Topic: Intervention

Abstract

Ticagrelor in Patients with Stable Coronary Disease and Diabetes.

Steg PG, Bhatt DL, Simon T, Fox K, ... Leiter LA,
Background
Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.
Methods
In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.
Results
A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02).
Conclusions
In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).

Copyright © 2019 Massachusetts Medical Society.

N Engl J Med: 02 Oct 2019; 381:1309-1320
Steg PG, Bhatt DL, Simon T, Fox K, ... Leiter LA,
N Engl J Med: 02 Oct 2019; 381:1309-1320 | PMID: 31475798
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Abstract

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

Makkar RR, Thourani VH, Mack MJ, Kodali SK, ... Leon MB,
Background
There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk.
Methods
We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke.
Results
At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery.
Conclusions
Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 26 Mar 2020; 382
Makkar RR, Thourani VH, Mack MJ, Kodali SK, ... Leon MB,
N Engl J Med: 26 Mar 2020; 382 | PMID: 31995682
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Abstract

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

Kang DH, Park SJ, Lee SA, Lee S, ... Lee JW, Park SW
Background
The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.
Methods
In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up.
Results
In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.
Conclusions
Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Copyright © 2019 Massachusetts Medical Society.

N Engl J Med: 08 Jan 2020; 382
Kang DH, Park SJ, Lee SA, Lee S, ... Lee JW, Park SW
N Engl J Med: 08 Jan 2020; 382 | PMID: 31733181
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Abstract

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

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

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Mar 2022; 108:500-506
Kite TA, Ladwiniec A, Arnold JR, McCann GP, Moss AJ
Heart: 30 Mar 2022; 108:500-506 | PMID: 34234006
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Abstract

Coronary revascularisation outcomes in patients with cancer.

Leedy D, Tiwana JK, Mamas M, Hira R, Cheng R
Cancer and coronary artery disease (CAD) overlap in traditional risk factors as well as molecular mechanisms underpinning the development of these two disease states. Patients with cancer are at increased risk of developing CAD, representing a high-risk population that are increasingly undergoing coronary revascularisation. Over 1 in 10 patients with CAD that require revascularisation with either percutaneous coronary intervention or coronary artery bypass grafting have either a history of cancer or active cancer. These patients are typically older, have more comorbidities and have more extensive CAD compared with patients without cancer. Haematological abnormalities with competing risks of thrombosis and bleeding pose further unique challenges during and after revascularisation. Management of patients with concurrent cancer and CAD requiring revascularisation is challenging as these patients carry a higher risk of morbidity and mortality compared with those without cancer, often driven by the underlying cancer and associated comorbidities. However, due to variability by different types and stages of cancer, revascularisation outcomes are specific to cancer characteristics such as the timing of onset, cancer subtype and site, stage, presence of metastases, and cancer-related therapies received. Recent studies have provided insights into defining revascularisation outcomes, procedural considerations and best practices in managing patients with cancer. Nevertheless, many gaps remain that require further studies to inform clinical best practices in this population.

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Mar 2022; 108:507-516
Leedy D, Tiwana JK, Mamas M, Hira R, Cheng R
Heart: 30 Mar 2022; 108:507-516 | PMID: 34415850
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Abstract

CT or Invasive Coronary Angiography in Stable Chest Pain.

Maurovich-Horvat P, Bosserdt M, Kofoed KF, Rieckmann N, ... Martus P, Dewey M
Background
In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain.
Methods
We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris.
Results
Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48).
Conclusions
Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Copyright © 2022 Massachusetts Medical Society.

N Engl J Med: 03 Mar 2022; epub ahead of print
Maurovich-Horvat P, Bosserdt M, Kofoed KF, Rieckmann N, ... Martus P, Dewey M
N Engl J Med: 03 Mar 2022; epub ahead of print | PMID: 35240010
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Abstract

Long-Term Outcomes and Associations With Major Adverse Limb Events After Peripheral Artery Revascularization.

Hess CN, Wang TY, Weleski Fu J, Gundrum J, ... Rogers RK, Hiatt WR
Background
Long-term cardiovascular and limb outcomes after revascularization for peripheral artery disease and, in particular, prognosis after post-procedure major adverse limb events (MALE) are not well-studied.
Objectives
This study sought to describe outcomes after peripheral revascularization and assess relationships between post-procedure MALE hospitalization and subsequent events.
Methods
Patients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2015, in the Premier Healthcare Database were examined for the co-primary outcomes of interest, composite myocardial infarction (MI) or stroke and composite major amputation or peripheral revascularization. Multivariable adjusted Cox proportional hazards models with post-procedure MALE hospitalization included as a time-dependent covariate were developed to estimate hazard ratios for outcomes.
Results
Among 393,017 revascularized patients followed for a median of 2.7 years (interquartile range: 1.3 to 4.4 years), the cumulative incidence of MI or stroke was 9.8% and that of major amputation or peripheral revascularization was 41.9%. A total of 50,750 patients (12.9%) had at least 1 post-procedure MALE hospitalization. In time-dependent covariate adjusted models, post-procedure MALE hospitalization was associated with greater risk of subsequent MI or stroke (hazard ratio: 1.34; 95% confidence interval: 1.28 to 1.40) and major amputation or peripheral revascularization (hazard ratio: 8.13; 95% confidence interval: 7.96 to 8.29). After peripheral revascularization with or without post-procedure MALE hospitalization, risk of limb events increased rapidly post-procedure and more slowly after the first year, whereas cardiac risk increased steadily during follow-up.
Conclusions
Revascularized peripheral artery disease patients face earlier limb and later cardiovascular ischemic risk that is heightened among patients with post-procedure MALE hospitalization. Increased provider awareness of these long-term risks may guide efforts to improve post-procedural outcomes.

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

J Am Coll Cardiol: 10 Feb 2020; 75:498-508
Hess CN, Wang TY, Weleski Fu J, Gundrum J, ... Rogers RK, Hiatt WR
J Am Coll Cardiol: 10 Feb 2020; 75:498-508 | PMID: 32029132
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Abstract

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

Linde JJ, Kelbæk H, Hansen TF, Sigvardsen PE, ... Køber LV, Kofoed KF
Background
In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease.
Objectives
The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS.
Methods
The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard.
Results
Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group.
Conclusions
Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

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

J Am Coll Cardiol: 10 Feb 2020; 75:453-463
Linde JJ, Kelbæk H, Hansen TF, Sigvardsen PE, ... Køber LV, Kofoed KF
J Am Coll Cardiol: 10 Feb 2020; 75:453-463 | PMID: 32029126
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Abstract

Stent-Related Adverse Events >1 Year After Percutaneous Coronary Intervention.

Madhavan MV, Kirtane AJ, Redfors B, Généreux P, ... Pocock SJ, Stone GW
Background
The majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (>1-year) stent-related MACE have not been well described.
Objectives
The purpose of this study was to assess the frequency and predictors of very-late stent-related events or MACE by stent type.
Methods
Individual patient data from 19 prospective, randomized metallic stent trials maintained at a leading academic research organization were pooled. Very-late MACE (a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]), and target lesion failure (cardiac death, target-vessel MI, or ID-TLR) were assessed within year 1 and between 1 and 5 years after PCI with bare-metal stents (BMS), first-generation drug-eluting stents (DES1) and second-generation drug-eluting stents (DES2). A network meta-analysis was performed to evaluate direct and indirect comparisons.
Results
Among 25,032 total patients, 3,718, 7,934, and 13,380 were treated with BMS, DES1, and DES2, respectively. MACE rates within 1 year after PCI were progressively lower after treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1%, respectively, p < 0.0001). Between years 1 and 5, very-late MACE occurred in 9.4% of patients (including 2.9% cardiac death, 3.1% MI, and 5.1% ID-TLR). Very-late MACE occurred in 9.7%, 11.0%, and 8.3% of patients treated with BMS, DES1, and DES2, respectively (p < 0.0001), linearly increasing between 1 and 5 years. Similar findings were observed for target lesion failure in 19,578 patients from 12 trials. Findings were confirmed in the network meta-analysis.
Conclusions
In this large-scale, individual patient data pooled study, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident. New approaches are required to improve long-term outcomes after PCI.

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

J Am Coll Cardiol: 17 Feb 2020; 75:590-604
Madhavan MV, Kirtane AJ, Redfors B, Généreux P, ... Pocock SJ, Stone GW
J Am Coll Cardiol: 17 Feb 2020; 75:590-604 | PMID: 32057373
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Abstract

Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis.

