Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events.

Bos D, Arshi B, van den Bouwhuijsen QJA, Ikram MK, ... Kavousi M, van der Lugt A
Background
Increasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic individuals remain scarce.
Objectives
This study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting.
Methods
Between 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage [IPH], lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors.
Results
During a median of 5.1 years\' follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 [95% confidence interval: 1.30 to 4.50], and 1.95 [95% confidence interval: 1.20 to 3.14]). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD.
Conclusions
The presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.

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

J Am Coll Cardiol: 22 Mar 2021; 77:1426-1435

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

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

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

Eur Heart J: 25 Mar 2021; epub ahead of print

Association of Phosphodiesterase-5 Inhibitors Versus Alprostadil With Survival in Men With Coronary Artery Disease.

Andersson DP, Landucci L, Lagerros YT, Grotta A, ... Lehtihet M, Holzmann MJ
Background
Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI).
Objectives
This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease.
Methods
All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil.
Results
This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.
Conclusions
In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design.

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

J Am Coll Cardiol: 29 Mar 2021; 77:1535-1550

Discordance of High-Sensitivity Troponin Assays in Patients With Suspected Acute Coronary Syndromes.

Karády J, Mayrhofer T, Ferencik M, Nagurney JT, ... Koenig W, Hoffmann U
Background
High-sensitivity cardiac troponin (hs-cTn) assays have different analytic characteristics.
Objectives
The goal of this study was to quantify differences between assays for common analytical benchmarks and to determine whether they may result in differences in the management of patients with suspected acute coronary syndrome (ACS).
Methods
The authors included patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) I and II trials, with blood samples taken at emergency department presentation (ROMICAT-I and -II) or at 2 and 4 h thereafter (ROMICAT-II). hs-cTn concentrations were measured using 3 assays (Roche Diagnostics, Elecsys 2010 platform; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista). Per blood sample, we determined concordance across analytic benchmarks (<limit of detection [<LOD]/LOD-99th percentile/>99th percentile). Per-patient, the authors determined concordance of management recommendations (rule-out/observe/rule-in) per the 0/2-h algorithm, and their association with diagnostic test findings (coronary artery stenosis >50% on coronary computed tomography angiography or inducible ischemia on perfusion imaging) and ACS.
Results
Among 1,027 samples from 624 patients (52.8 ± 10.0 years; 39.4% women), samples were classified as <LOD (56.3% vs. 10.4% vs. 41.2%; p < 0.001), LOD-99th percentile (36.5% vs. 83.5% vs. 52.6; p < 0.001), >99th percentile (7.2% vs. 6.0% vs. 6.2%) by Roche, Abbott, and Siemens, respectively. A total of 37.4% (n = 384 of 1,027) of blood samples were classified into the same analytical benchmark category, with low concordance across benchmarks (<LOD 11.1%; LOD-99th percentile 29.3%; >99th percentile 43.6%). Serial samples were available in 242 patients (40.1% women; mean age: 52.8 ± 8.0 years). The concordance of management recommendations across assays was 74.8% (n = 181 of 242) considering serial hs-cTn measurements. Of patients who were recommended to discharge, 19.6% to 21.1% had positive diagnostic test findings and 2.8% to 4.3% had ACS at presentation.
Conclusions
Caregivers should be aware that there are significant differences between hs-cTn assays in stratifying individual samples and patients with intermediate likelihood of ACS according to analytical benchmarks that may result in different management recommendations. (Rule Out Myocardial Infarction by Computer Assisted Tomography [ROMICAT]; NCT00990262) (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

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

J Am Coll Cardiol: 29 Mar 2021; 77:1487-1499

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

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

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

Eur Heart J: 04 Apr 2021; epub ahead of print

Long-Term Outcomes of Patients With Late Presentation of ST-Segment Elevation Myocardial Infarction.

Cho KH, Han X, Ahn JH, Hyun DY, ... Jeong MH, KAMIR-NIH Investigators
Background
Real-world data on baseline characteristics, clinical practice, and outcomes of late presentation (12 to 48 h of symptom onset) in patients with ST-segment elevation myocardial infarction (STEMI) are limited.
Objectives
This study aimed to investigate real-world features of STEMI late presenters in the contemporary percutaneous coronary intervention (PCI) era.
Methods
Of 13,707 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health database, 5,826 consecutive patients diagnosed with STEMI within 48 h of symptom onset during 2011 to 2015 were categorized as late (12 to 48 h; n = 624) or early (<12 h; n = 5,202) presenters. Coprimary outcomes were 180-day and 3-year all-cause mortality.
Results
Late presenters had remarkably worse clinical outcomes than early presenters (180-day mortality: 10.7% vs. 6.8%; 3-year mortality: 16.2% vs. 10.6%; both log-rank p < 0.001), whereas presentation at ≥12 h of symptom onset was not independently associated with increased mortality after STEMI. The use of invasive interventional procedures abruptly decreased from the first (<12 h) to the second (12 to 24 h) 12-h interval of symptom-to-door time (\"no primary PCI strategy\" increased from 4.9% to 12.4%, and \"no PCI\" from 2.3% to 6.6%; both p < 0.001). Mortality rates abruptly increased from the first to the second 12-h interval of symptom-to-door time (from 6.8% to 11.2% for 180-day mortality; from 10.6% to 17.3% for 3-year mortality; all p < 0.05).
Conclusions
Data from a nationwide prospective Korean registry reveal that inverse steep differences in the use of invasive interventional procedures and mortality rates were found between early and late presenters after STEMI. A multidisciplinary approach is required in identifying late presenters of STEMI who can benefit from invasive interventional procedures until further studied.

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

J Am Coll Cardiol: 19 Apr 2021; 77:1859-1870

Long Working Hours and Risk of Recurrent Coronary Events.

Trudel X, Brisson C, Talbot D, Gilbert-Ouimet M, Milot A
Background
Evidence from prospective studies has suggested that long working hours are associated with incident coronary heart disease (CHD) events. However, no previous study has examined whether long working hours are associated with an increased risk of recurrent CHD events among patients returning to work after a first myocardial infarction (MI).
Objectives
The purpose of this study was to examine the effect of long working hours on the risk of recurrent CHD events.
Methods
This is a prospective cohort study of 967 men and women age 35 to 59 years who returned to work after a first MI. Patients were recruited from 30 hospitals across the province of Quebec, Canada. The mean follow-up duration was 5.9 years. Long working hours were assessed on average 6 weeks after their return to work. Incident CHD events (fatal or nonfatal MI and unstable angina) occurring during follow-up were determined using patients\' medical files. Hazard ratios were estimated using Cox proportional hazard regression models. Splines and fractional polynomial regressions were used for flexible exposure and time modeling.
Results
Recurrent CHD events occurred among 205 patients. Participants working long hours (≥55 h/week) had a higher risk of recurrent CHD events after controlling for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors (hazard ratio vs. 35 to 40 h/week: 1.67; 95% confidence interval: 1.10 to 2.53). These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain.
Conclusions
Among patients returning to work after a first MI, longer working hours per week is associated with an increased risk of recurrent CHD events. Secondary prevention interventions aiming to reduce the number of working hours among these patients may lower the risk of CHD recurrence.

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

J Am Coll Cardiol: 05 Apr 2021; 77:1616-1625

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Rheumatic Aortic Stenosis.

Mentias A, Saad M, Desai MY, Krishnaswamy A, ... Kapadia S, Sarrazin MV
Background
Patients with rheumatic aortic stenosis (AS) were excluded from transcatheter aortic valve replacement (TAVR) trials.
Objectives
The authors sought to examine outcomes with TAVR versus surgical aortic valve replacement (SAVR) in patients with rheumatic AS, and versus TAVR in nonrheumatic AS.
Methods
The authors identified Medicare beneficiaries who underwent TAVR or SAVR from October 2015 to December 2017, and then identified patients with rheumatic AS using prior validated International Classification of Diseases, Version 10 codes. Overlap propensity score weighting analysis was used to adjust for measured confounders. The primary study outcome was all-cause mortality. Multiple secondary outcomes were also examined.
Results
The final study cohort included 1,159 patients with rheumatic AS who underwent aortic valve replacement (SAVR, n = 554; TAVR, n = 605), and 88,554 patients with nonrheumatic AS who underwent TAVR. Patients in the SAVR group were younger and with lower prevalence of most comorbidities and frailty scores. After median follow-up of 19 months (interquartile range: 13 to 26 months), there was no difference in all-cause mortality with TAVR versus SAVR (11.2 vs. 7.0 per 100 person-year; adjusted hazard ratio: 1.53; 95% confidence interval: 0.84 to 2.79; p = 0.2). Compared with TAVR in nonrheumatic AS, TAVR for rheumatic AS was associated with similar mortality (15.2 vs. 17.7 deaths per 100 person-years (adjusted hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.09; p = 0.2) after median follow-up of 17 months (interquartile range: 11 to 24 months). None of the rheumatic TAVR patients, <11 SAVR patients, and 242 nonrheumatic TAVR patients underwent repeat aortic valve replacement (124 redo-TAVR and 118 SAVR) at follow-up.
Conclusions
Compared with SAVR, TAVR could represent a viable and possibly durable option for patients with rheumatic AS.

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

J Am Coll Cardiol: 12 Apr 2021; 77:1703-1713

Eruptive Calcified Nodules as a Potential Mechanism of Acute Coronary Thrombosis and Sudden Death.

Torii S, Sato Y, Otsuka F, Kolodgie FD, ... Finn AV, Virmani R
Background
Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied.
Objectives
The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes.
Methods
A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification.
Results
The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs.
Conclusions
Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.

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

J Am Coll Cardiol: 05 Apr 2021; 77:1599-1611

Effects of Fluoroquinolones on Outcomes of Patients With Aortic Dissection or Aneurysm.

Chen SW, Chan YH, Chien-Chia Wu V, Cheng YT, ... Chu PH, Chou AH
Background
Recent population-based studies have revealed that the use of fluoroquinolones (FQs) is associated with an increased risk of aortic dissection (AD) and aneurysm (AA). However, no evidence is available on whether FQs increase adverse events in patients who had been diagnosed with AD or AA.
Objectives
This study investigated whether the use of FQs increases the risk of aortic-related adverse events and death in this high-risk population.
Methods
A retrospective cohort study was conducted by using the Taiwan National Health Insurance Research Database. A total of 31,570 adult patients who survived after admission for AD or AA between 2001 and 2013 were identified. We divided each calendar year into 6 data units (2 months) for each patient and each year during follow-up. Covariates and exposure of interest (FQs) were reassessed every 2 months. We used another common antibiotic, amoxicillin, as a negative control exposure.
Results
Exposure to FQs was associated with a higher risk of all-cause death (adjusted hazard ratio: 1.61; 95% confidence interval: 1.50 to 1.73), aortic death (adjusted hazard ratio: 1.80; 95% confidence interval: 1.50 to 2.15), and later aortic surgery. However, amoxicillin exposure was not significantly associated with risk of any of the outcomes. A subgroup analysis revealed that the effect of FQs was not significantly different between the AD and AA groups.
Conclusions
Relative to amoxicillin use, FQ exposure in patients with AD or AA was associated with a higher risk of adverse outcomes. FQs should not be used by high-risk patients unless no other treatment options are available.

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

J Am Coll Cardiol: 19 Apr 2021; 77:1875-1887

Endovascular Aortic Repair in Nonagenarian Patients.

Prendes CF, Dayama A, Panneton JM, Stana J, ... Wanhainen A, Tsilimparis N
Background
The increasing proportion of elderly patients being treated for abdominal aortic aneurysm (AAA) in the endovascular era is controversial.
Objectives
This study compared 30-day outcomes of endovascular aortic repair (EVAR) in nonagenarians (NAs) with non-nonagenarians (NNAs).
Methods
This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database included EVAR procedures performed from 2011 to 2017. Multivariate logistic regression in the unadjusted cohort, followed by propensity-score matching (PSM), was performed. Primary outcomes were 30-day mortality and 30-day major adverse events.
Results
A total of 12,267 patients were included (365 NAs). Ruptured aneurysms accounted for 6.7% (n = 819): 15.7% (n = 57) in NAs versus 6.5% (n = 762) in NNAs (p < 0.001). Mean aneurysm diameter was 6.5 ± 1.8 cm in NAs versus 5.8 ± 1.7 cm in NNAs (p < 0.001). The unadjusted 30-day mortality was 9.9% in NA versus 2.2% in NNAs (p < 0.001). Multivariate analysis revealed age ≥90 years (odds ratio [OR]: 3.36), male sex (OR: 1.78), functional status (OR: 4.22), pre-operative ventilator dependency (OR: 3.80), bleeding disorders (OR: 1.52), dialysis (OR: 2.56), and ruptured aneurysms (OR: 17.21) as independent predictors of mortality. After PSM, no differences in 30-day mortality (intact AAA [iAAA]: 5.3% NA vs. 3% NNA [p = 0.15]; ruptured AAA [rAAA]: 38% NA vs. 28.6% NNA [p = 0.32]) or 30-day major adverse events (iAAA: 7% NA vs. 4.6% NNA [p = 0.22]; rAAA: 28% NA vs. 36.7% NNA [p = 0.35]) were observed.
Conclusions
Age was identified as an independent predictor of 30-day mortality after EVAR on multivariate analysis. However, no differences were found after PSM, suggesting that being ≥90 years of age but with similar comorbidities to younger patients is not associated with a higher short-term mortality after EVAR. Age ≥90 years alone should not exclude patients from EVAR, and tailored indications and carefully balanced risk assessment are advised.

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

J Am Coll Cardiol: 19 Apr 2021; 77:1891-1899

Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction.

Broch K, Anstensrud AK, Woxholt S, Sharma K, ... Aukrust P, Gullestad L
Background
Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.
Objectives
This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.
Methods
The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.
Results
We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.
Conclusions
Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).

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

J Am Coll Cardiol: 19 Apr 2021; 77:1845-1855

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

VARC-3 WRITING COMMITTEE, Généreux P, Piazza N, Alu MC, ... Cohen DJ, Leon MB
Aims
The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.
Methods and results
Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.
Conclusions
Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

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

Eur Heart J: 18 Apr 2021; epub ahead of print

Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

Hijazi Z, Alexander JH, Li Z, Wojdyla DM, ... Storey RF, Lopes RD
Background
In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y₁₂ inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function.
Methods
In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial.
Results
Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min^-1·1.73 m^-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min^-1·1.73 m^-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min^-1·1.73 m^-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively.
Conclusions
The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.



Circulation: 22 Mar 2021; 143:1215-1223

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

Peng AW, Dardari ZA, Blumenthal RS, Dzaye O, ... Page J, Blaha MJ
Background
There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations.
Methods
Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).
Results
Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm²), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups.
Conclusions
Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.



Circulation: 19 Apr 2021; 143:1571-1583

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 signaling 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 acute aortic dissection by inhibiting vascular smooth muscle cell phenotype switching, suggesting that Anxa1 signaling may be a potential target for AAD pharmacological therapy.
Translational perspective
Our studies herein may lead to a paradigm shift for pharmacologic therapy towards acute aortic dissection. Through careful examination of the pathological changes that occur during AAD onset in experimental animal models, we demonstrated that VSMC phenotype switching plays a critical role in the development of AAD. Inhibition of VSMC phenotype switching and its attendant impacts on aortic function may be a viable approach for future treatment. Toward that end, our studies highlighted the protective benefit of Anxa1 and its mimetic peptide Ac2-26 in AAD through prevention of the switching of VSMC to a synthetic phenotype.

