Topic: General Cardiology

Abstract

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

Weinreich DM, Sivapalasingam S, Norton T, Ali S, ... Yancopoulos GD, Trial Investigators
Background
In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.
Methods
In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.
Results
Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.
Conclusions
REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 28 Sep 2021; epub ahead of print
Weinreich DM, Sivapalasingam S, Norton T, Ali S, ... Yancopoulos GD, Trial Investigators
N Engl J Med: 28 Sep 2021; epub ahead of print | PMID: 34587383
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Abstract

Myocarditis after Covid-19 Vaccination in a Large Health Care Organization.

Witberg G, Barda N, Hoss S, Richter I, ... Balicer RD, Kornowski R
Background
Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.
Methods
We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient\'s electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.
Results
Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.
Conclusions
Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 05 Oct 2021; epub ahead of print
Witberg G, Barda N, Hoss S, Richter I, ... Balicer RD, Kornowski R
N Engl J Med: 05 Oct 2021; epub ahead of print | PMID: 34614329
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Abstract

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

Mevorach D, Anis E, Cedar N, Bromberg M, ... Keinan-Boker L, Alroy-Preis S
Background
Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.
Methods
We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons.
Results
Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637.
Conclusions
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 05 Oct 2021; epub ahead of print
Mevorach D, Anis E, Cedar N, Bromberg M, ... Keinan-Boker L, Alroy-Preis S
N Engl J Med: 05 Oct 2021; epub ahead of print | PMID: 34614328
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Abstract

Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction.

Lee KK, Bularga A, O\'Brien R, Ferry AV, ... Gray AJ, Mills NL
Background
Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events.
Objectives
This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded.
Methods
This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge.
Results
Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA.
Conclusions
In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.

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

J Am Coll Cardiol: 04 Oct 2021; 78:1407-1417
Lee KK, Bularga A, O'Brien R, Ferry AV, ... Gray AJ, Mills NL
J Am Coll Cardiol: 04 Oct 2021; 78:1407-1417 | PMID: 34593122
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Abstract

Day-to-day measurement of physical activity and risk of atrial fibrillation.

Bonnesen MP, Frodi DM, Haugan KJ, Kronborg C, ... Svendsen JH, Diederichsen SZ
Aims 
The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF).
Methods and results 
A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)].
Conclusions 
Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall.
Clinical trial registration
ClinicalTrials.gov, identifier: NCT02036450.

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

Eur Heart J: 06 Oct 2021; 42:3979-3988
Bonnesen MP, Frodi DM, Haugan KJ, Kronborg C, ... Svendsen JH, Diederichsen SZ
Eur Heart J: 06 Oct 2021; 42:3979-3988 | PMID: 34471928
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Abstract

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

Dreyfus J, Audureau E, Bohbot Y, Coisne A, ... Obadia JF, Messika-Zeitoun D
Aims 
Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR).
Methods and results 
All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63).
Conclusion 
We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

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

Eur Heart J: 28 Sep 2021; epub ahead of print
Dreyfus J, Audureau E, Bohbot Y, Coisne A, ... Obadia JF, Messika-Zeitoun D
Eur Heart J: 28 Sep 2021; epub ahead of print | PMID: 34586392
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Abstract

Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study.

Banning AP, Serruys P, De Maria GL, Ryan N, ... Tijssen J, Escaned J
Aims
The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial.
Methods and results
SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events\' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35).
Conclusions
Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

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

Eur Heart J: 06 Oct 2021; epub ahead of print
Banning AP, Serruys P, De Maria GL, Ryan N, ... Tijssen J, Escaned J
Eur Heart J: 06 Oct 2021; epub ahead of print | PMID: 34617993
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Abstract

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

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

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

Eur Heart J: 30 Sep 2021; 42:3844-3852
Curzen N, Nicholas Z, Stuart B, Wilding S, ... Douglas P, Hlatky M
Eur Heart J: 30 Sep 2021; 42:3844-3852 | PMID: 34269376
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Abstract

Impact of COVID-19 pandemic restrictions on ST-elevation myocardial infarction: a cardiac magnetic resonance imaging study.

Lechner I, Reindl M, Tiller C, Holzknecht M, ... Metzler B, Reinstadler SJ
Aims
The severity of myocardial tissue damage following ST-elevation myocardial infarction (STEMI) strongly determines short- and long-term prognosis. This study explored the impact of the coronavirus disease 2019 (COVID-19) pandemic and associated public health restrictions on infarct severity.
Methods and results
STEMI patients treated with primary percutaneous coronary intervention (PCI) and included in the prospective Magnetic Resonance Imaging in Acute ST-Elevation Myocardial Infarction (MARINA-STEMI) cohort study from 2015- 2020 (n = 474) were categorized according to (i) timeframes with and without major public health restrictions in 2020, and (ii) timeframes of major public health restrictions during 2020 and during the corresponding timeframes between 2015-2019. Myocardial damage was evaluated by cardiac magnetic resonance imaging. During major public health restrictions in 2020 (n = 48), there was an increase in infarct size (22 [IQR 12-29] vs. 14 [IQR 6-23]%, P < 0.01), a higher frequency (77% vs. 52%, P < 0.01) and larger extent of microvascular obstruction (1.5 [IQR 0.1-11.4] vs. 0.2 [IQR 0.0-2.6]%, P < 0.01) and a higher rate of intramyocardial haemorrhage (56% vs. 34%, P = 0.02) as compared to the phases without major restrictions in 2020 (n = 101). These findings were confirmed in adjusted analysis and were consistent when comparing patients admitted in 2020 versus patients admitted in the \"pre-pandemic\" era (2015-2019). Patient characteristics were comparable between groups, except for a significantly longer total ischemia time (P < 0.01) and higher frequency of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow 0 during times of major restrictions (P = 0.03).
Conclusion
This study provides novel mechanistic insights demonstrating a significant increase in myocardial damage in STEMI patients admitted during the COVID-19 pandemic with a temporal relation to major public health restrictions.

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

Eur Heart J: 10 Oct 2021; epub ahead of print
Lechner I, Reindl M, Tiller C, Holzknecht M, ... Metzler B, Reinstadler SJ
Eur Heart J: 10 Oct 2021; epub ahead of print | PMID: 34632491
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Abstract

Towards personalized antithrombotic management with drugs and devices across the cardiovascular spectrum.

Lüscher TF, Davies A, Beer JH, Valgimigli M, ... Diener HC, Konstantinides SV
Intravascular thrombus formation and embolization are among the most frequent events leading to a number of cardiovascular conditions with high morbidity and mortality. The underlying causes are stasis of the circulating blood, genetic and acquired coagulation disorders, and reduced antithrombotic or prothrombotic properties of the vascular wall (Virchow\'s triad). In the venous system, intravascular thrombi can cause venous thrombosis and pulmonary and even peripheral embolism including ischaemic stroke [through a patent foramen ovale (PFO)]. Thrombi in the left atrium and its appendage or ventricle form in the context of atrial fibrillation and infarction, respectively. Furthermore, thrombi can form on native or prosthetic aortic valves, within the aorta (in particular at sites of ulcers, aortic dissection, and abdominal aneurysms), and in cerebral and peripheral arteries causing stroke and critical limb ischaemia, respectively. Finally, thrombotic occlusion may occur in arteries supplying vital organs such the heart, brain, kidney, and extremities. Thrombus formation and embolization can be managed with anticoagulants and devices depending on where they form and embolize and on patient characteristics. Vitamin K antagonists are preferred in patients with mechanical valves, while novel oral anticoagulants are first choice in most other cardiovascular conditions, in particular venous thromboembolism and atrial fibrillation. As anticoagulants are associated with a risk of bleeding, devices such as occluders of a PFO or the left atrial appendage are preferred in patients with an increased bleeding risk. Platelet inhibitors such as aspirin and/or P2Y12 antagonists are preferred in the secondary prevention of coronary artery disease, stroke, and peripheral artery disease either alone or in combination depending on the clinical condition. A differential and personalized use of anticoagulants, platelet inhibitors, and devices is recommended and reviewed in this article.

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

Eur Heart J: 07 Oct 2021; epub ahead of print
Lüscher TF, Davies A, Beer JH, Valgimigli M, ... Diener HC, Konstantinides SV
Eur Heart J: 07 Oct 2021; epub ahead of print | PMID: 34624084
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Abstract

Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: the FAPIC score.

Hwang J, Park SH, Lee SW, Lee SB, ... Shin JI, Smith L
Aims
The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality.
Methods and results
PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732-0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration.
Conclusions
Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants.

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

Eur Heart J: 13 Oct 2021; 42:4053-4063
Hwang J, Park SH, Lee SW, Lee SB, ... Shin JI, Smith L
Eur Heart J: 13 Oct 2021; 42:4053-4063 | PMID: 34545400
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Abstract

Hypertensive disorders of pregnancy and onset of chronic hypertension in France: the nationwide CONCEPTION study.

Boucheron P, Lailler G, Moutengou E, Regnault N, ... Blacher J, Olié V
Aims 
Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth.
Methods and results 
This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier.
Conclusion 
Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.

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

Eur Heart J: 12 Oct 2021; epub ahead of print
Boucheron P, Lailler G, Moutengou E, Regnault N, ... Blacher J, Olié V
Eur Heart J: 12 Oct 2021; epub ahead of print | PMID: 34643681
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Abstract

Maternal and neonatal complications in women with congenital heart disease: a nationwide analysis.

Lammers AE, Diller GP, Lober R, Möllers M, ... Enders D, Baumgartner H
Aims
The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD).
Methods and results
Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, ∼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001).
Conclusions
This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.

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

Eur Heart J: 11 Oct 2021; epub ahead of print
Lammers AE, Diller GP, Lober R, Möllers M, ... Enders D, Baumgartner H
Eur Heart J: 11 Oct 2021; epub ahead of print | PMID: 34638134
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Abstract

On-Treatment Blood Pressure and Cardiovascular Outcomes in Adults With Hypertension and Left Ventricular Hypertrophy.

Lee HH, Lee H, Cho SMJ, Kim DW, Park S, Kim HC
Background
Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH).
Objectives
This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH.
Methods
From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP).
Results
Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group.
Conclusions
In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients.

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

J Am Coll Cardiol: 11 Oct 2021; 78:1485-1495
Lee HH, Lee H, Cho SMJ, Kim DW, Park S, Kim HC
J Am Coll Cardiol: 11 Oct 2021; 78:1485-1495 | PMID: 34620404
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Abstract

Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events.

Cubedo J, Padró T, Vilahur G, Crea F, ... Gallinat A, Badimon L
Aim
Using proteomics, we previously found that serum levels of glycosylated (Glyc) forms of apolipoprotein J (ApoJ), a cytoprotective and anti-oxidant protein, decrease in the early phase of acute myocardial infarction (AMI). We aimed to investigate: (i) ApoJ-Glyc intracellular distribution and secretion during ischaemia; (ii) the early changes in circulating ApoJ-Glyc during AMI; and (iii) associations between ApoJ-Glyc and residual ischaemic risk post-AMI.
Methods and results
Glycosylated apolipoprotein J was investigated in: (i) cells from different organ/tissue origin; (ii) a pig model of AMI; (iii) de novo AMI patients (n = 38) at admission within the first 6 h of chest pain onset and without troponin T elevation at presentation (early AMI); (iv) ST-elevation myocardial infarction patients (n = 212) who were followed up for 6 months; and (v) a control group without any overt cardiovascular disease (n = 144). Inducing simulated ischaemia in isolated cardiac cells resulted in an increased intracellular accumulation of non-glycosylated ApoJ forms. A significant decrease in ApoJ-Glyc circulating levels was seen 15 min after ischaemia onset in pigs. Glycosylated apolipoprotein J levels showed a 45% decrease in early AMI patients compared with non-ischaemic patients (P < 0.0001), discriminating the presence of the ischaemic event (area under the curve: 0.934; P < 0.0001). ST-elevation myocardial infarction patients with lower ApoJ-Glyc levels at admission showed a higher rate of recurrent ischaemic events and mortality after 6-month follow-up (P = 0.008).
Conclusions
These results indicate that ischaemia induces an intracellular accumulation of non-glycosylated ApoJ and a reduction in ApoJ-Glyc secretion. Glycosylated apolipoprotein J circulating levels are reduced very early after ischaemia onset. Its continuous decrease indicates a worsening in the evolution of the cardiac event, likely identifying patients with sustained ischaemia after AMI.

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

Eur Heart J: 27 Sep 2021; epub ahead of print
Cubedo J, Padró T, Vilahur G, Crea F, ... Gallinat A, Badimon L
Eur Heart J: 27 Sep 2021; epub ahead of print | PMID: 34580705
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Abstract

Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy.

Nauffal V, Marstrand P, Han L, Parikh VN, ... Olivotto I, Ho CY
Aims 
Risk stratification algorithms for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) and regional differences in clinical practice have evolved over time. We sought to compare primary prevention implantable cardioverter defibrillator (ICD) implantation rates and associated clinical outcomes in US vs. non-US tertiary HCM centres within the international Sarcomeric Human Cardiomyopathy Registry.
Methods and results
We included patients with HCM enrolled from eight US sites (n = 2650) and five non-US (n = 2660) sites and used multivariable Cox-proportional hazards models to compare outcomes between sites. Primary prevention ICD implantation rates in US sites were two-fold higher than non-US sites (hazard ratio (HR) 2.27 [1.89-2.74]), including in individuals deemed at high 5-year SCD risk (≥6%) based on the HCM risk-SCD score (HR 3.27 [1.76-6.05]). US ICD recipients also had fewer traditional SCD risk factors. Among ICD recipients, rates of appropriate ICD therapy were significantly lower in US vs. non-US sites (HR 0.52 [0.28-0.97]). No significant difference was identified in the incidence of SCD/resuscitated cardiac arrest among non-recipients of ICDs in US vs. non-US sites (HR 1.21 [0.74-1.97]).
Conclusion 
Primary prevention ICDs are implanted more frequently in patients with HCM in US vs. non-US sites across the spectrum of SCD risk. There was a lower rate of appropriate ICD therapy in US sites, consistent with a lower-risk population, and no significant difference in SCD in US vs. non-US patients who did not receive an ICD. Further studies are needed to understand what drives malignant arrhythmias, optimize ICD allocation, and examine the impact of different ICD utilization strategies on long-term outcomes in HCM.

