocial risk factors to the model.
Methods and results
We developed and validated models using data from the prospective HAPIEE cohort study with 14 598 participants from Russia, Poland, and the Czech Republic (derivation cohort, median follow-up 7.2 years, 338 fatal CVD cases) and Estonian Biobank data with 4632 participants (validation cohort, median follow-up 8.3 years, 91 fatal CVD cases). The first model (recalibrated SCORE) used the same risk factors as in the SCORE model. The second model (HAPIEE SCORE) added education, employment, marital status, depression, body mass index, physical inactivity, and antihypertensive use. Discrimination of the original SCORE model (C-statistic 0.78 in the derivation and 0.83 in the validation cohorts) was improved in recalibrated SCORE (0.82 and 0.85) and HAPIEE SCORE (0.84 and 0.87) models. After dichotomizing risk at the clinically meaningful threshold of 5%, and when comparing the final HAPIEE SCORE model against the original SCORE model, the net reclassification improvement was 0.07 [95% confidence interval (CI) 0.02-0.11] in the derivation cohort and 0.14 (95% CI 0.04-0.25) in the validation cohort.
Conclusion
Our recalibrated SCORE may be more appropriate than the conventional SCORE for some Eastern European populations. The addition of seven quick, non-invasive, and cheap predictors further improved prediction accuracy.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 03 Oct 2020; epub ahead of print
Tillmann T, Läll K, Dukes O, Veronesi G, ... Kivimäki M, Bobak M
Eur Heart J: 03 Oct 2020; epub ahead of print | PMID: 33011775
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Abstract

Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake.

O\'Donnell M, Mente A, Alderman MH, Brady AJB, ... Yancy C, Yusuf S

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world\'s population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

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

Eur Heart J: 03 Oct 2020; epub ahead of print
O'Donnell M, Mente A, Alderman MH, Brady AJB, ... Yancy C, Yusuf S
Eur Heart J: 03 Oct 2020; epub ahead of print | PMID: 33011774
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Abstract

Association of Bioprosthetic Aortic Valve Leaflet Calcification on Hemodynamic and Clinical Outcomes.

Zhang B, Salaun E, Côté N, Wu Y, ... Pibarot P, Clavel MA
Background
The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR).
Objectives
The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex.
Methods
From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention.
Results
There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p < 0.001). The AVCd threshold combined with an MG progression threshold of 10 mm Hg amplified the stratification of patients at risk (log-rank, p < 0.001). The addition of AVCd threshold into the prediction model including traditional risk factors improved outcome prediction (net classification improvement: 0.25, p = 0.04; likelihood ratio test, p < 0.001).
Conclusions
Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Oct 2020; 76:1737-1748
Zhang B, Salaun E, Côté N, Wu Y, ... Pibarot P, Clavel MA
J Am Coll Cardiol: 12 Oct 2020; 76:1737-1748 | PMID: 33032735
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Impact:
Abstract

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.

, Horby P, Mafham M, Linsell L, ... Haynes R, Landray MJ
Background
Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.
Methods
In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.
Results
The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.
Conclusions
Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 07 Oct 2020; epub ahead of print
, Horby P, Mafham M, Linsell L, ... Haynes R, Landray MJ
N Engl J Med: 07 Oct 2020; epub ahead of print | PMID: 33031652
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Impact:
Abstract

Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

Juul Rasmussen I, Rasmussen KL, Nordestgaard BG, Tybjærg-Hansen A, Frikke-Schmidt R
Aims
Dementia is a major global challenge for health and social care in aging populations. A third of all dementia may be preventable due to cardiovascular risk factors. Intensive multi-domain intervention trials targeting primarily cardiovascular risk factors show improved cognitive function in people at risk. Such interventions will, however, be expensive to implement in all individuals at risk and will represent unrealistic economic tasks for most societies. Therefore, a risk score identifying high-risk individuals is warranted.
Methods and results
In 61 664 individuals from two prospective cohorts of the Danish general population, we generated 10-year absolute risk scores for all-cause dementia from cardiovascular risk factors and genetics. In both sexes, 10-year absolute risk of all-cause dementia increased with increasing age, number of apolipoprotein E (APOE) ɛ4 alleles, number of genome-wide association studies (GWAS) risk alleles, and cardiovascular risk factors. The highest 10-year absolute risks of all-cause dementia seen in smoking women with diabetes, low education, APOE ɛ44 genotype, and 22-31 GWAS risk alleles were 6%, 23%, 48%, and 66% in those aged 50-59, 60-69, 70-79, and 80-100, respectively. Corresponding values for men were 5%, 19%, 42%, and 60%, respectively.
Conclusion
Ten-year absolute risk of all-cause dementia increased with age, APOE ɛ4 alleles, GWAS risk alleles, diabetes, low education, and smoking in both women and men. Ten-year absolute risk charts for dementia will facilitate identification of high-risk individuals, those who likely will benefit the most from an early intervention against cardiovascular risk factors.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 05 Oct 2020; epub ahead of print
Juul Rasmussen I, Rasmussen KL, Nordestgaard BG, Tybjærg-Hansen A, Frikke-Schmidt R
Eur Heart J: 05 Oct 2020; epub ahead of print | PMID: 33022702
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Impact:
Abstract

Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk.

Corpataux N, Spirito A, Gragnano F, Vaisnora L, ... Windecker S, Valgimigli M
Aims
To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and <4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria.
Methods and results
All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals.
Conclusion
All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.

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

Eur Heart J: 07 Oct 2020; epub ahead of print
Corpataux N, Spirito A, Gragnano F, Vaisnora L, ... Windecker S, Valgimigli M
Eur Heart J: 07 Oct 2020; epub ahead of print | PMID: 33029615
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Impact:
Abstract

Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry.

DeFilippis EM, Collins BL, Singh A, Biery DW, ... Bhatt DL, Blankstein R
Aims
There are sex differences in presentation, treatment, and outcomes of myocardial infarction (MI) but less is known about these differences in a younger patient population. The objective of this study was to investigate sex differences among individuals who experience their first MI at a young age.
Methods and results
Consecutive patients presenting to two large academic medical centres with a Type 1 MI at ≤50 years of age between 2000 and 2016 were included. Cause of death was adjudicated using electronic health records and death certificates. In total, 2097 individuals (404 female, 19%) had an MI (mean age 44 ± 5.1 years, 73% white). Risk factor profiles were similar between men and women, although women were more likely to have diabetes (23.7% vs. 18.9%, P = 0.028). Women were less likely to undergo invasive coronary angiography (93.5% vs. 96.7%, P = 0.003) and coronary revascularization (82.1% vs. 92.6%, P < 0.001). Women were significantly more likely to have MI with non-obstructive coronary disease on angiography (10.2% vs. 4.2%, P < 0.001). They were less likely to be discharged with aspirin (92.2% vs. 95.0%, P = 0.027), beta-blockers (86.6% vs. 90.3%, P = 0.033), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53.4% vs. 63.7%, P < 0.001), and statins (82.4% vs. 88.4%, P < 0.001). There was no significant difference in in-hospital mortality; however, women who survived to hospital discharge experienced a higher all-cause mortality rate (adjusted HR = 1.63, P = 0.01; median follow-up 11.2 years) with no significant difference in cardiovascular mortality (adjusted HR = 1.14, P = 0.61).
Conclusions
Women who experienced their first MI under the age of 50 were less likely to undergo coronary revascularization or be treated with guideline-directed medical therapies. Women who survived hospitalization experienced similar cardiovascular mortality with significantly higher all-cause mortality than men. A better understanding of the mechanisms underlying these differences is warranted.

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

Eur Heart J: 12 Oct 2020; epub ahead of print
DeFilippis EM, Collins BL, Singh A, Biery DW, ... Bhatt DL, Blankstein R
Eur Heart J: 12 Oct 2020; epub ahead of print | PMID: 33049774
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Impact:
Abstract

Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial.

Szarek M, Bittner VA, Aylward P, Baccara-Dinet M, ... Schwartz GG,
Aims
Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.
Methods and results
Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.
Conclusion
Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 13 Oct 2020; epub ahead of print
Szarek M, Bittner VA, Aylward P, Baccara-Dinet M, ... Schwartz GG,
Eur Heart J: 13 Oct 2020; epub ahead of print | PMID: 33051646
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Impact:
Abstract

Incidence, Characteristics, Predictors, and Outcomes of Surgical Explantation After Transcatheter Aortic Valve Replacement.

Hirji SA, Percy ED, McGurk S, Malarczyk A, ... Shah PB, Kaneko T
Background
Currently, there is a paucity of information on surgical explantation after transcatheter aortic valve replacement (TAVR).
Objectives
The purpose of this study was to examine the incidence, patient characteristics, predictors, and outcomes of surgical explantation after TAVR using a population-based, nationally representative database.
Methods
We analyzed the Medicare Provider profile to include all U.S. patients undergoing TAVR from 2012 to 2017. Time to surgical explant was calculated from the index TAVR discharge to surgical explantation. Post-operative survival was assessed using time-dependent Cox proportional hazard regression analysis and landmark analysis.
Results
The incidence of surgical explantation was 0.2% (227 of 132,633 patients), and was 0.28% and 0.14% in the early and newer TAVR era, respectively. The median time to surgical explant was 212 days, whereas 8.8% and 70.9% underwent surgical explantation within 30 days and 1 year, respectively. The primary indication for reintervention was bioprosthetic failure (79.3%). Compared with the no-explant cohort, the explant cohort was significantly younger (mean age 73.7 years vs. 81.7 years), with a lower prevalence of heart failure (55.9% vs. 65.8%) but more likely a lower-risk profile cohort (15% vs. 2.4%; all p < 0.05). The 30-day and 1-year mortality rates were 13.2% and 22.9%, respectively, and did not vary by either time to surgical explant or TAVR era, or between patients with versus without endocarditis (all p > 0.05). The time-dependent Cox regression analysis demonstrated a higher mortality in those with surgical explantation (hazard ratio: 4.03 vs. no-explant group; 95% confidence interval: 1.81 to 8.98). Indication, time-to-surgical-explant, and year of surgical explantation were not associated with worse post-explantation survival (all p > 0.05).
Conclusions
The present study provides updated evidence on the incidence, timing, and outcomes of surgical explantation of a TAVR prosthesis. Although the overall incidence was low, short-term mortality was high. These findings stress the importance of future mechanistic studies on TAVR explantation and may have implications on lifetime management of aortic stenosis, particularly in younger patients.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Oct 2020; 76:1848-1859
Hirji SA, Percy ED, McGurk S, Malarczyk A, ... Shah PB, Kaneko T
J Am Coll Cardiol: 19 Oct 2020; 76:1848-1859 | PMID: 33059830
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Impact:
Abstract

Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial.

Pibarot P, Ternacle J, Jaber WA, Salaun E, ... Hahn RT,
Background
It is unknown whether transcatheter valves will have similar durability as surgical bioprosthetic valves. Definitions of structural valve deterioration (SVD), based on valve related reintervention or death, underestimate the incidence of SVD.
Objectives
This study sought to determine and compare the 5-year incidence of SVD, using new standardized definitions based on echocardiographic follow-up of valve function, in intermediate-risk patients with severe aortic stenosis given transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and registry.
Methods
In the PARTNER 2A trial, patients were randomly assigned to receive either TAVR with the SAPIEN XT or SAVR, whereas in the SAPIEN 3 registry, patients were assigned to TAVR with the SAPIEN 3. The primary endpoint was the incidence of SVD, that is, the composite of SVD-related hemodynamic valve deterioration during echocardiographic follow-up and/or SVD-related bioprosthetic valve failure (BVF) at 5 years.
Results
Compared with SAVR, the SAPIEN-XT TAVR cohort had a significantly higher 5-year exposure adjusted incidence rates (per 100 patient-years) of SVD (1.61 ± 0.24% vs. 0.63 ± 0.16%), SVD-related BVF (0.58 ± 0.14% vs. 0.12 ± 0.07%), and all-cause (structural or nonstructural) BVF (0.81 ± 0.16% vs. 0.27 ± 0.10%) (p ≤ 0.01 for all). The 5-year rates of SVD (0.68 ± 0.18% vs. 0.60 ± 0.17%; p = 0.71), SVD-related BVF (0.29 ± 0.12% vs. 0.14 ± 0.08%; p = 0.25), and all-cause BVF (0.60 ± 0.15% vs. 0.32 ± 0.11%; p = 0.32) in SAPIEN 3 TAVR were not significantly different to a propensity score matched SAVR cohort. The 5-year rates of SVD and SVD-related BVF were significantly lower in SAPIEN 3 versus SAPIEN XT TAVR matched cohorts.
Conclusions
Compared with SAVR, the second-generation SAPIEN XT balloon-expandable valve has a higher 5-year rate of SVD, whereas the third-generation SAPIEN 3 has a rate of SVD that was not different from SAVR. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII A [PARTNERII A]; NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Oct 2020; 76:1830-1843
Pibarot P, Ternacle J, Jaber WA, Salaun E, ... Hahn RT,
J Am Coll Cardiol: 19 Oct 2020; 76:1830-1843 | PMID: 33059828
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Impact:
Abstract

Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study.

Leistner DM, Kränkel N, Meteva D, Abdelwahed YS, ... Libby P, Landmesser U
Aims 
Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping.
Methods and results 
The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS.
Conclusions 
The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC.
Trial registration
The study was registered at clinicalTrials.gov (NCT03129503).

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

Eur Heart J: 19 Oct 2020; epub ahead of print
Leistner DM, Kränkel N, Meteva D, Abdelwahed YS, ... Libby P, Landmesser U
Eur Heart J: 19 Oct 2020; epub ahead of print | PMID: 33080003
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Impact:
Abstract

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

Baber U, Dangas G, Angiolillo DJ, Cohen DJ, ... Gibson CM, Mehran R
Aims 
The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Methods and results 
We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96).
Conclusion 
Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS.
Trial registration
Clinicaltrials.gov identifier: NCT02270242.

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

Eur Heart J: 30 Sep 2020; 41:3533-3545
Baber U, Dangas G, Angiolillo DJ, Cohen DJ, ... Gibson CM, Mehran R
Eur Heart J: 30 Sep 2020; 41:3533-3545 | PMID: 33085967
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Impact:
Abstract

A Randomized Pilot Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography for Post-Cardiac Arrest Patients Without ST-Segment Elevation: The PEARL Study.