Puls M, Beuthner BE, Topci R, Vogelgesang A, ... Jacobshagen C, Hasenfuß G
Aims
Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes.
Methods and results
One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson\'s trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF-) median percentage MF (≥11% or <11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003). In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. 2% in MF- patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0-369), P = 0.01].
Conclusion
Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI.

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

Eur Heart J: 11 Feb 2020; epub ahead of print
Puls M, Beuthner BE, Topci R, Vogelgesang A, ... Jacobshagen C, Hasenfuß G
Eur Heart J: 11 Feb 2020; epub ahead of print | PMID: 32049275
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Abstract

Ticagrelor With or Without Aspirin After PCI: The TWILIGHT Platelet Substudy.

Baber U, Zafar MU, Dangas G, Escolar G, ... Mehran R, Badimon JJ
Background
An evolving strategy in the setting of percutaneous coronary intervention (PCI) involves withdrawal of acetylsalicylic acid (ASA), or aspirin, while maintaining P2Y inhibition. However, the pharmacodynamic effects of this approach on blood thrombogenicity and platelet reactivity remain unknown.
Objectives
This study sought to compare the antithrombotic potency of ticagrelor alone versus ticagrelor plus ASA among high-risk patients undergoing PCI with drug-eluting stents.
Methods
This was a mechanistic substudy within the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, which randomized patients undergoing PCI to ticagrelor plus placebo versus ticagrelor plus ASA following 3 months of dual antiplatelet therapy. Substudy participants were enrolled after randomization, at which time ex vivo assays to quantify thrombus size under dynamic flow conditions and platelet reactivity were performed. Pharmacodynamic assessments were repeated 1 to 6 months thereafter. The primary endpoint was thrombus size at the post-randomization visit with platelet reactivity following stimuli to arachidonic acid, collagen, adenosine diphosphate, and thrombin as secondary endpoints. Results were analyzed using analysis of covariance.
Results
A total of 51 patients were enrolled, among whom 42 underwent perfusion assays at baseline and follow-up with a median time between studies of 1.5 months. The adjusted mean difference in post-randomization thrombus area was similar between groups: -218.2 μm (95% confidence interval [CI]: -575.9 to 139.9 μm; p = 0.22). Markers sensitive to cyclo-oxygenase-1 blockade, including platelet reactivity in response to arachidonic acid (mean difference: 10.9 U; 95% CI: 1.9 to 19.9 U) and collagen (mean difference: 9.8 U; 95% CI: 0.8 to 18.8 U) stimuli were higher among patients receiving placebo, whereas levels of platelet reactivity were similar with adenosine diphosphate and thrombin.
Conclusions
Among high-risk patients receiving drug-eluting stents, the antithrombotic potency of ticagrelor monotherapy is similar to that of ticagrelor plus ASA with respect to ex vivo blood thrombogenicity, whereas markers sensitive to cyclo-oxygenase-1 blockade are increased in the absence of ASA. (Platelet Substudy of the TWILIGHT Trial; NCT04001374).

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

J Am Coll Cardiol: 17 Feb 2020; 75:578-586
Baber U, Zafar MU, Dangas G, Escolar G, ... Mehran R, Badimon JJ
J Am Coll Cardiol: 17 Feb 2020; 75:578-586 | PMID: 32057371
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Abstract

Clinical Outcomes in Patients With Delayed Hospitalization for Non-ST-Segment Elevation Myocardial Infarction.

Cha JJ, Bae S, Park DW, Park JH, ... Jeong MH, Ahn TH
Background
Recently, the number of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) has reduced, whereas increased mortality was reported. A plausible explanation for increased mortality was prehospital delay because of patients\' reticence of their symptoms.
Objectives
The purpose of this study was to investigate the association between prehospital delay and clinical outcomes in patients with NSTEMI
Methods:
Among 13,104 patients from the Korea-Acute-Myocardial-Infarction-Registry-National Institutes of Health, the authors evaluated 6,544 patients with NSTEMI. Study patients were categorized into 2 groups according to symptom-to-door (StD) time (<24 or ≥24 hours). The primary outcome was 3-year all-cause mortality, and the secondary outcome was 3-year composite of all-cause mortality, recurrent MI, and hospitalization for heart failure.
Results
Overall, 1,827 (27.9%) patients were classified into the StD time ≥24 hours group. The StD time ≥24 hours group had higher all-cause mortality (17.0% vs 10.5%; P < 0.001) and incidence of secondary outcomes (23.3% vs 15.7%; P < 0.001) than the StD time <24 hours group. The higher all-cause mortality in the StD time ≥24 hours group was observed consistently in the subgroup analysis regarding age, sex, atypical chest pain, dyspnea, Q-wave in electrocardiogram, use of emergency medical services, hypertension, diabetes mellitus, chronic kidney disease, left ventricle dysfunction, TIMI (Thrombolysis In Myocardial Infarction) flow, and the GRACE risk score. In the multivariable analysis, independent predictors of prehospital delay were the elderly, women, nonspecific symptoms such as atypical chest pain or dyspnea, diabetes, and no use of emergency medical services.
Conclusions
Prehospital delay is associated with an increased risk of 3-year all-cause mortality in patients with NSTEMI. (iCReaT Study No. C110016).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Feb 2022; 79:311-323
Cha JJ, Bae S, Park DW, Park JH, ... Jeong MH, Ahn TH
J Am Coll Cardiol: 28 Feb 2022; 79:311-323 | PMID: 35086652
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Abstract

Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.

Ford TJ, Corcoran D, Padmanabhan S, Aman A, ... Davenport AP, Berry C
Aims
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD).
Methods and results
Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; -3.0 units in Duke Exercise Treadmill Score; -5.8 to -0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status.
Conclusion
We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina.
Trial registration
ClinicalTrials.gov: NCT03193294.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 22 Jan 2020; epub ahead of print
Ford TJ, Corcoran D, Padmanabhan S, Aman A, ... Davenport AP, Berry C
Eur Heart J: 22 Jan 2020; epub ahead of print | PMID: 31972008
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Abstract

Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography.

Furtado RHM, Nicolau JC, Guo J, Im K, ... Newby LK, Giugliano RP
Background
Mechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial.
Objectives
This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls.
Methods
Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days.
Results
In patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; p = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; p = 0.46).
Conclusions
When used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome; NCT00089895).

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

J Am Coll Cardiol: 27 Jan 2020; 75:289-300
Furtado RHM, Nicolau JC, Guo J, Im K, ... Newby LK, Giugliano RP
J Am Coll Cardiol: 27 Jan 2020; 75:289-300 | PMID: 31976867
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Impact:
Abstract

Extracellular Myocardial Volume in Patients With Aortic Stenosis.

Everett RJ, Treibel TA, Fukui M, Lee H, ... Moon JC, Dweck MR
Background
Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.
Objectives
This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.
Methods
Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.
Results
Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).
Conclusions
In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.

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

J Am Coll Cardiol: 27 Jan 2020; 75:304-316
Everett RJ, Treibel TA, Fukui M, Lee H, ... Moon JC, Dweck MR
J Am Coll Cardiol: 27 Jan 2020; 75:304-316 | PMID: 31976869
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Abstract

Coronary Artery Target Selection and Survival After Bilateral Internal Thoracic Artery Grafting.

Bakaeen FG, Ravichandren K, Blackstone EH, Houghtaling PL, ... Gillinov AM, Svensson LG
Background
The importance of a coronary artery, based on the myocardial mass it perfuses, is well documented, but little is known about the importance of a vessel that has been bypassed and its effect on survival in the context of bilateral internal thoracic artery (BITA) grafting.
Objectives
This study determined the effect of a dominant left anterior descending (LAD) artery and important non-LAD targets on outcomes after BITA grafting.
Methods
From January 1972 to January 2011, of 6,127 patients who underwent BITA grafting, 2,551 received 1 ITA grafted to the LAD and had an evaluable coronary angiogram. A dominant LAD was defined as one that was wrapped around the left ventricular apex. Non-LAD targets were graded based on their terminal reach toward the apex: important: >75% (n = 1,698); and less important: ≤75% (n = 853). Mean follow-up was 14 ± 8.7 years. Multivariable analysis was performed to identify risk factors for time-related mortality.
Results
A dominant LAD was present more frequently in patients with less important additional targets (51% vs. 35%; p < 0.0001). A total of 179 patients (7.0%) received a second ITA to multiple targets, 77 (43%) of which were to multiple important target vessels. Unadjusted late survival was similar regardless of degree of importance of the second ITA target-77% at 15 years (p = 0.70) for the important and less important targets, respectively. In the multivariable model, grafting the second ITA to multiple important targets was associated with better long-term survival (p = 0.005). In patients with a nondominant LAD, a second ITA grafted to a less important artery was associated with higher risk of operative mortality (2.4% vs. 0.51%; p = 0.007). A saphenous vein graft to an important or less important target did not influence long-term survival.
Conclusions
In BITA grafting, bypassing multiple important targets to maximize myocardium supplied by ITAs improved long-term survival. In patients with a nondominant LAD, selecting an important target for the second ITA lowered operative mortality.