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

Eur Heart J: 06 Oct 2021; 42:3932-3944
Nauffal V, Marstrand P, Han L, Parikh VN, ... Olivotto I, Ho CY
Eur Heart J: 06 Oct 2021; 42:3932-3944 | PMID: 34491319
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Impact:
Abstract

Modeling the Recommended Age for Initiating Coronary Artery Calcium Testing Among At-Risk Young Adults.

Dzaye O, Razavi AC, Dardari ZA, Shaw LJ, ... Mortensen MB, Blaha MJ
Background
There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis.
Objectives
The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile.
Methods
We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors.
Results
Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors.
Conclusions
Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.

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

J Am Coll Cardiol: 18 Oct 2021; 78:1573-1583
Dzaye O, Razavi AC, Dardari ZA, Shaw LJ, ... Mortensen MB, Blaha MJ
J Am Coll Cardiol: 18 Oct 2021; 78:1573-1583 | PMID: 34649694
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Abstract

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR.

Escaned J, Cao D, Baber U, Nicolas J, ... Pocock S, Mehran R
Aims
Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population.
Methods and results
This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status.
Conclusions
Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

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

Eur Heart J: 17 Oct 2021; epub ahead of print
Escaned J, Cao D, Baber U, Nicolas J, ... Pocock S, Mehran R
Eur Heart J: 17 Oct 2021; epub ahead of print | PMID: 34662382
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Abstract

Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohort-based study.

Wadström BN, Wulff AB, Pedersen KM, Jensen GB, Nordestgaard BG
Aims 
The atherogenic potential of cholesterol in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged. Elevated remnant cholesterol is associated with increased risk of myocardial infarction and ischaemic stroke. We tested the hypothesis that elevated remnant cholesterol is also associated with increased risk of peripheral artery disease (PAD).
Methods and results 
We studied 106 937 individuals from the Copenhagen General Population Study recruited in 2003-15. During up to 15 years of follow-up, 1586 were diagnosed with PAD, 2570 with myocardial infarction, and 2762 with ischaemic stroke. We also studied 13 974 individuals from the Copenhagen City Heart Study recruited in 1976-78. During up to 43 years of follow-up, 1033 were diagnosed with PAD, 2236 with myocardial infarction, and 1976 with ischaemic stroke. Remnant cholesterol was calculated from a standard lipid profile. Diagnoses were from Danish nationwide health registries. In the Copenhagen General Population Study, elevated remnant cholesterol levels were associated with higher risk of PAD, up to a multivariable adjusted hazard ratio (HR) of 4.8 (95% confidence interval 3.1-7.5) for individuals with levels ≥1.5 mmol/L (58 mg/dL) vs. <0.5 mmol/L (19 mg/dL). Corresponding results were 4.2 (2.9-6.1) for myocardial infarction and 1.8 (1.4-2.5) for ischaemic stroke. In the Copenhagen City Heart Study, corresponding HRs were 4.9 (2.9-8.5) for PAD, 2.6 (1.8-3.8) for myocardial infarction, and 2.1 (1.5-3.1) for ischaemic stroke.
Conclusion 
Elevated remnant cholesterol is associated with a five-fold increased risk of PAD in the general population, higher than for myocardial infarction and ischaemic stroke.

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

Eur Heart J: 17 Oct 2021; epub ahead of print
Wadström BN, Wulff AB, Pedersen KM, Jensen GB, Nordestgaard BG
Eur Heart J: 17 Oct 2021; epub ahead of print | PMID: 34661640
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Impact:
Abstract

Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation.

Ahn JM, Zimmermann FM, Arora S, Solberg OG, ... Gullestad L, Fearon WF
Aims
We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry.
Methods and results
Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2 weeks) and in 240 patients at 1 year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR ≤ 0.80), and microvascular dysfunction (either IMR ≥ 25 or CFR ≤ 2.0 with FFR > 0.80). The primary outcome was the composite of death or re-transplantation at 10 years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P = 0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P = 0.73) were not predictors of death and re-transplantation at 10 years. At 1 year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P = 0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P = 0.015) were associated with significantly increased risk of death or re-transplantation at 10 years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (χ2 improvement: 7.41, P = 0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes.
Conclusion
Abnormal coronary physiology 1 year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10 years.

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

Eur Heart J: 18 Oct 2021; epub ahead of print
Ahn JM, Zimmermann FM, Arora S, Solberg OG, ... Gullestad L, Fearon WF
Eur Heart J: 18 Oct 2021; epub ahead of print | PMID: 34665224
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Impact:
Abstract

Contributions of Systolic and Diastolic Blood Pressures to Cardiovascular Outcomes in the ALLHAT Study.

Itoga NK, Tawfik DS, Montez-Rath ME, Chang TI
Background
SBP and DBP have important associations with cardiovascular events, but are seldom considered simultaneously.
Objectives
This study sought to simultaneously analyze systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements on the associated risk of a primary composite outcome of all-cause mortality, myocardial infarction (MI), congestive heart failure (CHF), or stroke.
Methods
This study analyzed ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) data, which randomized adults to chlorthalidone, amlodipine, or lisinopril. The authors evaluated the simultaneous association of repeated SBP and DBP measurements on the primary composite outcome, and each outcome using proportional hazards regression. The authors report hazard ratios using a \"heat map\" to represent high and low risk according to SBP and DBP combinations.
Results
During a median follow-up of 4.4 years (interquartile range: 3.6-5.4 years), 33,357 participants experienced 2,636 MIs, 866 CHF events, 936 strokes, and 3,700 deaths; 8,138 patients (24.4%) had at least 1 event. For the composite outcome, all-cause mortality, MI, and CHF, a U-shaped association was observed with SBP and DBP, but the SBP and DBP associated with the lowest hazards differed for each outcome. For example, SBP/DBP of 140-155/70-80 mm Hg was associated with the lowest HR for all-cause mortality, compared with 110-120/85-90 mm Hg for MI and 125-135/70-75 mm Hg for CHF. In contrast, the association of SBP and stroke was linear.
Conclusions
The risk pattern of SBP and DBP differs by clinical outcomes, and the SBP and DBP associated with the lowest risk. Our results suggest individualization of blood pressure targets may depend in part on the cardiovascular event for which the patient is most at risk.

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

J Am Coll Cardiol: 25 Oct 2021; 78:1671-1678
Itoga NK, Tawfik DS, Montez-Rath ME, Chang TI
J Am Coll Cardiol: 25 Oct 2021; 78:1671-1678 | PMID: 34674811
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Impact:
Abstract

No-Touch Versus Conventional Vein Harvesting Techniques at 12 Months After Coronary Artery Bypass Grafting Surgery: Multicenter Randomized, Controlled Trial.

Tian M, Wang X, Sun H, Feng W, ... Huo X, Hu S
Background
Vein graft occlusion is deemed a major challenge in coronary artery bypass grafting. Previous studies implied that the no-touch technique for vein graft harvesting could reduce occlusion rate compared with the conventional approach; however, evidence on the clinical benefit and generalizability of the no-touch technique is scare.
Methods
From April 2017 to June 2019, we randomly assigned 2655 patients undergoing coronary artery bypass grafting at 7 hospitals in a 1:1 ratio to receive no-touch technique or conventional approach for vein harvesting. The primary outcome was vein graft occlusion on computed tomography angiography at 3 months and the secondary outcomes included 12-month vein graft occlusion, recurrence of angina, and major adverse cardiac and cerebrovascular events. The generalized estimate equation model was used to account for the cluster effect of grafts from the same patient.
Results
During the follow-up, 2533 (96.0%) participants received computed tomography angiography at 3 months after coronary artery bypass grafting and 2434 (92.2%) received it at 12 months. The no-touch group had significantly lower rates of vein graft occlusion than the conventional group both at 3 months (2.8% versus 4.8%; odds ratio, 0.57 [95% CI, 0.41-0.80]; P<0.001) and 12 months (3.7% versus 6.5%; odds ratio, 0.56 [95% CI, 0.41-0.76]; P<0.001). Recurrence of angina was also less common in the no-touch group at 12 months (2.3% versus 4.1%; odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). Rates of major adverse cardiac and cerebrovascular events were of no significant difference between the 2 groups. The no-touch technique was associated with higher rates of leg wound surgical interventions at 3-month follow-up (10.3% versus 4.3%; odds ratio, 2.55 [95% CI, 1.85-3.52]; P<0.001).
Conclusions
Compared with the conventional vein harvesting approach in coronary artery bypass grafting, the no-touch technique significantly reduced the risk of vein graft occlusion and improved patient prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03126409.



Circulation: 04 Oct 2021; 144:1120-1129
Tian M, Wang X, Sun H, Feng W, ... Huo X, Hu S
Circulation: 04 Oct 2021; 144:1120-1129 | PMID: 34510911
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Impact:
Abstract

Abbreviated Antiplatelet Therapy in Patients at High Bleeding Risk With or Without Oral Anticoagulant Therapy After Coronary Stenting: An Open-Label, Randomized, Controlled Trial.

Smits PC, Frigoli E, Tijssen J, Jüni P, ... Valgimigli M, MASTER DAPT Investigators
Background
The optimal duration of antiplatelet therapy (APT) in patients at high bleeding risk with or without oral anticoagulation (OAC) after coronary stenting remains unclear.
Methods
In the investigator-initiated, randomize, open-label MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen), 4579 patients at high bleeding risk were randomized after 1-month dual APT to abbreviated or nonabbreviated APT strategies. Randomization was stratified by concomitant OAC indication. In this subgroup analysis, we report outcomes of populations with or without an OAC indication. In the population with an OAC indication, patients changed immediately to single APT for 5 months (abbreviated regimen) or continued ≥2 months of dual APT and single APT thereafter (nonabbreviated regimen). Patients without an OAC indication changed to single APT for 11 months (abbreviated regimen) or continued ≥5 months of dual APT and single APT thereafter (nonabbreviated regimen). Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes (composite of all-cause death, myocardial infarction, stroke, and Bleeding Academic Research Consortium 3 or 5 bleeding events); major adverse cardiac and cerebral events (all-cause death, myocardial infarction, and stroke); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding.
Results
Net adverse clinical outcomes or major adverse cardiac and cerebral events did not differ with abbreviated versus nonabbreviated APT regimens in patients with OAC indication (n=1666; hazard ratio [HR], 0.83 [95% CI, 0.60-1.15]; and HR, 0.88 [95% CI, 0.60-1.30], respectively) or without OAC indication (n=2913; HR, 1.01 [95% CI, 0.77-1.33]; or HR, 1.06 [95% CI, 0.79-1.44]; Pinteraction=0.35 and 0.45, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding did not significantly differ in patients with OAC indication (HR, 0.83 [95% CI, 0.62-1.12]) but was lower with abbreviated APT in patients without OAC indication (HR, 0.55 [95% CI, 0.41-0.74]; Pinteraction=0.057). The difference in bleeding in patients without OAC indication was driven mainly by a reduction in Bleeding Academic Research Consortium 2 bleedings (HR, 0.48 [95% CI, 0.33-0.69]; Pinteraction=0.021).
Conclusions
Rates of net adverse clinical outcomes and major adverse cardiac and cerebral events did not differ with abbreviated APT in patients with high bleeding risk with or without an OAC indication and resulted in lower bleeding rates in patients without an OAC indication. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03023020.



Circulation: 11 Oct 2021; 144:1196-1211
Smits PC, Frigoli E, Tijssen J, Jüni P, ... Valgimigli M, MASTER DAPT Investigators
Circulation: 11 Oct 2021; 144:1196-1211 | PMID: 34455849
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Impact:
Abstract

Prognostication of Asymptomatic Penetrating Aortic Ulcers: A Modern Approach.

DeCarlo C, Latz CA, Boitano LT, Kim Y, ... Mohebali J, Dua A
Background
Literature detailing the natural history of asymptomatic penetrating aortic ulcers (PAUs) is sparse and lacks long-term follow-up. This study sought to determine the rate of asymptomatic PAU growth over time and adverse events from asymptomatic PAU.
Methods
A cohort of patients with asymptomatic PAU from 2005 to 2020 was followed. One ulcer was followed per patient. Primary end points were change in size over time and the composite of symptoms, radiographic progression, rupture, and intervention; cumulative incidence function estimated the incidence of the composite outcome. Ulcer size and rate of change were modeled using a linear mixed-effects model. Patient and anatomic factors were evaluated as potential predictors of the outcomes.
Results
There were 273 patients identified. The mean age was 75.5±9.6 years; 66.4% were male. The majority of ulcers were in the descending thoracic aorta (53.9%), followed by abdominal aorta (41.4%) and aortic arch (4.8%). Fusiform aneurysmal disease was present in 21.6% of patients at a separate location; 2.6% had an associated intramural hematoma; 23.6% had at least 1 other PAU. Symptoms developed in 1 patient who ruptured; 8 patients (2.9%) underwent an intervention for PAU (1 for rupture, 2 for radiographic progression, 5 for size/growth) at a median of 3.1 years (interquartile range, 1.0-6.5) after diagnosis. Five- and 10-year cumulative incidence of the primary outcome, adjusted for competing risk of death, was 3.6% (95% CI, 1.6%-6.9%) and 6.5% (95% CI, 3.1%-11.4%), respectively. For 191 patients with multiple computed tomography scans (760 total computed tomographies) with a median radiographic follow-up of 3.50 years (interquartile range, 1.20-6.63 years), mean initial ulcer width, ulcer depth, and total diameter were 13.6 mm, 8.5 mm, and 31.4 mm, respectively. A small but statistically significant change over time was observed for ulcer width (0.23 mm/y) and total diameter (0.24 mm/y); ulcer depth did not significantly change over time. Hypertension, hyperlipidemia, diabetes, initial ulcer width >20 mm, thrombosed PAU, and associated saccular aneurysm were associated with larger changes in ulcer size over time; however, the magnitude of difference was small, ranging from 0.4 to 1.9 mm/y.
Conclusions
Asymptomatic PAU displayed minimal growth and infrequent complications including rupture. Asymptomatic PAU may be conservatively managed with serial imaging and risk factor modification.