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

Cardiovasc Res: 22 Mar 2021; epub ahead of print

P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor.

Kim J, Jang WJ, Lee WS, Choi KH, ... Rha SW, Hahn JY
Objective
To compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).
Methods
The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.
Results
Among 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2- 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).
Conclusions
Compared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.
Trial registration number
NCT02079194.

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

Heart: 22 Mar 2021; epub ahead of print

Rituximab in Patients with Acute ST-elevation Myocardial Infarction (RITA-MI): an Experimental Medicine Safety Study.

Zhao TX, Ur-Rahman MA, Sage AP, Victor S, ... Hoole SP, Mallat Z
Aims
In pre-clinical models of acute myocardial infarction (MI), mature B cells mobilise inflammatory monocytes into the heart, leading to increased infarct size and deterioration of cardiac function, whilst anti-CD20 antibody mediated depletion of B cells limits myocardial injury and improves cardiac function. Rituximab is a monoclonal anti-CD20 antibody targeted against human B cells. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, we assessed the safety, feasibility and pharmacodynamic effect of rituximab given to patients with acute ST elevation MI (STEMI).
Methods and results
RITA-MI was a prospective, open-label, dose-escalation, single-arm, phase 1/2a clinical trial, which tested rituximab administered as a single intravenous dose in patients with STEMI within 48 hours of symptom onset. Four escalating doses (200, 500, 700 and 1000 mg) were used. The primary endpoint was safety, whilst secondary endpoints were changes in circulating immune cell subsets including B cells, and cardiac and inflammatory biomarkers. [NCT : 03072199]. A total of 24 patients were dosed. Rituximab appeared well tolerated. Seven serious adverse events were reported, none of which were assessed as being related to the rituximab infusion. Rituximab caused a mean 96.3% (95% CI 93.8-98.8%) depletion of circulating B cells within 30 mins of starting the infusion. Maximal B cell depletion was seen at day 6, which was significantly lower than baseline for all doses (p < 0.001). B cell repopulation at 6 months was dose-dependent, with modulation of returning B cell subsets. Immunoglobulin (IgG, IgM and IgA) levels were not affected during the 6 months of follow-up.
Conclusions
A single infusion of rituximab appears safe when given in the acute STEMI setting and substantially alters circulating B cell subsets. We provide important new insight into the feasibility and pharmacodynamics of rituximab in acute STEMI, which will inform further clinical translation of this potential therapy.
Clinical trial registration
NCT03072199 at https://www.clinicaltrials.gov/.
Translational perspective
Selective depletion of B cells using anti-CD20 antibody has been shown to be beneficial in various pre-clinical models of myocardial infarction with additional supportive clinical observational data. Our research provides the first translational step in using this strategy in patients. We found rituximab to be safe and effective in rapidly and profoundly depleting B cells in patients after an acute myocardial infarction. This work has directly led to the funding and setup of a multi-centre, international, randomised, double-blind, placebo-controlled, phase 2 b clinical trial which should give us an indication of this strategy\'s clinical efficacy.

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

Cardiovasc Res: 29 Mar 2021; epub ahead of print

Coronary revascularisation in patients with ischaemic cardiomyopathy.

Ryan M, Morgan H, Petrie MC, Perera D
Heart failure resulting from ischaemic heart disease is associated with a poor prognosis despite optimal medical treatment. Despite this, patients with ischaemic cardiomyopathy have been largely excluded from randomised trials of revascularisation in stable coronary artery disease. Revascularisation has multiple potential mechanisms of benefit, including the reversal of myocardial hibernation, suppression of ventricular arrhythmias and prevention of spontaneous myocardial infarction. Coronary artery bypass grafting is considered the first-line mode of revascularisation in these patients; however, evidence from the Surgical Treatment of Ischaemic Heart Failure (STICH) trial showed a reduction in mortality, though this only became apparent with extended follow-up due to an excess of early adverse events in the surgical arm. There is currently no randomised controlled trial evidence for percutaneous coronary intervention in patients with ischaemic cardiomyopathy; however, the REVIVED-BCIS2 trial has recently completed recruitment and will address this gap in the evidence. Future directions include (1) clinical trials of revascularisation in patients hospitalised with heart failure, (2) defining the role of viability and ischaemia testing in heart failure, (3) studies to enhance the understanding of the mechanistic effects of revascularisation and (4) generating models to refine pre- and post-revascularisation risk prediction.

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

Heart: 30 Mar 2021; 107:612-618

Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.

Barnes C, Fatovich DM, Macdonald SPJ, Alcock RF, ... Schultz CJ, Hillis GS
Objective
We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement.
Methods
This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days.
Results
The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort.
Conclusions
Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe.
Trial registration number
ACTRN12618000797279.

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

Heart: 29 Apr 2021; 107:721-727

Role of beta blockers following percutaneous coronary intervention for acute coronary syndrome.

Peck KY, Andrianopoulos N, Dinh D, Roberts L, ... Freeman M, Teh AW
Aims
There is a paucity of evidence supporting routine beta blocker (BB) use in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). The aim of this study was to evaluate BB use post PCI and its association with mortality. Furthermore, the study aimed to evaluate the association between BB and mortality in the subgroups of patients with left ventricular ejection fraction (LVEF) <35%, LVEF 35%-50% and LVEF >50%.
Methods
Using a large PCI registry, data from patients with ACS between January 2005 and June 2017 who were alive at 30 days were analysed. Those patients taking BB at 30 days were compared with those who were not taking BB. The primary outcome was all-cause mortality. The mean follow-up was 5.3±3.5 years.
Results
Of the 17 562 patients, 83.3% were on BB. Mortality was lower in the BB group (13.1% vs 19.5%, p=0.0001). Multivariable Cox proportional hazards model showed that BB use was associated with lower overall mortality (adjusted HR 0.87, 95% CI 0.78 to 0.97, p=0.014). In the subgroup analysis, BB use was associated with reduced mortality in LVEF <35% (adjusted HR 0.63, 95% CI 0.44 to 0.91, p=0.013), LVEF 35%-50% (adjusted HR 0.80, 95% CI 0.68 to 0.95, p=0.01), but not LVEF >50% (adjusted HR 1.03, 95% CI 0.87 to 1.21, p=0.74).
Conclusion
BB use remains high and is associated with reduced mortality. This reduction in mortality is primarily seen in those with reduced ejection fraction, but not in those with preserved ejection fraction.

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

Heart: 29 Apr 2021; 107:728-733

Point: patients with native aortic regurgitation can be treated with transcatheter aortic valve implantation.

Khan SA, Baron SJ
Approximately 2% of people between the ages of 70 and 83 suffer from moderate or greater aortic regurgitation (AR) in the United States. Left untreated, this disease is progressive and fatal; however, up to 8% of patients with AR, who meet the criteria for surgical intervention, do not receive treatment. As such, there is a pressing need to address the lack of treatment options for the thousands of patients with AR who meet a class I indication for aortic valve replacement but who still do not receive surgery. The advent of transcatheter aortic valve implantation (TAVI) has significantly altered the paradigm of treatment for valvular heart disease and is now a well-established therapeutic option for patients with severe aortic stenosis. While transcatheter devices dedicated for the treatment of AR are under investigation, they are not commercially available at this time. Nevertheless, there is a growing body of data that demonstrate acceptable safety and efficacy for the off-label use of current TAVI devices for the treatment of severe AR. Given the dearth of treatment options for inoperable patients with severe AR, available TAVI devices should be considered for this patient population.

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

Heart: 15 Apr 2021; epub ahead of print

J-curve relationship between admission SBP and 2-year cardiovascular mortality in older patients admitted for acute coronary syndrome.

Jiang C, Wu S, Wang M, Zhao X, Li H
Objective
To investigate the relationship between admission SBP and subsequent cardiovascular and all-cause mortality in older patients hospitalized for acute coronary syndrome (ACS).
Methods
This is a retrospective observational study. Data from the CBD Bank (Cardiovascular Center Beijing Friendship Hospital Database Bank) were used to analyze the cardiovascular and all-cause mortality during hospitalization and over the follow-up period in relation to admission SBP among patients aged at least 65 years admitted for ACS from December 2012 through July 2019. Results were presented according to SBP quartiles: Q1, less than 120 mmHg; Q2, from 120 to 129 mmHg; Q3, from 130 to 143 mmHg; and Q4, at or above 144 mmHg.
Results
A total of 6785 patients were included in this cohort study. Mean (SD) patient age was 74.0 (6.5) years, and 47.6% were women. Mean (SD) follow-up time was 2.54 (1.82) years. A nonlinear relation was observed between SBP at admission and cardiovascular and all-cause mortality during hospitalization and over the follow-up period using restricted cubic splines. After adjustment for potential confounders, patients in Q1 had higher risk for 2-year cardiovascular death by Cox proportional hazard model compared with patients in Q2 [hazard ratio, 1.58; 95% confidence interval (CI), 1.12-2.21, P = 0.009], whereas patients in Q3 or Q4 exhibited a trend towards increased risk for 2-year cardiovascular death (hazard ratio, 1.33, 95% CI, 0.95-1.86, P = 0.094, for Q3 vs. Q2; and hazard ratio, 1.28, 95% CI, 0.91-1.82, P = 0.160, for Q4 vs. Q2). Meanwhile, when compared with patients in Q1, patients in Q2 had lower risk for 2-year cardiovascular death (hazard ratio, 0.64; 95% CI, 0.45-0.89, P = 0.009) whereas patients in Q3 or Q4 had similar risk for cardiovascular death (hazard ratio, 0.85, 95% CI, 0.63-1.14, P = 0.272, for Q3 vs. Q1; and hazard ratio, 0.82, 95% CI, 0.59-1.13, P = 0.221, for Q4 vs. Q1). However, low-admission SBP was not an independent predictor of 2-year all-cause mortality in this population.
Conclusion
Among patients aged at least 65 years admitted for ACS, there is a J-curve relationship between supine admission SBP and risk for 2-year cardiovascular death, with a nadir at 120-129 mmHg.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

J Hypertens: 30 Apr 2021; 39:926-934

Effect of Glomerular Filtration Rates on Outcomes Following Percutaneous Left Atrial Appendage Closure.

Faroux L, Cruz-González I, Arzamendi D, Freixa X, ... O\'Hara G, Rodés-Cabau J
Scarce data support the prescription of oral anticoagulation in patients with concomitant advanced chronic kidney disease (CKD) and atrial fibrillation, and left atrial appendage closure (LAAC) may provide a favorable risk-benefit ratio in this population. However, outcomes of LAAC in CKD patients are unknown. We aimed to investigate the impact of moderate-to-severe CKD on clinical outcomes following percutaneous LAAC. This was a multicenter study including 1094 patients who underwent LAAC. Moderate-to-severe CKD was defined as an eGFR<45 mL/min. Death, ischemic stroke, severe bleeding (≥BARC 3a) and serious adverse event (SAE; composite of death, stroke or severe bleeding) were recorded. A total of 300 patients (27.4%) had moderate-to-severe CKD. There were no differences between groups in periprocedural complications or device related thrombosis. At a median follow-up of 2 (1 to 3) years, patients with moderate-to-severe CKD did not present an increased risk of ischemic stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.22 to 1.92; p = 0.435) but were at a higher risk of death (HR: 2.84; 95% CI: 2.22 to 3.64; p <0.001), severe bleeding (HR: 1.96; 95% CI: 1.36 to 2.81; p <0.001) and SAE (HR: 2.23; 95% CI: 1.80 to 2.77; p <0.001). By multivariable analysis, an eGFR<45 ml/min (HR: 1.92; 95% CI: 1.34 to 2.76; p <0.001) and previous bleeding (HR: 2.30; 95% CI: 1.27 to 4.17; p = 0.006) were associated with an increased risk of severe bleeding. In conclusion, patients with moderate-to-severe CKD who underwent LAAC had very high thrombotic and bleeding risks. Although the rates of device related thrombosis or ischemic stroke after-LAAC were not influenced by kidney dysfunction, patients with moderate-to-severe CKD remained at higher risk of severe bleeding events.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:77-84

Comparison of Outcomes Among Patients With Cardiogenic Shock Admitted on Weekends Versus Weekdays.

Harhash AA, Kennedy KF, Fendler TJ, Khumri TM, ... Magalski A, Sperry BW
Cardiogenic shock (CS) is associated with high mortality and often requires involvement of a multidisciplinary provider team to deliver timely care. Care coordination is more difficult on weekends, which may lead to a delay in care. We sought to assess the effect of weekend admissions on outcomes in patients admitted with CS. Patients admitted with CS were identified from 2005 to 2014 in the National Inpatient Sample using ICD9 code 785.51. Baseline demographics, in-hospital procedures, and outcomes were obtained and compared by day of admission. A multivariable model was used to assess the impact of weekend admission on in-hospital mortality. A total of 875,054 CS admissions were identified (age 67.4 ± 15.1 years, 40.2% female, 72.1% Caucasian), with 23% of patients being admitted on weekends. Baseline co-morbidities were similar between groups. Weekend admissions were associated with higher in-hospital mortality (40.6% vs 37.5%) and cardiac arrest (20.3% vs 18.1%, p < 0.001 for both) consistently over the study period. Use of temporary and permanent mechanical support devices and heart transplantation were slightly less common for weekend admissions. In a multivariable model adjusting for relevant confounders, weekend admission was associated with a 10% increased mortality in patients with CS. In conclusion, patients with CS admitted on weekends had higher in-hospital mortality and were slightly less likely to receive mechanical support and advanced therapies compared with those admitted on weekdays. Future studies and health system initiatives should focus on rectifying these disparities with around-the-clock multidisciplinary coordinated care for CS.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:20-25

Dual Antiplatelet Therapy De-escalation Strategies.

Sinnaeve PR, Adriaenssens T
Dual antiplatelet therapy (DAPT), the combination of aspirin (ASA), and a P2Y₁₂ inhibitor, protects against stent thrombosis and new atherothrombotic events after a stent implantation or an acute coronary syndrome, but exposes patients to an increased risk of bleeding. In most current practices, the P2Y₁₂ inhibitor is stopped at 6 to 12 months and ASA is continued indefinitely. The advent of safer stents, with less risk of stent thrombosis, has challenged this standard of care, however. A number of alternative strategies involving earlier de-escalation of the antiplatelet therapy have therefore been proposed. In these approaches, standard DAPT is switched to a less potent antithrombotic combination at an earlier time-point than recommended by guidelines. Three different de-escalation variations have been tested to date. The first one maintains DAPT but switches from the potent P2Y₁₂ inhibitors ticagrelor or prasugrel to either a lower dose or to clopidogrel, while maintaining ASA. The 2 other approaches involve changing DAPT to a single antiplatelet at some earlier time-point after the percutaneous coronary intervention procedure, by stopping either the P2Y₁₂ inhibitor or ASA. These strategies have all demonstrated some benefit in clinical trials so far, but especially the contribution of ASA in secondary prevention is clearly evolving as its role in increasing bleeding complications while not providing increased ischemic benefit is becoming more and more clear. In contemporary practice, the type and duration of DAPT should now be based on an individualized decision, and the de-escalation strategies, if used wisely, can be added to the existing options.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:S23-S31

Six-Month Outcomes for COVID-19 Negative Patients with Acute Myocardial Infarction Before Versus During the COVID-19 Pandemic.