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

J Am Coll Cardiol: 27 Jan 2020; 75:258-268
Bakaeen FG, Ravichandren K, Blackstone EH, Houghtaling PL, ... Gillinov AM, Svensson LG
J Am Coll Cardiol: 27 Jan 2020; 75:258-268 | PMID: 31976863
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Abstract

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome.

Bittner VA, Szarek M, Aylward PE, Bhatt DL, ... Schwartz GG,
Background
Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).
Objectives
A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).
Methods
One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.
Results
Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).
Conclusions
Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

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

J Am Coll Cardiol: 20 Jan 2020; 75:133-144
Bittner VA, Szarek M, Aylward PE, Bhatt DL, ... Schwartz GG,
J Am Coll Cardiol: 20 Jan 2020; 75:133-144 | PMID: 31948641
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Abstract

Acute Stroke During Pregnancy and Puerperium.

Elgendy IY, Gad MM, Mahmoud AN, Keeley EC, Pepine CJ
Background
Acute stroke during pregnancy or within 6 weeks of childbirth is devastating for the mother and her family, yet data regarding incidence and contemporary trends are very limited.
Objectives
This study sought to investigate the incidence and outcomes of acute stroke and transient ischemic attack during pregnancy or within 6 weeks of childbirth in a large database.
Methods
The National Inpatient Sample was queried to identify women age ≥18 years in the United States with pregnancy-related hospitalizations from January 1, 2007, to September 30, 2015. Temporal trends in acute stroke (ischemic and hemorrhagic)/transient ischemic attack incidence and in-hospital mortality were extracted.
Results
Among 37,360,772 pregnancy-related hospitalizations, 16,694 (0.045%) women had an acute stroke. The rates of acute stroke did not change (42.8 per 100,000 hospitalizations in 2007 vs. 42.2 per 100,000 hospitalizations in 2015; p = 0.10). Among those with acute stroke, there were increases in prevalence of obesity, smoking, hyperlipidemia, migraine, and gestational hypertension. Importantly, in-hospital mortality rates were almost 385-fold higher among those who had a stroke (42.1 per 1,000 pregnancy-related hospitalizations vs. 0.11 per 1,000 pregnancy-related hospitalizations; p < 0.0001). The rates of in-hospital mortality among pregnant women with acute stroke decreased (5.5% in 2007 vs. 2.7% in 2015; p < 0.001).
Conclusions
In this contemporary analysis of pregnancy-related hospitalizations, acute stroke occurred in 1 of every 2,222 hospitalizations, and these rates did not decrease over approximately 9 years. The prevalence of most stroke risk factors has increased. Acute stroke during pregnancy and puerperium was associated with high maternal mortality, although it appears to be trending downward. Future studies to better identify mechanisms and approaches to prevention and management of acute stroke during pregnancy and puerperium are warranted.

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

J Am Coll Cardiol: 20 Jan 2020; 75:180-190
Elgendy IY, Gad MM, Mahmoud AN, Keeley EC, Pepine CJ
J Am Coll Cardiol: 20 Jan 2020; 75:180-190 | PMID: 31948647
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Abstract

Comparison of newer generation self-expandable vs. balloon-expandable valves in transcatheter aortic valve implantation: the randomized SOLVE-TAVI trial.

Thiele H, Kurz T, Feistritzer HJ, Stachel G, ... de Waha-Thiele S, Desch S
Aims
Transcatheter aortic valve implantation (TAVI) has emerged as established treatment option in patients with symptomatic aortic stenosis. Technical developments in valve design have addressed previous limitations such as suboptimal deployment, conduction disturbances, and paravalvular leakage. However, there are only limited data available for the comparison of newer generation self-expandable valve (SEV) and balloon-expandable valve (BEV).
Methods and results
SOLVE-TAVI is a multicentre, open-label, 2 × 2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVI comparing SEV (Evolut R, Medtronic Inc., Minneapolis, MN, USA) with BEV (Sapien 3, Edwards Lifesciences, Irvine, CA, USA). The primary efficacy composite endpoint of all-cause mortality, stroke, moderate/severe prosthetic valve regurgitation, and permanent pacemaker implantation at 30 days was powered for equivalence (equivalence margin 10% with significance level 0.05). The primary composite endpoint occurred in 28.4% of SEV patients and 26.1% of BEV patients meeting the prespecified criteria of equivalence [rate difference -2.39 (90% confidence interval, CI -9.45 to 4.66); Pequivalence = 0.04]. Event rates for the individual components were as follows: all-cause mortality 3.2% vs. 2.3% [rate difference -0.93 (90% CI -4.78 to 2.92); Pequivalence < 0.001], stroke 0.5% vs. 4.7% [rate difference 4.20 (90% CI 0.12 to 8.27); Pequivalence = 0.003], moderate/severe paravalvular leak 3.4% vs. 1.5% [rate difference -1.89 (90% CI -5.86 to 2.08); Pequivalence = 0.0001], and permanent pacemaker implantation 23.0% vs. 19.2% [rate difference -3.85 (90% CI -10.41 to 2.72) in SEV vs. BEV patients; Pequivalence = 0.06].
Conclusion
In patients with aortic stenosis undergoing transfemoral TAVI, newer generation SEV and BEV are equivalent for the primary valve-related efficacy endpoint. These findings support the safe application of these newer generation percutaneous valves in the majority of patients with some specific preferences based on individual valve anatomy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 11 Feb 2020; epub ahead of print
Thiele H, Kurz T, Feistritzer HJ, Stachel G, ... de Waha-Thiele S, Desch S
Eur Heart J: 11 Feb 2020; epub ahead of print | PMID: 32049283
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Abstract

Anxa1 in smooth muscle cells protects against acute aortic dissection.

Zhou C, Lin Z, Cao H, Chen Y, ... Pan B, Zheng L
Aims
Acute aortic dissection (AAD) is a life-threatening disease with high morbidity and mortality. Previous studies have showed that vascular smooth muscle cell (VSMC) phenotype switching modulates vascular function and AAD progression. However, whether an endogenous signalling system that protects AAD progression exists remains unknown. Our aim is to investigate the role of Anxa1 in VSMC phenotype switching and the pathogenesis of AAD.
Methods and results
We first assessed Anxa1 expression levels by immunohistochemical staining in control aorta and AAD tissue from mice. A strong increase of Anxa1 expression was seen in the mouse AAD tissues. In line with these findings, micro-CT scan results indicated that Anxa1 plays a role in the development of AAD in our murine model, with systemic deficiency of Anxa1 markedly progressing AAD. Conversely, administration of Anxa1 mimetic peptide, Ac2-26, rescued the AAD phenotype in Anxa1-/- mice. Transcriptomic studies revealed a novel role for Anxa1 in VSMC phenotype switching, with Anxa1 deficiency triggering the synthetic phenotype of VSMCs via down-regulation of the JunB/MYL9 pathway. The resultant VSMC synthetic phenotype rendered elevated inflammation and enhanced matrix metalloproteinases (MMPs) production, leading to augmented elastin degradation. VSMC-restricted deficiency of Anxa1 in mice phenocopied VSMC phenotype switching and the consequent exacerbation of AAD. Finally, our studies in human AAD aortic specimens recapitulated key findings in murine AAD, specifically that the decrease of Anxa1 is associated with VSMC phenotype switch, heightened inflammation, and enhanced MMP production in human aortas.
Conclusions
Our findings demonstrated that Anxa1 is a novel endogenous defender that prevents AAD by inhibiting VSMC phenotype switching, suggesting that Anxa1 signalling may be a potential target for AAD pharmacological therapy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 06 May 2022; 118:1564-1582
Zhou C, Lin Z, Cao H, Chen Y, ... Pan B, Zheng L
Cardiovasc Res: 06 May 2022; 118:1564-1582 | PMID: 33757117
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Impact:
Abstract

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

Al-Hussaini A, Abdelaty AMSEK, Gulsin GS, Arnold JR, ... McCann GP, Adlam D
Aims
To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury.
Methods and results
One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass].
Conclusion
The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

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

Eur Heart J: 02 Jan 2020; epub ahead of print
Al-Hussaini A, Abdelaty AMSEK, Gulsin GS, Arnold JR, ... McCann GP, Adlam D
Eur Heart J: 02 Jan 2020; epub ahead of print | PMID: 31898721
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Impact:
Abstract

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial.