Circulation: 04 Oct 2021; 144:1091-1101
DeCarlo C, Latz CA, Boitano LT, Kim Y, ... Mohebali J, Dua A
Circulation: 04 Oct 2021; 144:1091-1101 | PMID: 34376058
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Impact:
Abstract

Epigenetic Age and the Risk of Incident Atrial Fibrillation.

Roberts JD, Vittinghoff E, Lu AT, Alonso A, ... Horvath S, Marcus GM
Background: The most prominent risk factor for atrial fibrillation (AF) is chronological age, however underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge, a phenomenon termed epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF.
Methods:
Measures for 4 epigenetic clocks (Horvath, Hannum, DNAm PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 levels (DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analysis. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF.
Results:
Among 5,600 individuals (mean age: 65.5 years; 60.1% female; 50.7% black), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. Following multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR]: 1.19; 95% confidence intervals [CI]: 1.09-1.31; p<0.01) and 15% (adjusted HR: 1.15; 95% CI: 1.05-1.25; p<0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. Conclusions: Our study identified adjusted associations between EAA measures and incident AF, suggesting biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.




Circulation: 29 Sep 2021; epub ahead of print
Roberts JD, Vittinghoff E, Lu AT, Alonso A, ... Horvath S, Marcus GM
Circulation: 29 Sep 2021; epub ahead of print | PMID: 34587750
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Abstract

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity.

Reynolds HR, Shaw LJ, Min JK, Page CB, ... Maron DJ, Hochman JS
Background
The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.
Methods
In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).
Results
Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar.
Conclusions
Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.



Circulation: 27 Sep 2021; 144:1024-1038
Reynolds HR, Shaw LJ, Min JK, Page CB, ... Maron DJ, Hochman JS
Circulation: 27 Sep 2021; 144:1024-1038 | PMID: 34496632
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Abstract

Predictors of Development of Atrial Fibrillation in Patients With Embolic Stroke Of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.

Bahit MC, Sacco RL, Easton JD, Meyerhoff J, ... Segura T, Granger CB
Background: A proportion of patients with embolic stroke of undetermined source (ESUS) have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke due to underlying AF. The RE-SPECT ESUS trial provides an opportunity to assess predictors for developing AF and associated recurrent stroke.
Methods:
RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with ESUS. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF.
Results:
In the multivariable model, older age (odds ratio [OR] for 10-year increase 1.99 [1.78-2.23]; P<0.001), hypertension (1.36 [1.03-1.79]; P=0.0304), diabetes (OR 0.74 [0.56-0.96]; P=0.022), and body mass index (OR for 5-unit increase 1.29 [1.16-1.43]; P<0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performances of several published predictive models were assessed, including the HAVOC and CHA2DS2-VASc scores, and higher scores were associated with higher rates of developing AF. Conclusions: Besides age as the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after ESUS. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring.




Circulation: 14 Oct 2021; epub ahead of print
Bahit MC, Sacco RL, Easton JD, Meyerhoff J, ... Segura T, Granger CB
Circulation: 14 Oct 2021; epub ahead of print | PMID: 34649459
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Abstract

Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.

Lopes RD, Higano CS, Slovin SF, Nelson AJ, ... Alexander JH, PRONOUNCE Study Investigators
Background
The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.
Methods
In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.
Results
Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).
Conclusions
PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.



Circulation: 18 Oct 2021; 144:1295-1307
Lopes RD, Higano CS, Slovin SF, Nelson AJ, ... Alexander JH, PRONOUNCE Study Investigators
Circulation: 18 Oct 2021; 144:1295-1307 | PMID: 34459214
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Abstract

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.

Blumenthal JA, Hinderliter AL, Smith PJ, Mabe S, ... Liao L, Sherwood A
Background
Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown.
Methods
One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure.
Results
Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596).
Conclusions
Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.



Circulation: 11 Oct 2021; 144:1212-1226
Blumenthal JA, Hinderliter AL, Smith PJ, Mabe S, ... Liao L, Sherwood A
Circulation: 11 Oct 2021; 144:1212-1226 | PMID: 34565172
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Abstract

Reduction in Acute Limb Ischemia with Rivaroxaban versus Placebo in Peripheral Artery Disease after Lower Extremity Revascularization: Insights from VOYAGER PAD.

Hess CN, Debus ES, Nehler MR, Anand SS, ... Bauersachs RM, Bonaca MP
Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Prior lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking.
Methods:
VOYAGER PAD (NCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan Meier estimates, and Cox proportional-hazards models were used to generate hazard ratios and associated confidence intervals. Analyses were performed as intention-to-treat.
Results:
Among 6,564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, prior LER, baseline ABI <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (HR 2.59, 95% CI 1.98-3.39) and major amputation (HR 24.87, 95% CI 18.68-33.12). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction 2.6% at 3 years, HR 0.67, 95% CI 0.55-0.82, P=0.0001), with benefit starting early (HR 0.45, 95% CI 0.24-0.85, P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and ICU stay, HR 0.58, 95% CI 0.40-0.83, P=0.003) and regardless of LER type (surgical vs endovascular revascularization, p-interaction=0.42) or clopidogrel use (p-interaction=0.59). Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.




Circulation: 11 Oct 2021; epub ahead of print
Hess CN, Debus ES, Nehler MR, Anand SS, ... Bauersachs RM, Bonaca MP
Circulation: 11 Oct 2021; epub ahead of print | PMID: 34637332
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Abstract

Effect of Long-Term Marine Omega-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM
Background: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine omega-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose related.
Methods:
The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012 and December 31, 2020 in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine omega-3 fatty acids that reported results for AF, either as pre-specified outcome, adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median followup of at least one year were included. RCTs specifically examining shorter term effects of omega-3 fatty acids on recurrent AF in patients with established AF or post-operative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was metaanalyzed using random-effects model with Knapp-Hartung adjustment and evaluated a doseresponse relationship with a meta-regression model.
Results:
Of 4049 screened records, seven studies were included in the meta-analysis. Of those, five were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81,210 patients from 7 trials, 58,939 (72.6%) were enrolled in trials testing ≤1gram per day (g/d) and 22,271 (27.4%) in trials testing >1g/d of omega-3 fatty acids. The mean age was 65 years and 31,842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine omega-3 fatty acid supplements was associated with an increased risk of AF (n=2,905; HR 1.25, 95%CI 1.07-1.46, P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1g/d (HR 1.49, 95%CI 1.04-2.15, P=0.042) as compared with those testing ≤1 g/d (HR 1.12, 95%CI 1.03-1.22, P=0.024, P for interaction<0.001). In metaregression, the HR for AF increased per 1 gr increase of omega-3 fatty acids dosage (HR 1.11, 95%CI 1.06-1.15, P=0.001). Conclusions: In RCTs examining cardiovascular outcomes, marine omega-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1g/d.




Circulation: 05 Oct 2021; epub ahead of print
Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM
Circulation: 05 Oct 2021; epub ahead of print | PMID: 34612056
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Abstract

Cardiac Surgery in Women in the Current Era: What Are the Gaps in Care?

Cho L, Kibbe MR, Bakaeen F, Aggarwal NR, ... Zwischenberger BA, Lindley KJ
Cardiovascular disease remains the leading cause of morbidity and mortality for women in United States and worldwide. One in 3 women dies from cardiovascular disease, and 45% of women >20 years old have some form of CVD. Historically, women have had higher morbidity and mortality after cardiac surgery. Sex influences pathogenesis, pathophysiology, presentation, postoperative complications, surgical outcomes, and survival. This review summarizes current cardiovascular surgery outcomes as they pertain to women. Specifically, this article seeks to address whether sex disparities in research, surgical referral, and outcomes still exist and to provide strategies to close these gaps. In addition, with the growing population of women of reproductive age with cardiovascular disease and cardiovascular risk factors, indications for cardiac surgery arise in pregnant women. The current review will also address the unique issues associated with this special population.



Circulation: 04 Oct 2021; 144:1172-1185
Cho L, Kibbe MR, Bakaeen F, Aggarwal NR, ... Zwischenberger BA, Lindley KJ
Circulation: 04 Oct 2021; 144:1172-1185 | PMID: 34606298
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Impact:
Abstract

Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study.

Thielmann M, Corteville D, Szabo G, Swaminathan M, ... Molitoris B, Mazer CD
Background
Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI.
Methods
This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments.
Results
A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment.
Conclusions
The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02610283.



Circulation: 04 Oct 2021; 144:1133-1144
Thielmann M, Corteville D, Szabo G, Swaminathan M, ... Molitoris B, Mazer CD
Circulation: 04 Oct 2021; 144:1133-1144 | PMID: 34474590
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Abstract

Opioid Use and Its Relationship to Cardiovascular Disease and Brain Health: A Presidential Advisory From the American Heart Association.

Chow SL, Sasson C, Benjamin IJ, Califf RM, ... Robson C, Sanchez EJ
The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent data suggest that commonly used opioids for the management of pain may produce undesirable pharmacological actions and interfere with critical medications commonly used in cardiovascular disease and stroke; however, the impact on outcomes remains controversial. The American Heart Association developed an advisory statement for health care professionals and researchers in the setting of cardiovascular and brain health to synthesize the current literature, to provide approaches for identifying patients with opioid use disorder, and to address pain management and overdose. A literature and internet search spanning from January 1, 2012, to February 15, 2021, and limited to epidemiology studies, reviews, consensus statements, and guidelines in human subjects was conducted. Suggestions and considerations listed in this document are based primarily on published evidence from this review whenever possible, as well as expert opinion. Several federal and institutional consensus documents and clinical resources are currently available to both patients and clinicians; however, none have specifically addressed cardiovascular disease and brain health. Although strategic tools and therapeutic approaches for recognition of opioid use disorder and safe opioid use are available for health care professionals who manage patients with cardiovascular disease and stroke, high-quality evidence does not currently exist. Therefore, there is an urgent need for more research to identify the most effective approaches to improve care for these patients.



Circulation: 27 Sep 2021; 144:e218-e232
Chow SL, Sasson C, Benjamin IJ, Califf RM, ... Robson C, Sanchez EJ
Circulation: 27 Sep 2021; 144:e218-e232 | PMID: 34407637
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Impact:
Abstract

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

Debus ES, Nehler MR, Govsyeyev N, Bauersachs RM, ... Hiatt WR, Bonaca MP
Background
Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER.
Methods
The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee.
Results
Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased.
Conclusions
The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.



Circulation: 04 Oct 2021; 144:1104-1116
Debus ES, Nehler MR, Govsyeyev N, Bauersachs RM, ... Hiatt WR, Bonaca MP
Circulation: 04 Oct 2021; 144:1104-1116 | PMID: 34380322
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Impact:
Abstract

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

Reynolds HR, Picard MH, Spertus JA, Peteiro J, ... Maron DJ, Hochman JS
Background
Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA.
Methods
CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did.
Results
INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029).
Conclusions
Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.



Circulation: 27 Sep 2021; 144:1008-1023
Reynolds HR, Picard MH, Spertus JA, Peteiro J, ... Maron DJ, Hochman JS
Circulation: 27 Sep 2021; 144:1008-1023 | PMID: 34058845
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Impact:
Abstract

Social Vulnerability and Premature Cardiovascular Mortality Among US Counties, 2014 to 2018.

Khan SU, Javed Z, Lone AN, Dani SS, ... Cainzos-Achirica M, Nasir K
Background
Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain.
Methods
In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles.
Results
Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes.
Conclusions
In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.



Circulation: 18 Oct 2021; 144:1272-1279
Khan SU, Javed Z, Lone AN, Dani SS, ... Cainzos-Achirica M, Nasir K
Circulation: 18 Oct 2021; 144:1272-1279 | PMID: 34662161
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Impact:
Abstract

Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Ruetzler K, Smilowitz NR, Berger JS, Devereaux PJ, ... Critical Care, Perioperative and Resuscitation; Council on Clinical Cardiology; and Council on Cardiovascular Surgery and Anesthesia
Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.



Circulation: 03 Oct 2021:CIR0000000000001024; epub ahead of print
Ruetzler K, Smilowitz NR, Berger JS, Devereaux PJ, ... Critical Care, Perioperative and Resuscitation; Council on Clinical Cardiology; and Council on Cardiovascular Surgery and Anesthesia
Circulation: 03 Oct 2021:CIR0000000000001024; epub ahead of print | PMID: 34601955
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Impact:
Abstract

Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial.

Gray AJ, Roobottom C, Smith JE, Goodacre S, ... Newby DE, RAPID-CTCA Investigators
Objectives
To establish if the use of early computed tomography (CT) coronary angiography improves one year clinical outcomes in patients presenting to the emergency department with acute chest pain and at intermediate risk of acute coronary syndrome and subsequent clinical events.
Design
Randomised controlled trial.
Setting
37 hospitals in the UK.
Participants
Adults with suspected or a provisional diagnosis of acute coronary syndrome and one or more of previous coronary heart disease, raised levels of cardiac troponin, or abnormal electrocardiogram.
Interventions
Early CT coronary angiography and standard of care compared with standard of care only.
Main outcome measures
Primary endpoint was all cause death or subsequent type 1 or 4b myocardial infarction at one year.
Results
Between 23 March 2015 and 27 June 2019, 1748 participants (mean age 62 years (standard deviation 13), 64% men, mean global registry of acute coronary events (GRACE) score 115 (standard deviation 35)) were randomised to receive early CT coronary angiography (n=877) or standard of care only (n=871). Median time from randomisation to CT coronary angiography was 4.2 (interquartile range 1.6-21.6) hours. The primary endpoint occurred in 51 (5.8%) participants randomised to CT coronary angiography and 53 (6.1%) participants who received standard of care only (adjusted hazard ratio 0.91 (95% confidence interval 0.62 to 1.35), P=0.65). Invasive coronary angiography was performed in 474 (54.0%) participants randomised to CT coronary angiography and 530 (60.8%) participants who received standard of care only (adjusted hazard ratio 0.81 (0.72 to 0.92), P=0.001). There were no overall differences in coronary revascularisation, use of drug treatment for acute coronary syndrome, or subsequent preventive treatments between the two groups. Early CT coronary angiography was associated with a slightly longer time in hospital (median increase 0.21 (95% confidence interval 0.05 to 0.40) days from a median hospital stay of 2.0 to 2.2 days).
Conclusions
In intermediate risk patients with acute chest pain and suspected acute coronary syndrome, early CT coronary angiography did not alter overall coronary therapeutic interventions or one year clinical outcomes, but reduced rates of invasive angiography while modestly increasing length of hospital stay. These findings do not support the routine use of early CT coronary angiography in intermediate risk patients with acute chest pain and suspected acute coronary syndrome.
Trial registration
ISRCTN19102565, NCT02284191.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ: 28 Sep 2021; 374:n2106
Gray AJ, Roobottom C, Smith JE, Goodacre S, ... Newby DE, RAPID-CTCA Investigators
BMJ: 28 Sep 2021; 374:n2106 | PMID: 34588162
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Impact:
Abstract

Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease.