Aldujeli A, Hamadeh A, Tecson KM, Krivickas Z, ... Zaliaduonyte D, McCullough PA
The Coronavirus disease 2019 (COVID-19) pandemic has changed the way patients seek medical attention and how medical services are provided. We sought to compare characteristics, clinical course, and outcomes of patients presenting with acute myocardial infarction (AMI) during the pandemic compared with before it. This is a multicenter, retrospective cohort study of consecutive COVID-19 negative patients with AMI in Lithuania from March 11, 2020 to April 20, 2020 compared with patients admitted with the same diagnosis during the same period in 2019. All patients underwent angiography. Six-month follow-up was obtained for all patients. A total of 269 patients were included in this study, 107 (40.8%) of whom presented during the pandemic. Median pain-to-door times were significantly longer (858 [quartile 1=360, quartile 3 = 2,600] vs 385.5 [200, 745] minutes, p <0.0001) and post-revascularization ejection fractions were significantly lower (35 [30, 45] vs 45 [40, 50], p <0.0001) for patients presenting during vs. prior to the pandemic. While the in-hospital mortality rate did not differ, we observed a higher rate of six-month major adverse cardiovascular events for patients who presented during versus prior to the pandemic (30.8% vs 13.6%, p = 0.0006). In conclusion, 34% fewer patients with AMI presented to the hospital during the COVID-19 pandemic, and those who did waited longer to present and experienced more 6-month major adverse cardiovascular events compared with patients admitted before the pandemic.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 22 Mar 2021; epub ahead of print

Effect of Losartan or Atenolol on Children and Young Adults With Bicuspid Aortic Valve and Dilated Aorta.

Flyer JN, Sleeper LA, Colan SD, Singh MN, Lacro RV
Bicuspid aortic valve aortopathy is defined by dilation of the aortic root (AoRt) and/or ascending aorta (AsAo), and increases risk for aortic aneurysm and dissection. The effects of medical prophylaxis on aortic growth rates in moderate to severe bicuspid aortopathy have not yet been evaluated. This was a single-center retrospective study of young patients (1 day to 29 years) with bicuspid aortopathy (AoRt or AsAo z-score ≥ 4 SD, or absolute dimension ≥ 4 cm), treated with either losartan or atenolol. Maximal diameters and BSA-adjusted z-scores obtained from serial echocardiograms were utilized in a mixed linear effects regression model. The primary outcome was the annual rate of change in AoRt and AsAo z-scores during treatment, compared with before treatment. The mean ages (years) at treatment initiation were 14.2 ± 5.1 (losartan; n = 27) and 15.2 ± 4.9 (atenolol; n = 18). Median treatment duration (years) was 3.1 (IQR 2.4, 6.0) for losartan, and 3.7 (IQR 1.4, 6.6) for atenolol. Treatment was associated with decreases in AoRt and AsAo z-scores (SD/year), for both losartan and atenolol (pre- vs post-treatment): losartan/AoRt: +0.06 ± 0.02 vs -0.14 ± 0.03, p < 0.001; losartan/AsAo: +0.20 ± 0.03 vs -0.09 ± 0.05, p < 0.001; atenolol/AoRt: +0.07 ± 0.03 vs -0.02 ± 0.04, p = 0.04; atenolol/AsAo: +0.21 ± 0.04 vs -0.06 ± 0.06, p < 0.001. Treatment was also associated with decreases in absolute growth rates (cm/year) for all comparisons (p ≤ 0.02). Medical prophylaxis reduced proximal aortic growth rates in young patients with at least moderate and progressive bicuspid aortopathy.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:111-117

Patient-centered contrast thresholds to reduce acute kidney injury in high-risk patients undergoing percutaneous coronary intervention.

Malik AO, Amin A, Kennedy K, Qintar M, ... Mehran R, Spertus JA
Background
Contrast volume used during percutaneous coronary intervention has a direct relationship with contrast-associated acute kidney injury. While several models estimate the risk of contrast-associated acute kidney injury, only the strategy of limiting contrast volume to 3 × estimated glomerular filtration rate (eGFR) gives actionable estimates of safe contrast volume doses. However, this method does not consider other patient characteristics associated with risk, such as age, diabetes or heart failure.
Methods
Using the National Cardiovascular Data Registry acute kidney injury risk model, we developed a novel strategy to define safe contrast limits by entering a contrast term into the model and using it to meet specific (eg, 10%) relative risk reductions. We then estimated acute kidney injury rates when our patient-centered model-derived thresholds were and were not exceeded using data from CathPCI version 5 between April 2018 and June 2019. We repeated the same analysis in a sub-set of patients who received ≤3 × eGFR contrast.
Results
After excluding patients on hemodialysis, below average risk (<7%), missing data and multiple percutaneous coronary interventions, our final analytical cohort included 141,133 patients at high risk for acute kidney injury. The rate of acute kidney injury was 10.0% when the contrast thresholds derived from our patient-centered model were met and 18.2% when they were exceeded (P < .001). In patients who received contrast ≤3 × eGFR (n = 82,318), contrast-associated acute kidney injury rate was 9.8% when the contrast thresholds derived from our patient centered model were met and 14.5% when they were exceeded (P < .001).
Conclusions
A novel strategy for developing personalized contrast volume thresholds, provides actionable information for providers that could decrease rates of contrast-associated acute kidney injury. This strategy needs further prospective testing to assess efficacy in improving patient outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:51-59

Late kidney injury after transcatheter aortic valve replacement.

Adachi Y, Yamamoto M, Shimura T, Yamaguchi R, ... Hayashida K, OCEAN-TAVI Investigators
Background
Information on early to late-phase kidney damage in patients who underwent transcatheter aortic valve replacement (TAVR) is scarce. We aimed to identify the predictive factors for late kidney injury (LKI) at 1-year and patient prognosis beyond 1-year after TAVR.
Methods
We retrospectively reviewed 1,705 patients\' data from the Japanese TAVR multicenter registry. Acute kidney injury (AKI) and LKI, defined as an increase of at least 0.3 mg/dL in creatinine level, a relative 50% decrease in kidney function from baseline to 48 hours and 1-year, were evaluated. The patients were categorized into the 4 groups as AKI-/LKI- (n = 1.362), AKI+/LKI- (n = 95), AKI-/LKI+ (n = 199), and AKI+/LKI+ (n = 46).
Results
The cumulative 3-year mortality rates were significantly increased across the four groups (12.5%, 15.8%, 24.6%, 25.8%, P < .001). Multivariate analysis revealed that chronic kidney disease, coronary artery disease, periprocedural AKI, and heart failure-related re-admission within 1-year were significantly associated with LKI. The Cox regression analysis revealed that AKI-/LKI+ and AKI+/LKI+ were independent predictors of increased late mortality beyond 1-year after TAVR (P = .001 and P = .01).
Conclusions
LKI was influenced by adverse cardio-renal events and was associated with increased risks of late mortality beyond 1-year after TAVR.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:122-130

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

Ge Z, Kan J, Gao XF, Kong XQ, ... Zhang JJ, Chen SL
Background
Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion.
Trial design
DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure.
Conclusions
DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:101-110

Comparison of Hospitalization Trends and Outcomes in Acute Myocardial Infarction Patients With Versus Without Opioid Use Disorder.

Ranka S, Dalia T, Acharya P, Taduru SS, ... Shah Z, Gupta K
Discrepancies in medical care are well known to adversely affect patients with opioid abuse disorders (OUD), including management and outcomes of acute myocardial infarction (AMI) in patients with OUD. We used the National Inpatient Sample was queried from January 2006 to September 2015 to identify all patients ≥18 years admitted with a primary diagnosis of AMI (weighted N = 13,030; unweighted N = 2,670) and concomitant OUD. Patients using other nonopiate illicit drugs were excluded. Propensity matching (1:1) yielded 2,253 well-matched pairs in which intergroup comparison of invasive revascularization strategies and cardiac outcomes were performed. The prevalence of OUD patients with AMI over the last decade has doubled, from 163 (2006) to 326 cases (2015) per 100,000 admissions for AMI. The OUD group underwent less cardiac catheterization (63.2% vs 72.2%; p <0.001), percutaneous coronary intervention (37.0% vs 48.5%; p <0.001) and drug-eluting stent placement (32.3% vs 19.5%; p <0.001) compared with non-OUD. No differences in in-hospital mortality/cardiogenic shock were noted. Among subgroup of ST-elevation myocardial infarction patients (26.2% of overall cohort), the OUD patients were less likely to receive percutaneous coronary intervention (67.9% vs 75.5%; p = 0.002), drug-eluting stent (31.4% vs 47.9%; p <0.001) with a significantly higher mortality (7.4% vs 4.3%), and cardiogenic shock (11.7% vs 7.9%). No differences in the frequency of coronary bypass grafting were noted in AMI or its subgroups. In conclusion, OUD patients presenting with AMI receive less invasive treatment compared with those without OUD. OUD patients presenting with ST-elevation myocardial infarction have worse in-hospital outcomes with increased mortality and cardiogenic shock.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:18-24

Prevalence and Determinants of Atrial Fibrillation-Associated In-Hospital Ischemic Stroke in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Patil S, Gonuguntla K, Rojulpote C, Kumar M, ... Nardino RJ, Pickett C
Atrial fibrillation (AF) is an established risk factor ischemic stroke (IS) and is commonly encountered in patient hospitalized with acute myocardial infarction (AMI). Uncommonly, IS can occur as a complication resulting from percutaneous coronary intervention (PCI). There is limited real world data regarding AF-associated in-hospital IS (IH-IS) in patients admitted with AMI undergoing PCI. We queried the National Inpatient Sample database from January 2010 to December 2014 to identify patients admitted with AMI who underwent PCI. In this cohort, we determined the prevalence of AF associated IH-IS and compared risk factors for IH-IS between patients with AF and without AF using multivariable logistic regression models. IH-IS was present in 0.46% (n = 5,938) of the patients with AMI undergoing PCI (n = 1,282,829). Prevalence of IH-IS in patients with AF was higher compared with patients without AF (1.05% vs 0.4%; adjusted odds ratio: 1.634, 95% confidence interval: 1.527 to 1.748, p <0.001). Regardless of AF status, prevalence and risk of IH-IS was higher in females and increased with advancing age. There was significant overlap among risk-factors associated with increased risk of IH-IS in AF and non-AF cohorts, except for obesity in AF patients (adjusted odds ratio: 1.268, 95% confidence interval: 1.023 to 1.572, p = 0.03) in contrast to renal disease, malignancy, and peripheral vascular disease in non-AF patients. In conclusion, IH-IS is a rare complication affecting patients undergoing PCI for AMI and is more likely to occur in AF patients, females, and older adults, with heterogeneity among risk factors in patients with and without AF.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:1-7

Trends, Outcomes, and Predictive Score For Emergency Coronary Artery Bypass Graft Surgery After Elective Percutaneous Coronary Intervention (from a Nationwide Dataset).

Pancholy SB, Patel GA, Patel NR, Patel DD, ... Mamas MA, Patel TM
The temporal trends and preprocedural predictors of emergency coronary artery bypass graft surgery (ECABG) after elective percutaneous coronary intervention (PCI) in the contemporary era are largely unknown. From January 2003 to December 2014 elective hospitalizations with PCI as the primary procedure were extracted from the Nationwide Inpatient Sample. ECABG was identified as CABG within 24 hours of elective PCI. Temporal trends of elective PCI, ECABG, comorbidities, and in-hospital mortality were analyzed. Logistic regression model was used to identify preprocedural independent predictors of ECABG and post-PCI ECABG risk score was developed using the regression coefficients from the logistic regression model in the development cohort. The score was then validated in the validation cohort. Of 1,605,641 elective PCI procedures included in the final analysis, 5,561 (0.3%) patients underwent ECABG. The incidence of ECABG, co-morbidities and overall in-hospital mortality increased over the study period, whereas the in-hospital mortality after ECABG remained unchanged. An increasing trend of elective PCI performed at facilities without on-site CABG was noted, with a higher unadjusted in-hospital mortality in this cohort. ECABG risk score, performed well with a significantly higher risk of ECABG in those patients with a score in the highest tertile compared with those with lower ECABG score (0.6% vs 0.3%, p = 0.0005). In conclusion, an increasing trend of adverse outcomes after elective PCI is observed. We describe an easy-to-use predictive score using preprocedural variables that may allow the operator to triage the patient to an appropriate setting in an effort to improve outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:46-51

Short-Term Outcomes of Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Kidney Transplant Recipients (from the US Nationwide Representative Study).

Abdelfattah OM, Saad AM, Abushouk A, Hassanein M, ... Krishnaswamy A, Kapadia S
Kidney transplant recipients (KTRs) are considered high-risk patients for surgical interventions. Transcatheter aortic valve implantation (TAVI) has been introduced as an alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) at high operative risk. However, the outcomes of TAVI compared with SAVR KTRs have not been well-studied in nationally representative data. Patients with prior history of functioning kidney transplant who were hospitalized for TAVI and SAVR between January 2012 and December 2017 were identified retrospectively in the Nationwide Readmissions Database. Our study included 762 TAVI and 1,278 SAVR KTRs. Compared with SAVR, TAVI patients generally had higher rates of co-morbidities with lower risk of in-hospital mortality (3.1% vs 6.3, p = 0.002), blood transfusion (11.5% vs 38.6%, p <0.001), acute myocardial infarction (3.9% vs 6.5%, p = 0.16), acute kidney injury (24.5% vs 42.1%, p <0.001), sepsis (3.9% vs 9.5%, p <0.001) and discharge with disability (42.6% vs 68.4%, p <0.001). However, the rate of permanent pacemaker implantation was significantly higher in TAVI group (11.4% vs 3.9%, p <0.001). Of note, in-hospital stroke and 30-day readmission were comparable between both groups. These findings were confirmed after adjusting for other co-morbidities. TAVI is growing as a valid and safe alternative for KTRs with severe AS.

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Am J Cardiol: 31 Mar 2021; 144:83-90

Rate of Incomplete Revascularization Following Coronary Artery Bypass Grafting at a Single Institution Between 2007 and 2017.

Soukup CR, Schmidt CW, Chan-Tram C, Garberich RF, Sun BC, Traverse JH
Incomplete revascularization following coronary artery bypass grafting (CABG) is associated with increased repeat revascularization, myocardial infarction and death. Whether the rate of incomplete revascularization is increasing over time has not been previously described. All patients with multivessel coronary artery disease who underwent isolated and elective CABG at our Institution in 2007 (n = 291) were compared to patients who underwent CABG in 2017 (n = 290). A Revascularization Index Score was created to compare rates of incomplete revascularization between the 2 years based on the coronary anatomy and degree of stenosis. Comparison of the 2 years disclose that the rate of incomplete revascularization increased from 17.9% in 2007 to 28.3% in 2017 (p = 0.003) and was accompanied by a decline in the Revascularization Index Score from 0.73 to 0.67 (p = 0.005). Left ventricular function improved in both groups following CABG. Two-year cardiovascular mortality was significantly higher in the 2017 cohort compared to the 2007 cohort. These differences may be attributable to patient factors including more severe coronary artery disease associated with older age, greater incidence of smoking and previous percutaneous coronary intervention. In conclusion, the rate of incomplete revascularization following CABG significantly increased in 2017 compared to 2007 and was associated with higher cardiovascular mortality.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:33-36

Assessing the Best Prognostic Score for Transcatheter Aortic Valve Implantation (from the RISPEVA Registry).