Prabhakaran D, Chandrasekaran AM, Singh K, Mohan B, ... Kinra S,
Background
Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly).
Objectives
This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial.
Methods
The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks.
Results
MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes).
Conclusions
Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

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

J Am Coll Cardiol: 06 Apr 2020; 75:1551-1561
Prabhakaran D, Chandrasekaran AM, Singh K, Mohan B, ... Kinra S,
J Am Coll Cardiol: 06 Apr 2020; 75:1551-1561 | PMID: 32241371
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Abstract

Clinical impact of conduction disturbances in transcatheter aortic valve replacement recipients: a systematic review and meta-analysis.

Faroux L, Chen S, Muntané-Carol G, Regueiro A, ... Nazif T, Rodés-Cabau J
Aims
The clinical impact of new-onset persistent left bundle branch block (NOP-LBBB) and permanent pacemaker implantation (PPI) on transcatheter aortic valve replacement (TAVR) recipients remains controversial. We aimed to evaluate the impact of (i) periprocedural NOP-LBBB and PPI post-TAVR on 1-year all-cause death, cardiac death, and heart failure hospitalization and (ii) NOP-LBBB on the need for PPI at 1-year follow-up.
Methods and results
We performed a systematic search from PubMed and EMBASE databases for studies reporting raw data on 1-year clinical impact of NOP-LBBB or periprocedural PPI post-TAVR. Data from 30 studies, including 7792 patients (12 studies) and 42 927 patients (21 studies) for the evaluation of the impact of NOP-LBBB and PPI after TAVR were sourced, respectively. NOP-LBBB was associated with an increased risk of all-cause death [risk ratio (RR) 1.32, 95% confidence interval (CI) 1.17-1.49; P < 0.001], cardiac death (RR 1.46, 95% CI 1.20-1.78; P < 0.001), heart failure hospitalization (RR 1.35, 95% CI 1.05-1.72; P = 0.02), and PPI (RR 1.89, 95% CI 1.58-2.27; P < 0.001) at 1-year follow-up. Periprocedural PPI after TAVR was associated with a higher risk of all-cause death (RR 1.17, 95% CI 1.11-1.25; P < 0.001) and heart failure hospitalization (RR 1.18, 95% CI 1.03-1.36; P = 0.02). Permanent pacemaker implantation was not associated with an increased risk of cardiac death (RR 0.84, 95% CI 0.67-1.05; P = 0.13).
Conclusion
NOP-LBBB and PPI after TAVR are associated with an increased risk of all-cause death and heart failure hospitalization at 1-year follow-up. Periprocedural NOP-LBBB also increased the risk of cardiac death and PPI within the year following the procedure. Further studies are urgently warranted to enhance preventive measures and optimize the management of conduction disturbances post-TAVR.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 02 Jan 2020; epub ahead of print
Faroux L, Chen S, Muntané-Carol G, Regueiro A, ... Nazif T, Rodés-Cabau J
Eur Heart J: 02 Jan 2020; epub ahead of print | PMID: 31899484
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Impact:
Abstract

Long-Term Outcomes in Women and Men Following Percutaneous Coronary Intervention.

Kosmidou I, Leon MB, Zhang Y, Serruys PW, ... Mehran R, Stone GW
Background
Studies examining sex-related outcomes following percutaneous coronary intervention (PCI) have reported conflicting results.
Objectives
The purpose of this study was to examine the sex-related risk of 5-year cardiovascular outcomes after PCI.
Methods
The authors pooled patient-level data from 21 randomized PCI trials and assessed the association between sex and major adverse cardiac events (MACE) (cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]) as well as its individual components at 5 years.
Results
Among 32,877 patients, 9,141 (27.8%) were women. Women were older and had higher body mass index, more frequent hypertension and diabetes, and less frequent history of surgical or percutaneous revascularization compared with men. By angiographic core laboratory analysis, lesions in women had smaller reference vessel diameter and shorter lesion length. At 5 years, women had a higher unadjusted rate of MACE (18.9% vs. 17.7%; p = 0.003), all-cause death (10.4% vs. 8.7%; p = 0.0008), cardiac death (4.9% vs. 4.0%; p = 0.003) and ID-TLR (10.9% vs. 10.2%; p = 0.02) compared with men. By multivariable analysis, female sex was an independent predictor of MACE (hazard ratio [HR:]: 1.14; 95% confidence interval [CI:]: 1.01 to 1.30; p = 0.04) and ID-TLR (HR: 1.23; 95% CI: 1.05 to 1.44; p = 0.009) but not all-cause death (HR: 0.91; 95% CI: 0.75 to 1.09; p = 0.30) or cardiac death (HR: 0.97; 95% CI: 0.73 to 1.29; p = 0.85).
Conclusions
In the present large-scale, individual patient data pooled analysis of contemporary PCI trials, women had a higher risk of MACE and ID-TLR compared with men at 5 years following PCI.

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

J Am Coll Cardiol: 13 Apr 2020; 75:1631-1640
Kosmidou I, Leon MB, Zhang Y, Serruys PW, ... Mehran R, Stone GW
J Am Coll Cardiol: 13 Apr 2020; 75:1631-1640 | PMID: 32273029
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Impact:
Abstract

Association between DBP and major adverse cardiovascular events in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

Liu YH, Dai YN, Wang LT, Chen PY, ... Tan N, He PC
Background
In patients with stable coronary artery disease, low DBP is associated with an increased risk of myocardial infarction and cardiovascular death, but its association with clinical outcomes in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) is unknown.
Methods
Consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI from January 2010 to June 2016 were enrolled. The patients were divided into five groups according to the quintiles of DBP at admission. The primary outcome was in-hospital major adverse cardiovascular events (MACE) including all-cause death, stroke, target vessel revascularization, and recurrent myocardial infarction.
Results
A total of 2198 patients were enrolled, of whom 157 (7.1%) developed in-hospital MACE. Patients with DBP lower than 60 mmHg was associated with a higher rate of in-hospital MACE (14.8, 7.8, 5.6, 6.1, and 3.8%, P < 0.001) and all-cause death (12.5, 6.4, 4.3, 3.9, and 1.9%, P < 0.001) compared with those with DBP 60-69, 70-79, 80-89, and at least 90 mmHg. Multivariate logistic regression analysis demonstrated that DBP higher than 90 mmHg was a significant predictor of lower risk of in-hospital MACE (OR = 0.16, 95% CI = 0.04-0.61, P = 0.007). Cubic spline models for the association between DBP and MACE did not demonstrate a U-type relationship after adjusting for potential risk factors. During the follow-up, lower DBP was associated with a higher risk of all-cause death (P < 0.0001).
Conclusion
Lower DBP is independently associated with an elevated risk of in-hospital MACE and follow-up all-cause death.

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

J Hypertens: 31 Mar 2022; 40:692-698
Liu YH, Dai YN, Wang LT, Chen PY, ... Tan N, He PC
J Hypertens: 31 Mar 2022; 40:692-698 | PMID: 34889864
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Impact:
Abstract

Improved Outcomes Following the Ross Procedure Compared With Bioprosthetic Aortic Valve Replacement.

Mazine A, David TE, Stoklosa K, Chung J, Lafreniere-Roula M, Ouzounian M
Background
The ideal aortic valve substitute for young and middle-aged adults remains elusive.
Objectives
This study sought to compare the long-term outcomes of patients undergoing the Ross procedure and those receiving bioprosthetic aortic valve replacements (AVRs).
Methods
Consecutive patients aged 16-60 years who underwent a Ross procedure or surgical bioprosthetic AVR at the Toronto General Hospital between 1990 and 2014 were identified. Propensity score matching was used to account for differences in baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included valve reintervention, valve deterioration, endocarditis, thromboembolic events, and permanent pacemaker implantation.
Results
Propensity score matching yielded 108 pairs of patients. The median age was 41 years (IQR: 34-47 years). Baseline characteristics were similar between the matched groups. There was no operative mortality in either group. Mean follow-up was 14.5 ± 7.2 years. All-cause mortality was lower following the Ross procedure (HR: 0.35; 95% CI: 0.14-0.90; P = 0.028). Using death as a competing risk, the Ross procedure was associated with lower rates of reintervention (HR: 0.21; 95% CI: 0.10-0.41; P < 0.001), valve deterioration (HR: 0.25; 95% CI: 0.14-0.45; P < 0.001), thromboembolic events (HR: 0.15; 95% CI: 0.05-0.50; P = 0.002), and permanent pacemaker implantation (HR: 0.22; 95% CI: 0.07-0.64; P = 0.006).
Conclusions
In this propensity-matched study, the Ross procedure was associated with better long-term survival and freedom from adverse valve-related events compared with bioprosthetic AVR. In specialized centers with sufficient expertise, the Ross procedure should be considered the primary option for young and middle-aged adults undergoing AVR.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Mar 2022; 79:993-1005
Mazine A, David TE, Stoklosa K, Chung J, Lafreniere-Roula M, Ouzounian M
J Am Coll Cardiol: 14 Mar 2022; 79:993-1005 | PMID: 35272805
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Abstract

Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation.