Kern KB, Radsel P, Jentzer JC, Seder DB, ... Hsu CH, Noc M

The benefit of emergent coronary angiography after resuscitation from out-of-hospital cardiac arrest (OHCA) is uncertain for patients without ST-segment elevation (STE). The aim of this randomized trial was to evaluate the efficacy and safety of early coronary angiography and to determine the prevalence of acute coronary occlusion in resuscitated OHCA patients without STE.Adult (>18 years) comatose survivors without STE after resuscitation from OHCA were prospectively randomized in a 1:1 fashion under exception to informed consent regulations to early coronary angiography versus no early coronary angiography in this multi-center study. Early angiography was defined as ≤ 120 minutes from arrival at the percutaneous coronary intervention capable facility. The primary endpoint was a composite of efficacy and safety measures, including efficacy parameters of survival to discharge, favorable neurological status at discharge (Cerebral Performance Category ≤ 2), echocardiographic measures of left ventricular ejection fraction >50% and a normal regional wall motion score of 16 within 24 hours of admission. Adverse events included re-arrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension (systolic arterial pressure ≤90 mmHg), and pneumonia. Secondary endpoints included the incidence of culprit vessels with acute occlusion.The study was prematurely terminated before enrolling the target number of patients. A total of 99 patients were enrolled from 2015-2018, including 75 with initially shockable rhythms. Forty-nine patients were randomized to early coronary angiography. The primary endpoint of efficacy and safety was not different between the two groups (55.1% vs 46.0%; p=0.64). Early coronary angiography was not associated with any significant increase in survival (55.1% vs 48.0%; p=0.55 or adverse events (26.5% vs 26.0%; p=1.00). Early coronary angiography revealed a culprit vessel in 47%, with a total of 14% of patients undergoing early coronary angiography having an acutely occluded culprit coronary artery.This underpowered study, when considered together with previous clinical trials, does not support early coronary angiography for comatose survivors of cardiac arrest without ST elevation. Whether early detection of occluded potential culprit arteries leads to interventions that improve outcomes requires additional study.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02387398.



Circulation: 27 Sep 2020; epub ahead of print
Kern KB, Radsel P, Jentzer JC, Seder DB, ... Hsu CH, Noc M
Circulation: 27 Sep 2020; epub ahead of print | PMID: 32985249
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Impact:
Abstract

P-COSCA (Pediatric Core Outcome Set for Cardiac Arrest) in Children: An Advisory Statement From the International Liaison Committee on Resuscitation.

Topjian AA, Scholefield BR, Pinto NP, Fink EL, ... Hazinski MF, Slomine BS

Studies of pediatric cardiac arrest use inconsistent outcomes, including return of spontaneous circulation and short-term survival, and basic assessments of functional and neurological status. In 2018, the International Liaison Committee on Resuscitation sponsored the COSCA initiative (Core Outcome Set After Cardiac Arrest) to improve consistency in reported outcomes of clinical trials of adult cardiac arrest survivors and supported this P-COSCA initiative (Pediatric COSCA). The P-COSCA Steering Committee generated a list of potential survival, life impact, and economic impact outcomes and assessment time points that were prioritized by a multidisciplinary group of healthcare providers, researchers, and parents/caregivers of children who survived cardiac arrest. Then expert panel discussions achieved consensus on the core outcomes, the methods to measure those core outcomes, and the timing of the measurements. The P-COSCA includes assessment of survival, brain function, cognitive function, physical function, and basic daily life skills. Survival and brain function are assessed at discharge or 30 days (or both if possible) and between 6 and 12 months after arrest. Cognitive function, physical function, and basic daily life skills are assessed between 6 and 12 months after cardiac arrest. Because many children have prearrest comorbidities, the P-COSCA also includes documentation of baseline (ie, prearrest) brain function and calculation of changes after cardiac arrest. Supplementary outcomes of survival, brain function, cognitive function, physical function, and basic daily life skills are assessed at 3 months and beyond 1 year after cardiac arrest if resources are available.



Circulation: 23 Sep 2020:CIR0000000000000911; epub ahead of print
Topjian AA, Scholefield BR, Pinto NP, Fink EL, ... Hazinski MF, Slomine BS
Circulation: 23 Sep 2020:CIR0000000000000911; epub ahead of print | PMID: 32967446
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Impact:
Abstract

Cardiorenal Protection With the Newer Antidiabetic Agents in Patients With Diabetes and Chronic Kidney Disease: A Scientific Statement From the American Heart Association.

Rangaswami J, Bhalla V, de Boer IH, Staruschenko A, ... McCullough PA,

Chronic kidney disease (CKD) with type 2 diabetes (T2D) is a major public health problem, resulting in significant cardiovascular and kidney adverse outcomes worldwide. Despite the widespread use of standard-of-care therapies for CKD with T2D over the past few decades, rates of progression to end-stage kidney disease remain high with no beneficial impact on its accompanying burden of cardiovascular disease. The advent of the newer classes of antihyperglycemic agents, including SGLT2 (sodium glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide-1) receptor agonists, has changed the landscape of therapeutic options for patients with CKD with T2D, with demonstration of significant reductions in cardiovascular adverse events and progression to end-stage kidney disease. Several potential mechanisms exist through which these beneficial effects are achieved in both drug classes, which may be independent of their antihyperglycemic effects. This scientific statement summarizes the current literature on the cardiorenal protective effects with SGLT2 inhibitors and GLP-1 receptor agonists in patients with CKD and T2D. It reviews potential mechanistic pathways that may drive these benefits and summarizes the literature on adverse effects in patients with CKD and T2D at risk for or with established cardiovascular disease. Last, it provides practical guidance on a proposed collaborative care model bridging cardiologists, nephrologists, endocrinologists, and primary care physicians to facilitate the prompt and appropriate integration of these therapeutic classes in the management of patients with T2D and CKD.



Circulation: 27 Sep 2020:CIR0000000000000920; epub ahead of print
Rangaswami J, Bhalla V, de Boer IH, Staruschenko A, ... McCullough PA,
Circulation: 27 Sep 2020:CIR0000000000000920; epub ahead of print | PMID: 32981345
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Abstract

Postoperative Atrial Fibrillation and Long-Term Risk of Stroke After Isolated Coronary Artery Bypass Graft Surgery.

Benedetto U, Gaudino MF, Dimagli A, Gerry S, ... Taggart DP,
Background
Postoperative atrial fibrillation (pAF) after coronary artery bypass grafting is a common complication. Whether pAF is associated with an increased risk of cerebrovascular accident (CVA) remains uncertain. We investigated the association between pAF and long-term risk of CVA by performing a post hoc analysis of 10-year outcomes of the ART (Arterial Revascularization Trial).
Methods
For the present analysis, among patients enrolled in the ART (n=3102), we excluded those who did not undergo surgery (n=25), had a history of atrial fibrillation (n=45), or had no information on the incidence of pAF (n=9). The final population consisted of 3023 patients, of whom 734 (24.3%) developed pAF with the remaining 2289 maintaining sinus rhythm. Competing risk and Cox regression analyses were used to investigate the association between pAF and the risk of CVA.
Results
At 10 years, the cumulative incidence of CVA was 6.3% (4.6%-8.1%) versus 3.7% (2.9%-4.5%) in patients with pAF and sinus rhythm, respectively. pAF was an independent predictor of CVA at 10 years (hazard ratio, 1.53 [95% CI, 1.06-2.23]; =0.025) even when CVAs that occurred during the index admission were excluded from the analysis (hazard ratio, 1.47 [95% 1.02-2.11]; =0.04).
Conclusions
Patients with pAF after coronary artery bypass grafting are at higher risk of CVA. These findings challenge the notion that pAF is a benign complication.



Circulation: 05 Oct 2020; 142:1320-1329
Benedetto U, Gaudino MF, Dimagli A, Gerry S, ... Taggart DP,
Circulation: 05 Oct 2020; 142:1320-1329 | PMID: 33017213
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Abstract

Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque.

Drobni ZD, Alvi RM, Taron J, Zafar A, ... Hoffmann U, Neilan TG

Immune checkpoint inhibitors (ICI) treat an expanding range of cancers. Consistent basic data suggest that these same checkpoints are critical negative regulators of atherosclerosis. Therefore, our objectives were to test whether ICIs were associated with accelerated atherosclerosis and a higher risk of atherosclerosis-related cardiovascular events.The study was situated in a single academic medical center. The primary analysis evaluated whether exposure to an ICI was associated with atherosclerotic cardiovascular events in 2842 patients and 2842 controls, matched by age, a history of cardiovascular events and cancer type. In a second design, a case-crossover analysis was performed with an \"at-risk period\" defined as the two-year period after and the \"control period\" as the two-year prior to treatment. The primary outcome was a composite of atherosclerotic cardiovascular events (myocardial infarction, coronary revascularization and ischemic stroke). Secondary outcomes included the individual components of the primary outcome. Additionally, in an imaging sub-study (n=40), the rate of atherosclerotic plaque progression was compared from before and after starting an ICI. All study measures and outcomes were blindly adjudicated.In the matched cohort study, there was a 3-fold higher risk for cardiovascular events after starting an ICI (HR, 3.3 [95% CI, 2.0-5.5]; <0.001). There was a similar increase in each of the individual components of the primary outcome. In the case-crossover, there was also an increase in cardiovascular events from 1.37 to 6.55 per 100 person-years at two years (adjusted HR, 4.8 [95% CI, 3.5-6.5]; <0.001). In the imaging study, the rate of progression of total aortic plaque volume was >3-fold higher with ICIs (from 2.1%/year pre-to 6.7%/year post). This association between ICI use and increased atherosclerotic plaque progression was attenuated with concomitant use of statins or corticosteroids.Cardiovascular events were higher after initiation of ICIs, potentially mediated by accelerated progression of atherosclerosis. Optimization of cardiovascular risk factors and increased awareness of cardiovascular risk, prior to, during and after treatment, should be considered among patients on an ICI.



Circulation: 01 Oct 2020; epub ahead of print
Drobni ZD, Alvi RM, Taron J, Zafar A, ... Hoffmann U, Neilan TG
Circulation: 01 Oct 2020; epub ahead of print | PMID: 33003973
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Abstract

Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients with Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial.

Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, ... McGuire DK,

In patients with type 2 diabetes mellitus (T2DM), sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes.VERTIS CV, a double-blind, placebo-controlled trial, randomized patients with T2DM and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF/CV death, overall and stratified by prespecified characteristics. Cox proportional hazard modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF/CV death events.8246 patients were randomized to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pre-trial ejection fraction (EF) available, including n=959 with EF≤45%. Ertugliflozin did not significantly reduce first HHF/CV death (HR, 0.88; 95% CI, 0.75, 1.03). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70; 95% CI, 0.54, 0.90; =0.006). Prior HF did not modify this effect (HF: HR, 0.63; 95% CI, 0.44, 0.90; no HF: HR, 0.79; 95% CI, 0.54, 1.15;interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF≤45% vs preserved EF>45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF≤45% (HR, 0.48; 95% CI, 0.30, 0.76) versus EF>45% (HR, 0.86; 95% CI, 0.58, 1.29). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in three populations with baseline eGFR<60mL/min/1.73m, albuminuria, and diuretic use (eachinteraction<0.05). Ertugliflozin reduced total events of HHF (RR, 0.70; 95% CI, 0.56, 0.87) and total HHF/CV death (RR, 0.83; 95% CI, 0.72, 0.96).In patients with T2DM with or without baseline HF, ertugliflozin reduced risk for first and total HHF and total HHF/CV death, adding further support for the use of SGLT2 inhibitors in primary and secondary prevention of HHF.URL: https://clinicaltrials.gov Unique Identifier: NCT01986881.



Circulation: 06 Oct 2020; epub ahead of print
Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, ... McGuire DK,
Circulation: 06 Oct 2020; epub ahead of print | PMID: 33026243
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Abstract

Progress Toward Cardiac Xenotransplantation.

Pierson RN, Fishman JA, Lewis GD, D\'Alessandro DA, ... Madsen JC, Azimzadeh AM

Consistent survival of life-supporting pig heart xenograft recipients beyond 90 days was recently reported using genetically modified pigs and a clinically applicable drug treatment regimen. If this remarkable achievement proves reproducible, published benchmarks for clinical translation of cardiac xenografts appear to be within reach. Key mechanistic insights are summarized here that informed recent pig design and therapeutic choices, which together appear likely to enable early clinical translation.



Circulation: 05 Oct 2020; 142:1389-1398
Pierson RN, Fishman JA, Lewis GD, D'Alessandro DA, ... Madsen JC, Azimzadeh AM
Circulation: 05 Oct 2020; 142:1389-1398 | PMID: 33017208
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Abstract

Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator.

Paulsen MJ, Imbrie-Moore AM, Baiocchi M, Wang H, ... MacArthur JW, Woo YJ
Background
Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown.
Methods
Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey\'s correction.
Results
Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups.
Conclusions
In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.



Circulation: 05 Oct 2020; 142:1361-1373
Paulsen MJ, Imbrie-Moore AM, Baiocchi M, Wang H, ... MacArthur JW, Woo YJ
Circulation: 05 Oct 2020; 142:1361-1373 | PMID: 33017215
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Abstract

National Variation in Congenital Heart Surgery Outcomes.

Pasquali SK, Thibault D, O\'Brien SM, Jacobs JP, ... Backer CL, Mayer JE
Background
Optimal strategies to improve national congenital heart surgery outcomes and reduce variability across hospitals remain unclear. Many policy and quality improvement efforts have focused primarily on higher-risk patients and mortality alone. Improving our understanding of both morbidity and mortality and current variation across the spectrum of complexity would better inform future efforts.
Methods
Hospitals participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2014-2017) were included. Case mix-adjusted operative mortality, major complications, and postoperative length of stay were evaluated using Bayesian models. Hospital variation was quantified by the interdecile ratio (IDR, upper versus lower 10%) and 95% credible intervals (CrIs). Stratified analyses were performed by risk group (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery [STAT] category) and simulations evaluated the potential impact of reductions in variation.
Results
A total of 102 hospitals (n=84 407) were included, representing ≈85% of US congenital heart programs. STAT category 1 to 3 (lower risk) operations comprised 74% of cases. All outcomes varied significantly across hospitals: adjusted mortality by 3-fold (upper versus lower decile 5.0% versus 1.6%, IDR 3.1 [95% CrI 2.5-3.7]), mean length of stay by 1.8-fold (19.2 versus 10.5 days, IDR 1.8 [95% CrI 1.8-1.9]), and major complications by >3-fold (23.5% versus 7.0%, IDR 3.4 [95% CrI 3.0-3.8]). The degree of variation was similar or greater for low- versus high-risk cases across outcomes, eg, ≈3-fold mortality variation across hospitals for STAT 1 to 3 (IDR 3.0 [95% CrI 2.1-4.2]) and STAT 4 or 5 (IDR 3.1 [95% CrI 2.4-3.9]) cases. High-volume hospitals had less variability across outcomes and risk categories. Simulations suggested potential reductions in deaths (n=282), major complications (n=1539), and length of stay (101 183 days) over the 4-year study period if all hospitals were to perform at the current median or better, with 37% to 60% of the improvement related to the STAT 1 to 3 (lower risk) group across outcomes.
Conclusions
We demonstrate significant hospital variation in morbidity and mortality after congenital heart surgery. Contrary to traditional thinking, a substantial portion of potential improvements that could be realized on a national scale were related to variability among lower-risk cases. These findings suggest modifications to our current approaches to optimize care and outcomes in this population are needed.