Pepe M, Corcione N, Petronio AS, Berti S, ... Biondi-Zoccai G, Giordano A
The ACC/TVT score is a specific predictive model of in-hospital mortality for patients undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to test its predictive accuracy in comparison with standard surgical risk models (Logistic Euroscore, Euroscore II, and STS-PROM) in the population of TAVI patients included in the multicenter RISPEVA (Registro Italiano GISE sull\'impianto di Valvola Aortica Percutanea) registry. The study cohort included 3293 patients who underwent TAVI between 2008 and 2019. The 4 risk scores were calculated for all patients. For all scores, the capability to predict 30-day mortality was assessed by means of several analyses testing calibration and discrimination. The ACC/TVT score showed moderate discrimination, with a C-statistics for 30-day mortality of 0.63, not significantly different from the standard surgical risk models. The ACC/TVT score demonstrated, in contrast, better calibration compared with the other scores, as proved by a greater correspondence between estimated probabilities and the actual observations. However, when the ACC/TVT score was tested in the subgroup of patients treated in a more contemporary period (from 2016 on), it revealed a slight tendency to lose discrimination and to overestimate mortality risk. In conclusion, in comparison with the standard surgical risk models, the ACC/TVT score demonstrated better prediction accuracy for estimation of 30-day mortality in terms of calibration. Nevertheless, its predictive reliability remained suboptimal and tended to worsen in patients treated more recently.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 31 Mar 2021; 144:91-99

Prognostic Value and Interplay Between Myocardial Tissue Velocities in Patients Undergoing Coronary Artery Bypass Grafting.

Olsen FJ, Lindberg S, Fritz-Hansen T, Modin D, ... Møgelvang R, Biering-Sørensen T
Early diastolic tissue velocity (e\') by tissue Doppler imaging represents an early marker of left ventricular (LV) dysfunction in ischemic heart disease. We assessed the value of e\' for predicting mortality in patients undergoing coronary artery bypass grafting (CABG). We retrospectively investigated patients treated with CABG between 2006-2011. Before surgery, all patients underwent an echocardiogram with tissue Doppler imaging to measure tissue velocities: systolic (s\'), e\', and late diastolic (a\'). The primary outcome was all-cause mortality. Survival analysis was applied. Improvement of EuroSCORE-II was assessed by net reclassification index. Of 660 patients, 72 (11%) died during a median follow-up time of 3.8 years. Mean age was 68 years, LVEF 50%, and 84% were men. All tissue velocities showed a significant negative association with outcome and e\' provided highest Harrell\'s C-statistics (c-stat=0.68). After multivariable adjustment for EuroSCORE-II, LV hypertrophy, LV internal diameter, and global longitudinal strain, declining e\' was associated with a higher risk of mortality (HR=1.35 (1.12 to 1.61), p = 0.001, per 1cm/s absolute decrease). LVEF≤40% modified the relationship between both s\' and e\' and outcome (p for interaction=0.021 and 0.024, respectively), such that neither predicted mortality when LVEF was ≤40%. In patients with LVEF>40%, only e\' remained a predictor after multivariable adjustments (HR=1.36 (1.10 to 1.69), p = 0.005, per 1cm/s absolute decrease). A net reclassification index improvement of 0.14 was observed when adding global e\' to the EuroSCORE-II. In conclusion, e\' is an independent predictor of all-cause mortality in patients undergoing CABG, especially in patients with LVEF>40%, and improves the predictive value of EuroSCORE-II.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:37-45

Transcatheter Aortic Valve Implantation for Failed Surgical Aortic Bioprostheses Using a Self-Expanding Device (from the Prospective VIVA Post Market Study).

Kornowski R, Chevalier B, Verhoye JP, Holzhey D, ... Tchétché D, VIVA Investigators
Patients with symptomatic aortic stenosis are often treated with a surgical valve replacement. Surgical bioprosthetic valves degenerate over time and therefore may necessitate a redo surgery. This analysis reports the 2-year clinical outcomes of the Valve-in-Valve study, which evaluated transcatheter aortic valve implantation using the CoreValve and Evolut R devices in patients with degenerated surgical aortic bioprostheses at high risk for surgery. The prospective Valve-in-Valve study enrolled 202 eligible patients with failing surgical aortic bioprostheses due to stenosis, regurgitation, or a combination of both. The Evolut R bioprosthesis was used in 90.5% of valve-in-valve transcatheter aortic valve implantation cases. Two-year all-cause and cardiovascular mortality rates were 16.5% and 11.1%, respectively. Other clinical events included stroke (7.9%), disabling stroke (1.7%), and new pacemaker implantation (10.1%). The 2-year all-cause mortality rate was significantly higher in patients with discharge mean gradients ≥20 mmHg vs. those with lower mean gradients (21.0% vs 7.6%, p = 0.025). Discharge mean gradients ≥20 mm Hg were associated with smaller surgical bioprostheses (OR, 7.2 [95% CI 2.3 to 22.1]. In patients with failing surgical aortic bioprostheses, valve-in-valve treatment using a supra-annular self-expanding bioprosthesis provides significant functional improvements with acceptable rates of complications, especially if a postprocedural mean gradient of <20 mmHg can be achieved.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:118-124

Transcatheter Aortic Valve Implantation in Patients With Severe Aortic Stenosis Hospitalized With Acute Heart Failure.

Kaewkes D, Ochiai T, Flint N, Patel V, ... Cheng W, Makkar R
Optimal timing and outcomes of transcatheter aortic valve implantation (TAVI) in patients presenting with acute heart failure (AHF) remain unclear. In this consecutive cohort of 1,547 patients with severe aortic stenosis undergoing TAVI, the AHF status at admission was collected, and patients were classified into AHF and elective TAVI groups. In the AHF group, early TAVI was defined as TAVI performed ≤60 hours after emergency room arrival. The primary outcome was all-cause mortality at 30-day and 2-year after TAVI. There were 139 (9%) patients who underwent TAVI while hospitalized with AHF. At baseline, this group had higher rates of chronic kidney disease, higher Society of Thoracic Surgeons score, and lower left ventricular ejection fraction. After adjusting for baseline differences, the AHF group had significantly higher all-cause mortality at 30-day and 2-year than the elective TAVI group (8% vs 2%; p = 0.002, and 33% vs 18%; p = 0.002, respectively). In the AHF group, 43 (31%) patients underwent early treatment with TAVI. No significant difference in all-cause mortality at 30-day was observed between early and non-early TAVI groups (5% vs 10%; p = 0.617). All-cause mortality at 2-year was lower in the early TAVI groups (16% vs 40%, log-rank p = 0.022); however, after multivariable adjustment, the difference was barely statistically significant (p = 0.053). In conclusion, TAVI in patients with AHF was associated with worse short and long-term outcomes. In AHF setting, early TAVI did not significantly reduce all-cause mortality at 30-day; however, it showed a strong trend for lower all-cause mortality at 2-year.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:100-110

Incidence, Predictors, and Outcome of In-Hospital Bleeding in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.

Ratcovich H, Josiassen J, Helgestad OKL, Linde L, ... Møller JE, Holmvang L
Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2021; 144:13-19

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

Fagel ND, Amoroso G, Vink MA, Slagboom T, ... de Winter RJ, Riezebos RK
Background
In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor.
Methods
In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated.
Results
In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49).
Conclusions
In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:42-50

Meta-Analysis Comparing the Safety and Efficacy of Single vs Dual Antiplatelet Therapy in Post Transcatheter Aortic Valve Implantation Patients.

Ullah W, Zghouzi M, Ahmad B, Biswas S, ... Prasad A, Alraies MC
The relative safety and efficacy of aspirin versus dual antiplatelet therapy (DAPT; aspirin+clopidogrel) in patients who underwent transcatheter aortic valve implantation (TAVI) and did not have a long-term indication for oral anticoagulation remains controversial. Digital databases were searched to identify relevant articles. The major safety end point was bleeding, while the efficacy end points included after-TAVI ischemic and thrombotic events. Data were analyzed using a random effect model to calculate the pooled unadjusted odds ratio (OR) for dichotomous outcomes. Eleven studies comprising 4805 patients (aspirin 2258, DAPT 2547) were included in the quantitative analysis. Patients receiving aspirin-alone had significantly lower odds of all cause bleeding (OR 0.41, 95% CI 0.29 to .057, p <0.00001), major vascular bleeding (OR 0.51, 95% CI 0.34 to 0.77, p = 0.001), Valve Academic Research Consortium 2 (VARC-2) major bleeding (OR 0.50, 95% CI 0.30 to 0.83 p = 0.008), VARC-2 minor bleeding (OR 0.55, 95% CI 0.31 to 0.97, p = 0.04), transfusion requirement (OR 0.39, 95%CI 0.15 to 0.0.98, p = 0.05) and major vascular complications (OR0.41, 95% CI 0.26 to 0.66, p = 0.0002) compared with after-TAVI patients receiving both aspirin and clopidogrel. These was no significant difference in the odds of VARC-2 life threatening bleeding (OR 0.52, 95% CI 0.25 to 1.07, p = 0.08), prosthetic valve thrombosis (OR 1.17, 95% CI 0.22 to 6.30, p = 0.85), cardiac tamponade (OR 0.77, 95% CI 0.20 to 2.98, p = 0.70), conversion to open procedure (OR 1.99, 95 % CI 0.42 to 9.44, p = 0.39), MI (OR 0.79 95% CI 0.38 to 1.64, p = 0.52), transient ischemic attack (TIA) (OR 0.89, 95% CI 0.12 to 6.44, p = 0.91), major stroke (OR 0.68 95 % CI 0.43 to 1.08, p = 0.10), disabling stroke (0R 1.01, 95% CI 0.41 to 2.48, p = 0.99), cardiovascular mortality (OR 0.81 95% CI 0.38 to 1.74, p = 0.59) and all-cause mortality (OR 0.86, 95% CI 0.63 to 1.16, p = 0.31) between the 2 groups. In conclusion, after-TAVI patients who received aspirin alone had lower bleeding events with no significant differences in mortality and stroke rate compared with those who received DAPT.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:111-118

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Versus Without Chronic Kidney Disease.

Yamamoto K, Natsuaki M, Morimoto T, Shiomi H, ... Nakagawa Y, Kimura T
Chronic kidney disease (CKD) might be an important determinant in choosing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, there is a scarcity of studies evaluating the effect of CKD on long-term outcomes after PCI relative to CABG in the population including severe CKD. Among 30257 consecutive patients patients who underwent first coronary revascularization with PCI or isolated CABG in the CREDO-Kyoto PCI/CABG registry Cohort-2 (n = 15330) and Cohort-3 (n = 14,927), we identified the current study population of 12,878 patients with multivessel or left main disease, and compared long-term clinical outcomes between PCI and CABG stratified by the subgroups based on the stages of CKD (no CKD: eGFR >=60 ml/min/1.73m², moderate CKD: 60> eGFR >=30 ml/min/1.73m², and severe CKD: eGFR <30 ml/min/1.73m² or dialysis). There were 6,999 patients without CKD (PCI: n = 5,268, and CABG: n = 1,731), 4,427 patients with moderate CKD (PCI: n = 3,226, and CABG: n = 1,201), and 1,452 patients with severe CKD (PCI: n = 989, and CABG: n = 463). During median 5.6 years of follow-up, the excess mortality risk of PCI relative to CABG was significant regardless of the stages of CKD without interaction (no CKD: HR, 1.36; 95%CI, 1.12 to 1.65; p = 0.002, moderate CKD: HR, 1.40; 95%CI, 1.17 to 1.67; p <0.001, and severe CKD: HR, 1.33; 95%CI, 1.09 to 1.62; p = 0.004, Interaction p = 0.83). There were no significant interactions between CKD and the effect of PCI relative to CABG for all the outcome measures evaluated. In conclusion, PCI compared with CABG was associated with significantly higher risk for all-cause death regardless of the stages of CKD without any significant interaction.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:37-46

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Graftinge Among Patients with Unprotected Left Main Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From the CREDO-Kyoto PCI/CABG Registry Cohort-3).

Yamamoto K, Shiomi H, Morimoto T, Kadota K, ... Kimura T, CREDO-Kyoto PCI/CABG Registry Cohort-3 investigators
Long-term safety of percutaneous coronary intervention (PCI) as compared with coronary artery bypass grafting (CABG) is still controversial in patients with unprotected left main coronary artery disease (ULMCAD), and there is a scarcity of real-world data on the comparative long-term clinical outcomes between PCI and CABG for ULMCAD in new-generation drug-eluting stents era. The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013, and we identified 855 patients with ULMCAD (PCI: N = 383 [45%], and CABG: N = 472 [55%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.5 (interquartile range: 3.9 to 6.6) years. The cumulative 5-year incidence of all-cause death was not significantly different between the PCI and CABG groups (21.9% vs 17.6%, Log-rank p = 0.13). After adjusting confounders, the excess risk of PCI relative to CABG remained insignificant for all-cause death (HR, 1.00; 95% CI, 0.68 to 1.47; p = 0.99). There were significant excess risks of PCI relative to CABG for myocardial infarction and any coronary revascularization (HR, 2.07; 95% CI, 1.30 to 3.37; p = 0.002, and HR, 2.96; 95% CI, 1.96 to 4.46; p < 0.001), whereas there was no significant excess risk of PCI relative to CABG for stroke (HR, 0.85; 95% CI, 0.50 to 1.41; p = 0.52). In conclusion, there was no excess long-term mortality risk of PCI relative to CABG, while the excess risks of PCI relative to CABG were significant for myocardial infarction and any coronary revascularization in the present study population reflecting real-world clinical practice in Japan.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:47-57

Supravalvular Aortic Stenosis and the Risk of Premature Death Among Patients With Homozygous Familial Hypercholesterolemia.

Zhang R, Xie J, Zhou J, Xu L, ... Wang L, Yang Y
Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:58-63

Comparison of Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Among Patients With Three-Vessel Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From CREDO-Kyoto PCI/CABG Registry Cohort-3).

Matsumura-Nakano Y, Shiomi H, Morimoto T, Yamaji K, ... Kimura T, On behalf the CREDO-Kyoto PCI/CABG Registry Cohort-3 Investigators
There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:25-36

Meta-Analysis of Transcatheter Aortic Valve Implantation in Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valve.

Majmundar M, Kumar A, Doshi R, Shah P, ... Kalra A, Panaich SS
Most of the trials investigating the role of transcatheter aortic valve implantation (TAVI) across various strata of risk categories have excluded patients with bicuspid aortic stenosis (BAS) due to its anatomical complexities. The aim of this study was to perform a meta-analysis with meta-regression of studies comparing clinical, procedural, and after-procedural echocardiographic outcomes in BAS versus tricuspid aortic stenosis (TAS) patients who underwent TAVI. We searched the PubMed and Cochrane databases for relevant articles from the inception of the database to October 2019. Continuous and categorical variables were pooled using inverse variance and Mantel-Haenszel method, respectively, using the random-effect model. To rate the certainty of evidence for each outcome, we used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. Nineteen articles were included in the final analysis. There was no difference in the risk of 30-day mortality, 1-year mortality, 30-day cardiovascular mortality, major and/or life-threatening bleeding, major vascular complications, acute kidney injury, permanent pacemaker implantation, device success, annular rupture, after-procedural aortic valve area, and mean pressure gradient between the 2 groups. BAS patients who underwent TAVI had a higher risk of 30-day stroke, conversion to surgery, need for second valve implantation, and moderate to severe paravalvular leak. In conclusion, the present meta-analysis supports the feasibility of TAVI in surgically ineligible patients with BAS. However, the incidence of certain procedural complications such as stroke, conversion to surgery, second valve implantation, and paravalvular leak is higher among BAS patients compared with TAS patients, which must be discussed with the patient during the decision-making process.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:102-110

Comparison of Outcomes and Mortality in Patients Having Left Ventricular Assist Device Implanted Early -vs- Late After Diagnosis of Cardiomyopathy.