Scully PR, Patel KP, Treibel TA, Thornton GD, ... Hawkins PN, Moon JC
Aims
Cardiac amyloidosis is common in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI). We hypothesized that patients with dual aortic stenosis and cardiac amyloid pathology (AS-amyloid) would have different baseline characteristics, periprocedural and mortality outcomes.
Methods and results
Patients aged ≥75 with severe AS referred for TAVI at two sites underwent blinded bone scintigraphy prior to intervention (Perugini Grade 0 negative, 1-3 increasingly positive). Baseline assessment included echocardiography, electrocardiogram (ECG), blood tests, 6-min walk test, and health questionnaire, with periprocedural complications and mortality follow-up. Two hundred patients were recruited (aged 85 ± 5 years, 50% male). AS-amyloid was found in 26 (13%): 8 Grade 1, 18 Grade 2. AS-amyloid patients were older (88 ± 5 vs. 85 ± 5 years, P = 0.001), with reduced quality of life (EQ-5D-5L 50 vs. 65, P = 0.04). Left ventricular wall thickness was higher (14 mm vs. 13 mm, P = 0.02), ECG voltages lower (Sokolow-Lyon 1.9 ± 0.7 vs. 2.5 ± 0.9 mV, P = 0.03) with lower voltage/mass ratio (0.017 vs. 0.025 mV/g/m2, P = 0.03). High-sensitivity troponin T and N-terminal pro-brain natriuretic peptide were higher (41 vs. 21 ng/L, P < 0.001; 3702 vs. 1254 ng/L, P = 0.001). Gender, comorbidities, 6-min walk distance, AS severity, prevalence of disproportionate hypertrophy, and post-TAVI complication rates (38% vs. 35%, P = 0.82) were the same. At a median follow-up of 19 (10-27) months, there was no mortality difference (P = 0.71). Transcatheter aortic valve implantation significantly improved outcome in the overall population (P < 0.001) and in those with AS-amyloid (P = 0.03).
Conclusions
AS-amyloid is common and differs from lone AS. Transcatheter aortic valve implantation significantly improved outcome in AS-amyloid, while periprocedural complications and mortality were similar to lone AS, suggesting that TAVI should not be denied to patients with AS-amyloid.

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

Eur Heart J: 07 Apr 2020; epub ahead of print
Scully PR, Patel KP, Treibel TA, Thornton GD, ... Hawkins PN, Moon JC
Eur Heart J: 07 Apr 2020; epub ahead of print | PMID: 32267922
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Abstract

Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction: COMPLETE Trial.

Wood DA, Cairns JA, Wang J, Mehran R, ... Mehta SR,
Background
The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD).
Objectives
The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization.
Methods
Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days.
Results
For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI.
Conclusions
Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Dec 2019; 74:2713-2723
Wood DA, Cairns JA, Wang J, Mehran R, ... Mehta SR,
J Am Coll Cardiol: 02 Dec 2019; 74:2713-2723 | PMID: 31779786
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Abstract

2-Year Outcomes After Stenting of Lipid-Rich and Nonrich Coronary Plaques.

Yamamoto MH, Maehara A, Stone GW, Kini AS, ... Muller JE, Weisz G
Background
Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.
Objectives
The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.
Methods
In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate.
Results
Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI (hazard ratio of maxLCBI per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.
Conclusions
Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid.

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

J Am Coll Cardiol: 30 Mar 2020; 75:1371-1382
Yamamoto MH, Maehara A, Stone GW, Kini AS, ... Muller JE, Weisz G
J Am Coll Cardiol: 30 Mar 2020; 75:1371-1382 | PMID: 32216905
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Abstract

Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time.

McCartney PJ, Maznyczka AM, Eteiba H, McEntegart M, ... Berry C,
Background
Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.
Objectives
This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.
Methods
This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).
Results
Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).
Conclusion
In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).

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

J Am Coll Cardiol: 30 Mar 2020; 75:1406-1421
McCartney PJ, Maznyczka AM, Eteiba H, McEntegart M, ... Berry C,
J Am Coll Cardiol: 30 Mar 2020; 75:1406-1421 | PMID: 32216909
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Abstract

Left atrial appendage occlusion with the Amplatzer™ Amulet™ device: full results of the prospective global observational study.

Hildick-Smith D, Landmesser U, Camm AJ, Diener HC, ... Nielsen-Kudsk JE, Tondo C
Aims
To evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) with the Amplatzer™ Amulet™ occluder.
Methods and results
Patients with atrial fibrillation eligible for LAAO were recruited to a prospective global study. Implant procedures were undertaken with echocardiographic guidance. Transoesophageal echocardiography (TOE) was undertaken 1-3 months post-LAAO. Implant and follow-up TOEs were evaluated by a CoreLab. The primary endpoint was a composite of ischaemic stroke and cardiovascular death at 2 years. Serious adverse events were adjudicated by an independent clinical events committee. A total of 1088 patients were enrolled, aged 75.2 ± 8.5 years; 64.5% were male. CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.6 and 3.3 ± 1.1, respectively. A total of 71.7% had prior major bleeding, and 82.8% had contraindications to oral anticoagulants. Implant success was 99.1%. Major adverse events (≤7 days post-procedure) occurred in 4.0%, including death (0.3%), stroke (0.4%), major vascular (1.3%), and device embolization (0.2%). A total of 80.2% of patients were discharged on antiplatelet therapy alone. Peridevice flow was <3 mm in 98.4% at follow-up TOE. Device-related thrombus (DRT) was seen in 1.6% of cases. Cardiovascular death or ischaemic stroke occurred in 8.7% of patients at 2 years. The ischaemic stroke rate was 2.2%/year-a 67% reduction compared to the CHA2DS2-VASc predicted rate. Major bleeding (Bleeding Academic Research Consortium type ≥ 3) occurred at rates of 10.1%/year (year 1) and 4.0%/year (year 2).
Conclusion
Following LAAO with the Amplatzer Amulet device, the ischaemic stroke rate was reduced by 67% compared to the predicted risk. Closure was complete in 98.4% of cases and DRT seen in only 1.6%.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 02 Apr 2020; epub ahead of print
Hildick-Smith D, Landmesser U, Camm AJ, Diener HC, ... Nielsen-Kudsk JE, Tondo C
Eur Heart J: 02 Apr 2020; epub ahead of print | PMID: 32243499
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Abstract

Nonculprit Lesion Myocardial Infarction Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome.

Scirica BM, Bergmark BA, Morrow DA, Antman EM, ... Braunwald E, Wiviott SD
Background
Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients.
Objectives
The authors sought to examine the effect of more potent antiplatelet therapy on the basis of the timing and etiology of recurrent myocardial infarction (MI) or cardiovascular death following PCI for ACS.
Methods
In the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38), which randomized patients to prasugrel or clopidogrel, 12,844 patients with ACS received at least 1 stent. MI and cardiovascular death were categorized as: 1) procedural (related to revascularization); 2) definite or probable stent thrombosis (ST); or 3) spontaneous (non-ST or non-procedure-related). Median follow-up was 14.5 months.
Results
Among the first events occurring within 30 days, 584 (69.0%) were procedural, 126 (14.9%) ST-related, and 136 (16.1%) spontaneous. After 30 days, 22 (4.7%) were procedural, 63 (13.5%) were ST-related, and 383 (81.8%) spontaneous. Prasugrel significantly reduced the incidence of MI or cardiovascular death for ST-related (1.0% vs. 2.1%; p < 0.001) and spontaneous events (3.9% vs. 4.8%; p = 0.012), with a directionally consistent numerical reduction for procedural events (4.4% vs. 5.1%; p = 0.078). Prasugrel increased spontaneous, but not procedural, major bleeding.
Conclusions
Long-term potent antithrombotic therapy reduces de novo (spontaneous) atherothrombotic events in addition to preventing complications associated with stenting of the culprit lesion following ACS. In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events. (Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

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

J Am Coll Cardiol: 16 Mar 2020; 75:1095-1106
Scirica BM, Bergmark BA, Morrow DA, Antman EM, ... Braunwald E, Wiviott SD
J Am Coll Cardiol: 16 Mar 2020; 75:1095-1106 | PMID: 32164882
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Abstract

Dual antithrombotic treatment in chronic coronary syndrome: European Society of Cardiology criteria vs. CHADS-P2A2RC score.