Circulation: 05 Oct 2020; 142:1351-1360
Pasquali SK, Thibault D, O'Brien SM, Jacobs JP, ... Backer CL, Mayer JE
Circulation: 05 Oct 2020; 142:1351-1360 | PMID: 33017214
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Abstract

Randomized, Controlled Trial Comparing Mitral Valve Repair With Leaflet Resection Versus Leaflet Preservation on Functional Mitral Stenosis: The CAMRA CardioLink-2 Study.

Chan V, Mazer CD, Ali FM, Quan A, ... Leong-Poi H, Verma S
Background
Equipoise exists between the use of leaflet resection and preservation for surgical repair of mitral regurgitation caused by prolapse. We therefore performed a randomized, controlled trial comparing these 2 techniques, particularly in regard to functional mitral stenosis.
Methods
One hundred four patients with degenerative mitral regurgitation surgically amenable to either leaflet resection or preservation were randomized at 7 specialized cardiac surgical centers. Exclusion criteria included anterior leaflet or commissural prolapse, as well as a mixed cause for mitral valve disease. Using previous data, we determined that a sample size of 88 subjects would provide 90% power to detect a 5-mm Hg difference in mean mitral valve gradient at peak exercise, assuming an SD of 6.7 mm with a 2-sided test with α=5% and 10% patient attrition. The primary end point was the mean mitral gradient at peak exercise 12 months after repair.
Results
Patient age, proportion who were female, and Society of Thoracic Surgeons risk score were 63.9±10.4 years, 19%, and 1.4±2.8% for those who were assigned to leaflet resection (n=54), and 66.3±10.8 years, 16%, and 1.9±2.6% for those who underwent leaflet preservation (n=50). There were no perioperative deaths or conversions to replacement. At 12 months, moderate mitral regurgitation was observed in 3 subjects in the leaflet resection group and 2 in the leaflet preservation group. The mean transmitral gradient at 12 months during peak exercise was 9.1±5.2 mm Hg after leaflet resection and 8.3±3.3 mm Hg after leaflet preservation (=0.43). The participants had similar resting peak (8.3±4.4 mm Hg versus 8.4±2.6 mm Hg; =0.96) and mean resting (3.2±1.9 mm Hg versus 3.1±1.1 mm Hg; =0.67) mitral gradients after leaflet resection and leaflet preservation, respectively. The 6-minute walking distance was 451±147 m for those in the leaflet resection versus 481±95 m for the leaflet preservation group (=0.27).
Conclusions
In this adequately powered randomized trial, repair of mitral prolapse with either leaflet resection or leaflet preservation was associated with similar transmitral gradients at peak exercise at 12 months postoperatively. These data do not support the hypothesis that a strategy of leaflet resection (versus preservation) is associated with a risk of functional mitral stenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT02552771.



Circulation: 05 Oct 2020; 142:1342-1350
Chan V, Mazer CD, Ali FM, Quan A, ... Leong-Poi H, Verma S
Circulation: 05 Oct 2020; 142:1342-1350 | PMID: 33017212
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Abstract

Treatment of Masked Hypertension with a Chinese Herbal Formula: A Randomized, Placebo-Controlled Trial.

Zhang DY, Cheng YB, Guo QH, Shan XL, ... Li Y, Wang JG

Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP) lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules (GUG), in patients with masked hypertension.Patients with an office BP of <140/90 mmHg and daytime ambulatory BP of 135-150 mmHg systolic and/or 85-95 mmHg diastolic were randomized 1:1 to the treatment of GUG or placebo 5-10 grams twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP.At baseline, office and daytime BP of the 251 participants (mean age 50.4 years, 53.4% men, mean body mass index 24.5 kg/m, and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes mellitus, and smoking, respectively) averaged 129/82 and 135/89 mmHg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44 /3.39 and 2.91/1.60 mmHg in the GUG and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mmHg, ≤0.025) and 24-h BP (2.33/1.49 mmHg, ≤0.012), but not for the clinic and nighttime BPs (≥0.162). The per-protocol analysis in 229 patients produced similar results. Only one adverse event (sleepiness during the day) was reported and no serious adverse event occurred.BP lowering treatment with Chinese traditional medicine GUG is efficacious for patients with masked hypertension.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02156024.



Circulation: 05 Oct 2020; epub ahead of print
Zhang DY, Cheng YB, Guo QH, Shan XL, ... Li Y, Wang JG
Circulation: 05 Oct 2020; epub ahead of print | PMID: 33019798
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Abstract

Assessing and Addressing Cardiovascular Health in LGBTQ Adults: A Scientific Statement From the American Heart Association.

Caceres BA, Streed CG, Corliss HL, Lloyd-Jones DM, ... Ross LM,

There is mounting evidence that lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) adults experience disparities across several cardiovascular risk factors compared with their cisgender heterosexual peers. These disparities are posited to be driven primarily by exposure to psychosocial stressors across the life span. This American Heart Association scientific statement reviews the extant literature on the cardiovascular health of LGBTQ adults. Informed by the minority stress and social ecological models, the objectives of this statement were (1) to present a conceptual model to elucidate potential mechanisms underlying cardiovascular health disparities in LGBTQ adults, (2) to identify research gaps, and (3) to provide suggestions for improving cardiovascular research and care of LGBTQ people. Despite the identified methodological limitations, there is evidence that LGBTQ adults (particularly lesbian, bisexual, and transgender women) experience disparities across several cardiovascular health metrics. These disparities vary by race, sex, sexual orientation, and gender identity. Future research in this area should incorporate longitudinal designs, elucidate physiological mechanisms, assess social and clinical determinants of cardiovascular health, and identify potential targets for behavioral interventions. There is a need to develop and test interventions that address multilevel stressors that affect the cardiovascular health of LGBTQ adults. Content on LGBTQ health should be integrated into health professions curricula and continuing education for practicing clinicians. Advancing the cardiovascular health of LGBTQ adults requires a multifaceted approach that includes stakeholders from multiple sectors to integrate best practices into health promotion and cardiovascular care of this population.



Circulation: 07 Oct 2020:CIR0000000000000914; epub ahead of print
Caceres BA, Streed CG, Corliss HL, Lloyd-Jones DM, ... Ross LM,
Circulation: 07 Oct 2020:CIR0000000000000914; epub ahead of print | PMID: 33028085
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Abstract

Comparison of Self-Expanding Bioprostheses for Transcatheter Aortic Valve Replacement in Patients with Symptomatic Severe Aortic Stenosis: The SCOPE 2 Randomized Clinical Trial.

Tamburino C, Bleiziffer S, Thiele H, Scholtz S, ... Hengstenberg C, Capodanno D

There are few randomized trials comparing bioprostheses for transcatheter aortic valve replacement (TAVR), and no trials compared TAVR bioprostheses with supra-annular design. The SCOPE 2 trial was designed to compare the clinical outcomes of the ACURATE neo and CoreValve Evolut valves.SCOPE 2 was a randomized trial performed at 23 centers in 6 countries between April 2017 and April 2019. Patients ≥75 years with an indication for transfemoral TAVR as agreed by the Heart Team were randomly assigned to receive treatment with either the ACURATE neo (n=398) or the CoreValve Evolut bioprostheses (n=398). The primary endpoint, powered for non-inferiority of the ACURATE neo valve, was all-cause death or stroke at 1 year. The key secondary endpoint, powered for superiority of the ACURATE neo valve, was new permanent pacemaker implantation at 30 days.Among 796 randomized patients (mean age 83.2±4.3 years; mean STS-PROM score 4.6± 2.9%), clinical follow-up information was available for 778 (98%) patients. Within 1 year, the primary endpoint occurred in 15.8% of patients in the ACURATE neo group and in 13.9% of patients in the CoreValve Evolut group (absolute risk difference 1.8%, upper one-sided 95% confidence limit 6.1%, p=0.0549 for noninferiority). The 30-day rates of new permanent pacemaker implantation were 10.5% in the ACURATE neo group and 18.0% in the CoreValve Evolut group (absolute risk difference -7.5%, 95% confidence interval -12.4 to -2.60, p=0.0027). No significant differences were observed in the components of the primary endpoint. Cardiac death at 30 days (2.8% vs. 0.8%, p=0.03) and 1 year (8.4% vs. 3.9%, p=0.01), and moderate or severe aortic regurgitation at 30 days (10% vs. 3%, p=0.002) were significantly increased in the ACURATE neo group.Transfemoral TAVR with the self-expanding ACURATE neo did not meet non-inferiority compared to the self-expanding CoreValve Evolut in terms of all-cause death or stroke at 1 year, and was associated with a lower incidence of new permanent pacemaker implantation. In secondary analyses, the ACURATE neo was associated with more moderate or severe aortic regurgitation at 30 days and cardiac death at 30 days and 1 year.URL: https://clinicaltrials.gov/ Unique Identifier: NCT03192813.



Circulation: 14 Oct 2020; epub ahead of print
Tamburino C, Bleiziffer S, Thiele H, Scholtz S, ... Hengstenberg C, Capodanno D
Circulation: 14 Oct 2020; epub ahead of print | PMID: 33054367
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Abstract

Primary Results from the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low Ejection Fraction (UNTOUCHED) Trial.

Gold MR, Lambiase PD, El-Chami MF, Knops RE, ... Boersma LV,

The Subcutaneous ICD (S-ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, less left ventricular dysfunction and received more inappropriate shocks (IAS) than in typical transvenous (TV)-ICD trials. The UNTOUCHED trial was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms.Primary prevention patients with left ventricular ejection fraction (LVEF) ≤ 35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥ 250 beats per minute (bpm) and morphology discrimination for rates ≥200 and < 250 bpm. Patients were followed for 18 months. The primary endpoint was the IAS free rate compared to a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study. Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of endpoints.S-ICD implant was attempted in 1116 patients and 1111 patients were included in post-implant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% women, 23.4% black race, 53.5% with ischemic heart disease, 87.7% with symptomatic heart failure and a mean LVEF of 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (Lower confidence limit LCL 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the three-incision technique, no history of atrial fibrillation, and ischemic etiology. The 18-month all cause shock free rate was 90.6% (LCL 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication free rate at 18 months was 92.7%.This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of co-morbidities in comparison to earlier S-ICD trials. The inappropriate shock rate (3.1% at one year) is the lowest reported for the S-ICD and lower than many TV ICD studies using contemporary programming to reduce IAS.URL https://clinicaltrials.gov Unique Identifier NCT02433379.



Circulation: 18 Oct 2020; epub ahead of print
Gold MR, Lambiase PD, El-Chami MF, Knops RE, ... Boersma LV,
Circulation: 18 Oct 2020; epub ahead of print | PMID: 33073614
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Abstract

Comprehensive Metabolic Phenotyping Refines Cardiovascular Risk in Young Adults.

Murthy VL, Reis JP, Pico AR, Kitchen R, ... Clish CB, Shah RV

Whereas cardiovascular disease (CVD) metrics define risk in individuals above age 40 years, the earliest lesions of CVD appear well before this age. Despite the role of metabolism in CVD antecedents, studies in younger, biracial populations to define precise metabolic risk phenotypes are lacking.We studied 2330 white and Black young adults (mean age 32 years, 45% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study to identify metabolite profiles associated with an adverse CVD phenome (myocardial structure/function, fitness, vascular calcification), mechanisms, and outcomes over two decades. Statistical learning methods (elastic nets/principal components analysis) and Cox regression generated parsimonious, metabolite-based risk scores validated in >1800 individuals in the Framingham Heart Study (FHS).In CARDIA, metabolite profiles quantified in early adulthood were associated with subclinical CVD development over 20 years, specifying known and novel pathways of CVD (e.g., transcriptional regulation, BDNF, NO, renin-angiotensin). We found two multi-parametric, metabolite-based scores linked independently to vascular and myocardial health, with metabolites included in each score specifying microbial metabolism, hepatic steatosis, oxidative stress, NO modulation, and collagen metabolism. The metabolite-based vascular scores were lower in men, and myocardial scores were lower in Blacks. Over nearly 25 year median follow-up in CARDIA, the metabolite-based vascular score (HR = 0.68 per SD; 95% CI 0.50-0.92, P=0.01) and myocardial score (HR=0.60 per SD; 95% CI 0.45-0.80, P=0.0005) in the third and fourth decade of life were associated with clinical CVD with a synergistic association with outcome (P=0.009). We replicated these findings in 1898 individuals in FHS over 2 decades, with a similar association with outcome (including interaction), reclassification, and discrimination. In FHS, the metabolite scores exhibited an age interaction (P=0.0004 for a combined myocardial-vascular score with incident CVD), such that young adults with poorer metabolite-based health scores had highest hazard of future CVD.Metabolic signatures of myocardial and vascular health in young adulthood specify known/novel pathways of metabolic dysfunction relevant to CVD, associated with outcome in two independent cohorts. Efforts to include precision measures of metabolic health in risk stratification to interrupt CVD at its earliest stage are warranted.



Circulation: 18 Oct 2020; epub ahead of print
Murthy VL, Reis JP, Pico AR, Kitchen R, ... Clish CB, Shah RV
Circulation: 18 Oct 2020; epub ahead of print | PMID: 33073606
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Abstract

Growth Differentiation Factor-15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized with COVID-19.

Myhre PL, Prebensen C, Strand H, Røysland R, ... Berdal JE, Omland T

Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic importance of GDF-15 in COVID-19 is unknown.Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID MECH study. Biobank samples were collected at baseline, day 3 and day 9. The primary endpoint was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers.Of the 123 patients enrolled, 35 (28%) reached the primary endpoint; these patients were older, more often had diabetes mellitus, had lower oxygen saturations and higher National Early Warning Score on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both p<0.001). Patients reaching the primary endpoint had higher concentrations of GDF-15 (median 4225 [IQR 3197-5972] pg/mL vs 2187 [1344-3620] pg/mL, p<0.001). The C-statistic value was 0.78 (95% confidence interval 0.70-0.86). The association between GDF-15 and outcome persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate and previous myocardial infarction, heart failure or atrial fibrillation (p<0.001), and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary endpoint (median 1208 [IQR 0-4305] pg/mL versus -86 [IQR -322-491] pg/mL, p<0.001).GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia and worse outcome. The prognostic importance of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers.