Patorno E, Htoo PT, Glynn RJ, Schneeweiss S, ... Everett BM, Kim SC
Background
Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD).
Objective
To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD.
Design
Population-based cohort study.
Setting
Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017).
Participants
1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy.
Measurements
Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates.
Results
The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]).
Limitation
Treatment selection was not randomized.
Conclusion
Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD.
Primary funding source
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\'s Hospital and Harvard Medical School.



Ann Intern Med: 27 Sep 2021; epub ahead of print
Patorno E, Htoo PT, Glynn RJ, Schneeweiss S, ... Everett BM, Kim SC
Ann Intern Med: 27 Sep 2021; epub ahead of print | PMID: 34570599
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Abstract

Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, ... American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease
High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.



Arterioscler Thromb Vasc Biol: 13 Oct 2021:ATV0000000000000147; epub ahead of print
Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, ... American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease
Arterioscler Thromb Vasc Biol: 13 Oct 2021:ATV0000000000000147; epub ahead of print | PMID: 34647487
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Abstract

Medication Adherence and Blood Pressure Control: A Scientific Statement From the American Heart Association.

Choudhry NK, Kronish IM, Vongpatanasin W, Ferdinand KC, ... Hyman DJ, American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology
The widespread treatment of hypertension and resultant improvement in blood pressure have been major contributors to the dramatic age-specific decline in heart disease and stroke. Despite this progress, a persistent gap remains between stated public health targets and achieved blood pressure control rates. Many factors may be important contributors to the gap between population hypertension control goals and currently observed control levels. Among them is the extent to which patients adhere to prescribed treatment. The goal of this scientific statement is to summarize the current state of knowledge of the contribution of medication nonadherence to the national prevalence of poor blood pressure control, methods for measuring medication adherence and their associated challenges, risk factors for antihypertensive medication nonadherence, and strategies for improving adherence to antihypertensive medications at both the individual and health system levels.



Hypertension: 06 Oct 2021:HYP0000000000000203; epub ahead of print
Choudhry NK, Kronish IM, Vongpatanasin W, Ferdinand KC, ... Hyman DJ, American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology
Hypertension: 06 Oct 2021:HYP0000000000000203; epub ahead of print | PMID: 34615363
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Impact:
Abstract

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

Kotecha D, Garcia-Guimaraes M, Premawardhana D, Pellegrini D, ... Alfonso F, Adlam D
Objective
To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.
Methods
SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).
Results
SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.
Conclusion
While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.

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

Heart: 29 Sep 2021; 107:1398-1406
Kotecha D, Garcia-Guimaraes M, Premawardhana D, Pellegrini D, ... Alfonso F, Adlam D
Heart: 29 Sep 2021; 107:1398-1406 | PMID: 34006503
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Impact:
Abstract

Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation.

Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Objective
Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.
Methods
We performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.
Results
Major bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score-matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score-matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.
Conclusions
Our study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

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

Heart: 29 Sep 2021; 107:1376-1382
Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Heart: 29 Sep 2021; 107:1376-1382 | PMID: 33262185
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Impact:
Abstract

Effect of blood pressure lowering drugs and antibiotics on abdominal aortic aneurysm growth: a systematic review and meta-analysis.

Golledge J, Singh TP
Objective
There is currently no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. The aim of this systematic review and meta-analysis was to pool data from previous randomised controlled trials assessing the efficacy of blood pressure-lowering and antibiotic medications in limiting AAA growth and AAA-related events, that is, rupture or repair.
Methods
A systematic literature search was performed to identify randomised controlled trials that examined the efficacy of blood pressure-lowering medications or antibiotics in reducing AAA growth and AAA-related events. AAA growth (mm/year) was measured by ultrasound or computed tomography imaging. Meta-analyses were performed using random effects models. A subanalysis was conducted including trials that investigated tetracycline or macrolide antibiotics.
Results
Ten randomised controlled trials including 2045 participants with an asymptomatic AAA were included. Follow-up was between 18 and 63 months. Neither blood pressure-lowering medications (mean growth±SD 2.0±2.4 vs 2.3±2.7 mm/year; standardised mean difference (SMD) -0.07, 95% CI -0.19 to 0.06; p=0.288) or antibiotics (mean growth±SD 2.6±2.1 vs 2.6±2.5 mm/year; SMD -0.11, 95% CI -0.38 to 0.16; p=0.418) reduced AAA growth or AAA-related events (blood pressure-lowering medications: 92 vs 95 events; risk ratio (RR) 0.86, 95% CI 0.66 to 1.11; p=0.244; and antibiotics: 69 vs 73 events; RR 0.93, 95% CI 0.69 to 1.25; p=0.614). The subanalysis of antibiotics showed similar results.
Conclusions
This meta-analysis suggests that neither blood pressure-lowering medications or antibiotics limit growth or clinically relevant events in people with AAAs.

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

Heart: 29 Sep 2021; 107:1465-1471
Golledge J, Singh TP
Heart: 29 Sep 2021; 107:1465-1471 | PMID: 33199361
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Impact:
Abstract

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

Girnius A, Zentner D, Valente AM, Pieper PG, ... Mulder BJM, Veldtman GR
Background/objectives
Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.
Methods
We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.
Results
We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).
Conclusions
Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.

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

Heart: 29 Sep 2021; 107:1390-1397
Girnius A, Zentner D, Valente AM, Pieper PG, ... Mulder BJM, Veldtman GR
Heart: 29 Sep 2021; 107:1390-1397 | PMID: 33234672
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Impact:
Abstract

Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges.

Packard C, Chapman MJ, Sibartie M, Laufs U, Masana L
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of \'lower is better\'. With the advent of combination therapy using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors in addition to statins, the routine attainment of extremely low LDL-C levels in the clinic has become a reality. Moreover, clinical trials in this setting have shown that, over the 5-7 years of treatment experience to date, profound LDL-C lowering leads to further reduction in cardiovascular events compared with more moderate lipid lowering, with no associated safety concerns. These reassuring findings are bolstered by genetic studies showing lifelong very low LDL-C levels (<1.4 mmol/L; <55 mg/dL) are associated with lower cardiovascular risk than in the general population, with no known detrimental health effects. Nevertheless, long-term safety studies are required to consolidate the present evidence base. This review summarises key data supporting the ESC/EAS recommendation to reduce markedly LDL-C levels, with aggressive goals for LDL-C in patients at highest risk, and provides expert opinion on its significance for clinical practice.

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

Heart: 29 Sep 2021; 107:1369-1375
Packard C, Chapman MJ, Sibartie M, Laufs U, Masana L
Heart: 29 Sep 2021; 107:1369-1375 | PMID: 33795379
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Impact:
Abstract

Lipoprotein(a) is robustly associated with aortic valve calcium.

Kaiser Y, Singh SS, Zheng KH, Verbeek R, ... Stroes ESG, Bos D
Objectives
To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.
Methods
We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.
Results
The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).
Conclusions
Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

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

Heart: 29 Sep 2021; 107:1422-1428
Kaiser Y, Singh SS, Zheng KH, Verbeek R, ... Stroes ESG, Bos D
Heart: 29 Sep 2021; 107:1422-1428 | PMID: 33963048
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Impact:
Abstract

Prognostic value of electrocardiographic abnormalities in adults from the Brazilian longitudinal study of adults\' health.

Pinto-Filho MM, Brant LC, Dos Reis RP, Giatti L, ... Barreto SM, Ribeiro ALP
Objective
Cardiovascular diseases (CVDs) are highly preventable non-communicable diseases. ECG is a potential tool for risk stratification with respect to CVD. Our aim was to evaluate ECG\'s role in all-cause and cardiovascular mortality prediction.
Methods
Participants from the Brazilian Longitudinal Study of Adult Health, free of known CVD at baseline were included. A 12-lead ECG was obtained at baseline (2008-2010). Participants were followed up to 2018 by annual interviews. Deaths were independently reviewed. Cox as well as Fine and Grey multivariable regression models were applied to evaluate if the presence of any major electrocardiographic abnormality (MEA), defined according to the Minnesota Code system, would predict total and cardiovascular deaths. We also evaluated the Net Reclassification Index of adding MEA to the Systematic Coronary Risk Evaluation (SCORE).
Results
The 13 428 participants (median age 51 years, 45% men) were followed up for 8±1 years. All-cause and cardiovascular mortality occurred in 2.8% and 1.2% of the population, respectively. Prevalent MEA was an independent predictor of overall (HR=2.3, 95% CI 1.7 to 2.9) and cardiovascular mortality (HR=4.6, 95% CI 3.0 to 7.0) after adjustments for age, race, education and traditional cardiovascular risk factors. Adding MEA to the SCORE resulted in 9% mis-reclassification in the non-event subgroup and 33% correct reclassification in those with a fatal cardiovascular event.
Conclusion
Presence of MEA was an independent predictor of overall and cardiovascular mortality. ECG may have a role in risk prediction of cardiovascular mortality in primary care.

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

Heart: 29 Sep 2021; 107:1560-1566
Pinto-Filho MM, Brant LC, Dos Reis RP, Giatti L, ... Barreto SM, Ribeiro ALP
Heart: 29 Sep 2021; 107:1560-1566 | PMID: 33361354
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Impact:
Abstract

Vaping and cardiac disease.

Shahandeh N, Chowdhary H, Middlekauff HR
Tobacco cigarette smoking is the most prevalent reversible risk factor for cardiovascular disease in the USA. Electronic cigarettes, invented as an alternative nicotine source for smokers unable or unwilling to stop smoking, have gained skyrocketing popularity, but their cardiovascular risk remains uncertain. Although data recently analysed in a Cochran report do support their superior effectiveness to other forms of nicotine replacement therapies for smoking cessation, electronic cigarettes are also frequently used by non-smokers-especially high school students. There are no long-term outcome studies on the cardiovascular risk of vaping electronic cigarettes, but the effects of electronic cigarettes on known risk factors for cardiovascular disease, including neurohumoural activation, oxidative stress and inflammation, endothelial function and thrombosis, have been studied. In this review, we summarise evidence in humans that supports the notion that while electronic cigarettes may be less harmful than traditional cigarettes, they are not harmless. Additionally, the increasing popularity of vaping marijuana with its unknown cardiovascular risks as well as the outbreak in 2019 of EVALI (electronic cigarette, or vaping, product use-associated lung injury) related to bootlegged vaping products raise further concerns. Before physicians can confidently advise their smoking patients about the role of electronic cigarettes as a means of smoking cessation to lower cardiovascular risk, improved regulation and quality control is necessary.

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

Heart: 29 Sep 2021; 107:1530-1535
Shahandeh N, Chowdhary H, Middlekauff HR
Heart: 29 Sep 2021; 107:1530-1535 | PMID: 33574049
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Impact:
Abstract

Dyslipidemia and aortic valve disease.

Mata P, Alonso R, Pérez de Isla L, Badimón L
Purpose of review
Degenerative aortic stenosis (AS) is one of the most prevalent heart valve diseases in the adult population. The understanding of AS pathophysiology and involved risk factors have recently undergone a great advance, with low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) [Lp(a)] and other clinical conditions taking on a relevant role. Although little is known about the prevention of AS, we can progressively find more evidence of the possible use of drugs to control risk factors as tools that may delay the progression to severe AS and aortic valve replacement.
Recent findings
Several factors have shown to be solid predictors of the development of AS. Mendelian randomization and observational studies on risk factors specifically lipid factors, such as hypercholesterolemia, Lp(a), proprotein convertase subtilisin/kexin type 9 and hypertension have provided meaningful new information. The SAFEHEART study has significantly contributed to define the role of LDL-C and Lp(a) in AS.
Summary
In this review we discuss the interrelationship of dyslipidemia, especially hypercholesterolemia and Lp(a) in the development and prognosis of valvular AS. New imaging tools may contribute to its early detection. Future studies with proprotein convertase subtilisin/kexin type 9 inhibitors and specific therapies to lower Lp(a) might contribute to delay AS development.

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

Curr Opin Lipidol: 07 Oct 2021; epub ahead of print
Mata P, Alonso R, Pérez de Isla L, Badimón L
Curr Opin Lipidol: 07 Oct 2021; epub ahead of print | PMID: 34629429
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Impact:
Abstract

Anticoagulant prescribing for atrial fibrillation and risk of incident dementia.

Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
Objective
The aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).
Methods
Using linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.
Results
Of 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68-83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.
Conclusions
Incident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.

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

Heart: 12 Oct 2021; epub ahead of print
Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
Heart: 12 Oct 2021; epub ahead of print | PMID: 34645643
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Impact:
Abstract

Aspirin versus P2Y inhibitors with anticoagulation therapy for atrial fibrillation.

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

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

Heart: 30 Oct 2021; 107:1731-1738
Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Heart: 30 Oct 2021; 107:1731-1738 | PMID: 34261738
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Impact:
Abstract

Prediction of incident atrial fibrillation in community-based electronic health records: a systematic review with meta-analysis.

Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
Objective
Atrial fibrillation (AF) is common and is associated with an increased risk of stroke. We aimed to systematically review and meta-analyse multivariable prediction models derived and/or validated in electronic health records (EHRs) and/or administrative claims databases for the prediction of incident AF in the community.
Methods
Ovid Medline and Ovid Embase were searched for records from inception to 23 March 2021. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation.
Results
Eleven studies met inclusion criteria, describing nine prediction models, with four eligible for meta-analysis including 9 289 959 patients. The CHADS (Congestive heart failure, Hypertension, Age>75, Diabetes mellitus, prior Stroke or transient ischemic attack) (summary c-statistic 0.674; 95% CI 0.610 to 0.732; 95% PI 0.526-0.815), CHA2DS2-VASc (Congestive heart failure, Hypertension, Age>75 (2 points), Stroke/transient ischemic attack/thromboembolism (2 points), Vascular disease, Age 65-74, Sex category) (summary c-statistic 0.679; 95% CI 0.620 to 0.736; 95% PI 0.531-0.811) and HATCH (Hypertension, Age, stroke or Transient ischemic attack, Chronic obstructive pulmonary disease, Heart failure) (summary c-statistic 0.669; 95% CI 0.600 to 0.732; 95% PI 0.513-0.803) models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance. No model met eligibility for inclusion in meta-analysis if studies at high risk of bias were excluded and certainty of effect estimates was \'low\'. Models derived by machine learning demonstrated strong discriminative performance, but lacked rigorous external validation.
Conclusions
Models externally validated for prediction of incident AF in community-based EHR demonstrate moderate predictive ability and high risk of bias. Novel methods may provide stronger discriminative performance.
Systematic review registration
PROSPERO CRD42021245093.

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

Heart: 03 Oct 2021; epub ahead of print
Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
Heart: 03 Oct 2021; epub ahead of print | PMID: 34607811
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Impact:
Abstract

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy.

Wu G, Liu J, Wang S, Yu S, ... Wang J, Song L
Objective
Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.
Methods
The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell\'s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson\'s staining was analysed.
Results
During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson\'s trichrome staining in the myocardium (r=0.198, p<0.05).
Conclusion
NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

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

Heart: 29 Sep 2021; 107:1576-1583
Wu G, Liu J, Wang S, Yu S, ... Wang J, Song L
Heart: 29 Sep 2021; 107:1576-1583 | PMID: 33361398
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Impact:
Abstract

Sex differences in heart failure hospitalisation risk following acute myocardial infarction.

Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Objective
We evaluated the sex differences in 6-month heart failure (HF) hospitalisation risk in acute myocardial infarction (AMI) survivors.
Methods
For this retrospective cohort analysis, adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The primary outcome was a HF hospitalisation within 6 months. Secondary outcomes were fatal HF hospitalisation and the composite of index in-hospital HF or 6-month HF hospitalisation.
Results
Of 237 549 AMI survivors, females (37.9%) were older (70±14 years vs 65±13 years; p<0.001), had a higher prevalence of cardiac comorbidities and a lower revascularisation rate compared with males. The primary outcome occurred in 12 934 patients (5.4%), at a 49% higher rate in females (6.8% vs 4.6% in males, p<0.001), which was attenuated to a 19% higher risk after multivariable adjustment. Findings were consistent across subgroups of age, AMI type and major risk factors. In the propensity-matched time-to-event analysis, female sex was associated with a 13% higher risk for 6-month HF readmission (6.4% vs 5.8% in males; HR 1.13, 95% CI 1.05 to 1.21, p<0.001), and the increased risk was evident early on after the AMI. Fatal HF rate was similar between groups (4.7% vs 4.6%, p=0.936), but females had a higher rate of the composite HF outcome (36.2% vs 27.5%, p<0.001).
Conclusion
In a large all-comers AMI survivors\' cohort, females had a higher HF hospitalisation risk that persisted after adjustment for baseline risk differences. This was consistent across several clinically relevant subgroups and was evident early on after the AMI.

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

Heart: 29 Sep 2021; 107:1657-1663
Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Heart: 29 Sep 2021; 107:1657-1663 | PMID: 33431424
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Impact:
Abstract

Risk of out-of-hospital cardiac arrest in patients with bipolar disorder or schizophrenia.

Barcella CA, Mohr G, Kragholm K, Christensen D, ... Gislason GH, Bach Søndergaard K
Objective
Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated.
Methods
We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs.
Results
We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders.
Conclusions
Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms.

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

Heart: 29 Sep 2021; 107:1544-1551
Barcella CA, Mohr G, Kragholm K, Christensen D, ... Gislason GH, Bach Søndergaard K
Heart: 29 Sep 2021; 107:1544-1551 | PMID: 33452118
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Impact:
Abstract

Fried-food consumption and risk of cardiovascular disease and all-cause mortality: a meta-analysis of observational studies.

Qin P, Zhang M, Han M, Liu D, ... Hu D, Hu F
Objective
We performed a meta-analysis, including dose-response analysis, to quantitatively determine the association of fried-food consumption and risk of cardiovascular disease and all-cause mortality in the general adult population.
Methods
We searched PubMed, EMBASE and Web of Science for all articles before 11 April 2020. Random-effects models were used to estimate the summary relative risks (RRs) and 95% CIs.
Results
In comparing the highest with lowest fried-food intake, summary RRs (95% CIs) were 1.28 (1.15 to 1.43; n=17, I2=82.0%) for major cardiovascular events (prospective: 1.24 (1.12 to 1.38), n=13, I2=75.7%; case-control: 1.91 (1.15 to 3.17), n=4, I2=92.1%); 1.22 (1.07 to 1.40; n=11, I2=77.9%) for coronary heart disease (prospective: 1.16 (1.05 to 1.29), n=8, I2=44.6%; case-control: 1.91 (1.05 to 3.47), n=3, I2=93.9%); 1.37 (0.97 to 1.94; n=4, I2=80.7%) for stroke (cohort: 1.21 (0.87 to 1.69), n=3, I2=77.3%; case-control: 2.01 (1.27 to 3.19), n=1); 1.37 (1.07 to 1.75; n=4, I2=80.0%) for heart failure; 1.02 (0.93 to 1.14; n=3, I2=27.3%) for cardiovascular mortality; and 1.03 (95% CI 0.96 to 1.12; n=6, I2=38.0%) for all-cause mortality. The association was linear for major cardiovascular events, coronary heart disease and heart failure.
Conclusions
Fried-food consumption may increase the risk of cardiovascular disease and presents a linear dose-response relation. However, the high heterogeneity and potential recall and misclassification biases for fried-food consumption from the original studies should be considered.

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

Heart: 29 Sep 2021; 107:1567-1575
Qin P, Zhang M, Han M, Liu D, ... Hu D, Hu F
Heart: 29 Sep 2021; 107:1567-1575 | PMID: 33468573
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Impact:
Abstract

Cross-sectional study of aortic valve calcification and cardiovascular risk factors in older Danish men.

Khurrami L, Møller JE, Lindholt JS, Urbonaviciene G, ... Fredgart MH, Diederichsen ACP
Objective
Aortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60-74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.
Methods
Participants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.
Results
14 073 men aged 60-74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0-82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.
Conclusions
AVC was prevalent in the general population of men aged 60-74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.
Trial registration number
NCT03946410 and ISRCTN12157806.

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

Heart: 29 Sep 2021; 107:1536-1543
Khurrami L, Møller JE, Lindholt JS, Urbonaviciene G, ... Fredgart MH, Diederichsen ACP
Heart: 29 Sep 2021; 107:1536-1543 | PMID: 34376488
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Impact:
Abstract

Weight management and determinants of weight change in patients with coronary artery disease.

Tijssen A, Snaterse M, Minneboo M, Lachman S, ... Peters RJ, Jørstad HT
Objective
To study the effects of a comprehensive secondary prevention programme on weight loss and to identify determinants of weight change in patients with coronary artery disease (CAD).
Methods
We performed a secondary analysis focusing on the subgroup of overweight CAD patients (BMI ≥27 kg/m2) in the Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists-2 (RESPONSE-2) multicentre randomised trial. We evaluated weight change from baseline to 12-month follow-up; multivariable logistic regression with backward elimination was used to identify determinants of weight change.
Results
Intervention patients (n=280) lost significantly more weight than control patients (n=257) (-2.4±7.1 kg vs -0.2±4.6 kg; p<0.001). Individual weight change varied widely, with weight gain (≥1.0 kg) occurring in 36% of interventions versus 41% controls (p=0.21). In the intervention group, weight loss of ≥5% was associated with higher age (OR 2.94), lower educational level (OR 1.91), non-smoking status (OR 2.92), motivation to start with weight loss directly after the baseline visit (OR 2.31) and weight loss programme participation (OR 3.33), whereas weight gain (≥1 kg) was associated with smoking cessation ≤6 months before or during hospitalisation (OR 3.21), non-Caucasian ethnicity (OR 2.77), smoking at baseline (OR 2.70), lower age (<65 years) (OR 1.47) and weight loss programme participation (OR 0.59).
Conclusion
The comprehensive secondary prevention programme was, on average, effective in achieving weight loss. However, wide variation was observed. As weight gain was observed in over one in three participants in both groups, prevention of weight gain may be as important as attempts to lose weight.
Trial registration number
NTR3937.

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

Heart: 29 Sep 2021; 107:1552-1559
Tijssen A, Snaterse M, Minneboo M, Lachman S, ... Peters RJ, Jørstad HT
Heart: 29 Sep 2021; 107:1552-1559 | PMID: 34326136
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Impact:
Abstract

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

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

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

Heart: 29 Sep 2021; 107:1637-1643
McIntyre D, Thiagalingam A, Klimis H, Von Huben A, Marschner S, Chow CK
Heart: 29 Sep 2021; 107:1637-1643 | PMID: 34290036
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Impact:
Abstract

Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis.

Kaiser Y, Nurmohamed NS, Kroon J, Verberne HJ, ... Zheng KH, Boekholdt SM
Objective
To assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).
Methods
We performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18F-NaF uptake.
Results
52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64-117) mg/dL and 7 (5-11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18F-NaF uptake (β=0.17; 95% CI -0.44 to 0.88, p=0.305 for the high Lp(a) group).
Conclusion
Among patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.

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

Heart: 29 Sep 2021; epub ahead of print
Kaiser Y, Nurmohamed NS, Kroon J, Verberne HJ, ... Zheng KH, Boekholdt SM
Heart: 29 Sep 2021; epub ahead of print | PMID: 34593533
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Impact:
Abstract

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease.

Campens L, Baris L, Scott NS, Broberg CS, ... Roos-Hesselink JW, ROPAC investigators group
Background
Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying aortopathy.
Methods
The ESC EORP Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective global registry that enrolled 5739 women with pre-existing cardiac disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with thoracic aortic disease.
Results
Thoracic aortic disease was reported in 189 women (3.3%). Half of them were patients with Marfan syndrome (MFS), 26% had a BAV, 8% Turner syndrome, 2% vascular Ehlers-Danlos syndrome and 11% had no underlying genetic defect or associated congenital heart defect. Aortic dilatation was reported in 58% of patients and 6% had a history of aortic dissection. Four patients, of whom three were patients with MFS, had an acute aortic dissection (three type A and one type B aortic dissection) without maternal or fetal mortality. No complications occurred in women with a history of aortic dissection. There was no significant difference in median fetal birth weight if treated with a beta-blocker or not (2960 g (2358-3390 g) vs 3270 g (2750-3570 g), p value 0.25).
Conclusion
This ancillary analysis provides the largest prospective data review on pregnancy risk for patients with thoracic aortic disease. Overall pregnancy outcomes in women with thoracic aortic disease followed according to current guidelines are good.

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

Heart: 30 Oct 2021; 107:1704-1709
Campens L, Baris L, Scott NS, Broberg CS, ... Roos-Hesselink JW, ROPAC investigators group
Heart: 30 Oct 2021; 107:1704-1709 | PMID: 33468574
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Impact:
Abstract

Antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease.

Bossard M, Gao P, Boden W, Steg G, ... Yusuf S, Mehta SR
Objective
Approximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated.
Methods
We analysed data from the Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organisation to Assess Strategies in Ischaemic Symptoms trial randomising patients with ACS referred for early intervention to receive either double-dose (600 mg, day 1; 150 mg, days 2-7; then 75 mg/day) or standard-dose (300 mg, day 1; then 75 mg/day) clopidogrel. Outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) versus those with obstructive coronary artery disease (CAD) and their relation to standard-dose versus double-dose clopidogrel were evaluated. The primary outcome was cardiovascular (CV) death, MI or stroke at 30 days.
Results
We included 23 783 patients with MI and 1599 (6.7%) with MINOCA. Patients with MINOCA were younger, presented more frequently with non-ST-segment elevation MI and had fewer comorbidities. All-cause mortality (0.6% vs 2.3%, p=0.005), CV mortality (0.6% vs 2.2%, p=0.006), repeat MI (0.5% vs 2.3%, p=0.001) and major bleeding (0.6% vs 2.4%, p<0.0001) were lower among patients with MINOCA than among those with obstructive CAD. Among patients with MINOCA, 2.1% of patients in the double-dose clopidogrel group and 0.6% in the standard-dose group experienced a primary outcome (HR 3.57, 95% CI 1.31 to 9.76), whereas in those with obstructive CAD, rates were 4.3% and 4.7%, respectively (HR 0.91, 95% CI 0.80 to 1.03; p value for interaction=0.011).
Conclusions
Patients with MINOCA are at lower risk of recurrent CV events compared with patients with MI with obstructive CAD. Compared with a standard clopidogrel-based dual antiplatelet therapy (DAPT) regimen, an intensified dosing strategy appears to offer no additional benefit with a signal of possible harm. Further randomised trials evaluating the effects of potent DAPT in patients with MINOCA are warranted.
Trial registration number
NCT00335452.

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

Heart: 30 Oct 2021; 107:1739-1747
Bossard M, Gao P, Boden W, Steg G, ... Yusuf S, Mehta SR
Heart: 30 Oct 2021; 107:1739-1747 | PMID: 33504513
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Impact:
Abstract

Multicentre comparative analysis of long-term outcomes after aortic valve replacement in children.