Würtz M, Olesen KKW, Mortensen MB, Eikelboom JW, ... Kristensen SD, Maeng M
Aims
According to the 2019 European Society of Cardiology (ESC) guidelines on chronic coronary syndromes (CCS), adding a P2Y12 inhibitor or rivaroxaban to aspirin should be considered in high-risk patients. We estimated the proportion of patients eligible for treatment with the ESC criteria and examined if a recently validated risk score (CHADS-P2A2RC) could improve risk prediction.
Methods and results
We included 61 338 CCS patients undergoing first-time coronary angiography in Western Denmark (2003-16) and classified them according to the ESC criteria and the CHADS-P2A2RC score. The ESC criteria identified 33.9% as high risk, 53.3% as moderate risk, and 12.8% as low risk. The CHADS-P2A2RC score identified 24.9% as high risk (≥4 points), 48.1% as moderate risk (2-3 points), and 27.0% as low risk (≤1 points). Major adverse cardiovascular events per 100 person-years were 4.8 [95% confidence interval (CI) 4.6-5.0] in patients considered high risk with both schemes, 2.1 (95% CI 2.0-2.2) in patients considered high risk with the ESC but low-to-moderate risk with the CHADS-P2A2RC criteria, 3.8 (95% CI 3.6-4.1) in patients considered low-to-moderate risk with the ESC but high risk with the CHADS-P2A2RC criteria, and 1.5 (95% CI 1.5-1.6) in patients considered low-to-moderate risk with both schemes. The CHADS-P2A2RC score enabled correct downward risk reclassification of 5161 patients (8%) without events, yielding an improved specificity of 9.7%, a loss of sensitivity of 4.4%, and an overall net reclassification index of 0.053.
Conclusion
Based on the 2019 ESC guidelines, dual antithrombotic treatment should be considered in one-third of CCS patients. The CHADS-P2A2RC score improved risk classification and may particularly identify low-risk patients with limited benefit from treatment.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 06 Mar 2022; 43:996-1004
Würtz M, Olesen KKW, Mortensen MB, Eikelboom JW, ... Kristensen SD, Maeng M
Eur Heart J: 06 Mar 2022; 43:996-1004 | PMID: 34871376
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Abstract

Long-term clinical outcome and performance of transcatheter aortic valve replacement with a self-expandable bioprosthesis.

Testa L, Latib A, Brambilla N, De Marco F, ... Petronio AS, Bedogni F
Aims 
In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU).
Methods and results 
Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4 years (interquartile range 1.4-6.7 years). Longest FU reached 11 years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan-Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ≤ II at 8 years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9 ± 4 mmHg at discharge, 9 ± 5 mmHg at 8 years, P = 0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ≥5 years in paired analysis (P = 0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8 years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1-4.3%] and 1.6% (95% CI 0.6-3.9%), respectively, while late BVF was 2.5% (95% CI 1.2-5%).
Conclusion 
While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 05 Jan 2020; epub ahead of print
Testa L, Latib A, Brambilla N, De Marco F, ... Petronio AS, Bedogni F
Eur Heart J: 05 Jan 2020; epub ahead of print | PMID: 31904800
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Impact:
Abstract

Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study.

Schnorbus B, Daiber A, Jurk K, Warnke S, ... Münzel T, Gori T
Aims
In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome.
Methods and results
The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P < 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68-3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31-2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI -0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group.
Conclusion
As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting.
Eudract-no
2011-005305-73.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 02 Jan 2020; epub ahead of print
Schnorbus B, Daiber A, Jurk K, Warnke S, ... Münzel T, Gori T
Eur Heart J: 02 Jan 2020; epub ahead of print | PMID: 31899473
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Impact:
Abstract

Survival After Coronary Revascularization With Paclitaxel-Coated Balloons.

Scheller B, Vukadinovic D, Jeger R, Rissanen TT, ... Lansky A, Mahfoud F
Background
Drug-coated balloons (DCBs) are accepted treatment strategies for coronary in-stent restenosis and are under clinical investigation for lesions without prior stent implantation. A recently published meta-analysis suggested an increased risk of death associated with the use of paclitaxel-coated devices in the superficial femoral artery. The reasons are incompletely understood as potential underlying pathomechanisms remain elusive, and no relationship to the administered dose has been documented.
Objectives
The purpose of this analysis was to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomized controlled trials (RCTs).
Methods
PubMed, Web of science, and the Cochrane library database were searched, and a meta-analysis from RCT was performed comparing DCB with non-DCB devices (such as conventional balloon angioplasty, bare-metal stents, or drug-eluting stents) for the treatment of coronary in-stent restenosis or de novo lesions. The primary outcome was all-cause death. The number of patients lost to follow-up was observed at different time points. Risk estimates are reported as risk ratios (RRs) with 95% confidence intervals (CIs).
Results
A total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analyzed. At follow-up of 6 to 12 months, no significant difference in all-cause mortality was found, however, with numerically lower rates after DCB treatment (RR: 0.74; 95% CI: 0.51 to 1.08; p = 0.116). Risk of death at 2 years (n = 1,477, 8 RCTs) was similar between the 2 groups (RR: 0.84; 95% CI: 0.51 to 1.37; p = 0.478). After 3 years of follow-up (n = 1,775, 9 RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR: 0.73; 95% CI: 0.53 to 1.00; p = 0.047) with a number needed to treat of 36 to prevent 1 death. A similar reduction was seen in cardiac mortality (RR: 0.53; 95% CI: 0.33 to 0.85; p = 0.009).
Conclusions
In this meta-analysis, the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality, as has been suggested for peripheral arteries. On the contrary, use of coronary paclitaxel-coated balloons was associated with a trend toward lower mortality when compared with control treatments.

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

J Am Coll Cardiol: 09 Mar 2020; 75:1017-1028
Scheller B, Vukadinovic D, Jeger R, Rissanen TT, ... Lansky A, Mahfoud F
J Am Coll Cardiol: 09 Mar 2020; 75:1017-1028 | PMID: 32138961
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Impact:
Abstract

Repeat Transcatheter Aortic Valve Replacement for Transcatheter Prosthesis Dysfunction.

Landes U, Webb JG, De Backer O, Sondergaard L, ... Leon MB, Barbanti M
Background
Transcatheter aortic valve replacement (TAVR) use is increasing in patients with longer life expectancy, yet robust data on the durability of transcatheter heart valves (THVs) are limited. Redo-TAVR may play a key strategy in treating patients in whom THVs fail.
Objectives
The authors sought to examine outcomes following redo-TAVR.
Methods
The Redo-TAVR registry collected data on consecutive patients who underwent redo-TAVR at 37 centers. Patients were classified as probable TAVR failure or probable THV failure if they presented within or beyond 1 year of their index TAVR, respectively.
Results
Among 63,876 TAVR procedures, 212 consecutive redo-TAVR procedures were identified (0.33%): 74 within and 138 beyond 1 year of the initial procedure. For these 2 groups, TAVR-to-redo-TAVR time was 68 (38 to 154) days and 5 (3 to 6) years. The indication for redo-TAVR was THV stenosis in 12 (16.2%) and 51 (37.0%) (p = 0.002) and regurgitation or combined stenosis-regurgitation in 62 (83.8%) and 86 (62.3%) (p = 0.028), respectively. Device success using VARC-2 criteria was achieved in 180 patients (85.1%); most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%). At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg; valve area 1.63 ± 0.61 cm and 1.51 ± 0.57 cm; and regurgitation ≤mild in 91% and 91%, respectively. Peri-procedural complication rates were low (3 stroke [1.4%], 7 valve malposition [3.3%], 2 coronary obstruction [0.9%], 20 new permanent pacemaker [9.6%], no mortality), and symptomatic improvement was substantial. Survival at 30 days was 94.6% and 98.5% (p = 0.101) and 83.6% and 88.3% (p = 0.335) at 1 year for patients presenting with early and late valve dysfunction, respectively.
Conclusions
Redo-TAVR is a relatively safe and effective option for selected patients with valve dysfunction after TAVR. These results are important for applicability of TAVR in patients with long life expectancy in whom THV durability may be a concern.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 27 Apr 2020; 75:1882-1893
Landes U, Webb JG, De Backer O, Sondergaard L, ... Leon MB, Barbanti M
J Am Coll Cardiol: 27 Apr 2020; 75:1882-1893 | PMID: 32327098
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Abstract

Transvalvular Flow Rate Determines Prognostic Value of Aortic Valve Area in Aortic Stenosis.