Circulation: 14 Oct 2020; epub ahead of print
Myhre PL, Prebensen C, Strand H, Røysland R, ... Berdal JE, Omland T
Circulation: 14 Oct 2020; epub ahead of print | PMID: 33058695
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Abstract

Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Greif R, Bhanji F, Bigham BL, Bray J, ... Finn JC,

For this , the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.



Circulation: 19 Oct 2020; 142:S222-S283
Greif R, Bhanji F, Bigham BL, Bray J, ... Finn JC,
Circulation: 19 Oct 2020; 142:S222-S283 | PMID: 33084395
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2020 International Consensus on First Aid Science With Treatment Recommendations.

Singletary EM, Zideman DA, Bendall JC, Berry DC, ... Woodin JA,

This is the summary publication of the International Liaison Committee on Resuscitation\'s . It addresses the most recent published evidence reviewed by the First Aid Task Force science experts. This summary addresses the topics of first aid methods of glucose administration for hypoglycemia; techniques for cooling of exertional hyperthermia and heatstroke; recognition of acute stroke; the use of supplementary oxygen in acute stroke; early or first aid use of aspirin for chest pain; control of life-threatening bleeding through the use of tourniquets, hemostatic dressings, direct pressure, or pressure devices; the use of a compression wrap for closed extremity joint injuries; and temporary storage of an avulsed tooth. Additional summaries of scoping reviews are presented for the use of a recovery position, recognition of a concussion, and 6 other first aid topics. The First Aid Task Force has assessed, discussed, and debated the certainty of evidence on the basis of Grading of Recommendations, Assessment, Development, and Evaluation criteria and present their consensus treatment recommendations with evidence-to-decision highlights and identified priority knowledge gaps for future research.



Circulation: 19 Oct 2020; 142:S284-S334
Singletary EM, Zideman DA, Bendall JC, Berry DC, ... Woodin JA,
Circulation: 19 Oct 2020; 142:S284-S334 | PMID: 33084394
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Pediatric Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Maconochie IK, Aickin R, Hazinski MF, Atkins DL, ... de Caen AR,

This(CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children.



Circulation: 19 Oct 2020; 142:S140-S184
Maconochie IK, Aickin R, Hazinski MF, Atkins DL, ... de Caen AR,
Circulation: 19 Oct 2020; 142:S140-S184 | PMID: 33084393
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Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Wyckoff MH, Wyllie J, Aziz K, de Almeida MF, ... Weiner GM,

This(CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.



Circulation: 19 Oct 2020; 142:S185-S221
Wyckoff MH, Wyllie J, Aziz K, de Almeida MF, ... Weiner GM,
Circulation: 19 Oct 2020; 142:S185-S221 | PMID: 33084392
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Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Olasveengen TM, Mancini ME, Perkins GD, Avis S, ... Morley PT,

This(CPR)on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.



Circulation: 19 Oct 2020; 142:S41-S91
Olasveengen TM, Mancini ME, Perkins GD, Avis S, ... Morley PT,
Circulation: 19 Oct 2020; 142:S41-S91 | PMID: 33084391
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Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Berg KM, Soar J, Andersen LW, Böttiger BW, ... Nolan JP,

Thisfor advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.



Circulation: 19 Oct 2020; 142:S92-S139
Berg KM, Soar J, Andersen LW, Böttiger BW, ... Nolan JP,
Circulation: 19 Oct 2020; 142:S92-S139 | PMID: 33084390
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Part 7: Systems of Care: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Berg KM, Cheng A, Panchal AR, Topjian AA, ... Lavonas EJ,

Survival after cardiac arrest requires an integrated system of people, training, equipment, and organizations working together to achieve a common goal. Part 7 of thefocuses on systems of care, with an emphasis on elements that are relevant to a broad range of resuscitation situations. Previous systems of care guidelines have identified a Chain of Survival, beginning with prevention and early identification of cardiac arrest and proceeding through resuscitation to post-cardiac arrest care. This concept is reinforced by the addition of recovery as an important stage in cardiac arrest survival. Debriefing and other quality improvement strategies were previously mentioned and are now emphasized. Specific to out-of-hospital cardiac arrest, this Part contains recommendations about community initiatives to promote cardiac arrest recognition, cardiopulmonary resuscitation, public access defibrillation, mobile phone technologies to summon first responders, and an enhanced role for emergency telecommunicators. Germane to in-hospital cardiac arrest are recommendations about the recognition and stabilization of hospital patients at risk for developing cardiac arrest. This Part also includes recommendations about clinical debriefing, transport to specialized cardiac arrest centers, organ donation, and performance measurement across the continuum of resuscitation situations.



Circulation: 19 Oct 2020; 142:S580-S604
Berg KM, Cheng A, Panchal AR, Topjian AA, ... Lavonas EJ,
Circulation: 19 Oct 2020; 142:S580-S604 | PMID: 33081524
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Abstract

Heart Failure and Atrial Fibrillation Modify the Associations of Nocturnal Blood Pressure Dipping Pattern With Mortality in Hemodialysis Patients.

Mayer CC, Schmaderer C, Loutradis C, Matschkal J, ... Wassertheurer S, Sarafidis PA

Heart failure (HF), hypertension, and abnormal nocturnal blood pressure dipping are highly prevalent in hemodialysis patients. Atrial fibrillation (AF) and HF might be important mediators for the association of abnormal dipping patterns with worse prognosis. Thus, the aim of this study is to investigate the association of dipping with mortality in hemodialysis patients and to assess the influence of AF and HF. In total, 525 hemodialysis patients underwent 24-hour ambulatory blood pressure monitoring. All-cause and cardiovascular mortality served as end points. Patients were categorized according to their systolic dipping pattern (dipper, nondipper, and reverse dipper). Cox regression analysis was performed to determine the association between dipping pattern and study end points with dipping as reference. Subgroup analysis was performed for patients with and without AF or HF. In total, 185 patients with AF or HF and 340 patients without AF or HF were included. During a median follow-up of 37.8 months, 177 patients died; 81 from cardiovascular causes. Nondipping and reverse dipping were significantly associated with all-cause mortality in the whole cohort (nondipper: hazard ratio, 1.95 [1.22-3.14]; =0.006; reverse dipper: hazard ratio, 2.31 [1.42-3.76]; <0.001) and in patients without AF or HF (nondipper: hazard ratio, 2.78 [1.16-6.66]; =0.02; reverse dipper: hazard ratio, 4.48 [1.87-10.71]; <0.001) but not in patients with AF or HF. For cardiovascular mortality, associations were again significant in patients without AF or HF and in the whole cohort. The observed associations remained significant after adjustment for possible confounders. This study provides well-powered evidence for the association between abnormal dipping patterns and mortality in hemodialysis patients and suggests that HF or AF modifies this association.



Hypertension: 29 Sep 2020; 76:1231-1239
Mayer CC, Schmaderer C, Loutradis C, Matschkal J, ... Wassertheurer S, Sarafidis PA
Hypertension: 29 Sep 2020; 76:1231-1239 | PMID: 32862707
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Abstract

Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families: The Lifelines Cohort Study.

Tegegne BS, Man T, van Roon AM, Asefa NG, ... Nolte I, Snieder H

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all <0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (-0.20/-0.16) and with diastolic BP (-0.15/-0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, -0.08 to -0.23) and diastolic BP (range, -0.20 to -0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.



Hypertension: 29 Sep 2020; 76:1256-1262
Tegegne BS, Man T, van Roon AM, Asefa NG, ... Nolte I, Snieder H
Hypertension: 29 Sep 2020; 76:1256-1262 | PMID: 32829661
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Twenty-Four-Hour Urinary Sodium and Potassium Excretion and Their Associations With Blood Pressure Among Adults in China: Baseline Survey of Action on Salt China.

Li Y, Zhang P, Wu J, Ma J, ... MacGregor GA, Li X

This study aimed to assess current level of sodium and potassium intake and their associations with blood pressure (BP) using the 24-hour urinary data in a large sample of China. Data from participants aged 18 to 75 years were collected as the baseline survey of Action on Salt China in 2018. Of 5454 adults, 5353 completed 24-hour urine collection. The average sodium, potassium excretion, and sodium-to-potassium molar ratio were 4318.1±1814.1 mg/d (equivalent to 11.0±4.6 g/d of salt), 1573.7±627.1 mg/d, and 5.0±2.1, respectively. After adjusting for potential confounding factors and correcting for regression dilution, each 1000-mg increase in sodium excretion was associated with increased systolic BP (1.32 mm Hg [95% CI, 0.92-1.81]) and diastolic BP (0.34 mm Hg [95% CI, 0.09-0.60]). Each 1000-mg increase in potassium excretion was inversely associated with systolic BP (-3.19 mm Hg [95% CI, -4.38 to -2.20]) and diastolic BP (-1.56 mm Hg [95% CI, -2.29 to -0.90]). Each unit increase in sodium-to-potassium molar ratio was associated with an increase of systolic BP by 1.21 mm Hg (95% CI, 0.91-1.60) and diastolic BP by 0.44 mm Hg (95% CI, 0.24-0.64). The relationships between sodium and BP mostly increase with the rise of BP quantiles. Potassium shows the opposite trend. The current sodium intake in Chinese adults remains high and potassium intake is low. Sodium and sodium-to-potassium ratio were positively associated with BP, whereas potassium was inversely associated with BP. Registration- URL: https://tinyurl.com/vdr8rpr; Unique identifier: ChiCTR1800017553. URL: https://tinyurl.com/w8c7x3w; Unique identifier: ChiCTR1800016804. URL: https://tinyurl.com/s3ajldw; Unique identifier: ChiCTR1800018119.



Hypertension: 27 Sep 2020:HYPERTENSIONAHA12015238; epub ahead of print
Li Y, Zhang P, Wu J, Ma J, ... MacGregor GA, Li X
Hypertension: 27 Sep 2020:HYPERTENSIONAHA12015238; epub ahead of print | PMID: 32981359
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Heart Failure in Women With Hypertensive Disorders of Pregnancy: Insights From the Cardiovascular Disease in Norway Project.

Honigberg MC, Riise HKR, Daltveit AK, Tell GS, ... Natarajan P, Rich-Edwards JW

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84-2.35], =0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50-2.68, <0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.



Hypertension: 30 Oct 2020; 76:1506-1513
Honigberg MC, Riise HKR, Daltveit AK, Tell GS, ... Natarajan P, Rich-Edwards JW
Hypertension: 30 Oct 2020; 76:1506-1513 | PMID: 32829667
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PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.

Kuliopulos A, Gurbel PA, Rade JJ, Kimmelstiel CD, ... Covic L,
Objective
Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention. Approach and Results: In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02-0.75); =0.02.
Conclusions
In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials.
Registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02561000.



Arterioscler Thromb Vasc Biol: 07 Oct 2020:ATVBAHA120315168; epub ahead of print
Kuliopulos A, Gurbel PA, Rade JJ, Kimmelstiel CD, ... Covic L,
Arterioscler Thromb Vasc Biol: 07 Oct 2020:ATVBAHA120315168; epub ahead of print | PMID: 33028101
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Natural History of Hypertension in Turner Syndrome During a 12-Year Pragmatic Interventional Study.

Sandahl K, Wen J, Erlandsen M, Andersen NH, Gravholt CH

Turner syndrome is caused by complete or partial X monosomy in some or all cells. Cardiovascular complications are dominant, including increased blood pressure (BP), leading to early-onset hypertension. The aim is to describe the debut, development, and treatment of hypertension in Turner syndrome during a 12-year pragmatic interventional study to help identify risk factors associated with hypertension. One hundred and two women (aged 38±11 years, range: 18-62 years) with Turner syndrome verified by karyotyping (45, X: n=58 [57%]) were included consecutively. Ambulatory BPs were recorded over 24 hours with oscillometric measurements every 20 minutes. Antihypertensive treatment was recommended if the BP was above 135/85 mm Hg during the daytime. Overall, systolic BP, diastolic BP, and pulse pressure increased during the study, while heart rate decreased. The number of patients treated with antihypertensive medicine increased from 29 (28.71%) at baseline to 34 (53.13%) at the end of study. Twenty-four-hour systolic BP and 24-hour pulse pressure increased significantly with age, while 24-hour heart rate decreased with age, and diastolic BP was insignificantly affected by age. Antihypertensive treatment lowered systolic BP (24-hour: -5 mm Hg), diastolic BP (24-hour: -5 mm Hg), and diminished the pulse pressure (24-hour: -6 mm Hg) but did not affect nighttime systolic BP. Antihypertensive treatment did not affect heart rate. Our study showed that both systolic and diastolic BP increases significantly in women with Turner syndrome resulting in an increased risk of cardiovascular comorbidities. This increment should be considered of multifactorial origin with many contributing factors which is supported by our results.



Hypertension: 30 Oct 2020; 76:1608-1615
Sandahl K, Wen J, Erlandsen M, Andersen NH, Gravholt CH
Hypertension: 30 Oct 2020; 76:1608-1615 | PMID: 32895020
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Angiogenic Factors and Long-Term Cardiovascular Risk in Women That Developed Preeclampsia During Pregnancy.

Garrido-Gimenez C, Mendoza M, Cruz-Lemini M, Galian-Gay L, ... Llurba E, Alijotas-Reig J

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein (=0.341; =0.006), and negatively with global longitudinal strain (=-0.581; <0.001), carotid intima-media thickness (=-0.251; =0.045), and mean arterial blood pressure (=-0.252; =0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein (=-0.372; =0.002) and apolipoprotein A-1 (=-0.257; =0.040), and positively with carotid intima-media thickness (=0.269; =0.032) and left ventricular posterior wall thickness (=0.368; =0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.



Hypertension: 04 Oct 2020:HYPERTENSIONAHA12015830; epub ahead of print
Garrido-Gimenez C, Mendoza M, Cruz-Lemini M, Galian-Gay L, ... Llurba E, Alijotas-Reig J
Hypertension: 04 Oct 2020:HYPERTENSIONAHA12015830; epub ahead of print | PMID: 33012203
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Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial.

Ormesher L, Higson S, Luckie M, Roberts SA, ... Johnstone ED, Myers JE

Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months\' treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance (=0.59) or systolic function (global longitudinal strain: =0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E\'[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: =0.04) and left ventricular remodeling (relative wall thickness: =0.01; left ventricular mass index: =0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT03466333.