Chen E, Nesseler N, Martins RP, Goéminne C, ... Flécher E, Galand V
LVAD implantation in patients with a recently diagnosed cardiomyopathy has been poorly investigated. This work aims at describing the characteristics and outcomes of patients receiving a LVAD within 30 days following the diagnosis of cardiomyopathy. Patients from the ASSIST-ICD study was divided into recently and remotely diagnosed cardiomyopathy based on the time from initial diagnosis of cardiomyopathy to LVAD implantation using the cut point of 30 days. The primary end point of the study was all-cause mortality at 30-day and during follow-up. A total of 652 patients were included and followed during a median time of 9.1 (2.5 to 22.1) months. In this population, 117 (17.9%) had a recently diagnosed cardiomyopathy and had LVAD implantation after a median time of 15.0 (9.0 to 24.0) days following the diagnosis. This group of patients was significantly younger, with more ischemic cardiomyopathy, more sudden cardiac arrest (SCA) events at the time of the diagnosis and were more likely to receive temporary mechanical support before LVAD compared with the remotely diagnosed group. Postoperative in-hospital survival was similar in groups, but recently diagnosed patients had a better long-term survival after hospital discharge. SCA before LVAD and any cardiac surgery combined with LVAD implantation were identified as 2 independent predictors of postoperative mortality in recently diagnosed patients. In conclusion, rescue LVAD implantation for recently diagnosed severe cardiomyopathy is common in clinical practice. Such patients experience a relatively low postoperative mortality and have a better long-term survival compared with remotely diagnosed patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:82-88

Standardized Measurement of Femoral Artery Depth by Computed Tomography to Predict Vascular Complications After Transcatheter Aortic Valve Implantation.

Durand E, Penso M, Hemery T, Levesque T, ... Dacher JN, Eltchaninoff H
Vascular complications (VCs) are difficult to predict and remain an important issue after transfemoral (TF) transcatheter aortic valve implantation (TAVI) although their incidence has decreased with size reduction of introducers. We aimed to evaluate a standardized measurement of femoral artery depth (FAD) using computed tomography (CT) to predict VCs after TAVI. We performed a retrospective study of 679 TF TAVI patients. We evaluated a standardized CT method to measure FAD immediately above the bifurcation. Sheath-to-femoral-artery ratio (SFAR), calcification, and tortuosity were also evaluated. VCs were defined by the Valve Academic Research Consortium (VARC)-2. Receiver operating characteristic (ROC) curves were used to predict major VCs and the need for a stent-graft. The median values of FAD and SFAR were 49.0 (36.2 to 66.7) mm and 0.95 (0.81 to 1.18), respectively. Major VCs occurred in 37 (5.4%) patients and a stent-graft was required in 49 (7.1%) patients. FAD predicted the need for a stent-graft [0.61 (0.51 to 0.70), p = 0.04] but not major VCs [0.52 (0.40 to 0.63), p = 0.76]. In contrast, SFAR did not predict the need for a stent-graft [0.53 (0.43 to 0.62), p = 0.61] but predicted major VCs [0.70 (0.58 to 0.81), p = 0.001]. Calcification and tortuosity predicted neither major VCs nor the need for a stent-graft. In conclusion, the results of our study suggest that CT measurements of FAD and SFAR provide additional information to predict major VCs and the need for a femoral stent-graft after TF TAVI.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Apr 2021; 145:119-127

Effect of Transaortic Valve Intervention for Aortic Stenosis on Myocardial Mechanics.

Harrington CM, Sorour N, Gottbrecht M, Nagy A, ... Chung ES, Aurigemma GP
Chronic afterload excess in aortic stenosis results in compensatory concentric hypertrophy which mitigates the increased systolic load. Surgical aortic valve replacement has been shown to decrease afterload and improve left ventricular (LV) ejection fraction (EF). The extent to which these changes take place in patients undergoing TAVI (transcatheter aortic valve intervention) may be different than what has been observed in the surgical aortic valve replacement patients who were generally younger with few co-morbidities. Accordingly, we analyzed indices of LV structure and ventricular mechanics pre- and 1-year after TAVI in 397 patients (mean age 81±9, 46% women) with severe symptomatic aortic stenosis, complete echocardiographic data was available in 156 patients and these patients compromised our study population. Our principal findings are: (1) LV remodeling occurs after TAVI; (2) afterload decreases significantly; (3) LV chamber and myocardial function, assessed by left ventricular ejection fraction and midwall fractional shortening, and stroke volume, respectively, remain unchanged or decrease. In conclusion, TAVI effects LV remodeling despite significant co-morbidities. Thus, TAVI reduces afterload and leads to LV remodeling. Surprisingly, however, systolic function does not improve. These data run counter to the paradigm that afterload reduction improves systolic function and suggest that the response to afterload reduction is complex in the TAVI population.

Copyright © 2021. Published by Elsevier Inc.

Am J Cardiol: 30 Apr 2021; 146:56-61

Meta-Analysis of Valve-in-Valve Transcatheter Aortic Valve Implantation Versus Redo-surgical Aortic Valve Replacement in Failed Bioprosthetic Aortic Valve.

Al-Abcha A, Saleh Y, Boumegouas M, Prasad R, ... Rayamajhi S, Abela GS
This meta-analysis was conducted to compare clinical outcomes of valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) versus redo-surgical aortic valve replacement (Redo-SAVR) in failed bioprosthetic aortic valves. We conducted a comprehensive review of previous publications of all relevant studies through August 2020. Twelve observational studies were included with a total of 8,430 patients, and a median-weighted follow-up period of 1.74 years. A pooled analysis of the data showed no significant difference in all-cause mortality (OR 1.15; 95% CI 0.93 to 1.43; p = 0.21), cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, and the rate of moderate to severe paravalvular leakage between ViV-TAVI and Redo-SAVR groups. The rate of major bleeding (OR 0.36; 95% CI 0.16 to 0.83, p = 0.02), procedural mortality (OR 0.41; 95% CI 0.18 to 0.96, p = 0.04), 30-day mortality (OR 0.58; 95% CI 0.45 to 0.74, p <0.0001), and the rate of stroke (OR 0.65; 95% CI 0.52 to 0.81, p = 0.0001) were significantly lower in the ViV- TAVI arm when compared with Redo-SAVR arm. The mean transvalvular pressure gradient was significantly higher post-implantation in the ViV-TAVI group when compared with the Redo-SAVR arm (Mean difference 3.92; 95% CI 1.97 to 5.88, p < 0.0001). In conclusion, compared with Redo-SAVR, ViV-TAVI is associated with a similar risk of all-cause mortality, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, and the rate of moderate to severe paravalvular leakage. However, the rate of major bleeding, stroke, procedural mortality and 30-day mortality were significantly lower in the ViV-TAVI group when compared with Redo-SAVR.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:74-81

Long-term Implications of Post-Procedural Left Ventricular End-Diastolic Pressure in Patients Undergoing Transcatheter Aortic Valve Implantation.

Szekely Y, Borohovitz A, Hochstadt A, Topilsky Y, ... Finkelstein A, Arbel Y
Current risk models have only limited accuracy in predicting transcatheter aortic valve Implantation (TAVI) outcomes and there is a paucity of clinical variables to guide patient management after the procedure. The prognostic impact of elevated left ventricular end-diastolic pressure (LVEDP) in TAVI patients is unknown. The aim of the present study was to evaluate the prognostic value of after-procedural LVEDP in patients who undewent TAVI. Consecutive patients with severe symptomatic aortic stenosis who undewent TAVI were divided into 2 groups according to after-procedural LVEDP above and below or equal 12 mm Hg. Collected data included baseline clinical, laboratory and echocardiographic variables. We evaluated the impact of elevated vs. normal LVEDP on in-hospital outcomes, short- and long-term mortality. Eight hundred forty-five patients were included in the study with complete in-hospital and late mortality data available for all survivors (median follow-up 29.5 months [IQR 16.5 to 48.0]). The mean age (±SD) was 82.3±6.2 years and mean Society of Thoracic Surgery score was 4.0%±3.0%. Patients with LVEDP>12 mm Hg (n = 591, 70%) and LVEDP≤12 mm Hg (n = 254, 30%) had a 6-months mortality rate of 6.8% and 2%, respectively (P=0.004) and a 1-year mortality rate of 10.1% vs 4.9%, respectively (p = 0.017). By multivariable analysis, after-procedural LVEDP>12 mm Hg was independently associated with all-cause mortality (HR 2.45, 95% CI 1.58 to 3.76, p <0.001) during long-term follow-up. In conclusion, elevated after-procedural LVEDP in patients who undewent TAVI is an independent predictor of mortality following TAVI. Further research regarding the use of LVEDP as a tool for after-procedural medical management is warranted.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:62-68

Comparison of Patients With Nonobstructive Coronary Artery Disease With Versus Without Myocardial Infarction (from the VA Clinical Assessment Reporting and Tracking [CART] Program).

Kovach CP, Hebbe A, O\'Donnell CI, Plomondon ME, ... Waldo SW, Valle JA
Comparisons of the outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA) and patients with nonobstructive coronary artery disease (CAD) without myocardial infarction (MI) are limited. Here we compare the outcomes of patients with MINOCA and patients with nonobstructive CAD without MI and assess the influence of medical therapy on outcomes in these patients. Veterans who underwent coronary angiography between 2008 to 2017 with nonobstructive CAD were divided into those with or without pre-procedural troponin elevation. Patients with prior revascularization, heart failure, or who presented with cardiogenic shock, STEMI, or unstable angina were excluded. After propensity matching, outcomes were compared between groups. The primary outcome was major adverse cardiovascular events (MACE: mortality, myocardial infarction, and revascularization) within one year: 3,924 patients with nonobstructive CAD and a troponin obtained prior to angiography were identified (n=1,986 with elevated troponin) and restricted to 1,904 patients after propensity-matching. There was a significantly higher risk of MACE among troponin-positive patients compared with those with a negative troponin (HR 2.37; 95% CI, 1.67 to 3.34). Statin (HR 0.32; 95% CI, 0.22 to 0.49) and ACE inhibitor (HR 0.49; 95% CI, 0.32 to 0.75) therapy after angiography was associated with decreased MACE, while P2Y12 inhibitor, calcium-channel and beta-blocker therapy were not associated with outcomes. In conclusion, Veterans with MINOCA are at increased risk for MACE compared with those with nonobstructive CAD and negative troponin at the time of angiography. Specific medications were associated with a reduction in MACE, suggesting an opportunity to explore novel approaches for secondary prevention in this population.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:1-7

Acute Chylopericardium With Tamponade and Cardiac Arrest With Pseudomyxoma Peritonei.

Milandt N, Birkelund T, Engholm M
A 51-year-old woman with pseudomyxoma peritonei developed cardiac arrest 5 days after surgery. Acute echocardiography demonstrated pericardial tamponade. Emergency pericardiocentesis evacuated milky fluid and circulation was re-established. Analysis of the pericardial fluid suggested chylopericardium. In conclusion, this case demonstrates that chylopericardium may be life-threatening and underlines the importance of acute echocardiography in critical management of patients with unexplained shock.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:134-136

The Mechanism of Balloon Impact in Percutaneous Transluminal Coronary Angioplasty in Eccentric Coronary Artery Narrowings.

Saner H, Saner B, Meier B
In the early days of percutaneous transluminal coronary angioplasty (PTCA) and in particular before the stent era, the selection of the appropriate balloon diameter was crucial for risk and success of the intervention. With larger balloon diameters the risk of vessel wall dissection was increased but the rate of restenosis was much higher when smaller balloons were used. In retrospect, it is surprising how few histopathological studies have been performed during this time period to study the mechanism of PTCA. A main reason for this may have been that PTCA has been working well in most cases and was very effective for the relief of angina symptoms. This lack of basic research led even to the erroneous assumption by the PTCA pioneer Andreas Gruentzig, that the angioplasty procedure be characterized \"by a concentric expansion of the vessel over a suitable portion of its length.\" This view has been challenged by Professor Jesse E. Edwards, a distinguished cardiovascular pathologist from Minneapolis, MN/USA, with a world-wide reputation. The disagreement was based on the finding that 70% of coronary stenoses have been found to be eccentric and only 30% to be concentric narrowings. Jesse E. Edwards therefore initiated a histopathological study about the mechanism of balloon angioplasty in coronary arteries of freshly autopsied hearts. The study was performed in 1982 by one of the authors (HS), then a young cardiology fellow in the laboratories of Professor Kurt A. Amplatz. Kurt A. Amplatz was in an early stage of his career to later become a world famous pioneer for the development of a variety of catheters, wires, instruments, and devices for the closure of the patent foramen ovale, atrial and ventricular septal defects, and the left atrial appendage. The study documents were unavailable for almost 40 years but have recently been made accessible again. Conclusion: This manuscript discusses the main findings of the histopathological study on the mechanism of coronary balloon dilatation and is dedicated to 2 giants of cardiovascular research, Jesse E. Edwards and Kurt A. Amplatz.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Apr 2021; 146:128-131

Clinical Features and Outcomes in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction: Early versus Recent Experience with Impella.

Singh H, Mehta RH, O\'Neill W, Kapur NK, ... Rosman H, Kaki A
Objectives
To compare clinical features and outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) treated in the early experience with Impella percutaneous ventricular assist device and patients treated recently.
Background
Since pre-market approval (PMA) of Impella device as treatment for AMICS, use of the device has grown considerably.
Methods
We retrospectively analyzed 649 AMICS patients treated with perioperative Impella, with 291 patients treated from 2008 to 2014 comprising the early experience cohort and 358 patients treated from 2017 to 2019 comprising the recent experience cohort. The primary end point was risk adjusted in-hospital mortality.
Results
Mean age and gender distribution of patients was similar in the two cohorts. The recent cohort had more invasive hemodynamic monitoring (64% vs 46%; p<0.001) and less use of an intra-aortic balloon pump prior to Impella (15% vs 41%; p<0.001). Recently treated patients were significantly more likely to receive Impella support prior to PCI (58% vs 44%; p=0.005). In-hospital mortality was lower in the recent cohort (48% versus 56%; p=0.043). This difference was however no longer significant after risk adjustment (adjusted OR 0.89, 95% CI 0.59-1.34, p=0.59). Rates of acute kidney injury, major bleeding, and vascular complications requiring surgery were also significantly lower in the recent cohort.
Conclusions
Use of Impella for AMICS during recent years is associated with lower unadjusted in-hospital mortality, which may reflect better patient selection, earlier device implantation, and improved management algorithms. In-depth understanding of these factors may inform the development of future treatment protocols.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 09 Apr 2021; epub ahead of print

Bleeding risk prediction in elderly patients managed invasively for acute coronary syndromes: External validation of the PRECISE-DAPT and PARIS scores.