Namasivayam M, He W, Churchill TW, Capoulade R, ... Levine RA, Hung J
Background
Aortic valve area (AVA) ≤1.0 cm is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic value of AVA ≤1.0 cm is unknown and is not incorporated into AS assessment.
Objectives
This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS.
Methods
In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients.
Results
Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s.
Conclusions
Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS.

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

J Am Coll Cardiol: 20 Apr 2020; 75:1758-1769
Namasivayam M, He W, Churchill TW, Capoulade R, ... Levine RA, Hung J
J Am Coll Cardiol: 20 Apr 2020; 75:1758-1769 | PMID: 32299587
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Abstract

Dysfunctional HDLs are Associated with a Greater Incidence of Acute Coronary Syndrome in a Population at High Cardiovascular Risk: A Nested-Case Control Study.

Soria-Florido MT, Castañer O, Lassale C, Estruch R, ... Hernáez Á, Fitó M

Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that HDL atheroprotective role lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been comprehensively investigated.We conducted a case-control study nested within the PREDIMED () cohort, originally a randomized trial where participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (=167) were individually matched (1:2) to controls by sex, age, intervention group, body mass index, and follow-up time. We investigated its two individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristics: HDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B-depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between one standard deviation increments in HDL functional characteristics and clinical outcomes.Low values of cholesterol efflux capacity (OR: 0.58, 95% CI: 0.40-0.83), and levels of sphingosine-1-phosphate (OR: 0.70, 95% CI: 0.52-0.92), and apolipoprotein A-I (OR: 0.58, 95% CI: 0.42-0.79) were associated with higher odds of acute coronary syndrome. Higher HDL oxidative inflammatory index values were marginally linked to acute coronary syndrome risk (OR: 1.27, 95% CI: 0.99-1.63). Low values of cholesterol efflux capacity (OR: 0.33, 95% CI: 0.18-0.61), sphingosine-1-phosphate (OR: 0.60, 95% CI: 0.40-0.89) and apolipoprotein A-I (OR: 0.59, 95% CI: 0.37-0.93) were particularly linked to myocardial infarction, whereas high HDL oxidative-inflammatory index values (OR: 1.53, 95% CI: 1.01-2.33) and low apolipoprotein A-I levels (OR: 0.52, 95% CI: 0.31-0.88) were associated with unstable angina.Low cholesterol efflux capacity values, pro-oxidant/pro-inflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in high cardiovascular risk subjects.URL: http://www.controlled-trials.com Unique identifier: ISRCTN35739639.



Circulation: 15 Jan 2020; epub ahead of print
Soria-Florido MT, Castañer O, Lassale C, Estruch R, ... Hernáez Á, Fitó M
Circulation: 15 Jan 2020; epub ahead of print | PMID: 31941372
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Abstract

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, ... Windecker S,
Background
Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear.
Methods
We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns.
Results
After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53).
Conclusions
In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Copyright © 2019 Massachusetts Medical Society.

N Engl J Med: 15 Nov 2019; epub ahead of print
Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, ... Windecker S,
N Engl J Med: 15 Nov 2019; epub ahead of print | PMID: 31733180
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Abstract

Contrast-Associated Acute Kidney Injury and Serious Adverse Outcomes Following Angiography.

Weisbord SD, Palevsky PM, Kaufman JS, Wu H, ... Gallagher M,
Background
Contrast-associated acute kidney injury (CA-AKI) associates with an increased relative risk for serious adverse outcomes. However, the magnitude of this risk and the incidence of clinically significant CA-AKI derived from analyses of large cohorts with prospective assessment of CA-AKI and subsequent outcomes are unknown.
Objectives
This study sought to characterize the relative risk for and incidence of serious adverse outcomes following the development of CA-AKI and to explore whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate with adverse outcomes.
Methods
Among 4,418 participants in the PRESERVE (Prevention of Serious Adverse Outcomes Following Angiography) trial with comprehensive baseline and outcome data, we assessed whether CA-AKI was associated with the 90-day outcome comprising death, need for dialysis, or persistent impairment in kidney function. We calculated the incidence of clinically significant CA-AKI (i.e., proportion of patients who developed CA-AKI and the 90-day outcome) and examined whether CA-AKI was a mediator of the association of baseline kidney function with the 90-day outcome.
Results
CA-AKI was associated with an increased relative risk for 90-day death, need for dialysis, or persistent kidney impairment (odds ratio: 3.93; 95% confidence interval: 2.82 to 5.49; p < 0.0001). The incidence of clinically significant CA-AKI was 1.2% (53 of 4,418 patients). CA-AKI was not a mediator of the association of pre-angiography estimated glomerular filtration rate with the primary outcome.
Conclusions
Whereas CA-AKI is associated with an increased relative risk of serious, adverse 90-day outcomes, the incidence of clinically significant CA-AKI is very low. CA-AKI does not mediate the association of the pre-angiography estimated glomerular filtration rate with these outcomes.

Published by Elsevier Inc.

J Am Coll Cardiol: 23 Mar 2020; 75:1311-1320
Weisbord SD, Palevsky PM, Kaufman JS, Wu H, ... Gallagher M,
J Am Coll Cardiol: 23 Mar 2020; 75:1311-1320 | PMID: 32192658
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Abstract

Transvalvular Flow, Sex, and Survival After Valve Replacement Surgery in Patients With Severe Aortic Stenosis.

Guzzetti E, Poulin A, Annabi MS, Zhang B, ... Pibarot P, Clavel MA
Background
The respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are unknown.
Objectives
This study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences.
Methods
This study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women [37%]), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR.
Results
In this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m) and women (32 ml/m). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines\' threshold (35 ml/m) does not.
Conclusions
Paradoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m for men and <32 ml/m for women) to define low-flow outperforms the guidelines\' threshold of 35 ml/m in risk stratification after AVR.

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

J Am Coll Cardiol: 27 Apr 2020; 75:1897-1909
Guzzetti E, Poulin A, Annabi MS, Zhang B, ... Pibarot P, Clavel MA
J Am Coll Cardiol: 27 Apr 2020; 75:1897-1909 | PMID: 32327100
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Abstract

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease: a meta-analysis of randomized controlled trials.

Ahmad Y, Howard JP, Arnold AD, Cook CM, ... Stone GW, Karmpaliotis D
Aims 
The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD.
Methods and results 
We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81-1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79-1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35-1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96-1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49-2.02; P < 0.001).
Conclusion 
The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinical decision-making between cardiologists, surgeons, and patients with LMCAD.

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

Eur Heart J: 01 Mar 2020; epub ahead of print
Ahmad Y, Howard JP, Arnold AD, Cook CM, ... Stone GW, Karmpaliotis D
Eur Heart J: 01 Mar 2020; epub ahead of print | PMID: 32118272
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Abstract

Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome.

Milleron O, Arnoult F, Delorme G, Detaint D, ... Boileau C, Jondeau G
Background
Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene.
Objectives
This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter.
Methods
Patients carrying an FBN1 pathogenic variant who visited our reference center at least twice were included, provided they had not undergone aortic surgery or had an aortic dissection before their first visit. Aortic events (aortic surgery or aortic dissection) and deaths were evaluated during the 2 years following each patient visit. The risk was calculated as the number of events divided by the number of years of follow-up.
Results
A total of 954 patients were included (54% women; mean age 23 years). During follow-up (9.1 years), 142 patients underwent prophylactic aortic root surgery, 5 experienced type A aortic dissection, and 12 died (noncardiovascular causes in 3, unknown etiology in 3, post-operative in 6). When aortic root diameter was <50 mm, risk for proven type A dissection (0.4 events/1,000 patient-years) and risk for possible aortic dissection (proven aortic dissection plus death of unknown cause, 0.7 events/1,000 patients-years) remained low in this population that was treated according to guidelines. Three type A aortic dissections occurred in this population during the 8,594 years of follow-up, including 1 in a patient with a tubular aortic diameter of 50 mm, but none in patients with a family history of aortic dissection. The risk for type B aortic dissection in the same population was 0.5 events/1,000 patient-years.
Conclusions
In patients with FBN1 pathogenic variants who receive beta-blocker therapy and who limit strenuous exercise, aortic risk remains low when maximal aortic diameter is <50 mm. The risk of type B aortic dissection is close to the remaining risk of type A aortic dissection in this population, which underlines the global aortic risk.