Hypertension: 04 Oct 2020:HYPERTENSIONAHA12015875; epub ahead of print
Ormesher L, Higson S, Luckie M, Roberts SA, ... Johnstone ED, Myers JE
Hypertension: 04 Oct 2020:HYPERTENSIONAHA12015875; epub ahead of print | PMID: 33012200
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Cardiovascular Events and Costs With Home Blood Pressure Telemonitoring and Pharmacist Management for Uncontrolled Hypertension.

Margolis KL, Dehmer SP, Sperl-Hillen J, O\'Connor PJ, ... Trower NK, Maciosek MV

Uncontrolled hypertension is a leading contributor to cardiovascular disease. A cluster-randomized trial in 16 primary care clinics showed that 12 months of home blood pressure telemonitoring and pharmacist management lowered blood pressure more than usual care (UC) for 24 months. We report cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, hospitalized heart failure, coronary revascularization, and cardiovascular death) and costs over 5 years of follow-up. In the telemonitoring intervention (TI group, n=228), there were 15 cardiovascular events (5 myocardial infarction, 4 stroke, 5 heart failure, 1 cardiovascular death) among 10 patients. In UC group (n=222), there were 26 events (11 myocardial infarction, 12 stroke, 3 heart failure) among 19 patients. The cardiovascular composite end point incidence was 4.4% in the TI group versus 8.6% in the UC group (odds ratio, 0.49 [95% CI, 0.21-1.13], =0.09). Including 2 coronary revascularizations in the TI group and 10 in the UC group, the secondary cardiovascular composite end point incidence was 5.3% in the TI group versus 10.4% in the UC group (odds ratio, 0.48 [95% CI, 0.22-1.08], =0.08). Microsimulation modeling showed the difference in events far exceeded predictions based on observed blood pressure. Intervention costs (in 2017 US dollars) were $1511 per patient. Over 5 years, estimated event costs were $758 000 in the TI group and $1 538 000 in the UC group for a return on investment of 126% and a net cost savings of about $1900 per patient. Telemonitoring with pharmacist management lowered blood pressure and may have reduced costs by avoiding cardiovascular events over 5 years. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781365.



Hypertension: 29 Sep 2020; 76:1097-1103
Margolis KL, Dehmer SP, Sperl-Hillen J, O'Connor PJ, ... Trower NK, Maciosek MV
Hypertension: 29 Sep 2020; 76:1097-1103 | PMID: 32862713
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Abstract

Effects of Intensive Versus Standard Office-Based Hypertension Treatment Strategy on White-Coat Effect and Masked Uncontrolled Hypertension: From the SPRINT ABPM Ancillary Study.

Ghazi L, Cohen LP, Muntner P, Shimbo D, Drawz PE

Guidelines recommend using out-of-office blood pressure (BP) measurements to confirm the diagnoses of hypertension and in the titration of antihypertensive medication. The prevalence of out-of-office BP phenotypes for an office systolic/diastolic BP goal <140/90 mm Hg has been reported. However, the prevalence of these phenotypes when targeting an office systolic/diastolic BP goal <120/80 is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory BP Ancillary study evaluated out-of-office BP using ambulatory BP monitoring in 897 participants 27 months after randomization to intensive versus standard BP targets (office systolic BP <120 versus <140 mm Hg). We used office and daytime BP to assess the proportion of participants with white-coat effect (standard target: office BP ≥140/90 mm Hg and daytime BP <135/85 mm Hg versus intensive target: office BP ≥120/80 mm Hg and daytime BP <120/80 mm Hg) and masked uncontrolled hypertension (standard target: office BP <140/90 mm Hg and daytime BP ≥135/85 mm Hg versus intensive target: office BP <120/80 mm Hg and daytime BP ≥120/80 mm Hg) in each treatment arm. The prevalence of white-coat effect and masked uncontrolled hypertension was 9% and 34%, in both treatment groups. Among participants with uncontrolled office BP, white-coat effect was present in 20% and 23% in the intensive and standard groups, respectively. Among participants with controlled office BP, masked uncontrolled hypertension was present in 62% and 56% in the intensive and standard groups, respectively. In conclusion, a more intensive BP target resulted in a similar proportion of patients with white-coat effect and masked uncontrolled hypertension compared with a standard target.



Hypertension: 29 Sep 2020; 76:1090-1096
Ghazi L, Cohen LP, Muntner P, Shimbo D, Drawz PE
Hypertension: 29 Sep 2020; 76:1090-1096 | PMID: 32829666
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Abstract

Antihypertensive Drugs and Risk of Depression: A Nationwide Population-Based Study.

Kessing LV, Rytgaard HC, Ekstrøm CT, Torp-Pedersen C, Berk M, Gerds TA

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and β-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.



Hypertension: 29 Sep 2020; 76:1263-1279
Kessing LV, Rytgaard HC, Ekstrøm CT, Torp-Pedersen C, Berk M, Gerds TA
Hypertension: 29 Sep 2020; 76:1263-1279 | PMID: 32829669
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Abstract

Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk.

Lewandowski AJ, Levy PT, Bates ML, McNamara PJ, Nuyt AM, Goss KN

Preterm birth accounts for over 15 million global births per year. Perinatal interventions introduced since the early 1980s, such as antenatal glucocorticoids, surfactant, and invasive ventilation strategies, have dramatically improved survival of even the smallest, most vulnerable neonates. As a result, a new generation of preterm-born individuals has now reached early adulthood, and they are at increased risk of cardiovascular diseases. To better understand the sequelae of preterm birth, cardiovascular follow-up studies in adolescents and young adults born preterm have focused on characterizing changes in cardiac, vascular, and pulmonary structure and function. Being born preterm associates with a reduced cardiac reserve and smaller left and right ventricular volumes, as well as decreased vascularity, increased vascular stiffness, and higher pressure of both the pulmonary and systemic vasculature. The purpose of this review is to present major epidemiological evidence linking preterm birth with cardiovascular disease; to discuss findings from clinical studies showing a long-term impact of preterm birth on cardiac remodeling, as well as the systemic and pulmonary vascular systems; to discuss differences across gestational ages; and to consider possible driving mechanisms and therapeutic approaches for reducing cardiovascular burden in individuals born preterm.



Hypertension: 29 Sep 2020; 76:1028-1037
Lewandowski AJ, Levy PT, Bates ML, McNamara PJ, Nuyt AM, Goss KN
Hypertension: 29 Sep 2020; 76:1028-1037 | PMID: 32816574
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Abstract

Attainment of Targets of the 20-Year Infancy-Onset Dietary Intervention and Blood Pressure Across Childhood and Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

Laitinen TT, Nuotio J, Niinikoski H, Juonala M, ... Raitakari OT, Pahkala K

We examined whether success in achieving the key targets of an infancy-onset 20-year dietary intervention was associated with blood pressure (BP) from infancy to young adulthood. In the prospective randomized STRIP (Special Turku Coronary Risk Factor Intervention Project; n=877 children), dietary counseling was provided biannually based on the Nordic Nutrition Recommendations primarily to improve the quality of dietary fat in children\'s diets and secondarily to promote intake of vegetables, fruits, and whole grains. Dietary data and BP were accrued annually from the age of 13 months to 20 years. The dietary targets for fat quality were defined as the ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids <1:2 and intake of saturated fatty acids <10 E%, dietary fiber intake in the top age-specific quintile, and dietary sucrose intake as being in the lowest age-specific quintile. Attaining a higher number of the dietary targets was associated with lower systolic BP (mean [SE] systolic BP, 107.3 [0.3], 107.6 [0.3], 106.8 [0.3], and 106.7 [0.5] mm Hg in participants meeting 0, 1, 2, and 3 to 4 targets, respectively; =0.03) and diastolic BP (mean [SE] diastolic BP, 60.4 [0.2], 60.5 [0.2], 59.9 [0.2], and 59.9 [0.3] mm Hg; =0.02). When the lowest age-specific quintile of dietary cholesterol was added as an additional target, the association with systolic BP remained significant (=0.047), but the association with diastolic BP attenuated (=0.13). Achieving the key targets of an infancy-onset 20-year dietary intervention, reflecting dietary guidelines, was favorably albeit modestly associated with systolic and diastolic BP from infancy to young adulthood. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00223600.



Hypertension: 30 Oct 2020; 76:1572-1579
Laitinen TT, Nuotio J, Niinikoski H, Juonala M, ... Raitakari OT, Pahkala K
Hypertension: 30 Oct 2020; 76:1572-1579 | PMID: 32921196
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Abstract

Pregnancy and Preeclampsia Are Associated With Acute Adverse Peripheral Arterial Events.

DeCarlo C, Boitano LT, Molina RL, Weinberg I, ... Eagleton MJ, Dua A
Objective
Acute peripheral arterial events, such as aortic dissection, carotid artery dissection, vertebral artery dissection, and ruptured renoviseral aneurysms, have been reported during pregnancy in case series, but there is a paucity of population-based data. This study sought to establish pregnancy and preeclampsia as risk factors for acute peripheral arterial events. Approach and Results: All women who gave birth between 1998 and 2020 within a multicenter health care system were identified. Births that occurred in women <18 or >50 years of age were excluded. Primary outcome was any acute peripheral arterial event that was symptomatic or required intervention. Cox regression model was used to evaluate the association between vascular events and pregnancy as a time-varying covariate. The pregnancy exposure period was from the estimated date of conception to 3 months postpartum. There were 277 697 pregnancies (81.3% deliveries, 17.0% abortions, and 1.7% ectopics) among 176 635 women with 1.68 million patient-years of total follow-up (median, 7.9 years; interquartile range, 2.4-16.2). Preeclampsia complicated 5.3% of pregnancies; 67 790 of 225 763 (30.0%) deliveries were delivered by cesarean. Ninety-six acute arterial events occurred during follow-up, of which 24 occurred during pregnancy, including the postpartum period. Pregnancy (hazard ratio, 1.85 [95% CI, 1.01-3.38]; =0.046) and preeclampsia (hazard ratio, 10.9 [95% CI, 5.24-22.7]; <0.001) were significant independent predictors of acute arterial events.
Conclusions
While taking into account limitations from estimating conception and outcome dates, pregnancy, especially when complicated by preeclampsia, is associated with an increased risk of acute peripheral arterial events.



Arterioscler Thromb Vasc Biol: 14 Oct 2020:ATVBAHA120315174; epub ahead of print
DeCarlo C, Boitano LT, Molina RL, Weinberg I, ... Eagleton MJ, Dua A
Arterioscler Thromb Vasc Biol: 14 Oct 2020:ATVBAHA120315174; epub ahead of print | PMID: 33054392
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Abstract

Atrial fibrillation and the prothrombotic state: revisiting Virchow\'s triad in 2020.

Ding WY, Gupta D, Lip GYH

Atrial fibrillation (AF) is characterised by an increased risk of pathological thrombus formation due to a disruption of physiological haemostatic mechanisms that are better understood by reference to Virchow\'s triad of \'abnormal blood constituents\', \'vessel wall abnormalities\' and \'abnormal blood flow\'. First, there is increased activation of the coagulation cascade, platelet reactivity and impaired fibrinolysis as a result of AF per se, and these processes are amplified with pre-existing comorbidities. Several prothrombotic biomarkers including platelet factor 4, von Willebrand factor, fibrinogen, β-thromboglobulin and D-dimer have been implicated in this process. Second, structural changes such as atrial fibrosis and endothelial dysfunction are linked to the development of AF which promote further atrial remodelling, thereby providing a suitable platform for clot formation and subsequent embolisation. Third, these factors are compounded by the presence of reduced blood flow secondary to dilatation of cardiac chambers and loss of atrial systole which have been confirmed using various imaging techniques. Overall, an improved understanding of the various factors involved in thrombus formation will allow better clinical risk stratification and targeted therapies in AF.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1463-1468
Ding WY, Gupta D, Lip GYH
Heart: 29 Sep 2020; 106:1463-1468 | PMID: 32675218
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Abstract

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

Koo CY, Aung AT, Chen Z, Kristanto W, ... Kofidis T, Lee CH
Objective
Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG.
Methods
This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG.
Results
Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness.
Conclusion
Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG.
Trial registration number
NCT02701504.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1495-1502
Koo CY, Aung AT, Chen Z, Kristanto W, ... Kofidis T, Lee CH
Heart: 29 Sep 2020; 106:1495-1502 | PMID: 32423904
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Abstract

Association between age and readmission after percutaneous coronary intervention for acute myocardial infarction.

Qin Y, Wei X, Han H, Wen Y, ... Tomey MI, He J
Objective
This study aimed to investigate the association between age and the risk of 30-day unplanned readmission among adult patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).
Methods
This retrospective analysis included patients from the Nationwide Readmissions Database with AMI who underwent PCI during 2013-2014. We used multivariable logistic regression model to calculate adjusted odds ratios (AORs) for risk of readmission. To examine potential non-linear association, we performed logistic regression with restricted cubic splines (RCS).
Results
Of the 492 550 patients with AMI aged above 18 years undergoing PCI during the index hospitalisation, 48 630 (9.87%) were readmitted within 30 days. Although the crude readmission rate of younger patients (aged 18-54 years) was the lowest (7.27%), younger patients had higher risk of readmission compared with patients aged 55-64 years for all-causes (AOR 1.06 (1.01 to 1.11), p=0.0129) and specific causes, such as AMI and chest pain (both cardiac and non-specific) after adjusted for covariates. Patients aged 65-74 years were at lower risk of all-cause readmission. Older patients (age ≥75 years) had higher risk of readmission for heart failure (AOR 1.50 (1.29 to 1.74)) and infection (AOR 1.44 (1.16 to 1.79)), but lower risk for chest pain. RCS analyses showed a U-shaped relationship between age and readmission risk.
Conclusions
Our results suggest higher risk of readmission in younger patients for all-cause unplanned readmission after adjusted for covariates. The trends of readmission risk along with age were different for specific causes. Age-targeted initiatives are warranted to reduce preventable readmissions in patients with AMI undergoing PCI.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1595-1603
Qin Y, Wei X, Han H, Wen Y, ... Tomey MI, He J
Heart: 29 Sep 2020; 106:1595-1603 | PMID: 32144190
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Abstract

Arterial Stiffness Preceding Diabetes: A Longitudinal Study.