Knight JH, Sarvestani AL, Ibezim C, Turk E, ... Raghuveer G, Kochilas LK
Objective
The ideal valve substitute for surgical intervention of congenital aortic valve disease in children remains unclear. Data on outcomes beyond 10-15 years after valve replacement are limited but important for evaluating substitute longevity. We aimed to describe up to 25-year death/cardiac transplant by type of valve substitute and assess the potential impact of treatment centre. Our hypothesis was that patients with pulmonic valve autograft would have better survival than mechanical prosthetic.
Methods
This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a multi-institutional US-based registry of paediatric cardiac interventions, linked with the National Death Index and United Network for Organ Sharing through 2019. Children (0-20 years old) receiving aortic valve replacement (AVR) from 1982 to 2003 were identified. Kaplan-Meier transplant-free survival was calculated, and Cox proportional hazard models estimated hazard ratios for mechanical AVR (M-AVR) versus pulmonic valve autograft.
Results
Among 911 children, the median age at AVR was 13.4 years (IQR=8.4-16.5) and 73% were male. There were 10 cardiac transplants and 153 deaths, 5 after transplant. The 25-year transplant-free survival post AVR was 87.1% for autograft vs 76.2% for M-AVR and 72.0% for tissue (bioprosthetic or homograft). After adjustment, M-AVR remained related to increased mortality/transplant versus autograft (HR=1.9, 95% CI=1.1 to 3.4). Surprisingly, survival for patients with M-AVR, but not autograft, was lower for those treated in centres with higher in-hospital mortality.
Conclusion
Pulmonic valve autograft provides the best long-term outcomes for children with aortic valve disease, but AVR results may depend on a centre\'s experience or patient selection.

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

Heart: 04 Oct 2021; epub ahead of print
Knight JH, Sarvestani AL, Ibezim C, Turk E, ... Raghuveer G, Kochilas LK
Heart: 04 Oct 2021; epub ahead of print | PMID: 34611043
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Impact:
Abstract

Studying the role of chromatin organisation in cardiovascular diseases-future perspectives.

Gladka MM, Christoffels VM
Commentary on \'Single-cell measurement of higher-order 3D genome organization with scSPRITE.\'

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

Cardiovasc Res: 05 Oct 2021; epub ahead of print
Gladka MM, Christoffels VM
Cardiovasc Res: 05 Oct 2021; epub ahead of print | PMID: 34613365
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Impact:
Abstract

Environmental risk factors and cardiovascular diseases: a comprehensive review.

Münzel T, Hahad O, Sørensen M, Lelieveld J, ... Nieuwenhuijsen M, Daiber A
Noncommunicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease. The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night and climate change, including heat extremes, desert storms and wildfires. In addition to the traditional risk factors for cardiovascular disease such as diabetes, arterial hypertension, smoking, hypercholesterolemia and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on cardiovascular disease.

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

Cardiovasc Res: 04 Oct 2021; epub ahead of print
Münzel T, Hahad O, Sørensen M, Lelieveld J, ... Nieuwenhuijsen M, Daiber A
Cardiovasc Res: 04 Oct 2021; epub ahead of print | PMID: 34609502
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Impact:
Abstract

Influenza vaccine and risk of acute myocardial infarction in a population-based case-control study.

de Abajo FJ, Rodríguez-Martín S, Barreira D, Rodríguez-Miguel A, ... Gil M, García-Lledó A
Objective
To assess the relationship between influenza vaccination and risk of a first acute myocardial infarction (AMI) in the general population by different epidemic periods.
Methods
This is a population-based case-control study carried out in BIFAP (Base de datos para la investigación farmacoepidemiológica en atención primaria), over 2001-2015, in patients aged 40-99 years. Per each incident AMI case, five controls were randomly selected, individually matched for exact age, sex and index date (AMI diagnosis). A patient was considered vaccinated when he/she had a recorded influenza vaccination at least 14 days before the index date within the same season. The association between influenza vaccination and AMI risk was assessed through a conditional logistic regression, computing adjusted ORs (AOR) and their respective 95% CIs. The analysis was performed overall and by each of the three time epidemic periods per study year (pre-epidemic, epidemic and postepidemic).
Results
We identified 24 155 AMI cases and 120 775 matched controls. Of them, 31.4% and 31.2%, respectively, were vaccinated, yielding an AOR of 0.85 (95% CI 0.82 to 0.88). No effect modification by sex, age and background cardiovascular risk was observed. The reduced risk of AMI was observed shortly after vaccination and persisted over time. Similar results were obtained during the pre-epidemic (AOR=0.87; 95% CI 0.79 to 0.95), epidemic (AOR=0.89; 95% CI 0.82 to 0.96) and postepidemic (AOR=0.83; 95% CI 0.79 to 0.87) periods. No association was found with pneumococcal vaccine (AOR=1.10; 95% CI 1.06 to 1.15).
Conclusions
Results are compatible with a moderate protective effect of influenza vaccine on AMI in the general population, mostly in primary prevention, although bias due to unmeasured confounders may partly account for the results.

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

Heart: 12 Oct 2021; epub ahead of print
de Abajo FJ, Rodríguez-Martín S, Barreira D, Rodríguez-Miguel A, ... Gil M, García-Lledó A
Heart: 12 Oct 2021; epub ahead of print | PMID: 34645644
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Impact:
Abstract

Atrial fibrillation following transcatheter atrial septal defect closure: a systematic review and meta-analysis.

Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Objective
The ostium secundum atrial septal defect (ASD) is among the most common congenital cardiac anomalies diagnosed in adulthood. A known complication of transcatheter ASD closure is the development of new-onset atrial fibrillation and flutter (AFi/AFl). These arrhythmias confer an increased risk of postoperative stroke, thrombus formation and systemic emboli. This systematic review examines the burden of de novo AFi/AFl in adults following transcatheter closure and seeks to identify risk factors for AFi/AFl development.
Methods
Studies were identified by a search of MEDLINE, EMBASE and Cochrane databases from inception until 29 April 2020. A meta-analysis of AFi/AFl incidence was performed using a random-effects model.
Results
A total of 31 studies met inclusion criteria, comprising 4788 adult patients without a history of AFi/AFl. Twenty-three studies were included in quantitative synthesis and demonstrated an overall incidence rate of 1.82 patients per 100 person-years of follow-up (I2=83%). In studies that enrolled only patients ≥60 years old, the incidence was 5.21 patients per 100 person-years (I2=0%). Studies with follow-up duration ≤2 years reported an incidence of 4.05 per 100 person-years (I2=55%) compared with a rate of 1.19 per 100 person-years (I2=85%) for studies with follow-up duration >2 years.
Conclusions
The incidence of new-onset AFi/AFl is relatively low following transcatheter closure of secundum ASDs. The rate of de novo AFi/AFl, however, was significantly higher in elderly patients. Shorter follow-up time was associated with a higher reported incidence of AFi/AFl.

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

Heart: 20 Oct 2021; epub ahead of print
Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Heart: 20 Oct 2021; epub ahead of print | PMID: 34675040
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Impact:
Abstract

Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.

Nørgaard BL, Gaur S, Fairbairn TA, Douglas PS, ... Leipsic J, Abdulla J
Objectives
To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).
Methods
We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as \'all-cause mortality (ACM) or myocardial infarction (MI)\' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.
Results
Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001).
Conclusions
The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

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

Heart: 21 Oct 2021; epub ahead of print
Nørgaard BL, Gaur S, Fairbairn TA, Douglas PS, ... Leipsic J, Abdulla J
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686567
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Impact:
Abstract

Non-invasive markers for sudden cardiac death risk stratification in dilated cardiomyopathy.

Pooranachandran V, Nicolson W, Vali Z, Li X, Ng GA
Dilated cardiomyopathy (DCM) is a common yet challenging cardiac disease. Great strides have been made in improving DCM prognosis due to heart failure but sudden cardiac death (SCD) due to ventricular arrhythmias remains significant and challenging to predict. High-risk patients can be effectively managed with implantable cardioverter defibrillators (ICDs) but because identification of what is high risk is very limited, many patients unnecessarily experience the morbidity associated with an ICD implant and many others are not identified and have preventable mortality. Current guidelines recommend use of left ventricular ejection fraction and New York Heart Association class as the main markers of risk stratification to identify patients who would be at higher risk of SCD. However, when analysing the data from the trials that these recommendations are based on, the number of patients in whom an ICD delivers appropriate therapy is modest. In order to improve the effectiveness of therapy with an ICD, the patients who are most likely to benefit need to be identified. This review article presents the evidence behind current guideline-directed SCD risk markers and then explores new potential imaging, electrophysiological and genetic risk markers for SCD in DCM.

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

Heart: 19 Oct 2021; epub ahead of print
Pooranachandran V, Nicolson W, Vali Z, Li X, Ng GA
Heart: 19 Oct 2021; epub ahead of print | PMID: 34670824
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Impact:
Abstract

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

Marroquin L, Tirado-Conte G, Pracoń R, Streb W, ... Rodés-Cabau J, Nombela Franco L
Objective
Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus.
Methods
This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively.
Results
IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102).
Conclusion
In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up.

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

Heart: 21 Oct 2021; epub ahead of print
Marroquin L, Tirado-Conte G, Pracoń R, Streb W, ... Rodés-Cabau J, Nombela Franco L
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686564
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Impact:
Abstract

No prospective association of a polygenic risk score for coronary artery disease with venous thromboembolism incidence.

Folsom AR, de Vries PS, Cushman M
Background
Previous studies are inconsistent about whether chronic coronary artery disease or generalized atherosclerosis is a causal risk factor for venous thromboembolism. No study seems to have taken a genomic approach to this question.
Objective
To test in a prospective study whether a polygenic risk score for coronary artery disease is associated with risk of venous thromboembolism.
Participants/methods
Within the Atherosclerosis Risk in Communities Study cohort, we computed a previously validated polygenic risk score for coronary artery disease among 9144 White participants at baseline in 1987-1989. We followed the participants through 2015 for incident hospitalized venous thromboembolism events, validated by physician review. We used Cox proportional hazards regression to associate quintiles of the polygenic risk score to venous thromboembolism incidence rates.
Results
Over the median of 26 years of follow-up, 476 participants had a venous thromboembolism event. There was no apparent association between the coronary artery disease polygenic risk score and incident venous thromboembolism, with age, sex, body mass index adjusted hazard ratios across quintiles being 1 (reference), 0.87 (0.65, 1.15), 1.08 (0.82, 1.42), 0.96 (0.72, 1.27), and 1.03 (0.78, 1.37).
Conclusions
A genetic disposition to coronary artery disease did not confer an increased risk of venous thromboembolism in this prospective study.

© 2021 International Society on Thrombosis and Haemostasis.

J Thromb Haemost: 30 Oct 2021; 19:2841-2844
Folsom AR, de Vries PS, Cushman M
J Thromb Haemost: 30 Oct 2021; 19:2841-2844 | PMID: 34409733
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Impact:
Abstract

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

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

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

J Hypertens: 30 Sep 2021; 39:2092-2102
Bello H, Woodiwiss AJ, Naran R, Peterson VR, ... Sareli P, Norton GR
J Hypertens: 30 Sep 2021; 39:2092-2102 | PMID: 34232159
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Impact:
Abstract

Effects of blood pressure and heart rate circadian rhythms on left atrial function.

Zhao Y, Liu Y, Sun Q, Han J, ... Cong T, Jiang Y
Objective
We examined the associations among the circadian rhythms of blood pressure (BP), heart rate (HR) and left atrial function in essential hypertensive patients.
Methods
The study included 237 essential hypertensive patients who completed 24-h ambulatory BP, HR monitoring and two-dimensional speckle tracking echocardiography (2DSTE). The strain and strain rate images were studied, and the following parameters were measured: left atrial reservoir strain and strain rate (LAS-S and LASR-S), left atrial conduit strain and strain rate (LAS-E and LASR-E), and left atrial booster strain and strain rate (LAS-A and LASR-A). The left atrial stiffness index (LASI) was identified as the ratio of E/e\' to LAS-S. All participants were divided into three groups according to the percentage of nocturnal BP dipping (dippers, nondippers and reverse dippers).
Results
The LASI was significantly higher in BP reverse dippers than in dippers and nondippers. LAS-S, LAS-E and LASR-E were significantly lower in BP reverse dippers than dippers and nondippers. Multivariate logistic regression analysis demonstrated that age, night-time mean SBP and the percentage of nocturnal HR decline were independently related to an increased LASI.
Conclusion
Impairment of the left atrial reservoir and conduit functions was correlated with abnormal BP and HR circadian rhythms in hypertension. Increased left atrial stiffness was associated with night-time SBP and the percentage of nocturnal HR decline.

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

J Hypertens: 31 Oct 2021; 39:2318-2324
Zhao Y, Liu Y, Sun Q, Han J, ... Cong T, Jiang Y
J Hypertens: 31 Oct 2021; 39:2318-2324 | PMID: 34620813
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Impact:
Abstract

Biventricular function and shock severity predict mortality in cardiac intensive care unit patients.

Burstein B, van Diepen S, Wiley BM, Anavekar NS, Jentzer JC
Background
Ventricular function, including left ventricular systolic dysfunction (LVSD), right ventricular systolic dysfunction (RVSD), and biventricular dysfunction (BVD), contribute to shock in cardiac intensive care unit (CICU) patients, but the prognostic utility remains unclear.
Research question
Do patients with ventricular dysfunction have higher mortality at each Society for Cardiovascular Angiography and Intervention (SCAI) shock stage?
Study design and methods
We identified CICU patients admitted with available echocardiography data. LVSD was defined as left ventricular ejection fraction less than 40%, RVSD as moderate or greater systolic dysfunction by semi-quantitative measurement, and BVD as the presence of both. Multivariable logistic regression determined the relationship between ventricular dysfunction and adjusted in-hospital mortality as a function of SCAI stage.
Results
The study population included 3,158 patients with a mean age of 68.2 years (±14.6), of which 51.8% had acute coronary syndromes. LVSD was present in 22.3%, RVSD in 11.8%, and 16.4% had BVD. After adjustment for SCAI shock stage there was no difference in in-hospital mortality between patients with LVSD or RVSD and those without ventricular dysfunction (p >0.05), but BVD was independently associated with higher in-hospital mortality (adjusted HR 1.815, 95% CI 1.237-2.663, p = 0.0023). The addition of ventricular dysfunction to the SCAI staging criteria increased discrimination for hospital mortality (AUC 0.784 vs. 0.766, p <0.001).
Interpretation
Among patients admitted to the CICU, only BVD was independently associated with higher hospital mortality. The addition of echocardiography assessment to the SCAI shock criteria may facilitate improved clinical risk stratification.