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

J Am Coll Cardiol: 02 Mar 2020; 75:843-853
Milleron O, Arnoult F, Delorme G, Detaint D, ... Boileau C, Jondeau G
J Am Coll Cardiol: 02 Mar 2020; 75:843-853 | PMID: 32130918
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Abstract

Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT).

Rossello X, Raposeiras-Roubin S, Latini R, Dominguez-Rodriguez A, ... Ibáñez B, REBOOT-CNIC investigators
Aims
There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF).
Methods and results
The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle.
Conclusion
The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.

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

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:291-301
Rossello X, Raposeiras-Roubin S, Latini R, Dominguez-Rodriguez A, ... Ibáñez B, REBOOT-CNIC investigators
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:291-301 | PMID: 34351426
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Abstract

Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, ... Baan J, Ten Berg JM
Background
The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.
Methods
We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.
Results
Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31).
Conclusions
In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 28 Mar 2020; epub ahead of print
Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, ... Baan J, Ten Berg JM
N Engl J Med: 28 Mar 2020; epub ahead of print | PMID: 32223116
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Abstract

Ethnicity-dependent performance of the Global Registry of Acute Coronary Events risk score for prediction of non-ST-segment elevation myocardial infarction in-hospital mortality: nationwide cohort study.

Moledina SM, Kontopantelis E, Wijeysundera HC, Banerjee S, ... Shoaib A, Mamas MA
Aims
The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with the acute coronary syndrome with or without ST-segment elevation. Little is known about its performance at predicting in-hospital mortality for ethnic minority patients.
Methods and results
We identified 326 160 admissions with non-ST-segment elevation myocardial infarction (NSTEMI) in the Myocardial Infarction National Audit Project (MINAP), 2010-17, including White (n = 299 184) and ethnic minorities (excluding White minorities) (n = 26 976). We calculated the GRACE score for in-hospital mortality and assessed ethnic group baseline characteristics by low, intermediate and high risk. The performance of the GRACE risk score was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration (calibration plots). Ethnic minorities presented younger and had increased prevalence of cardiometabolic risk factors in all GRACE risk groups. The GRACE risk score for White [AUC 0.87, 95% confidence interval (CI) 0.86-0.87] and ethnic minority (AUC 0.87, 95% CI 0.86-0.88) patients had good discrimination. However, whilst the GRACE risk model was well calibrated in White patients (expected to observed (E : O) in-hospital death rate ratio 0.99; slope 1.00), it overestimated risk in ethnic minority patients (E : O ratio 1.29; slope: 0.94).
Conclusion
The GRACE risk score provided good discrimination overall for in-hospital mortality, but was not well calibrated and overestimated risk for ethnic minorities with NSTEMI.
Key question
Does the performance of the Global Registry of Acute Coronary Events (GRACE) (v2.0) score in predicting in-hospital mortality for non-ST-segment elevation myocardial infarction (NSTEMI) differ by ethnicity?
Key finding
The GRACE risk score provided good discrimination overall for in-hospital mortality but was not well calibrated and overestimated risk for ethnic minority patients with NSTEMI.
Take-home message
Ethnicity or race should be considered during the development of risk scoring systems. Existing systems can be recalibrated in the population they serve to better address risk.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 23 Feb 2022; epub ahead of print
Moledina SM, Kontopantelis E, Wijeysundera HC, Banerjee S, ... Shoaib A, Mamas MA
Eur Heart J: 23 Feb 2022; epub ahead of print | PMID: 35202472
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Abstract

2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, ... Huang J, Reardon MJ
Background
The Evolut Low Risk Trial (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients) showed that transcatheter aortic valve replacement (TAVR) with a supra-annular, self-expanding valve was noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke at 2 years. This finding was based on a Bayesian analysis performed after 850 patients had reached 1 year of follow-up.
Objectives
The goal of this study was to report the full 2-year clinical and echocardiographic outcomes for patients enrolled in the Evolut Low Risk Trial.
Methods
A total of 1,414 low-surgical risk patients with severe aortic stenosis were randomized to receive TAVR or surgical AVR. An independent clinical events committee adjudicated adverse events, and a central echocardiographic core laboratory assessed hemodynamic endpoints.
Results
An attempted implant was performed in 730 TAVR and 684 surgical patients from March 2016 to May 2019. The Kaplan-Meier rates for the complete 2-year primary endpoint of death or disabling stroke were 4.3% in the TAVR group and 6.3% in the surgery group (P = 0.084). These rates were comparable to the interim Bayesian rates of 5.3% with TAVR and 6.7% with surgery (difference: -1.4%; 95% Bayesian credible interval: -4.9% to 2.1%). All-cause mortality rates were 3.5% vs 4.4% (P = 0.366), and disabling stroke rates were 1.5% vs 2.7% (P = 0.119), respectively. Between years 1 and 2, there was no convergence of the primary outcome curves.
Conclusions
The complete 2-year follow-up from the Evolut Low Risk Trial found that TAVR is noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke, with event rates that were slightly better than those predicted by using the Bayesian analysis. (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients [Evolut Low Risk Trial]; NCT02701283).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 07 Mar 2022; 79:882-896
Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, ... Huang J, Reardon MJ
J Am Coll Cardiol: 07 Mar 2022; 79:882-896 | PMID: 35241222
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Impact:
Abstract

Sex-Specific Trends in Acute Myocardial Infarction Within an Integrated Healthcare Network, 2000 Through 2014.

Mefford MT, Li BH, Qian L, Reading SR, ... Woodward M, Reynolds K
Background
In recent decades, the rates of incident acute myocardial infarction (AMI) have declined in the United States, yet disparities by sex remain. In an integrated healthcare delivery system, we examined temporal trends in incident AMI among women and men.
Methods
We identified hospitalized AMI among members ≥35 years of age in Kaiser Permanente Southern California. The first hospitalization for AMI overall, and for ST-segment-elevation MI and non-ST-segment-elevation MI was identified byprimary discharge diagnosis codes in each calendar year from 2000 through 2014. Age- and sex-standardized incidence rates per 100 000 person-years were calculated by using direct adjustment to the 2010 US Census population. Average annual percent changes (AAPCs) and period percent changes were calculated, and trend tests were conducted using Poisson regression.
Results
We identified 45 331 AMI hospitalizations between 2000 and 2014. Age- and sex-standardized incidence rates of AMI declined from 322.4 (95% CI, 311.0-333.9) in 2000 to 174.6 (95% CI, 168.2-181.0) in 2014, representing an AAPC of -4.4% (95% CI, -4.2 to -4.6) and a period percent change of -46.6%. The AAPC for AMI in women was -4.6% (95% CI, -4.1 to -5.2) between 2000 and 2009 and declined to -2.3% (95% CI, -1.2 to -3.4) between 2010 and 2014. The AAPC for AMI in men was stable over the study period (-4.7% [95% CI, -4.4 to -4.9]). The AAPC for ST-segment-elevation MI hospitalization overall was -8.3% (95% CI, -8.0% to -8.6%).The AAPC in ST-segment-elevation MI changed among women in 2009 (2000-2009: -10.2% [95% CI, -9.3 to -11.1] and in 2010-2014: -5.2% [95% CI, -3.1 to -7.3]) while remaining stable among men (-8.0% [95% CI, -7.6 to -8.4]). The AAPC for non-ST-segment-elevation MI hospitalization was smaller than for ST-segment-elevation MI among both women and men (-1.9% [95% CI, -1.5 to -2.3] and -2.8% [95% CI, -2.5 to -3.2], respectively).
Conclusions
These results suggest that the incidence of hospitalized AMI declined between 2000 and 2014; however, declines in AMI have slowed among women in comparison with men in recent years. Determining unmet care needs among women may reduce these sex-based AMI disparities.



Circulation: 17 Feb 2020; 141:509-519
Mefford MT, Li BH, Qian L, Reading SR, ... Woodward M, Reynolds K
Circulation: 17 Feb 2020; 141:509-519 | PMID: 32065770
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Abstract

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA.

Johnston SC, Amarenco P, Denison H, Evans SR, ... Wang Y,
Background
Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.
Methods
We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.
Results
A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).
Conclusions
Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 15 Jul 2020; 383:207-217
Johnston SC, Amarenco P, Denison H, Evans SR, ... Wang Y,
N Engl J Med: 15 Jul 2020; 383:207-217 | PMID: 32668111
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