Zheng M, Zhang X, Chen S, Song Y, ... Gao X, Wu S

Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date.To explore the temporal relationship between arterial stiffness and fasting blood glucose (FBG) status.Included were 14,159 participants of the Kailuan study with assessment of brachial-ankle pulse wave velocity (baPWV) from 2010 to 2015, and free of diabetes, cardiovascular and cerebrovascular diseases and chronic kidney disease at baseline. FBG and baPWV were repeatedly measured at baseline and follow-ups. Cox proportional hazard regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident diabetes across baseline baPWV groups: <1,400 cm/s (ref), 1,400 {less than or equal to} baPWV < 1,800 cm/s, and {greater than or equal to}1,800cm/s. Path analysis was used to analyze the possible temporal causal relationship between baPWV and FBG, among 8,956 participants with repeated assessment of baPWV and FBG twice in 2010-2017. The mean baseline age of the observed population was 48.3{plus minus}12.0 years. During mean 3.72 years of follow-up, 979 incident diabetes cases were identified. After adjusting for potential confounders, the HR (95% CI) for risk of diabetes was 1.59 (1.34, 1.88) for the borderline arterial stiffness group and 2.11 (1.71, 2.61) for the elevated arterial stiffness group, compared with the normal ideal arterial stiffness group. In the path analysis, baseline baPWV was associated with follow-up FBG (the standard regression coefficient was 0.09; 95% CI: 0.05 to 0.10). In contrast, the standard regression coefficient of baseline FBG for follow-up baPWV (β = 0.00, 95% CI: -0.02 to 0.02) was not significant.Arterial stiffness, as measured by baPWV, was associated with risk of developing diabetes. Arterial stiffness appeared to precede the increase in FBG.



Circ Res: 27 Sep 2020; epub ahead of print
Zheng M, Zhang X, Chen S, Song Y, ... Gao X, Wu S
Circ Res: 27 Sep 2020; epub ahead of print | PMID: 32985370
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Abstract

Association of household income and adverse outcomes in patients with atrial fibrillation.

LaRosa AR, Claxton J, O\'Neal WT, Lutsey PL, ... Alonso A, Magnani JW
Background
Social determinants of health are relevant to cardiovascular outcomes but have had limited examination in atrial fibrillation (AF).
Objectives
The purpose of this study was to examine the association of annual household income and cardiovascular outcomes in individuals with AF.
Methods
We analysed administrative claims for individuals with AF from 2009 to 2015 captured by a health claims database. We categorised estimates of annual household income as <$40 000; $40-$59 999; $60-$74 999; $75-$99 999; and ≥$100 000. Covariates included demographics, education, cardiovascular disease risk factors, comorbid conditions and anticoagulation. We examined event rates by income category and in multivariable-adjusted models in reference to the highest income category (≥$100 000).
Results
Our analysis included 336 736 individuals (age 72.7±11.9 years; 44.5% women; 82.6% white, 8.4% black, 7.0% Hispanic and 2.1% Asian) with AF followed for median (25th and 75th percentile) of 1.5 (95% CI 0.6 to 3.0) years. We observed an inverse association between income and heart failure and myocardial infarction (MI) with evidence of progressive risk across decreased income categories. Individuals with household income <$40 000 had the greatest risk for heart failure (HR 1.17; 95% CI 1.05 to 1.30) and MI (HR 1.18; 95% CI 0.98 to 1.41) compared with those with income ≥$100 000.
Conclusions
We identified an association between lower household income and adverse outcomes in a large cohort of individuals with AF. Our findings support consideration of income in the evaluation of cardiovascular risk in individuals with AF.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2020; 106:1679-1685
LaRosa AR, Claxton J, O'Neal WT, Lutsey PL, ... Alonso A, Magnani JW
Heart: 30 Oct 2020; 106:1679-1685 | PMID: 32144188
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Abstract

The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease.

Chen L, Hao G

Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.

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

Cardiovasc Res: 30 Sep 2020; 116:1932-1936
Chen L, Hao G
Cardiovasc Res: 30 Sep 2020; 116:1932-1936 | PMID: 32267499
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Abstract

Place and causes of acute cardiovascular mortality during the COVID-19 pandemic.

Wu J, Mamas MA, Mohamed MO, Kwok CS, ... Deanfield JE, Gale CP
Objective
To describe the place and causes of acute cardiovascular death during the COVID-19 pandemic.
Methods
Retrospective cohort of adult (age ≥18 years) acute cardiovascular deaths (n=5 87 225) in England and Wales, from 1 January 2014 to 30 June 2020. The exposure was the COVID-19 pandemic (from onset of the first COVID-19 death in England, 2 March 2020). The main outcome was acute cardiovascular events directly contributing to death.
Results
After 2 March 2020, there were 28 969 acute cardiovascular deaths of which 5.1% related to COVID-19, and an excess acute cardiovascular mortality of 2085 (+8%). Deaths in the community accounted for nearly half of all deaths during this period. Death at home had the greatest excess acute cardiovascular deaths (2279, +35%), followed by deaths at care homes and hospices (1095, +32%) and in hospital (50, +0%). The most frequent cause of acute cardiovascular death during this period was stroke (10 318, 35.6%), followed by acute coronary syndrome (ACS) (7 098, 24.5%), heart failure (6 770, 23.4%), pulmonary embolism (2 689, 9.3%) and cardiac arrest (1 328, 4.6%). The greatest cause of excess cardiovascular death in care homes and hospices was stroke (715, +39%), compared with ACS (768, +41%) at home and cardiogenic shock (55, +15%) in hospital.
Conclusions and relevance
The COVID-19 pandemic has resulted in an inflation in acute cardiovascular deaths, nearly half of which occurred in the community and most did not relate to COVID-19 infection suggesting there were delays to seeking help or likely the result of undiagnosed COVID-19.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 27 Sep 2020; epub ahead of print
Wu J, Mamas MA, Mohamed MO, Kwok CS, ... Deanfield JE, Gale CP
Heart: 27 Sep 2020; epub ahead of print | PMID: 32988988
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Abstract

Cardiovascular risk factors and outcomes in early rheumatoid arthritis: a population-based study.

Nikiphorou E, de Lusignan S, Mallen CD, Khavandi K, ... Galloway J, Raza K
Objective
To assess the burden of cardiovascular disease (CVD) at and prior to diagnosis in people with early rheumatoid arthritis (RA) and subsequent CVD in these patients.
Methods
A retrospective case-control study using a large English primary care database. People with RA (n=6591) diagnosed between 2004 and 2016 (inclusive) were identified using a validated algorithm, matched 1:1 by age and gender to those without RA (n=6591) and followed for a median of 5.4 years. We assessed differences in CVD at, before and after diagnosis, and the impact of traditional and RA-related risk factors (C reactive protein, RA-related autoantibodies and medication use) on incident CVD (a composite of myocardial infarction (MI), stroke or heart failure).
Results
RA cases and their matched controls were both of mean age 58.7 (SD 15.5) at cohort entry, and 67.5% were female. Some CVD risk factors were more common at RA diagnosis including smoking and diabetes; however, total and low-density lipoprotein cholesterol were lower in patients with RA. CVD was more common in RA at cohort entry; stroke (3.9% vs 2.7%, p<0.001), heart failure (1.6% vs 1.0%, p=0.001), and non-significantly MI (3.1% vs 2.8%, p=0.092). Excess CVD developed in the 5 years preceding diagnosis. After adjustment for traditional and RA-related risk factors, RA was associated with greater risk of post-diagnosis CVD (HR 1.33, 95% CI 1.07 to 1.65, p=0.010).
Conclusions
An excess of stroke and heart failure occurs before diagnosis of RA. There is excess risk for further cardiovascular events after diagnosis, which is not explained by differences in traditional CVD or RA-related risk factors at diagnosis.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1566-1572
Nikiphorou E, de Lusignan S, Mallen CD, Khavandi K, ... Galloway J, Raza K
Heart: 29 Sep 2020; 106:1566-1572 | PMID: 32209618
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Abstract

Outcomes of transcatheter aortic valve implantations in high-volume or low-volume centres in Germany.

Oettinger V, Kaier K, Heidt T, Hortmann M, ... von Zur Mühlen C, Stachon P
Objective
Transcatheter aortic valve implantation (TAVI) is the most common aortic valve replacement in Germany. Since 2015, to ensure high-quality procedures, hospitals in Germany and other countries that meet the minimum requirement of 50 interventions per centre are being certified to perform TAVI. This study analyses the impact of these requirements on case number and in-hospital outcomes.
Methods
All isolated TAVI procedures and in-hospital outcomes between 2008 and 2016 were identified by International Classification of Diseases (ICD) and the German Operation and Procedure Classification codes.
Results
73 467 isolated transfemoral and transapical TAVI procedures were performed in Germany between 2008 and 2016. During this period, the number of TAVI procedures per year rose steeply, whereas the overall rates of hospital mortality and complications declined. In 2008, the majority of procedures were performed in hospitals with fewer than 50 cases per year (54.63%). Until 2014, the share of patients treated in low-volume centres constantly decreased to 5.35%. After the revision of recommendations, it further declined to 1.99%. In the 2 years after the introduction of the minimum requirements on case numbers, patients were at decreased risk for in-hospital mortality when treated in a high-volume centre (risk-adjusted OR 0.62, p=0.012). The risk for other in-hospital outcomes (stroke, permanent pacemaker implantation and bleeding events) did not differ after risk adjustment (p=0.346, p=0.142 and p=0.633).
Conclusion
A minimum volume of 50 procedures per centre and year appears suitable to allow for sufficient routine and thus better in-hospital outcomes, while ensuring nationwide coverage of TAVI procedures.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1604-1608
Oettinger V, Kaier K, Heidt T, Hortmann M, ... von Zur Mühlen C, Stachon P
Heart: 29 Sep 2020; 106:1604-1608 | PMID: 32071092
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Abstract

Cessation of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

Middeldorp ME, Gupta A, Elliott A, Kadhim K, ... Lau D, Sanders P
Objective
To characterise the rate, causes and predictors of cessation of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF).
Patients and methods
Consecutive patients with AF with a long-term anticoagulation indication treated with NOACs (dabigatran, apixaban and rivaroxaban) in our centre from September 2010 through December 2016 were included. Prospectively collected data with baseline characteristics, causes of cessation, mean duration-to-cessation and predictors of cessation were analysed.
Results
The study comprised 1415 consecutive patients with AF, of whom 439 had a CHADS-VASc≥1 and were on a NOAC. Mean age was 71.9±8.7 years and 37% were females. Over a median follow-up of 3.6 years (IQR=2.7-5.3), 147 (33.5%) patients ceased their index-NOAC (113 switched to a different form of OAC), at a rate of 8.8 per 100 patient-years. Serious adverse events warranting NOAC cessation occurred in 28 patients (6.4%) at a rate of 1.6 events per 100 patient-years. The mean duration-to-cessation was 4.9 years (95% CI 4.6 to 5.1) and apixaban had the longest duration-to-cessation with (5.1, 95% CI 4.8 to 5.4) years, compared with dabigatran (4.6, 95% CI 4.2 to 4.9) and rivaroxaban (4.5, 95% CI 3.9 to 5.1), pairwise log-rank p=0.002 and 0.025, respectively. In multivariable analyses, age was an independent predictor of index-NOAC cessation (HR 1.03, 95% CI 1.01 to 1.05; p=0.006). Female gender (HR 2.2, 95% CI 1.04 to 4.64; p=0.04) independently predicted serious adverse events.
Conclusion
In this \'real world\' cohort, NOAC use is safe and well-tolerated when prescribed in an integrated care clinic. Whether apixaban is better tolerated compared with other NOACs warrants further study.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Oct 2020; epub ahead of print
Middeldorp ME, Gupta A, Elliott A, Kadhim K, ... Lau D, Sanders P
Heart: 15 Oct 2020; epub ahead of print | PMID: 33067328
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Abstract

Cardiovascular disease in homeless versus housed individuals: a systematic review of observational and interventional studies.

Al-Shakarchi NJ, Evans H, Luchenski SA, Story A, Banerjee A
Objectives
To identify: (i) risk of cardiovascular disease (CVD) in homeless versus housed individuals and (ii) interventions for CVD in homeless populations.
Methods
We conducted a systematic literature review in EMBASE until December 2018 using a search strategy for observational and interventional studies without restriction regarding languages or countries. Meta-analyses were conducted, where appropriate and possible. Outcome measures were all-cause and CVD mortality, and morbidity.
Results
Our search identified 17 articles (6 case-control, 11 cohort) concerning risk of CVD and none regarding specific interventions. Nine were included to perform a meta-analysis. The majority (13/17, 76.4%) were high quality and all were based in Europe or North America, including 765 459 individuals, of whom 32 721 were homeless. 12/17 studies were pre-2011. Homeless individuals were more likely to have CVD than non-homeless individuals (pooled OR 2.96; 95% CI 2.80 to 3.13; p<0.0001; heterogeneity p<0.0001; I=99.1%) and had increased CVD mortality (age-standardised mortality ratio range: 2.6-6.4). Compared with non-homeless individuals, hypertension was more likely in homeless people (pooled OR 1.38-1.75, p=0.0070; heterogeneity p=0.935; I=0.0%).
Conclusions
Homeless people have an approximately three times greater risk of CVD and an increased CVD mortality. However, there are no studies of specific pathways/interventions for CVD in this population. Future research should consider design and evaluation of tailored interventions or integrating CVD into existing interventions.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1483-1488
Al-Shakarchi NJ, Evans H, Luchenski SA, Story A, Banerjee A
Heart: 29 Sep 2020; 106:1483-1488 | PMID: 32665359
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Abstract

Computed tomography aortic valve calcium scoring for the assessment of aortic stenosis progression.

Doris MK, Jenkins W, Robson P, Pawade T, ... Newby DE, Dweck MR
Objective
CT quantification of aortic valve calcification (CT-AVC) is useful in the assessment of aortic stenosis severity. Our objective was to assess its ability to track aortic stenosis progression compared with echocardiography.
Methods
Subjects were recruited in two cohorts: (1) awhere patients underwent repeat CT-AVC or echocardiography within 4 weeks and (2) awhere patients underwent annual CT-AVC and/or echocardiography. Cohen\'s d-statistic () was computed from the ratio of annualised progression and measurement repeatability and used to estimate group sizes required to detect annualised changes in CT-AVC and echocardiography.
Results
A total of 33 (age 71±8) and 81 participants (age 72±8) were recruited to the reproducibility and progression cohorts, respectively. Ten CT scans (16%) were excluded from the progression cohort due to non-diagnostic image quality. Scan-rescan reproducibility was excellent for CT-AVC (limits of agreement -12% to 10 %, intraclass correlation (ICC) 0.99), peak velocity (-7% to +17%; ICC 0.92) mean gradient (-25% to 27%, ICC 0.96) and dimensionless index (-11% to +15%; ICC 0.98). Repeat measurements of aortic valve area (AVA) were less reliable (-44% to +28%, ICC 0.85).CT-AVC progressed by 152 (65-375) AU/year. For echocardiography, the median annual change in peak velocity was 0.1 (0.0-0.3) m/s/year, mean gradient 2 (0-4) mm Hg/year and AVA -0.1 (-0.2-0.0) cm/year. Cohen\'s d-statistic was more than double for CT-AVC (=3.12) than each echocardiographic measure (peak velocity =0.71 ; mean gradient =0.66; AVA =0.59, dimensionless index =1.41).
Conclusion
CT-AVC is reproducible and demonstrates larger increases over time normalised to measurement repeatability compared with echocardiographic measures.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Heart: 04 Oct 2020; epub ahead of print
Doris MK, Jenkins W, Robson P, Pawade T, ... Newby DE, Dweck MR
Heart: 04 Oct 2020; epub ahead of print | PMID: 33020228
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Abstract

Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction.