Montalto C, Crimi G, Morici N, Piatti L, ... Savonitto S, De Servi S
Background
We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management.
Methods
Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials.
Results
After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3-5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ² > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%.
Conclusions
In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2021; 328:22-28

Iron deficiency for prognosis in acute coronary syndrome - A systematic review and meta-analysis.

Reinhold J, Papadopoulou C, Baral R, Vassiliou VS
Background
Iron deficiency (ID) is an important predictor of adverse outcomes in patients with heart failure, however it is unclear whether ID also affects prognosis in patients with acute coronary syndrome (ACS). The aim of this systematic review and meta-analysis was to assess the prognostic value of iron deficiency in patients with ACS.
Methods
We searched PubMed, Web of Science, and the Cochrane library and included cohort studies of patients with ACS that were stratified by ID status. There were no restrictions on definition of ACS or ID. Studies were systematically appraised and data extracted by two independent reviewers. Meta-analysis was performed where two or more studies reported on the same pre-determined outcome measure.
Results
Seven studies with 2821 participants were identified, reporting a high prevalence of ID in the ACS population. Three studies reported worse long-term outcomes in the ID population, whereas short-term outcomes were heterogeneous across studies.
Conclusions
Patients with ID presenting with ACS may have a worse long-term prognosis but more studies are required for confirmation. A role for ID in prognosis of patients with ACS and as a potentially treatable condition may have implication for the current management of this patient population.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2021; 328:46-54

Angiographic characteristics and long-term outcomes of single-vessel chronic total occlusion percutaneous coronary intervention in patients with and without previous myocardial infarction.

Hu X, Qiao S, Guan C, Guo C, ... Song L, Xu B
Objective
This study evaluated the angiographic characteristics and clinical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) among patients with and without a history of myocardial infarction (MI).
Background
The pathogenesis of CTO and myocardial viability are different in cases with or without previous MI. However, the lesion characteristics and clinical outcomes are unclear for these two groups.
Methods
We reviewed consecutive patients who underwent single-vessel CTO PCI from 2010 to 2013. Patients were classified according to their history of MI. Acute procedural results were classified as optimal recanalization, suboptimal recanalization, or technical failure. The primary endpoint was the 5 year rate of cardiac death.
Results
We identified 2,191 eligible patients, including 859 patients (39.2%) with previous MI. The overall technical success rate was 74.4%. Relative to the non-MI group, the MI group had a larger reference vessel diameter (3.0 ± 0.5 vs. 2.9 ± 0.4 mm, p = .002), a lower proportion of Werner grade ≥ 1 collateral circulation (65.4 vs. 79.2%, p < .001), a higher proportion of optimal recanalization (63.1 vs. 58.6%, p = .006), and a higher 5-year rate of cardiac death (3.9 vs. 2.1%, p = .02). In the MI group, suboptimal recanalization was associated with a significantly higher 5-year rate of spontaneous MI, relative to optimal recanalization and technical failure (11.7 vs. 4.6 vs. 4.1%, p = .006).
Conclusions
Patients with CTO and previous MI had a larger reference vessel diameter, lower level of collateral circulation, and higher proportion of optimal recanalization. However, suboptimal recanalization in these patients was associated with an increased risk of spontaneous MI.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 23 Mar 2021; epub ahead of print

Trends in the utilization and reimbursement of coronary revascularization in the United States Medicare population from 2010 to 2018.

Shah AM, Siddiqui E, Cuenca C, Drotar P, ... Waxman S, Sambol J
Objective
To determine utilization and reimbursement trends of coronary revascularization procedures in the US Medicare population from 2000 to 2018.
Background
US Medicare population is increasing, and coronary revascularization decreased in the 2000s.
Methods
This is a population-based, cross sectional study of US Medicare beneficiaries from 2010 to 2018. The Centers for Medicare and Medicaid Services\' database was queried for revascularization procedures using the coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) current procedural terminology (CPT) codes. Trends in Medicare enrollees, PCIs, CABGs, and physician reimbursements were analyzed.
Results
Total utilization and reimbursement decreased for both revascularization procedures. The national CABG and PCI utilization per enrollee has decreased by 40.7% (best fit line: b coefficient, 95% CI; -0.297, -0.358 to -0.235) and 26.4% (best fit line: -0.229, -0.373 to -0.0858), respectively. For PCI, annual Medicare payout per enrollee and physician compensation per procedure has decreased by 49.3% (best fit line: -0.250, -0.315 to -0.185) and 14.5% (best fit line: -11.54, -15.62 to -7.452), respectively, and for CABG, decreased by 53.3% (best fit line: -0.373, -0.560 to -0.186) and 36.6% (best fit line: -34.15, -49.35 to -18.95), respectively. Amongst the states, there was significant variability in procedure utilization, and CABG reimbursement rates but minimal variability in PCI reimbursement rates.
Conclusion
Even though the US population has aged, revascularization utilization and reimbursement continue to decline. Advancement in medical intervention strategies, particularly non-surgical management, may account for these trends. Further understanding of these trends will allow health systems to tailor resources to the aging population.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 23 Mar 2021; epub ahead of print

Zero contrast optical coherence tomography-guided percutaneous coronary intervention in patients with non-ST segment elevation myocardial infarction and chronic kidney disease.

Liu ZY, Yin ZH, Liang CY, He J, ... Zheng ZF, Pan HW
Objectives
To investigate a strategy for ultra-low volume contrast percutaneous coronary intervention (PCI) with the aims of preserving renal function and observing the 90-day clinical endpoint in patients with non-ST-elevated myocardial infarction (non-STEMI) and chronic kidney disease (CKD).
Background
The feasibility, safety, and clinical utility of PCI with ultra-low radio-contrast medium in patients with non-STEMI and CKD are unknown.
Methods
A total of 29 patients with non-STEMI and CKD (estimated glomerular filtration rate [eGFR] of ≤60 ml/min/1.73 m² ) were included. Ultra-low volume contrast PCI was performed after minimal contrast coronary angiography using zero contrast optical coherence tomography (OCT) guidance. Pre- and post-PCI angiographic measurements were performed using quantitative flow ratio (QFR) for pre-perfusion assessment and verifying improvement.
Results
The median creatinine level was 2.1 (inter-quartile range 1.8-3.3), and mean eGFR was 48 ± 8 ml/min/1.73 m² pre-PCI. During the PCI procedure, OCT revealed 15 (52%) cases of abnormalities post-dilation. There was no significant change in the creatinine level and eGFR in the short- or long-term, and no major adverse events were observed.
Conclusion
In non-STEMI patients with high-risk CKD who require revascularization, QFR and no contrast OCT-guided ultra-low contrast PCI may be performed safely without major adverse events.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 24 Mar 2021; epub ahead of print

Revascularisation strategies in patients with significant left main coronary disease during the COVID-19 pandemic.

Mohamed MO, Curzen N, de Belder M, Goodwin AT, ... Kinnaird T, Mamas MA
Background
There are limited data on the impact of the COVID-19 pandemic on left main (LM) coronary revascularisation activity, choice of revascularisation strategy, and post-procedural outcomes.
Methods
All patients with LM disease (≥50% stenosis) undergoing coronary revascularisation in England between January 1, 2017 and August 19, 2020 were included (n = 22,235), stratified by time-period (pre-COVID: 01/01/2017-29/2/2020; COVID: 1/3/2020-19/8/2020) and revascularisation strategy (percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). Logistic regression models were performed to examine odds ratio (OR) of 1) receipt of CABG (vs. PCI) and 2) in-hospital and 30-day postprocedural mortality, in the COVID-19 period (vs. pre-COVID).
Results
There was a decline of 1,354 LM revascularisation procedures between March 1, 2020 and July 31, 2020 compared with previous years\' (2017-2019) averages (-48.8%). An increased utilization of PCI over CABG was observed in the COVID period (receipt of CABG vs. PCI: OR 0.46 [0.39, 0.53] compared with 2017), consistent across all age groups. No difference in adjusted in-hospital or 30-day mortality was observed between pre-COVID and COVID periods for both PCI (odds ratio (OR): 0.72 [0.51. 1.02] and 0.83 [0.62, 1.11], respectively) and CABG (OR 0.98 [0.45, 2.14] and 1.51 [0.77, 2.98], respectively) groups.
Conclusion
LM revascularisation activity has significantly declined during the COVID period, with a shift towards PCI as the preferred strategy. Postprocedural mortality within each revascularisation group was similar in the pre-COVID and COVID periods, reflecting maintenance in quality of outcomes during the pandemic. Future measures are required to safely restore LM revascularisation activity to pre-COVID levels.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 24 Mar 2021; epub ahead of print

Association of the age shock index with coronary plaque characteristics in ST-segment elevation myocardial infarction: A 3-vessel optical coherence tomography study.

Zhao L, Du Z, Wu T, Cao M, ... Jia H, Yu B
Objectives
We investigated whether the age shock index (SI) was associated with coronary plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) using optical coherence tomography (OCT).
Background
The age SI is a simple clinical parameter that effectively predicts poor clinical outcomes among patients with STEMI.
Methods
This retrospective study evaluated 408 STEMI patients who underwent 3-vessel OCT during emergency percutaneous coronary interventions at a single center between January 2017 and October 2018. Patients were divided into groups with low or high age SI values (<41 vs. ≥41). Plaque characteristics were compared between the two groups for both culprit lesions (n = 408) and non-culprit lesions (n = 1,077).
Results
In culprit lesions, patients with a high age SI (≥41) were more likely to have plaque rupture (61.0% vs. 56.8%, p = .002) and thinner fibrous caps (fibrous cap thickness [FCT]: 40.0 [33.0-53.0] μm vs. 46.0 [36.0-63.8] μm, p = .021). In non-culprit lesions, patients with a high age SI were more likely to have high-risk plaques (29.9% vs. 17.8%, p = .018; simultaneous presence of a minimal lumen area of <3.5 mm² , maximum lipid arc of >180°, FCT of <75 μm, and macrophage accumulation). Plaque-based analyses revealed that patients with a high age SI had larger lipid cores and lesser FCT.
Conclusions
Patients with STEMI and a high age SI had increased risks of culprit plaque rupture and high-risk non-culprit plaques, and vulnerable plaque features at the culprit and non-culprit lesions. Therefore, a high age SI in patients with STEMI may indicate greater pancoronary vulnerability.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 28 Mar 2021; epub ahead of print

Comparison of the investigational device exemption and post-approval trials of the Melody transcatheter pulmonary valve.

Kreutzer J, Armstrong AK, Rome JJ, Zellers TM, ... Bergersen LJ, McElhinney DB
Objective
We compared 5-year outcomes of transcatheter pulmonary valve (TPV) replacement with the Melody TPV in the post-approval study (PAS) and the investigational device exemption (IDE) trial.
Background
As a condition of approval of the Melody TPV after the IDE trial, the Food and Drug Administration required that a PAS be conducted to evaluate outcomes of TPV replacement in a \"real-world\" environment. The 5-year outcomes of the PAS have not been published, and the IDE and PAS trials have not been compared.
Methods
The cohorts comprised all patients catheterized and implanted at 5 IDE sites and 10 PAS sites. Differences in trial protocols were detailed. Time-related outcomes and valve-related adverse events were compared between the two trials with Kaplan-Meier curves and log-rank testing.
Results
167 patients (median age, 19 years) were catheterized and 150 underwent TPV replacement in the IDE trial; 121 were catheterized (median age, 17 years) and 100 implanted in the PAS. Freedom from hemodynamic dysfunction (p = .61) or any reintervention (p = .74) over time did not differ between trials. Freedom from stent fracture (p = .003) and transcatheter reintervention (p = .010) were longer in PAS, whereas freedom from explant (p = .020) and TPV endocarditis (p = .007) were shorter. Clinically important adverse events (AEs) were reported in 14% of PAS and 7.2% of IDE patients (p = .056); the incidence of any particular event was low in both.
Conclusions
Hemodynamic and time-related outcomes in the PAS and IDE trials were generally similar, confirming the effectiveness of the Melody TPV with real-world providers. There were few significant complications and limited power to identify important differences in AEs. The lack of major differences in outcomes between the two studies questions the usefulness of mandated costly post-approval studies as part of the regulatory process for Class III medical devices.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 28 Mar 2021; epub ahead of print

A new over-the-wire percutaneous mitral balloon valvuloplasty technique.

Weich H, van Veyeren LM
Objectives
To develop and evaluate a new over-the-wire technique for mitral valvuloplasty that is both technically easier and less costly.
Background
Rheumatic heart disease (RHD) and resultant mitral stenosis (MS) carries a significant burden of disease worldwide. The prevalence is however concentrated in lower income countries where the current gold standard for percutaneous mitral valvuloplasty (PMBV)-the Inoue technique, is not always available due to cost and technical complexity.
Methods
The development of an over-the-wire technique involving a steerable catheter to aid crossing of the valve and a dedicated TAVI wire is described. The procedure evolved over the initial eight cases and the final standardized procedure was performed in 16 cases. Clinical, echocardiographic and procedural outcomes are described in 16 consecutive cases performed at a single center.
Results
The procedure was performed with 88% procedural success and only one technical failure during the development phase. 2/24 patients had moderate mitral regurgitation (MR) afterwards but one had unfavorable anatomy and the other had pre-procedural moderate MR. The average procedural duration was 66 min, which was shortened significantly over time. No procedural deaths or conversion to open surgery at 1 year. Procedural cost was 44% lower than the Inoue technique.
Conclusion
We present favorable results of a new PMBV technique that is cheaper and technically easier in our opinion.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 30 Mar 2021; epub ahead of print

Edge to edge repair using a MitraClip for severe tricuspid valve regurgitation after a Mustard operation.

Iriart X, Guérin P, Jalal Z, Thambo JB
A 48-year-old who underwent a Mustard operation in 1972 followed by a second cardiac intervention in 1996 for pulmonary venous baffle enlargement and residual baffle leak closure, complicated by recurrent atrial flutter, was admitted to our institution for severe systemic atrio-ventricular valve regurgitation (SAVVR) associated with severely impaired systemic right ventricular (RV) function. After careful preoperative anatomic assessment including three-dimensional transesophageal echocardiography (3DTEE) to define the clipping strategy and computed tomography to optimize the transvenous baffle puncture site, the intervention was performed under general anesthesia, fluoroscopic, and 3DTEE guidance. One XTR MitraClip was successfully implanted, achieving a significant reduction in regurgitation and immediate clinical improvement. The transbaffle puncture was closed using an 8 mm atrial septal defect (ASD) device without residual shunt or obstruction of the venous baffle. Post-operative clinical evaluation showed immediate improvement in the NYHA functional class (from III to II), but the patient presented with recurrent flutter at 1 week after the procedure, which was successfully treated by catheter ablation with another transbaffle approach next to the ASD device. Clinical improvement was maintained at 1- and 6-month follow-up with significant reduction in SAVVR, reduced systemic RV volumes and improved RV ejection fraction. This case demonstrates the feasibility of percutaneous treatment of systemic SAVV in patients with systemic RV after atrial redirection.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 Mar 2021; epub ahead of print

Timing of Impella implantation and outcomes in cardiogenic shock or high-risk percutaneous coronary revascularization.