Copyright © 2021. Published by Elsevier Inc.

Chest: 01 Oct 2021; epub ahead of print
Burstein B, van Diepen S, Wiley BM, Anavekar NS, Jentzer JC
Chest: 01 Oct 2021; epub ahead of print | PMID: 34610345
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Impact:
Abstract

Influence of aging and increased blood pressure on oscillometric cuff pressure waveform characteristics.

Pan F, He P, Pu X, Gao H, ... Feng J, Zheng D
Background
The oscillometric blood pressure (BP) measurement technique estimates BPs from analyzing the envelop of oscillometric cuff pressure waveform. The oscillometric waveform envelope shape is associated with physiological changes and influences BP measurement accuracy. The aim of this study was to comprehensively quantify BP- and age-related changes of oscillometric waveform envelope characteristics.
Method
Manual systolic and diastolic BPs were measured from 472 patients (219 female, 253 male), and the cuff pressure were digitally recorded during linear cuff deflation that was used to derive oscillometric waveform envelopes. All patients were divided into different categories according to their BP level and age. The envelope width in high-pressure region (above mean arterial pressure, MAP) and low-pressure region (below MAP) were compared between different BP and age categories to qualify their changes with increased BP and aging.
Results
The envelop widths increased significantly with increased BPs (P < 0.001 between optimal, normotensive and hypertensive groups) and aging (P < 0.001 for >50 years old group in comparison with younger groups). The envelope widths in high-pressure region were significantly larger than in low-pressure region in normal and hypertensive categories (all P < 0.05) and elderly patients aged over 60 years (all P < 0.001), and the envelope width ratios between them increased with increased BP and aging.
Conclusion
This study has concluded an asymmetrical oscillometric waveform envelope in normotensive and hypertensive categories, as well as in elderly group (aged over 60 years), and their asymmetrical features were significantly more obvious with increased BP and aging.

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

J Hypertens: 31 Oct 2021; 39:2157-2163
Pan F, He P, Pu X, Gao H, ... Feng J, Zheng D
J Hypertens: 31 Oct 2021; 39:2157-2163 | PMID: 34149015
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Impact:
Abstract

Prognostic value of masked uncontrolled apparent resistant hypertension detected through home blood pressure monitoring.

Barochiner J, Aparicio LS, Martínez R, Alfie J, Marín MJ
Objective
Resistant hypertension carries a poor prognosis and current guidelines recommend the exclusion of the white-coat phenomenon for proper diagnosis. However, guidelines do not focus on patients treated with at least three drugs whose blood pressure (BP) is controlled at the office but elevated out of it. We aimed at determining whether this masked uncontrolled apparent resistant hypertension (MUCRH) detected through home blood pressure monitoring (HBPM) has prognostic value for fatal and nonfatal events in these hypertensive patients.
Methods
Hypertensive patients treated with at least three drugs who performed a baseline HBPM between 2008 and 2015 were followed to register the occurrence of total mortality, cardiovascular mortality, and fatal and nonfatal cardiac and cerebrovascular events. MUCRH was defined as office blood pressure less than 140/90 mmHg and home BP at least 135 and/or 85 mmHg. Multivariable Cox proportional hazard models were adjusted to determine the independent prognostic value of MUCRH for the events of interest.
Results
We included 470 patients, 35.5% male, mean age 71.9 years, and treated with 3.3 antihypertensive drugs on average. Among study population, 15.5% had MUCRH (33.3% when considering only patients with adequate BP control at the office). Median follow-up was 6.7 years. In multivariable models, MUCRH was an independent predictor for cardiovascular mortality and cerebrovascular events: hazard ratio 4.9 (95% CI 1.2-19.9, P = 0.03) and 5.1 (95% CI 1.5-16.9, P = 0.01), respectively.
Conclusion
MUCRH is not rare and is independently associated with cardiovascular morbidity and mortality. The systematic monitoring of intensively treated individuals through HBPM would be useful for the detection of patients at increased risk of events.

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

J Hypertens: 31 Oct 2021; 39:2141-2146
Barochiner J, Aparicio LS, Martínez R, Alfie J, Marín MJ
J Hypertens: 31 Oct 2021; 39:2141-2146 | PMID: 34128493
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Impact:
Abstract

Lower ambulatory nocturnal SBP is associated with less cardiovascular and renal damage in normotensive hospitalized patients with chronic kidney disease.

Zhang J, Song J, Zhou L, Zhou W, ... Peng H, Lou T
Objective
The impact of nocturnal blood pressure (BP) on target organ damage (TOD) in chronic kidney disease (CKD) patients with normotension has not been established. In this study, we determined whether nocturnal BP is correlated with cardiovascular and renal damage independent of the 24-h BP in CKD patients with normotension or hypertension.
Methods
A total of 1166 hospitalized patients with CKD not requiring dialysis were enrolled in this cross-sectional study, 421 and 745 of whom had normotension and hypertension, respectively. TOD was assessed by the left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR) and presence of proteinuria. Univariate and multivariable regression analyses were used to evaluate the relationships between nocturnal BP and TOD.
Results
In the multivariable-adjusted models, including the 24-h BP, nocturnal SBP was independently associated with the LVMI, eGFR and proteinuria in patients with normotension (P < 0.05), while the nocturnal DBP was not correlated with proteinuria. The nocturnal SBP was associated with LVMI and proteinuria, but not the eGFR in patients with hypertension. We did not demonstrate an association between nocturnal DBP and TOD in these patients. When nocturnal SBP in patients with normotension was further divided into tertiles [tertile 1 (<104 mmHg), tertile 2 (104-114 mmHg) and tertile 3 (≥114 mmHg)], multivariate analysis showed that tertile 3 was independently associated with TOD.
Conclusion
Nocturnal SBP was shown to be an independent risk factor for TOD in patients with normotension. Targeting a nocturnal ambulatory SBP to less than 114 mmHg or even less than 104 mmHg may help prevent TOD in patients with CKD.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

J Hypertens: 31 Oct 2021; 39:2241-2249
Zhang J, Song J, Zhou L, Zhou W, ... Peng H, Lou T
J Hypertens: 31 Oct 2021; 39:2241-2249 | PMID: 34128492
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Impact:
Abstract

Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure.

Mariampillai JE, Prestgaard EE, Kjeldsen SE, Liestøl K, ... Erikssen JE, Skretteberg PT
Objective
Previous research has shown an association between moderate workload exercise blood pressure (BP) and coronary disease, whereas maximal exercise BP is associated with stroke. We aimed to investigate the association between the increase in BP during maximal exercise and the long-term risk of stroke in healthy, middle-aged men.
Methods
Two thousand and fourteen men were included in the Oslo Ischemia Study in the 1970s. In the present study, we examined baseline data of the 1392 participants who remained healthy and performed bicycle exercise tests both at baseline and 7 years later. Cox proportional hazard was used to assess the risk of stroke in participants divided into quartiles based on the difference between resting and maximal workload SBP (ΔSBP) at baseline, adjusting for resting BP, age, smoking, serum cholesterol and physical fitness. Follow-up was until the first ischemic or hemorrhagic stroke through 35 years.
Results
There were 195 incident strokes; 174 (89%) were ischemic. In univariate analyses, there were significant positive correlations between age, resting SBP, resting DBP and SBP at moderate and maximal workload, and risk of stroke. In the multivariate analysis, there was a 2.6-fold (P < 0.0001) increase in risk of stroke in ΔSBP quartile 4 (ΔSBP > 99 mmHg) compared with ΔSBP quartile 2 (ΔSBP 73-85 mmHg), which had the lowest risk of stroke. ΔSBP quartile 1 had a 1.7-fold (P = 0.02) increased risk compared with quartile 2, suggesting a J-shaped association to stroke risk.
Conclusion
Stroke risk increased with increasing difference between resting and maximal exercise SBP, independent of BP at rest, suggesting that an exaggerated BP response to physical exercise may be an independent predictor of stroke.

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

J Hypertens: 30 Sep 2021; 39:2022-2029
Mariampillai JE, Prestgaard EE, Kjeldsen SE, Liestøl K, ... Erikssen JE, Skretteberg PT
J Hypertens: 30 Sep 2021; 39:2022-2029 | PMID: 34102659
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Impact:
Abstract

Synergistic harmful interaction between sustained physical inactivity and hypertension/diabetes mellitus on the risk of all-cause mortality: a retrospective observational cohort study.

Lee CH, Han KD, Yoo J, Kwak MS
Objective
Hypertension, diabetes mellitus and physical inactivity can cause cardiovascular complications or premature death. However, it has not been clarified whether those major comorbidities and physical activity interact in affecting health outcomes. The aim of this study is to evaluate the potential interaction between temporal physical activity profiles and hypertension or diabetes mellitus on the risk for all-cause mortality.
Methods
This study used Korea National Health Insurance Service (KNHIS) database and included about 6.5 million participants who underwent health screening in 2009 and 2011. Physical activity was evaluated as 2-year change based on self-reported survey using 7-day recall method, and grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Participants were categorized into groups according to the presence of hypertension/diabetes mellitus. Outcome included all-cause mortality.
Results
In total, 6 554 082 participants (48.4 ± 13.3 years; 56.7% men) were included. During a median 6.4-year follow-up, 83 241 deaths occurred. Compared with the \'remained active\' group, other groups had a higher mortality risk after adjustment for covariates [adjusted hazard ratio (aHR) 1.17, 95% CI 1.13-1.21 in the \'inactive-to-active\' group, aHR 1.28, 95% CI 1.24-1.32 in the \'active-to-inactive\' group, aHR 1.52, 95% CI 1.48-1.57 in the \'remained inactive\' group). Hypertension and diabetes mellitus were significant effect modifiers in the association between physical activity and the risk of all-cause mortality (P for interaction <0.001). The harmful effects of persistent physical inactivity on all-cause mortality were the most obvious in those with both hypertension and diabetes mellitus among groups.
Conclusion
Sustained physical inactivity was associated with increased risk of all-cause mortality in those with hypertension or diabetes mellitus more strongly than in those without. Physicians should emphasize sustained physical activity even more in patients with hypertension or diabetes mellitus.

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

J Hypertens: 30 Sep 2021; 39:2058-2066
Lee CH, Han KD, Yoo J, Kwak MS
J Hypertens: 30 Sep 2021; 39:2058-2066 | PMID: 34102662
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Abstract

Isolated diastolic vs. systolic hypertension phenotypes and outcomes: prospective cohort of newly diagnosed individuals with hypertension.

Thomopoulos C, Andrikou I, Konstantinidis D, Iliakis P, ... Stergiou GS, Tsioufis C
Aims
To evaluate whether different hypertension phenotypes, namely, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic/diastolic hypertension (SDH) have a differential outcome effect by clinic and ambulatory blood pressure (BP) measurements.
Methods
We prospectively evaluated in 569 never-treated patients with sustained hypertension (age 52.6 ± 11.6 years; men 55%; clinic BP 150 ± 15/95.5 ± 10 mmHg, systolic/diastolic; 24-h ambulatory BP 128.9 ± 12.6/80.6 ± 9.7) the incidence of major cardiovascular (CV) events within 5 years, after adjustment for confounders, including the rate of BP control and the weighted follow-up BP.
Results
All participants received antihypertensive drug treatment (mean number of drugs 1.9 ± 1.1; follow-up visits 4.6/patient). Average clinic BP achieved during follow-up was 136 ± 12.6/83.9 ± 9.4 mmHg, with 39% of participants having clinic BP less than 140/90 mmHg in at least 75% of their visits, and 24% in 25-75% of visits. Prevalence of hypertension phenotypes defined using BP differed from that using ambulatory BP, whereas integration of both BP measurements reclassified the initial phenotype to another in 18% of participants. Although, no differential outcome effect was observed between clinic IDH and SDH assessed using clinic or ambulatory BP measurements, clinic BP-based ISH was associated with a higher outcome incidence than the IDH and SDH phenotypes (hazard ratio 4.8, 95% confidence interval 1.4-17.0, P = 0.015). ISH diagnosed by integration of clinic and ambulatory BP, also increased the outcome (hazard ratio 4.0, 95% confidence interval 1.0-15.6, P = 0.046).
Conclusion
In hypertensive patients at low/moderate CV risk, IDH and SDH phenotypes defined by clinic BP measurements, equally determined CV events but to a lower extent compared with ISH.

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

J Hypertens: 30 Sep 2021; 39:2001-2008
Thomopoulos C, Andrikou I, Konstantinidis D, Iliakis P, ... Stergiou GS, Tsioufis C
J Hypertens: 30 Sep 2021; 39:2001-2008 | PMID: 34102665
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Abstract

The cardio-ankle vascular index as a predictor of adverse pregnancy outcomes.