Vafadarnejad E, Rizzo G, Krampert L, Arampatzi P, ... Saliba AE, Cochain C
Rationale
After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage.
Objective
To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction.
Methods and results
We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils (, , ), and putative activity of transcriptional regulators involved in hypoxic response () and emergency granulopoiesis (). At 3 and 5 days, 2 major subsets of(enriched for eg,and ) and() neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of , heart infiltrating neutrophils acquired a unique SiglecF signature. SiglecF neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecF signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecF neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecF neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation.
Conclusions
Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF signature.



Circ Res: 08 Oct 2020; 127:e232-e249
Vafadarnejad E, Rizzo G, Krampert L, Arampatzi P, ... Saliba AE, Cochain C
Circ Res: 08 Oct 2020; 127:e232-e249 | PMID: 32811295
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Abstract

Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease.

Hageman SHJ, de Borst GJ, Dorresteijn JAN, Bots ML, ... Visseren FLJ,
Aim
To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.
Methods
Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.
Results
In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57).
Conclusions
The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2020; 106:1686-1692
Hageman SHJ, de Borst GJ, Dorresteijn JAN, Bots ML, ... Visseren FLJ,
Heart: 30 Oct 2020; 106:1686-1692 | PMID: 32170038
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Abstract

Sudden cardiac death in asymptomatic patients with aortic stenosis.

Minners J, Rossebo A, Chambers JB, Gohlke-Baerwolf C, ... Wachtell K, Jander N
Objective
We retrospectively analysed outcome data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study to assess the incidence and potential risk factors of sudden cardiac death (SCD) in this prospectively followed cohort of asymptomatic patients with aortic stenosis (AS).
Methods
Of the 1873 patients included in SEAS, 1849 (99%) with mild to moderate AS (jet velocity 2.5-4.0 m/s at baseline) and available clinical, echocardiographic and follow-up data were analysed. Patients undergoing aortic valve replacement were censored at the time of operation.
Results
During an overall follow-up of 46.1±14.6 months, SCD occurred in 27 asymptomatic patients (1.5%) after a mean of 28.3±16.6 months. The annualised event rate was 0.39%/year. The last follow-up echocardiography prior to the event showed mild to moderate stenosis in 22 and severe stenosis (jet velocity >4 m/s) in 5 victims of SCD. The annualised event rate after the diagnosis of severe stenosis was 0.60%/year compared with 0.46%/year in patients who did not progress to severe stenosis (p=0.79). Patients with SCD were older (p=0.01), had a higher left ventricular mass index (LVMI, p=0.001) and had a lower body mass index (BMI, p=0.02) compared with patients surviving follow-up. Cox regression analysis identified age (HR 1.06, 95% CI 1.01 to 1.11 per year, p=0.02), increased LVMI (HR 1.20, 95% CI 1.10 to 1.32 per 10 g/m, p<0.001) and lower BMI (HR 0.87, 95% CI 0.79 to 0.97 per kg/m, p=0.01) as independent risk factors of SCD.
Conclusion
SCD in patients with asymptomatic mild to moderate AS is rare and strongly related to left ventricular hypertrophy but not stenosis severity.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2020; 106:1646-1650
Minners J, Rossebo A, Chambers JB, Gohlke-Baerwolf C, ... Wachtell K, Jander N
Heart: 30 Oct 2020; 106:1646-1650 | PMID: 32737125
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Abstract

Utility of 3D printed cardiac models in congenital heart disease: a scoping review.

Illmann CF, Ghadiry-Tavi R, Hosking M, Harris KC
Objective
Three-dimensional printing (3DP) is a novel technology with applications in healthcare, particularly for congenital heart disease (CHD). We sought to explore the spectrum of use of 3D printed CHD models (3D-CM) and identify knowledge gaps within the published body of literature to guide future research.
Methods
We conducted a scoping review targeting published literature on the use of 3D-CMs. The databases of MEDLINE, EMBASE and Web of Science were searched from their inception until 19 July 2019. Inclusion criteria were primary research; studies reporting use of 3D-CMs; and human subjects. Exclusion criteria were studies where 3D-CMs were generated for proof of concept but not used; and studies focused on bioprinting or computational 3D-CMs. Studies were assessed for inclusion and data were extracted from eligible articles in duplicate.
Results
The search returned 648 results. Following assessment, 79 articles were included in the final qualitative synthesis. The majority (66%) of studies are case reports or series. 15% reported use of a control group. Three main areas of utilisation are for (1) surgical and interventional cardiology procedural planning (n=62), (2) simulation (n=25), and (3) education for medical personnel or patients and their families (n=17). Multiple studies used 3D-CMs for more than one of these areas.
Conclusions
3DP for CHD is a new technology with an evolving literature base. Most of the published literature are experiential reports as opposed to manuscripts on scientifically robust studies. Our study has identified gaps in the literature and addressed priority areas for future research.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2020; 106:1631-1637
Illmann CF, Ghadiry-Tavi R, Hosking M, Harris KC
Heart: 30 Oct 2020; 106:1631-1637 | PMID: 32727918
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Abstract

Socioeconomic characteristics of patients with coronary heart disease in relation to their cardiovascular risk profile.

De Bacquer D, van de Luitgaarden IAT, De Smedt D, Vynckier P, ... Wood D, De Backer G
Objective
People\'s socioeconomic status (SES) has a major impact on the risk of atherosclerotic cardiovascular disease (ASCVD) in primary prevention. In patients with existing ASCVD these associations are less documented. Here, we evaluate to what extent SES is still associated with patients\' risk profile in secondary prevention.
Methods
Based on results from a large sample of patients with coronary heart disease from the European Action on Secondary and Primary Prevention through Intervention to Reduce Events study, the relationship between SES and cardiovascular risk was examined. A SES summary score was empirically constructed from the patients\' educational level, self-perceived income, living situation and perception of loneliness.
Results
Analyses are based on observations in 8261 patients with coronary heart disease from 27 countries. Multivariate logistic regression analyses demonstrate that a low SES is associated (OR, 95% CI) with lifestyles such as smoking in men (1.63, 1.37 to 1.95), physical activity in men (1.51, 1.28 to 1.78) and women (1.77, 1.32 to 2.37) and obesity in men 1.28 (1.11 to 1.49) and women 1.65 (1.30 to 2.10). Patients with a low SES have more raised blood pressure in men (1.24, 1.07 to 1.43) and women (1.31, 1.03 to 1.67), used less statins and were less adherent to them. Cardiac rehabilitation programmes were less advised and attended by patients with a low SES. Access to statins in middle-income countries was suboptimal leaving about 80% of patients not reaching the low-density lipoprotein cholesterol target of <1.8 mmol/L. Patients\' socioeconomic level was also strongly associated with markers of well-being.
Conclusion
These results illustrate the complexity of the associations between SES, well-being and secondary prevention in patients with ASCVD. They emphasise the need for integrating innovative policies in programmes of cardiac rehabilitation and secondary prevention.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Oct 2020; epub ahead of print
De Bacquer D, van de Luitgaarden IAT, De Smedt D, Vynckier P, ... Wood D, De Backer G
Heart: 15 Oct 2020; epub ahead of print | PMID: 33067329
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Abstract

Cardiovascular disease recurrence and long-term mortality in a tri-ethnic British cohort.

Vyas M, Chaturvedi N, Hughes AD, Marmot M, Tillin T
Objective
Ethnic differences in cardiovascular disease incidence, but not cardiovascular disease recurrence, are reported. We characterised long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a British cohort of South Asians, African Caribbeans and Europeans.
Methods
We identified index and recurrent cardiovascular events and mortality between 1988 and 2017 using hospital records and death registry. Using multivariable hazards models, we separately calculated the adjusted HR of MACE and death following index event, adjusting for demographics, vascular and lifestyle risk factors. Using interaction terms, we evaluated if decade of index event modified the association between ethnicity and outcomes.
Results
South Asians were younger at the index event (median age 66 years, n=396) than Europeans (69 years, n=335) and African Caribbeans (70 years, n=70). During 4228 person-years, of the 801 patients, 537 developed MACE and 338 died, with the highest crude rate of MACE in South Asians. On adjustment of baseline factors, compared with the Europeans, the higher risk of MACE (HR 0.97, 95% CI 0.77 to 1.21) and the lower risk of mortality (HR 0.95, 95% CI 0.72 to 1.26) in South Asians was eliminated. African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 95% CI 0.74 to 1.47; and HR death 1.07, 95% CI 0.70 to 1.64). Long-term survival following an index event improved in South Asians (p 0.02) and African Caribbeans (p 0.07) compared with Europeans.
Conclusions
Baseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Heart: 15 Oct 2020; epub ahead of print
Vyas M, Chaturvedi N, Hughes AD, Marmot M, Tillin T
Heart: 15 Oct 2020; epub ahead of print | PMID: 33067326
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Abstract

Multiple arterial coronary bypass grafting is associated with greater survival in women.

Tam DY, Rocha RV, Fang J, Ouzounian M, ... Gaudino M, Fremes SE
Objective
Multiple arterial grafting (MAG) in coronary artery bypass grafting (CABG) is associated with higher survival and freedom from major adverse cardiac and cerebrovascular events (MACCEs) in observational studies of mostly men. It is not known whether MAG is beneficial in women. Our objectives were to compare the long-term clinical outcomes of MAG versus single arterial grafting (SAG) in women undergoing CABG for multivessel disease.
Methods
Clinical and administrative databases for Ontario, Canada, were linked to obtain all women with angiographic evidence of left main, triple or double vessel disease undergoing isolated non-emergent primary CABG from 2008 to 2019. 1:1 propensity score matching was performed. Late mortality and MACCE (composite of stroke, myocardial infarction, repeat revascularisation and death) were compared between the matched groups with a stratified log-rank test and Cox proportional-hazards model.
Results
2961 and 7954 women underwent CABG with MAG and SAG, respectively, for multivessel disease. Prior to propensity-score matching, compared with SAG, those who underwent MAG were younger (66.0 vs 68.9 years) and had less comorbidities. After propensity-score matching, in 2446 well-matched pairs, there was no significant difference in 30-day mortality (1.6% vs 1.8%, p=0.43) between MAG and SAG. Over a median and maximum follow-up of 5.0 and 11.0 years, respectively, MAG was associated with greater survival (HR 0.85, 95% CI 0.75 to 0.98) and freedom from MACCE (HR 0.85, 95% CI 0.76 to 0.95).
Conclusions
MAG was associated with greater survival and freedom from MACCE and should be considered for women with good life expectancy requiring CABG.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Oct 2020; epub ahead of print
Tam DY, Rocha RV, Fang J, Ouzounian M, ... Gaudino M, Fremes SE
Heart: 19 Oct 2020; epub ahead of print | PMID: 33082174
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Abstract

Newly diagnosed diabetes and outcomes after acute myocardial infarction in young adults.

Ding Q, Spatz ES, Lipska KJ, Lin H, ... Bueno H, Krumholz HM
Objective
To examine prevalence and characteristics of newly diagnosed diabetes (NDD) in younger adults hospitalised with acute myocardial infarction (AMI) and investigate whether NDD is associated with health status and clinical outcomes over 12-month post-AMI.
Methods
In individuals (18-55 years) admitted with AMI, without established diabetes, we defined NDD as (1) baseline or 1-month HbA1c≥6.5%; (2) discharge diabetes diagnosis or (3) diabetes medication initiation within 1 month. We compared baseline characteristics of NDD, established diabetes and no diabetes, and their associations with baseline, 1-month and 12-month health status (angina-specific and non-disease specific), mortality and in-hospital complications.
Results
Among 3501 patients in Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study, 14.5% met NDD criteria. Among 508 patients with NDD, 35 (6.9%) received discharge diagnosis, 91 (17.9%) received discharge diabetes education and 14 (2.8%) initiated pharmacological treatment within 1 month. NDD was more common in non-White (OR 1.58, 95% CI 1.23 to 2.03), obese (OR 1.72, 95% CI 1.39 to 2.12), financially stressed patients (OR 1.27, 95% CI 1.02 to 1.58). Compared with established diabetes, NDD was independently associated with better disease-specific health status and quality of life (p≤0.04). No significant differences were found in unadjusted in-hospital mortality and complications between NDD and established or no diabetes.
Conclusions
NDD was common among adults≤55 years admitted with AMI and was more frequent in non-White, obese, financially stressed individuals. Under 20% of patients with NDD received discharge diagnosis or initiated discharge diabetes education or pharmacological treatment within 1 month post-AMI. NDD was not associated with increased risk of worse short-term health status compared with risk noted for established diabetes.
Trial registration number
NCT00597922.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Oct 2020; epub ahead of print
Ding Q, Spatz ES, Lipska KJ, Lin H, ... Bueno H, Krumholz HM
Heart: 19 Oct 2020; epub ahead of print | PMID: 33082173
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Abstract

Maternal myocardial dysfunction after normotensive fetal growth restriction compared with hypertensive pregnancies: a speckle-tracking study.

Orabona R, Mohseni Z, Sciatti E, Mulder EG, ... Ghossein-Doha C, Spaanderman MEA
Objective
Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR.
Methods
For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity.
Results
Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR.
Conclusion
Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.



J Hypertens: 29 Sep 2020; 38:1955-1963
Orabona R, Mohseni Z, Sciatti E, Mulder EG, ... Ghossein-Doha C, Spaanderman MEA
J Hypertens: 29 Sep 2020; 38:1955-1963 | PMID: 32890271
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Abstract

New progress on the study of aortic stiffness in age-related hypertension.