Tarantini G, Masiero G, Burzotta F, Pazzanese V, ... Chieffo A, IMPella Mechanical Circulatory Support Device in Italy (IMP-IT) Registry authors
Objective
To evaluate the role of the microaxial percutaneous mechanical circulatory support device (Impella® pump) implantation pre-percutaneous coronary intervention (PCI) versus during/after PCI in cardiogenic shock (CS) and high-risk PCI populations.
Background
A better understanding of the safety and effectiveness of the Impella and the role of timing of this support initiation in specific clinical settings is of utmost clinical relevance.
Methods
A total of 365 patients treated with Impella 2.5/CP in the 17 centers of the IMP-IT Registry were included. Through propensity-score weighting (PSW) analysis, 1-year clinical outcomes were assessed separately in CS and HR-PCI patients, stratified by timing of Impella support.
Results
Pre-procedural insertion was associated with an improvement in 1-year survival in patients with CS due to acute myocardial infarction (AMI) treated with PCI (p = .04 before PSW, p = .009 after PSW) and HR-PCI (p < .01 both before and after PSW). Among patients undergoing HR-PCI, early Impella support was also associated with a lower rate of the composite of mortality, re-hospitalization for heart failure, and need for left-ventricular assist device/heart transplantation at 1-year (p = .04 before PSW, p = .01 after PSW). Furthermore, Impella use during/after PCI was associated with an increased in-hospital life-threatening and severe bleeding among patients with AMI-CS receiving PCI (7 vs. 16%, p = .1) and HR-PCI (1 vs. 9%, p = .02).
Conclusions
Our findings suggested a survival benefit and reduced rates of major bleeding when a pre-PCI Impella implantation instead of during-after procedure was used in the setting of HR-PCI and AMI-CS.

© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 Mar 2021; epub ahead of print

Readmission following urgent transcatheter aortic valve implantation versus urgent balloon aortic valvuloplasty in patients with decompensated heart failure or cardiogenic shock.

Chakraborty S, Patel N, Bandyopadhyay D, Hajra A, ... Abbott JD, Naidu SS
Background
Urgent transcatheter aortic valve implantation (TAVI) is a feasible option for aortic stenosis (AS) patients with decompensated heart failure (HF) and cardiogenic shock (CS) as compared to the more traditional urgent balloon aortic valvuloplasty (BAV).
Objectives
We conducted a retrospective analysis to compare risk and cause of readmission in these two high-risk groups.
Methods
Nationwide Readmission Database (NRD) 2011-2014 was retrospectively analyzed to identify patients with AS having either urgent TAVI or urgent BAV using appropriate ICD-9 codes. Propensity scores were used to match patients with urgent TAVI as compared to patients with urgent BAV. Statistical analysis was performed using the Stata 15.1 software.
Results
We identified a weighted sample of 6,670 patients with urgent BAV and 6,964 patients with urgent TAVI. The all-cause 30- and 90-day readmission was lower in the urgent TAVI group compared to urgent BAV (15.4 vs. 22.5%, (aHR): 0.92 [0.90-0.95] p < .001). 30-day readmission due to CV cause and HF was also lower in the urgent TAVI group (aHR, 0.93: p < .001 and aHR, 0.98: p = .040, respectively). The 30-day gastrointestinal (GI) bleed readmission rate was three times higher in urgent TAVI group (aHR, 3.00:95% CI (1.23-7.33), p = .016), but was not statistically significant at 90-days. Cardiac causes of readmission were the predominant cause of readmission in both groups, but more pronounced in urgent BAV group (60.3 vs. 40.5%, p < .001).
Conclusion
Urgent TAVI appears beneficial in patients with AS and decompensated HF or CS driven by roughly 10 and 25% reductions in overall readmissions at 30 and 90 days, and marked reductions in reintervention, although offset partially by higher risk of readmission due to GI bleeding at 30 days.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 04 Apr 2021; epub ahead of print

The validation of the dual antiplatelet therapy score in East Asians receiving percutaneous coronary intervention with exclusively second generation drug-eluting stents.

Kim M, Park KW, Lee HS, Ki YJ, ... Koo BK, Kim HS
Objectives
We investigated whether the dual antiplatelet therapy (DAPT) score (DS) predicts clinical outcome in an East-Asian population that received exclusively second generation drug-eluting stent (DES).
Backgrounds
It is uncertain whether the DS could adequately risk stratify patients exclusively receiving second generation DES.
Methods
From the Grand-DES registry, we evaluated patients who were treated with DAPT for at least 12 months and were event-free at 12 months after DES implantation. Patients were classified into two categories: high DS (≧2) (n = 3,157); and low DS (<2) (n = 5,226). The primary ischemic outcome was a composite of stent thrombosis and all myocardial infarction (MI), and the primary bleeding outcome was TIMI major or minor bleeding. A propensity score (PS)-matched analysis was done to correct for baseline differences between extended DAPT group and the conventional group.
Results
Among 8,383 subjects, the primary ischemic outcome occurred in 48 patients (0.6%) and the primary bleeding outcome in 49 patients (0.6%). High DS was associated with a higher incidence of ischemic events (ischemic outcome: 0.8% vs. 0.4%, for high vs. low DS, Log-rank p = .039), but not with any differences in bleeding events (Log-rank p = .734). In the PS-matched analysis, extended group was associated with lower risk of composite endpoint of MI, stent thrombosis, or cardiac death in only the high DS group (1.8% vs. 3.7%, Log-rank p = .004; hazard ratio 0.45, 95% confidence interval 0.27-0.76; p = .003 after adjustment).
Conclusions
The DS was an adequate risk stratifier for future ischemic events in East Asians receiving exclusively second generation DES.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 04 Apr 2021; epub ahead of print

Impact of extended dual antiplatelet therapy on long-term prognosis in patients with acute coronary syndrome complicated with anemia: A sub-analysis of the real-world OPT-CAD study.

Zhao Y, Li J, Ma S, Jiang Z, ... Han Y, Li Y
Objectives
To evaluate the impact of extended dual antiplatelet therapy (DAPT) beyond 12 months on long-term prognosis in acute coronary syndrome (ACS) patients complicated with anemia undergoing percutaneous coronary intervention (PCI).
Background
Anemia is frequent among ACS patients and is associated with increased risk of adverse clinical outcomes.
Methods
A total of 6,953 patients were enrolled from the Optimal anti Platelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study. A landmark analysis comparing extended DAPT versus single antiplatelet therapy (SAPT) at 12-24 months were performed in anemia patients without premature discontinuation of DAPT before 9 months and major clinical adverse events within 12 months. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of all-cause death, myocardial infarction, and stroke.
Results
Patients with anemia (n = 1,728) had higher rates of MACCE, all-cause mortality, and BARC type 2, 3, 5 bleeding (p < .05) compared to those without anemia (n = 5,225). Anemia patients received extended DAPT (n = 1,010) were associated with a lower risk of stroke (0.3% vs. 1.8%; HR, 0.14; 95% CI, 0.03-0.71; p = .018) compared to those received SAPT (n = 342). The rates of MACCE and all revascularization were lower in patients with extended DAPT, but the differences were not statistically significant. Risk of all-cause mortality and bleeding were comparable between the two groups.
Conclusions
Extended DAPT beyond 12 months may reduce the incidence of stroke without increasing the risk of bleeding in anemic ACS patients who tolerate 12-month DAPT.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 04 Apr 2021; epub ahead of print

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

van Hemert ND, Rozemeijer R, Voskuil M, Stein M, ... Stella PR, ReCre8 Study Investigators
Objectives
The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics.
Background
The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics.
Methods
In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization.
Results
In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022).
Conclusions
Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 02 Apr 2021; epub ahead of print

Anatomical-functional discordance between quantitative coronary angiography and diastolic pressure ratio during wave-free period.

Nakamura S, Yonetsu T, Hoshino M, Hada M, ... Sasano T, Kakuta T
Objectives
This study sought to determine the predictors of anatomical-functional discordance between quantitative coronary angiography (QCA) derived diameter stenosis (QCA-DS) and diastolic pressure ratio during wave-free period (dPR_WFP ).
Background
The discrepancy between angiographical stenosis and physiological significance is frequently experienced in clinical practice. Although the anatomical-functional discordance between angiography and fractional flow reserve (FFR) has been intensively investigated, that of resting index including dPR_WFP remains to be elucidated.
Methods
In a total of 647 angiographically intermediate lesions with QCA-DS between 30 and 70% in 502 patients, predictors of having QCA-DS >50% and dPR_WFP > 0.89 (QCA-dPR_WFP mismatch), and those of having QCA-DS ≤50% and dPR_WFP ≤ 0.89 (QCA-dPR_WFP reverse mismatch) were determined. FFR ≤0.80 was defined as positive FFR and the predictors of QCA-FFR discordance were determined as well.
Results
QCA-dPR_WFP mismatch and reverse mismatch were observed in 27.5 and 17.6% of cases, respectively. The predictors of mismatch were non-left anterior descending artery (LAD) lesion, large minimal lumen diameter, low baseline heart rate, and high coronary flow reserve (CFR), while those of reverse mismatch were LAD lesion, non-culprit lesion of acute coronary syndrome, long lesion length, low left ventricular ejection fraction, and low CFR and index of microcirculatory resistance. Age, sex, and the culprit vessel of prior myocardial infarction were not significant determinants of QCA-dPR_WFP discordance unlike QCA-FFR discordance derived from the same cohort.
Conclusions
Anatomical-functional discordance between angiography and dPR_WFP was not uncommon. Predictors differed between QCA-dPR_WFP discordance and QCA-FFR discordance.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 01 Apr 2021; epub ahead of print

Use of edge-to-edge percutaneous mitral valve repair for severe mitral regurgitation in cardiogenic shock: A multicenter observational experience (MITRA-SHOCK study).

Falasconi G, Melillo F, Pannone L, Adamo M, ... Montorfano M, Agricola E
Objectives
The aim of this study was to evaluate the impact of edge-to-edge PMVR on short and mid-term clinical outcomes in patients with CS and severe MR.
Background
Severe mitral regurgitation (MR) in the setting of cardiogenic shock (CS) is associated with three times higher risk of 1-year mortality. In refractory CS, edge-to-edge percutaneous mitral valve repair (PMVR) can be a potential therapeutic option.
Methods
We retrospectively included consecutive patients with refractory CS and concomitant severe MR treated with MitraClip® system. CS was defined according to the criteria used in the SHOCK trial and procedural success according to Mitral Valve Academic Research Consortium (MVARC) criteria. The 30-day and 6-month mortality were the primary and secondary endpoints respectively.
Results
Thirty-one patients (median age 73 years [interquartile range, IQR 66-78], 25.8% female), STS mortality score 37.9 [IQR 30.4-42.4]), with CS and concomitant severe MR treated with edge-to-edge PMVR were retrospectively enrolled. Procedural success was 87.1%. Thirty-day and 6-month survival rates were 78.4 and 45.2% respectively. Univariate Cox Regression Model analysis showed that procedural success was a predictor of both 30-day (HR = 0.12, 95% CI 0.03-0.55, p < .01) and 6-month survival (HR = 0.22, 95% CI 0.06-0.84, p = .027).
Conclusions
Edge-to-edge PMVR in patients with CS and concomitant severe MR was associated with good procedural safety and success with acceptable short and mid-term survival rates. It could be considered a bailout option in this setting of patients.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 01 Apr 2021; epub ahead of print

Multicenter and all-comers validation of a score to select patients for manual thrombectomy, the DDTA score.

Cordero A, Cid-Alvarez B, Alegría E, Fernández-Cisnal A, ... Bertomeu-Gonzalez V, Ferreiro JL
Background
Routine manual thrombectomy (MT) is not recommended in primary percutaneous coronary intervention (P-PCI) but it is performed in many procedures. The objective of our study was validating the DDTA score, designed for selecting patients who benefit most from MT.
Methods
Observational and multicenter study of all consecutive patients undergoing P-PCI in five institutions. Results were compared with the design cohort and the performance of the DDTA was analyzed in all patients. Primary end-point of the analyses was TIMI 3 after MT; secondary endpoints were final TIMI 3, no-reflow incidence, in-hospital mortality and in-hospital major cardiovascular events (MACE). In-hospital prognosis was assessed by the Zwolle risk score.
Results
Three hundred forty patients were included in the validation cohort and no differences were observed as compared to the design cohort (618 patients) except for lower use of MT and higher IIb/IIIa inhibitors or drug-eluting stents. The probability of TIMI 3 after MT decreased as delay to P-PCI was higher. If DDTA score, MT was associated to TIMI 3 after MT (OR: 4.11) and final TIMI 3 (OR: 2.44). There was a linear and continuous relationship between DDTA score and all endpoints. DDTA score ≥ 4 was independently associated to lower no-reflow, in-hospital MACE or mortality. The lowest incidence of in-hospital mortality or MACE was in patients who had DDTA score ≥ 4 and Zwolle risk score 0-3.
Conclusions
MT is associated to higher rate of final TIMI3 in patients with the DDTA score ≥ 4. Patients with DDTA score ≥ 4 had lower no-reflow and in-hospital complications.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 07 Apr 2021; epub ahead of print

Incidence and outcomes of acute kidney injury stratified by cardiogenic shock severity.

Padkins M, Breen T, Van Diepen S, Barsness G, Kashani K, Jentzer JC
Background
Acute kidney injury (AKI) is common among patients with cardiogenic shock (CS) and it is independently associated with mortality. We sought to assess the prevalence, severity, and prognosis of AKI as a function of cardiogenic shock severity in unselected Cardiac Intensive Care Unit (CICU) patients.
Methods
We retrospectively reviewed admissions to the Mayo Clinic between 2007 to 2015 and stratified patients by the AKI stage (based on modified Kidney Disease: Improving Global Outcomes criteria) and Society for cardiovascular angiography and interventions (SCAI) shock stage. The association with in-hospital mortality was analyzed using multivariable logistic regression.
Results
We included 9,311 unique patients with a mean age of 67 years and 37% females. SCAI shock stages A, B, C, D, and E were present in 47%, 30%, 15%, 7%, and 1% of patients. The incidence of AKI of any severity was 39% in the CICU and 51% during the hospitalization. Hospital mortality occurred in 8% of all patients, and the risk increased as a function of the rising AKI and SCAI shock stage. Worsening AKI stage was associated with increased adjusted hospital mortality (adjusted OR per AKI stage 1.22, 95% CI 1.10-1.36, p < .001). Higher AKI stages were associated with increased adjusted hospital mortality in SCAI stage A/B (p < .001), but not in SCAI stage C, D, or E (all p > .05).
Conclusions
Higher AKI stages were independently associated with mortality in CICU patients after accounting for shock severity and may add incremental prognostic utility in patients with lower SCAI stages.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 05 Apr 2021; epub ahead of print

End-stage renal disease patients undergoing angioplasty and bypass for critical limb ischemia have worse outcomes compared to non-ESRD patients: Systematic review and meta-analysis.