Rueangjaroen P, Luewan S, Phrommintikul A, Leemasawat K, Tongsong T
Objective
To assess the association between maternal hemodynamic parameters; cardio-ankle vascular index (CAVI), representing arterial stiffness; mean arterial pressure (MAP), uterine artery pulsatility index (Ut-PI), and adverse pregnancy outcomes including preeclampsia (PE), fetal growth restriction (FGR), and gestational diabetes mellitus (GDM).
Methods
A prospective cohort study was conducted on low-risk pregnancies. All were serially measured for the mean CAVI, MAP, and Ut-PI for four times at gestational age (GA) 11-14, 18-22, 28-32, and after 36 weeks. Also, the women were followed up for pregnancy outcomes, focusing on PE, FGR, and GDM.
Results
Of 335 recruited cases meeting the inclusion criteria, 16 cases developed PE, 24 cases had FGR, and 83 cases had GDM. Compared to the non-PE group, women developing PE had a significant increase in CAVI at 18-22, 28-32, and after 36 weeks (P-value = 0.021, 0.003, and <0.001, respectively), a significant increase in MAP at all of the four periods (P-value < 0.001, for all periods), and a significant increase in Ut-PI during GA 18-22 weeks (P-value = 0.021). In pregnancies with FGR, there was a significant increase of CAVI at GA 18-22, 28-32 and after 36 weeks (P-value = 0.012, 0.015, and 0.004, respectively), an increase in Ut-PI in all gestational periods (P-value < 0.05) but no changes of MAP throughout pregnancy. In GDM, the three parameters were not significantly different from those in the non-GDM group in all of the four periods. CAVI could predict PE and FGR with AUC of 0.655-0.835 and 0.673-0.760, respectively. CAVI added predictive values when combined with MAP or Ut-PI.
Conclusion
Increased CAVI, like MAP and Ut-PI, can be used as a predictor of PE and FGR but not GDM. Also, it has an added predictive value when combined with MAP or Ut-PI.

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

J Hypertens: 30 Sep 2021; 39:2082-2091
Rueangjaroen P, Luewan S, Phrommintikul A, Leemasawat K, Tongsong T
J Hypertens: 30 Sep 2021; 39:2082-2091 | PMID: 34086620
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Abstract

Risk factors predisposing to acute stroke in India: a prospective study.

Ram CVS, Kumar S, Renjen PN, Kumar GP, ... Vasudevan A, Lackland D
Background
Stroke is an important neurological disorder with significant morbidity and mortality. In India, the risk factors for stroke (obesity, diabetes mellitus, alcoholism, hypertension, and sedentary lifestyle) are mounting with economic growth and increasing the disease burden.
Objective
To assess the severity and risk factors of stroke in India and identify any new predisposing factors.
Methods
A multicentric (six tertiary care hospitals across India) prospective observational study (from September 2016 to July 2017) was conducted on 526 stroke patients, presenting within the first 24 h to examine the risk factors for ischemic and hemorrhagic strokes. Severity was determined using the National Institutes of Health Stroke Scale (NIHSS).
Results
Predominantly male (72.3%), 75% of the sample was >50 years old, with a mean body mass index (BMI) of 25.8 ± 4.3 kg/m2 and 14.6% obese patients. Hypertension and diabetes mellitus were the commonest comorbidities, followed by a history of ischemic heart disease and familial history of stroke. 20.5% of patients had mild strokes, 57.4% had moderate, 8.4% experienced moderate-severe strokes, whereas 7.2% had severe strokes. Regarding the admission diagnoses, 56.8% were ischemic, 18.6% were hemorrhagic, 1.1% had a transient ischemic attack, 6.6% suffered recurrent strokes, and 17% were other forms.
Conclusion
The foremost risk factors for stroke in India, hypertension and diabetes, need to be controlled and treated like other global high-risk populations for stroke prevention. The NIHSS scores highlight the relationship between risk factors and stroke severity.

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

J Hypertens: 31 Oct 2021; 39:2183-2189
Ram CVS, Kumar S, Renjen PN, Kumar GP, ... Vasudevan A, Lackland D
J Hypertens: 31 Oct 2021; 39:2183-2189 | PMID: 34620808
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Abstract

A prospective study of multiple sleep dimensions and hypertension risk among white, black and Hispanic/Latina women: findings from the Sister Study.

Lunyera J, Park YM, Ward JB, Gaston SA, ... Sandler DP, Jackson CL
Background
Poor sleep is associated with increased hypertension risk, but few studies have evaluated multiple sleep dimensions or investigated racial/ethnic disparities in this association among women.
Method
We investigated multiple sleep dimensions (sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping and difficulty falling or staying asleep) and hypertension risk among women, and determined modification by age, race/ethnicity and menopausal status. We used data from the Sister Study, a national cohort of 50 884 women who had sisters diagnosed with breast cancer in the United States enrolled in 2003-2009 and followed through September 2018.
Results
Of 33 497 women without diagnosed hypertension at baseline (mean age ± standard deviation: 53.9 ± 8.8 years; 88.7% White, 6.4% Black and 4.9% Hispanic/Latina), 23% (n = 7686) developed hypertension over a median follow-up of 10.1 years [interquartile range: 8.2-11.9 years]. Very short, short or long sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping, insomnia, insomnia symptoms as well as short sleep and exploratory cumulative poor sleep score were associated with incident hypertension after adjustment for demographics factors. After additional adjustment for lifestyle and clinical factors, insomnia [hazard ratio = 1.09, 95% confidence interval (95% CI): 1.03-1.15] and insomnia symptoms plus short sleep (hazard ratio = 1.13, 95% CI: 1.05-1.21) remained associated with incident hypertension. These associations were stronger in younger (age<54 vs. ≥54 years) and premenopausal vs. postmenopausal women (all P-interaction < 0.05). Associations did not differ by race/ethnicity (all P-interaction > 0.05).
Conclusion
Thus, screening for multiple sleep dimensions and prioritizing younger and premenopausal women may help identify individuals at high risk for hypertension.

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

J Hypertens: 31 Oct 2021; 39:2210-2219
Lunyera J, Park YM, Ward JB, Gaston SA, ... Sandler DP, Jackson CL
J Hypertens: 31 Oct 2021; 39:2210-2219 | PMID: 34620810
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Impact:
Abstract

Sex-specific associations of brachial-ankle pulse wave velocity with adverse cardiac remodeling and long-term cardiovascular outcome.

Kwak S, Kim HL, Lim WH, Seo JB, ... Zo JH, Kim MA
Background
It remains unclear whether the cardiovascular consequences of arterial stiffness differ by sex. This study aimed to investigate the sex-specific association of brachial-ankle pulse wave velocity (baPWV) with adverse cardiac remodeling and cardiovascular outcome.
Method
We studied 11 767 patients (57.6% men) with cardiovascular risk factors, whose baPWV was measured. The primary endpoint was composite cardiovascular events. Restricted cubic spline (RCS) analyses were performed to delineate the association of baPWV with echocardiography parameters and risks of cardiovascular events.
Results
RCS curves showed that structural/functional echocardiography parameters gradually worsened with increasing baPWV more prominently in women than in men. The prevalence of left ventricular hypertrophy and diastolic dysfunction increases with baPWV increase more steeply in women (P-for-interaction by sex <0.001). During the median follow-up of 3.64 years (interquartile interval, 1.56-5.38 years), 350 cardiovascular events (3.0%) and 155 deaths (1.3%) occurred. Cumulative cardiovascular events and deaths were significantly higher in patients with elevated baPWV in both sexes (P < 0.001). Cox analyses showed that the increase in baPWV was associated with the higher risks of cardiovascular events and deaths more strongly in women [cardiovascular events: men, adjusted hazard ratio 1.10, 95% confidence interval (1.08-1.13), P < 0.001; women, adjusted hazard ratio 1.18, 95% confidence interval (1.13-1.24), P < 0.001 by 100 cm/s increase in baPWV; P-for-interaction by sex = 0.022].
Conclusion
The detrimental effects of baPWV on adverse cardiac remodeling and cardiovascular outcome were stronger in women than in men. The prognostic information provided by baPWV may be particularly crucial for women.

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

J Hypertens: 03 Oct 2021; epub ahead of print
Kwak S, Kim HL, Lim WH, Seo JB, ... Zo JH, Kim MA
J Hypertens: 03 Oct 2021; epub ahead of print | PMID: 34611109
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Abstract

Reference values of central blood pressure and central haemodynamic parameters and their relationship with cardiovascular risk factors in a Spanish population: early vascular ageing study.

Gómez-Sánchez M, Gómez-Sánchez L, Patino-Alonso C, Recio-Rodríguez JI, ... Gomez-Marcos MA, on behalf EVA investigators
Objectives
Central blood pressure (BP) predicts mortality independent of office brachial BP. The aim was to describe reference values for central blood pressure and pulsatile hemodynamic parameters, and their relationship with cardiovascular risk factors in an adult Spanish population without cardiovascular disease.
Methods
Cross-sectional study. We included 501 participants stratified by age and sex by random sampling, with a mean age of 56 years (50.3% women). The SphygmoCor System device\'s pulse wave analysis software was used to perform the measurements.
Results
The following values were obtained: central blood pressure median (109/76 mmHg), central pulse pressure (33 mmHg), pulse pressure amplification (8.5 mmHg), ejection duration (130 ms) and subendocardial viability ratio (163%). All parameters were greater in men, except heart rate and ejection duration. In the logistic regression analysis, controlled for age, sex and taking antihypertensive drugs, being hypertensive was associated with cSBP (OR = 1.265), cDBP (OR = 1.307), cPP (OR = 1.067), pulse wave amplification (OR = 1.034) and SEVR (OR = 0.982); being diabetic was associated with SEVR (OR = 0.982); being obese was associated with cSBP (OR = 1.028) and cDBP (OR = 1.058) and being a smoker was associated with ejection duration (OR = 0.980) and SEVR (OR = 0.984).
Conclusion
This study provides reference values for central blood pressure and parameters derived from the pulse wave analysis in a random sample of the Spanish population. The only risk factor that is not associated with any of the parameters analysed is dyslipidaemia.
Trial registration number
https://clinicaltrials.gov/ct2/show/NCT02623894.

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

J Hypertens: 31 Oct 2021; 39:2147-2156
Gómez-Sánchez M, Gómez-Sánchez L, Patino-Alonso C, Recio-Rodríguez JI, ... Gomez-Marcos MA, on behalf EVA investigators
J Hypertens: 31 Oct 2021; 39:2147-2156 | PMID: 34343142
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Abstract

Effects of enhanced versus reduced vasodilating treatment on brachial and central blood pressure in patients with chronic kidney disease: a randomized controlled trial.

Khatir DS, Carlsen RK, Ivarsen P, Jespersen B, ... Christensen KL, Buus NH
Background
Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions.
Methods
Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating β-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison.
Results
Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32).
Conclusion
In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT.

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

J Hypertens: 31 Oct 2021; 39:2232-2240
Khatir DS, Carlsen RK, Ivarsen P, Jespersen B, ... Christensen KL, Buus NH
J Hypertens: 31 Oct 2021; 39:2232-2240 | PMID: 34313633
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Abstract

Football beats hypertension: results of the 3F (Fit&Fun with Football) study.

Schrader B, Schrader J, Vaske B, Elsässer A, ... Gehlenborg E, Lüders S
Objectives
Football as the most popular sport could improve insufficient physical activity in patients with cardiovascular risk factors. A modified \'healthy\' football training format could motivate hypertensive patients to return to sport and improve risk factors.
Methods
The 3F study: \'Fit and Fun with Football\' a prospective interventional study with 1 year follow-up. Football group: n = 103, structured \'health\'-football training (1×/week, 90 min) led by Deutscher Fußball Bund-licensed football coaches. Hypertensive patients at least 45 years who have not exercised for several years were compared with a control group (n = 105).
Primary study objective
Reduction of office (OBP) and/or 24-h ambulatory blood pressure (BP) monitoring (ABPM) and/or reduction of number or dosage of antihypertensive medication.
Main results
OBP values decreased significantly in the football group from 142.6/87.9 to 130.8/81.8 mmHg (P < 0.001), in the control group the values increased slightly (NS). ABPM values decreased significantly in the football group, while a slight increase was found in the control group. At the end of the study, the mean values in the football group of both OPB (P < 0.001) and ABPM (systolic P < 0.001, diastolic P = 0.017) were significantly lower than in the control group. Significantly more people in the football group were able to reduce antihypertensive patients than in the control group (football group:16, control group:6), while more participants in the control group intensified antihypertensive therapy (football group:3, control group:14) (P < 0.001). Among the secondary endpoints, there was a weight loss of 3 kg in the football group and an increase of 1.7 kg in the control group (P < 0.001).
Conclusion
Offering modified \'healthy\' football-training to middle-aged hypertensive patients can lead to better BP control and a reduction of antihypertensive medication. Therefore, the offer of \'health football\' should be established and supported by clubs, insurances and authorities.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

J Hypertens: 31 Oct 2021; 39:2290-2296
Schrader B, Schrader J, Vaske B, Elsässer A, ... Gehlenborg E, Lüders S
J Hypertens: 31 Oct 2021; 39:2290-2296 | PMID: 34261954
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Abstract

Association of self-measured home, ambulatory, and strictly measured office blood pressure and their variability with intracranial arterial stenosis.

Hisamatsu T, Ohkubo T, Hozawa A, Fujiyoshi A, ... Miura K, SESSA Research Group
Objective
Hypertension and intracranial artery stenosis (ICAS) are closely related; however, few studies have compared the strength of the relationship between strictly measured office and out-of-office blood pressure (BP) measurements. The relationship of day-by-day or short-term variability in BP to asymptomatic ICAS also remains unclear.
Methods
In apparently healthy 677 men (mean age, 70 years) from a population-based cohort, we examined the association of strictly measured office BP and 7-day home BP with ICAS on magnetic resonance angiography. We conducted 24-h ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and night-time variability, nocturnal decline, and morning pressor surge. Any ICAS was defined as either mild (1-49%) or severe (≥50%) stenosis.
Results
We observed mild and severe ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable-adjusted Poisson regression with robust error variance, higher SBP in office, home, or ambulatory BP monitoring was associated with the presence of any or severe ICAS. The associations with ICAS were comparable between office, home, and ambulatory SBP (all heterogeneity P values >0.1). Independent of mean SBP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or night-time variability, in SBP was associated with higher burden of any or severe ICAS.
Conclusion
The magnitude of association of strictly measured office BP for asymptomatic ICAS was comparable with that of BP measured at home or in ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring was positively associated with asymptomatic ICAS burden.

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

J Hypertens: 30 Sep 2021; 39:2030-2039
Hisamatsu T, Ohkubo T, Hozawa A, Fujiyoshi A, ... Miura K, SESSA Research Group
J Hypertens: 30 Sep 2021; 39:2030-2039 | PMID: 34173797
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