Onuh JO, Qiu H

: Hypertension is a worldwide known cause of morbidity and mortality in the elderly and is a major risk factor for cardiovascular complications such as stroke, myocardial infarction, renal complications and heart failure. Although the mechanisms of hypertension remain largely unknown, a recent new concept is that aortic stiffening is a cause of hypertension in middle-aged and older individuals, which highlighted the importance of aortic stiffening in the development of age-related hypertension. Understanding the pathogenesis of aortic stiffness therefore became one of the important approaches to preventing and controlling hypertension. This review discusses the recent progress of the potential causes of aortic stiffening and its implication on the pathogenesis of hypertension, in terms of aging, inflammation, metabolic syndromes, neuroendocrine and the interaction among these causes.



J Hypertens: 29 Sep 2020; 38:1871-1877
Onuh JO, Qiu H
J Hypertens: 29 Sep 2020; 38:1871-1877 | PMID: 32890259
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Abstract

Single nucleotide polymorphisms of ADIPOQ gene associated with cardiovascular disease risk factors in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

Salazar-Tortosa DF, Pascual-Gamarra JM, Labayen I, Rupérez AI, ... Castillo MJ, Ruiz JR
Objectives
Cardiovascular diseases (CVDs) are responsible of 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. Aims of present research are to examine the association of ADIPOQ gene polymorphisms with cardiovascular disease risk factors in European adolescents.
Methods
A total of 14 polymorphisms in the ADIPOQ gene were genotyped in 1057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. We measured serum lipids and a CVD risk score, along with weight, height, triceps, and subscapular skinfold thickness, leptin, insulin and other markers of glucose regulation.
Results
The rs822393, rs822395 and rs7649121 polymorphisms of ADIPOQ gene were significantly associated with several CVD risk factors [i.e. high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, SBP and CVD risk score] in European adolescents. We also found an association of the TGAAGT ADIPOQ haplotype (rs822393, rs16861210, rs822395, rs822396, rs12495941 and rs7649121) with HDL-C and ApoA1 levels.
Conclusion
Several individual polymorphisms (rs822393, rs822395 and rs7649121) and a haplotype of ADIPOQ gene were significantly associated with cardiovascular disease risk factors in European adolescents.



J Hypertens: 29 Sep 2020; 38:1971-1979
Salazar-Tortosa DF, Pascual-Gamarra JM, Labayen I, Rupérez AI, ... Castillo MJ, Ruiz JR
J Hypertens: 29 Sep 2020; 38:1971-1979 | PMID: 32890273
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Impact:
Abstract

Active gingival inflammation is linked to hypertension.

Pietropaoli D, Monaco A, D\'Aiuto F, Muñoz Aguilera E, ... Ferri C, Del Pinto R
Background
Cardiovascular diseases (CVD) including hypertension, are characterized by underlying systemic inflammation. Periodontitis, which can impact the systemic inflammatory burden has recently been linked to high blood pressure (BP). However, the relationship of gingival bleeding, as an easily accessible marker of periodontal disorder, with hypertension, remains unclear.
Methods
Survey-based propensity score matching (PSM) incorporating major confounders shared between hypertension and periodontal diseases was applied to cross-sectional NHANES III data from 5396 adults at least 30 years old who underwent BP measurement and periodontal examination, identifying two matched groups with and without gingival bleeding. The association of bleeding gums with SBP (mmHg) and high/uncontrolled BP was then assessed with generalized additive models incorporating inflammatory markers. Stratification by periodontal status (healthy; gingivitis; stable periodontitis; unstable periodontitis) was performed. Variables importance was estimated using machine learning.
Results
Gingival bleeding (gingivitis; unstable periodontitis) was independently associated with +2.6 mmHg (P < 0.001) SBP compared with no bleeding (healthy periodontium; stable periodontitis), and with greater odds (OR = 1.42; 95% CI = 1.19-1.68; P < 0.001) of high/uncontrolled BP. Participants with unstable periodontitis had higher SBP than those with stable periodontitis (+2.1 mmHg; P < 0.001) or gingivitis (+5.3 mmHg; P < 0.001). Unstable periodontitis and gingivitis were consistently associated with increased risk of high/uncontrolled BP (OR = 1.65, 95% CI = 2.14-1.82; OR = 1.49, 95% CI = 1.22-1.82, respectively). Inflammatory markers allowed a maximum of 12% gain in the models\' predictive power.
Conclusion
Gingival bleeding contributes to shaping the relationship between periodontal diseases and BP, but the burden represented by periodontitis is also crucial. Periodontal evaluation might be of importance in difficult to control hypertension.



J Hypertens: 29 Sep 2020; 38:2018-2027
Pietropaoli D, Monaco A, D'Aiuto F, Muñoz Aguilera E, ... Ferri C, Del Pinto R
J Hypertens: 29 Sep 2020; 38:2018-2027 | PMID: 32890278
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Abstract

Anxiety, depression, chronic inflammation and aortic stiffness in Crohn\'s disease: the brain--gut--vascular axis.

Zanoli L, Tuttolomondo A, Inserra G, Cappello M, ... Castellino P,
Background
Patients with Crohn\'s disease have an increased aortic stiffness, a known cardiovascular risk factor. Anxiety, a key factor of the brain--gut axis in patients with Crohn\'s disease, is implicated in the pathogenesis and progression of the disease, and is linked with aortic stiffening in other clinical settings.
Objectives
Considering that depression is frequently linked to anxiety in Crohn\'s disease, we performed a mediation analysis to reveal the potential link between anxiety, depression and aortic stiffness in these patients.
Methods
Multicentre observational cross-sectional study of 86 consecutive patients with Crohn\'s disease and 86 matched control individuals. The connections between anxiety, depression, disease duration, aortic pulse wave velocity (aPWV), brachial and central SBP were tested using partial least squares structural equations modelling.
Results
In patients with Crohn\'s disease, anxiety (path coefficient: 0.220, P = 0.01) and disease duration (path coefficient: 0.270, P = 0.02) were associated with aPWV that in turn was associated with brachial SBP (path coefficient: 0.184, P = 0.03). These associations were even stronger in patients with active disease. The connection between anxiety and aPWV was in part mediated by central SBP (indirect effect: 0.090, P = 0.01; indirect-to-total effect ratio: 41%) as well as, in a pilot substudy, by sympathetic hyperactivity. Anxiety and depression were highly correlated in patients with Crohn\'s disease. Consequently, results were confirmed when anxiety was substituted by depression.
Conclusion
The connections of anxiety, depression and chronic inflammation with aPWV and SBP could suggest the first evidence of a brain--gut--vascular axis and new potential targets for therapy in patients with Crohn\'s disease.



J Hypertens: 29 Sep 2020; 38:2008-2017
Zanoli L, Tuttolomondo A, Inserra G, Cappello M, ... Castellino P,
J Hypertens: 29 Sep 2020; 38:2008-2017 | PMID: 32890277
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Abstract

A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

Coca A, Kreutz R, Manolis AJ, Mancia G

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.



J Hypertens: 29 Sep 2020; 38:1890-1898
Coca A, Kreutz R, Manolis AJ, Mancia G
J Hypertens: 29 Sep 2020; 38:1890-1898 | PMID: 32890261
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Abstract

Visit-to-visit blood pressure variability and renal outcomes: results from ONTARGET and TRANSCEND trials.

Mancia G, Schumacher H, Böhm M, Mann JFE, ... Teo KK, Yusuf S
Aims
There is conflicting evidence on whether in treated hypertensive patients the risk of renal outcomes is associated with visit-to-visit SBP variability. Furthermore, limited evidence is available on how important is SBP variability for prediction of renal outcomes compared with on-treatment mean SBP. We addressed these issues in 28 790 participants of the Ongoing Treatment Alone and in combination with Ramipril Global End point Trial and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant Subjects with Cardiovascular Disease trials.
Methods and results
SBP variability was expressed as the coefficient of variation of the mean with which it showed no relationship. SBP variability and mean values were obtained from five visits during the first 2 years of treatment after the end of the titration phase. Incidence of several renal outcomes (end-stage renal disease, doubling of serum creatinine, new microalbuminuria, new macroalbuminuria and their composite) was calculated from the third year of treatment onward. Patients were divided in quintiles of SBP-coefficient of variation (SBP-CV) or mean SBP, which exhibited superimposable mean blood pressure and SBP-CV values, respectively. A progressive increase of SBP-CV was not accompanied by a parallel increase in a widely adjusted (baseline and on-treatment confounders) risk of most renal outcomes (end-stage renal disease, new macroalbuminuria, new microalbuminuria and their composite) in the subsequent on-treatment years. In contrast, the adjusted risk of most renal outcomes increased progressively from the lowest to the highest quintile of on-treatment mean SBP. Progression from lowest to highest mean on-treatment SBP, but not SBP-CV, was also associated with a less frequent return to normoalbuminuria in patients with initial micro or macroalbuminuria. Renal outcome prediction was slightly improved by the combined use of SBP-CV and mean SBP quintiles.
Conclusion
Visit-to-visit SBP variability had no major predictive value for the risk of renal outcomes, which, in contrast, was sensitively predicted by mean on-treatment SBP. A further slight increase in prediction of renal outcomes was seen by combining on-treatment mean SBP and variability.



J Hypertens: 29 Sep 2020; 38:2050-2058
Mancia G, Schumacher H, Böhm M, Mann JFE, ... Teo KK, Yusuf S
J Hypertens: 29 Sep 2020; 38:2050-2058 | PMID: 32890282
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Abstract

High-sensitivity cardiac troponin I in women with a history of early-onset preeclampsia.

Muijsers HEC, Westermann D, Birukov A, van der Heijden OWH, ... Zeller T, Roeleveld N
Objective
Preeclampsia is associated with an elevated risk of cardiovascular disease later in life. Women with a history of preeclampsia are at risk of developing hypertension as well as ischemic heart disease. Identification of women at the highest risk is important to initiate preventive strategies. We investigated whether high-sensitivity cardiac troponin I (hs-cTnI) levels are associated with a history of early-onset preeclampsia, and with hypertension in these high-risk women.
Methods
Approximately 9-10 years after pregnancy, hs-cTnI levels were measured for 339 women of the Preeclampsia Risk Evaluation in FEMales cohort, consisting of 177 women with a history of early-onset preeclampsia and 162 women with a previous uncomplicated index pregnancy. Associations were analyzed using several statistical tests and linear regression analysis.
Results
The median hs-cTnI levels (IQR) were 2.50 ng/l (2.30) in women with a history of early-onset preeclampsia and 2.35 ng/l (2.50) in women without a history of preeclampsia, P = 0.53. Among women with a history of early-onset preeclampsia, the hs-cTnI levels were higher in women who were hypertensive compared with their normotensive counterparts (medians 2.60 versus 2.30; P = 0.03). In addition, blood pressure levels increased with increasing hs-cTnI levels.
Conclusion
We did not find a difference in hs-cTnI levels between women with and without a history of early-onset preeclampsia. Nonetheless, hs-cTnI levels were statistically significantly higher in current hypertensive women with a history of preeclampsia compared with their normotensive counterparts. Therefore, hs-cTnI levels might improve risk prediction for women at the highest risk of cardiovascular disease.



J Hypertens: 29 Sep 2020; 38:1948-1954
Muijsers HEC, Westermann D, Birukov A, van der Heijden OWH, ... Zeller T, Roeleveld N
J Hypertens: 29 Sep 2020; 38:1948-1954 | PMID: 32890270
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Abstract

Blood pressure lability is associated with subcortical atrophy in early Parkinson\'s disease.

Yoo SW, Yun E, Bang M, Yoon U, ... Shin NY, Kim JS
Objective
Increased cerebral white matter intensities associated with blood pressure (BP) lability were reported in patients with Parkinson\'s disease. However, this type of cardiovascular dysautonomia has seldom been associated with disruptions in deep gray matter structures in Parkinson\'s disease. In the present study, the associations between BP lability and subcortical deep gray matter structures in early Parkinson\'s disease were evaluated.
Methods
The present study included 98 early nondemented Parkinson\'s disease patients. Supine and orthostatic BPs were measured using head-up tilt tests. BP variabilities, measured as standard deviations of 24-h daytime and nighttime BPs, were assessed using 24-h ambulatory BP monitoring. Every patient underwent brain MRI and measurement of deep gray matter volumes. The associations between BP lability and deep gray matter structures were analyzed.
Results
Parkinson\'s disease patients with orthostatic hypotension had smaller volumes of striatum, particularly caudate, than patients without OH after adjusting for covariates of age, sex, disease duration, and Mini-Mental Status Examination score. Nocturnal BP variability was inversely associated with thalamus, hippocampus, and globus pallidus volumes.
Conclusion
The results from the present study showed that BP lability was adversely associated with structural changes in early Parkinson\'s disease. Different forms of BP fluctuations influenced distinct deep gray matter structures.



J Hypertens: 29 Sep 2020; 38:2043-2049
Yoo SW, Yun E, Bang M, Yoon U, ... Shin NY, Kim JS
J Hypertens: 29 Sep 2020; 38:2043-2049 | PMID: 32890281
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Abstract

Chronic effects and optimal dosage of strength training on SBP and DBP: a systematic review with meta-analysis.

Oliver-Martínez PA, Ramos-Campo DJ, Martínez-Aranda LM, Martínez-Rodríguez A, Rubio-Arias JÁ
Background and objectives
Hypertension is a disease affecting a large part of the world\'s population that causes millions of deaths annually. Physical exercise is proposed as an alternative to pharmacologic therapies used to reduce blood pressure. The main objective was to compare the effect of different types of strength training in blood pressure, as well as to analyse several variables that can modify the effect of strength training not combined with medication in SBP and DBP (SBP-DBP).
Methods
The search was carried out in two scientific databases: PubMed and Web of Science. Articles were included following three criteria: analysing the chronic effect of strength training in blood pressure; the studies were conducted at least during 4 weeks; and the articles were published in English.
Results
The analysis showed a significant decrease of blood pressure for all types of training. The effect on SBP was greater when training without medication was carried out with isometric exercises than when training was performed with dynamic exercises. Moreover, the effects were no longer significant when the duration of the training programme exceeded 20 weeks as well as when training frequency was lower than three times per week were found.
Conclusion
Strength training is effective in reducing both blood pressures (SBP-DBP). Training programmes, consisting of dynamic strength training without medication at a moderate intensity and with a frequency of three times per week, seem to be optimal in order to reduce blood pressure.Prospective register of Systematic Reviews: CRD42019122421.



J Hypertens: 29 Sep 2020; 38:1909-1918
Oliver-Martínez PA, Ramos-Campo DJ, Martínez-Aranda LM, Martínez-Rodríguez A, Rubio-Arias JÁ
J Hypertens: 29 Sep 2020; 38:1909-1918 | PMID: 32890263
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