Dawson DB, Telles-Garcia NA, Atkins JL, Mina GS, ... Virk CS, Dominic PS
Background
End-stage renal disease (ESRD) is associated with increased morbidity and mortality following lower extremity amputation for critical limb ischemia (CLI). Angioplasty and bypass are used in ESRD patients with CLI; however, the treatment of choice remains controversial. We compared the long-term outcomes in patients with CLI undergoing angioplasty or bypass to evaluate the differences between patients with ESRD and those without ESRD.
Methods
Established databases were searched for observational studies comparing outcomes following bypass or angioplasty for CLI in patients with ESRD to those in non-ESRD patients. End points included survival, limb salvage, amputation-free survival (AFS), and primary and secondary patency at 1-year post-procedure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effect model.
Results
We included 20 studies with a total of 24,851 patients. ESRD patients compared to non-ESRD patients with CLI had significantly lower survival post-angioplasty (OR 0.51, 95% CI 0.36-0.72, p < .001) and post-bypass (OR 0.26, 95% CI 0.15-0.45, p < .001). ESRD patients had lower rates of limb salvage post-bypass (OR 0.33, 95% CI 0.21-0.53, p < .001) and post-angioplasty (OR 0.54, 95% CI 0.41-0.70, p < .001). AFS was significantly lower in ESRD patients compared to non-ESRD patients following angioplasty (OR 0.48, 95% CI 0.32-0.71, p < .001) and bypass (OR 0.28, 95% CI 0.16-0.47, p < .001) despite no significant differences in primary patency. ESRD patients had overall worse secondary patency post-angioplasty and/or bypass (OR 0.54, 95% CI 0.32-0.94, p = .03) compared to non-ESRD patients. A meta-analysis of four studies directly comparing survival in ESRD patients with CLI based on whether they underwent angioplasty or bypass showed no difference (OR 0.93, 95% CI 0.64-1.35, p = .69).
Conclusion
ESRD patients have worse survival, limb salvage, and AFS outcomes following angioplasty and bypass for CLI compared to non-ESRD patients. Large randomized controlled trials comparing these two modalities of treatment in this patient population are needed for further clarity.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 05 Apr 2021; epub ahead of print

Percutaneous deep venous arterialization at femoropopliteal segment for unhealed amputated stump ulcer after below the knee amputation.

Ichihashi S, Tamura Y, Maeda S, Kichikawa K
Efficacy of percutaneous deep venous arterialization (pDVA) has been reported for patients with no-option chronic limb threatening ischemia. To date, the procedure has been limited for below the knee/below the ankle occlusive disease. The present report describes the pDVA performed at a femoropopliteal segment for a patient with a stump complication after below the knee amputation. The patient was a 70-year-old male who had a history of endovascular treatment in the right superficial femoral artery (SFA) and below knee amputation 6 years before. He had an unhealed ulcer at the amputated stump for 3 years. Computed tomography angiography demonstrated occluded right SFA, with a stenotic popliteal artery. Revascularization was considered unfeasible due to the absence of run off vessels. In order to improve the perfusion at the ulcer, pDVA was performed at the distal SFA level, bridging SFA and femoral vein using stent grafts. The final angiogram demonstrated the revascularized SFA connecting to popliteal vein with a brisk flow. After pDVA, the stump ulcer improved and the stent grafts were kept patent after 6 months of the procedure. pDVA at the SFA level was technically feasible and could be a useful approach for stump complication after below knee amputation.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 05 Apr 2021; epub ahead of print

Can a self-expanding pediatric stent expand with an artery? Relationship of stent design to vascular biology.

Nia NV, Fishbein GA, Levi DS
Objectives
A large-diameter, intravascular, self-expanding stent system capable of continued expansion during somatic and vascular growth was modeled with finite element analysis (FEA), manufactured and tested in an animal model.
Background
Children can quickly outgrow intravascular stents. If a stent could expand after implantation in arteries this would be ideal for use in pediatric patients.
Methods
Computer-aided design and FEA were used to design and manufacture large-diameter, self-expanding nitinol stents with both high and low chronic outward force (COF). Four distinct stents with similar designs but with variable lengths and strut thicknesses were manufactured. Fourteen of these stents were implanted in the abdominal aortas or iliac arteries of four juvenile swine.
Results
All animals survived without complication to their designated time points of harvest (90 or 180-days), and all stents expanded to greater diameters than the adjacent non-stented artery. Luminal diameter growth was 34-49% and 20-23% for stented and non-stented segments, respectively. Histologic examination revealed variable degrees of the internal elastic lamina and/or medial disruption with a mean injury score ranging from 0.70 ± 0.56 to 1.23 ± 0.21 and low COF stents implanted in smaller arteries having a larger injury score. Inflammatory responses and stenosis formation were minimal and ranged from 0.50 ± 0.71 to 3.00 ± 0.00 and 5.52 ± 1.05% to 14.68 ± 9.12%, respectively. The stent\'s COF did not correlate with vessel expansion or vascular injury.
Conclusions
Self-expanding stents can mirror and even exceed somatic growth. Although longer-term testing is needed, it may be possible to custom tailor self-expanding stents to expand after arterial implantation in pediatric patients.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 05 Apr 2021; epub ahead of print

Changes in surgical revascularization strategy after fractional flow reserve.

Fournier S, Toth GG, De Bruyne B, Kala P, ... Pellicano M, Barbato E
Aims
In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge.
Methods and results
The intended and performed strategy (before and after FFR) were compared. Among 172 patients, 84 with 300 lesions were randomized to the FFR-guided group. The intended strategy was to bypass 236 stenoses:108 with a venous and 128 with an arterial graft. After disclosing FFR, a change in strategy occurred in 64 lesions (21.3%) of 48 (55%) patients. Among 64 lesions for which the intended strategy was medical therapy, 16 (25%) were bypassed after disclosing FFR. The number of procedures with >1 venous graft planned was significantly reduced from 37 to 27 patients (p = .031). The proportion of on-pump surgery was significantly reduced from 71 to 61 patients (p = .006). The rates of clinical events at 1 year were similar between patients with or without at least one change in strategy.
Discussion
FFR-guided CABG is associated with a simplified surgical procedure in 55% of the patients, with similar clinical outcomes.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 09 Apr 2021; epub ahead of print

Long-term outcomes of self-expanding versus balloon-expandable transcatheter aortic valves: Insights from the OBSERVANT study.

Costa G, D\'Errigo P, Rosato S, Valvo R, ... Barbanti M, OBSERVANT Research Group
Objectives
To compare clinical outcomes of balloon-expandable (BE) and self-expanding (SE) transcatheter aortic valves (TAVs) up to 5 years.
Background
To date, no robust, comparative data of BE and SE TAVs at long-term are available.
Methods
We considered a total of 1,440 patients enrolled in the multicenter OBSERVANT study and undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) with either supra-annular SE (n = 830, 57.6%) and intra-annular BE (n = 610, 42.4%) valves. Clinical outcomes of the two groups were compared after adjustment using inverse probability of treatment weighting (IPTW) and confirmed by sensitivity analysis with propensity score matching.
Results
Patients receiving SE valve showed a higher all-cause mortality at 5 years (Kaplan-Meier estimates 52.3% vs. 47.7%; Hazard ratio [HR] 1.18, 95% confidence interval [CI] 1.01-1.38, p = .04). Landmark analyses showed that there was a not statistically significant reversal of risk excess against the BE group starting from 3 years after TAVI (3-5 years HR 0.97, 95% CI 0.76-1.25, p = .86). Post-procedural, moderate/severe paravalvular regurgitation (PVR)(HR 1.46, 95% CI 1.14-1.87; p < .01) and acute kidney injury (AKI)(HR 3.89, 95% CI 2.47-6.38; p < .01) showed to be independent predictors of 5-year all-cause mortality in multivariable analysis.
Conclusions
Considering the intrinsic limitations of the OBSERVANT study, we found that patients undergoing TF-TAVI with a supra-annular SE valve had a higher all-cause mortality compared to those receiving an intra-annular BE valve at 5 years. A late catch up phenomenon of patients receiving the BE valve was observed beyond 3 years. Post-procedural moderate/severe PVR seems to play a crucial role in determining this finding. Comparative studies of new generation devices with longer follow-up are needed to evaluate the benefit of each specific TAV type.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 12 Apr 2021; epub ahead of print

Association of acute kidney injury with outcomes in patients undergoing percutaneous left atrial appendage closure.

Nazir S, Ahuja KR, Ariss RW, Hassanein M, ... Moukarbel GV, Jneid H
Objectives
Using a large nationally representative database, we aimed to examine risk factors for acute kidney injury (AKI) and its association with outcomes in patients undergoing percutaneous left atrial appendage closure (LAAC).
Background
Previous small-scale studies have reported poor outcomes with AKI following percutaneous LAAC.
Methods
We queried the Nationwide Readmission Database to identify LAAC procedures performed from 2016 to 2017. Multivariable logistic and linear regression models were used to identify risk factors for AKI and determine the association between AKI and clinical outcomes. The primary outcome of interest was in-hospital mortality.
Results
Of 20,703 patients who underwent LAAC during the study period, 1,097 (5.3%) had a diagnosis of AKI. Chronic kidney disease, non-elective admission, coagulopathy, weight loss, prior coronary artery disease, heart failure, diabetes mellitus, and anemia were independently associated with an increased risk of AKI after LACC. In patients undergoing LAAC, AKI was associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR], 16.01; 95% CI, 8.48-30.21), stroke/transient ischemic attack (aOR, 2.50; 95% CI, 1.69-3.70), systemic embolization (aOR, 3.78; 95% CI, 1.64-8.70), bleeding/transfusion (aOR, 1.96; 95% CI, 1.50-2.56), vascular complications (aOR, 3.53; 95% CI, 1.94-6.42), pericardial tamponade requiring intervention (aOR, 6.83; 95% CI, 4.37-10.66), index length of stay (adjusted parameter estimate, 7.46; 95% CI, 7.02-7.92), and 180-day all-cause readmissions (aOR, 1.43; 95% CI, 1.09-1.88).
Conclusion
AKI in the setting of LAAC is uncommon but is associated with poor clinical outcomes. Further studies are needed to determine if a similar association exists for long-term outcomes.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 14 Apr 2021; epub ahead of print

A novel technique for postclosure of large-bore sheaths using two Perclose devices.

Choi CH, Hall JK, Malaver D, Applegate RJ, Zhao DXM
Objectives
This study aimed to assess the feasibility, efficacy, and safety of a novel percutaneous postprocedure closure technique for large arterial sheath removal with the use of two Perclose ProGlide (Abbott Vascular Devices, Redwood City, CA) devices.
Background
Postprocedural closing of large-bore arteriotomies using the Perclose system can be difficult given the subsequent inability of the device to capture sufficient wall tissue.
Methods
Our study was a single-center retrospective analysis of 22 consecutive patients who underwent large arteriotomy closure via the postclosure technique with a 12-16-Fr sheath. Efficacy endpoints included successful deployment of the system and hemostasis. Safety endpoints included the incidence of major or minor vascular complications as defined by the Vascular Academic Research Consortium-2 (VARC-2) definitions at 30-day follow-up.
Results
The postclosure technique resulted in 100% technical success rate and no postprocedural bleeding or vascular complications.
Conclusion
Postclosure technique is a safe, highly effective, and feasible percutaneous method to achieve large-bore arteriotomy hemostasis with low rates of major bleeding or vascular complications and favorable early outcome.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 Mar 2021; 97:905-909

Feasibility of transcatheter closure for absent aortic rim in patients with atrial septal defect.

Takaya Y, Akagi T, Nakagawa K, Nakayama R, ... Toh N, Ito H
Objectives
This study aimed to assess the feasibility of transcatheter atrial septal defect (ASD) closure in patients with absent aortic rim.
Background
The indication of transcatheter closure for ASD with absent aortic rim is controversial.
Methods
We enrolled 547 patients with ASD who were scheduled for transcatheter closure. Morphologies of aortic rim were evaluated using transesophageal echocardiography (TEE).
Results
Aortic rim of <5 mm was observed in 396 (72%) patients; 128 (23%) had absent aortic rim of 0 mm, and 268 (49%) had deficient aortic rim of >0 to <5 mm. Patients with absent aortic rim frequently had aortic rim absence at an angle of 0° on TEE and septal malalignment. Of the 128 patients with absent aortic rim, 126 (98%) successfully underwent transcatheter closure, while 2 (2%) failed transcatheter closure due to a large defect with severe septal malalignment. The success rate of transcatheter closure was similar between patients with absent aortic rim and those with deficient aortic rim (98% vs. 99%, p = .45). After the procedure, no patients had erosion or device embolization during a median follow-up of 24 months.
Conclusions
Transcatheter closure was successfully performed without adverse events in patients with absent aortic rim, as well as in those with deficient aortic rim. Our findings can be valuable to determine the indication of transcatheter closure in patients with ASD.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 Mar 2021; 97:859-864

Transradial approach for carotid artery stenting: A position paper from the Italian Society of Interventional Cardiology (SICI-GISE).

Montorsi P, Cortese B, Cernetti C, Lanzellotti D, ... Marchese A, Cremonesi A
Carotid artery stenting (CAS) is a valid and effective alternative to endoatherectomy when performed by experienced operators. The conventional approach used is the transfemoral one, but in the last 10 years a transradial (TR) approach, the standard access for cardiac catheterization, became widely adopted for peripheral vascular interventions, included the extracranial carotids. Preliminary experiences suggest this approach as safe and effective, especially in specific anatomical and clinical settings that have been shown to be associated with high risk of complications from the femoral route. Lacking international guidelines, this document, promoted by the Italian Society of Interventional Cardiology - Gruppo Italiano Studi Emodinamici (SICI-GISE), was drawn-up by a panel of interventional cardiologists with a documented experience on the subject, focusing on the indications, techniques and materials that should be used for this type of intervention and the most recent literature on the subject.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 11 Apr 2021; epub ahead of print

Predictors and potential advantages of PERT and advanced therapy use in acute pulmonary embolism.

Parikh M, Chahine NM, Hammad TA, Tefera L, ... Schilz R, Shishehbor MH
Objectives
We sought to examine predictors of pulmonary embolism response team (PERT) utilization and identify those who could benefit from advanced therapy.
Background
PERT and advanced therapy use remain low. Current risk stratification tools heavily weight age and comorbidities, which may not always correlate with presentation\'s severity.
Methods
We prospectively studied patients with CT-confirmed PE between January 2019 and December 2019 at our hospital. PERT activation was left to the treating physician. Multivariable analyses were utilized to identify predictors of PERT activation and advanced therapy. Using the log odd ratio of each significant predictor of advanced therapy, we created a scoring system and a score of 2 was associated with the highest use. Primary outcomes were 30- and 90-day all-cause mortality, readmission, and major bleed.
Results
Of the 307 patients, PERT was activated in 22.5%. While abnormal vital signs and right ventricular (RV) strain were associated with PERT activation, pulmonary embolism severity index (PESI) was not. Advanced therapy use was significantly higher in the PERT cohort (35% vs 2%). Predictors of advanced therapy use were composite variable (heart rate > 110 or systolic blood pressure < 100 or respiratory rate > 30 or oxygen saturation < 90%) and right-to-left ventricular ratio > 0.9. PERT patients with advanced therapy use, when compared to the no-PERT patients who could have qualified (score of 2), had significantly lower 30- and 90-day mortality and 30-day readmission without difference in major bleed.
Conclusion
PERT has important therapeutic impact, yet no guidelines to direct activation. We recommend a multidisciplinary approach for higher acuity pulmonary embolism cases and physician education regarding PERT and the scope of advanced therapy use.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 11 Apr 2021; epub ahead of print