Left atrial appendage thrombus and cerebrovascular events post-transcatheter aortic valve implantation.

van Wiechen MP, Faure ME, Hokken TW, Ooms JF, ... Budde RPJ, Van Mieghem NM
Aims
To elucidate the frequency and clinical impact of left atrial appendage thrombus (LAAT) in patients set for transcatheter aortic valve implantation (TAVI).
Methods and results
All patients undergoing TAVI between January 2014 and June 2020 with analysable multislice computed tomography (MSCT) for LAAT were included. Baseline and procedural characteristics were collected, pre-procedural MSCT\'s were retrospectively analysed for LAAT presence. The primary endpoint was defined as the cumulative incidence of any cerebrovascular event (stroke or transient ischaemic attack) within the first year after TAVI. A Cox proportional hazards model was used to identify predictors.A total of 1050 cases had analysable MSCT. Median age was 80 [interquartile range (IQR) 74-84], median Society of Thoracic Surgeons\' Predicted Risk Of Mortality (STS-PROM) was 3.4% (IQR 2.3-5.5). Thirty-six percent were on oral anticoagulant therapy for atrial fibrillation (AF). LAAT was present in 48 (4.6%) of cases. Patients with LAAT were at higher operative risk [STS-PROM: 4.9% (2.9-7.1) vs. 3.4% (2.3-5.5), P = 0.01], had worse systolic left ventricular function [EF 52% (35-60) vs. 55% (45-65), P = 0.01] and more permanent pacemakers at baseline (35% vs. 10%, P < 0.01). All patients with LAAT had a history of AF and patients with LAAT were more often on vitamin K antagonist-treatment than patients without LAAT [43/47 (91%) vs. 232/329 (71%), P < 0.01]. LAAT [hazard ratio (HR) 2.94 (1.39-6.22), P < 0.01] and the implantation of more than one valve [HR 4.52 (1.79-11.25), P < 0.01] were independent predictors for cerebrovascular events.
Conclusion
Patients with MSCT-identified LAAT were at higher risk for cerebrovascular events during the first year after TAVI.

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

Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1345-1353

Clinical impact of left atrial appendage filling defects in patients undergoing transcatheter aortic valve implantation.

Okuno T, Lanz J, Stortecky S, Heg D, ... Windecker S, Pilgrim T
Aims
Incidental detection of left atrial appendage (LAA) filling defects is a common finding on multi-detector computed tomography in aortic stenosis patients under evaluation for transcatheter aortic valve implantation (TAVI). We aimed to investigate the incidence of LAA filling defects before TAVI and its impact on clinical outcomes.
Methods and results
In a prospective registry, LAA filling defects were retrospectively evaluated and categorized into one of four sub-types: thrombus-like, heterogeneous, horizontal, and Hounsfield Unit (HU)-run-off. The primary endpoint was the composite of cardiovascular death or disabling stroke up to 1-year follow-up. Among 1621 patients undergoing TAVI between August 2007 and June 2018, LAA filling defects were present in 177 patients (11%), and categorized as thrombus-like in 22 (1.4%), heterogeneous in 37 (2.3%), horizontal in 80 (4.9%), and HU-run-off in 38 (2.4%). Compared to patients with normal LAA filling, patients with LAA filling defects had greater prevalence of atrial fibrillation (84.7% vs. 26.4%, P < 0.001) and history of cerebrovascular events (16.4% vs. 10.9%, P = 0.045). The primary endpoint occurred in 131 patients (9.2%) with normal LAA filling and in 36 patients (21.2%) with LAA filling defects (P < 0.001). Subgroup analysis suggested that the risk of disabling stroke was greatest in the thrombus-like pattern (23.0%), followed by the HU-run-off (8.0%), the heterogeneous (6.2%), and the horizontal pattern (1.2%).
Conclusion
LAA filling defects were observed in 11% of aortic stenosis patients undergoing TAVI and associated with an increased risk of cardiovascular death and disabling stroke up to 1 year following TAVI.
Trial registration
https://www.clinicaltrials.gov. NCT01368250.

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

Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1354-1364

Measurement of compensatory arterial remodelling over time with serial coronary computed tomography angiography and 3D metrics.

van den Hoogen IJ, van Rosendael AR, Lin FY, Gianni U, ... Shaw LJ, Bax JJ
Aims
The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA).
Methods and results
From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281).
Conclusions
Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis.

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

Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1336-1344

Association of coronary artery calcium score with qualitatively and quantitatively assessed adverse plaque on coronary CT angiography in the SCOT-HEART trial.

Osborne-Grinter M, Kwiecinski J, Doris M, McElhinney P, ... Dey D, Williams MC
Aims
Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes is unknown.
Methods and results
In this post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1-9 AU), low (10-99 AU), moderate (100-399 AU), high (400-999 AU), and very high (≥1000 AU). Adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation, and total plaque burden; Autoplaque) assessments. Of 1769 patients, 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high, and 8% very high CACS. Amongst patients with a zero CACS, 14% had non-obstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques, and 13% had low-attenuation plaque burden >4%. Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal, and low CACS (P < 0.001), but there was no statistically significant difference between those with medium, high, and very high CACS. Myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS >1000 AU and low-attenuation plaque burden were the only predictors of myocardial infarction, independent of obstructive disease, and 10-year cardiovascular risk score.
Conclusion
In patients with stable chest pain, zero CACS is associated with a good but not perfect prognosis, and CACS cannot rule out obstructive coronary artery disease, non-obstructive plaque, or adverse plaque phenotypes, including low-attenuation plaque.

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

Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1210-1221

Outcomes after delayed primary percutaneous coronary intervention vs. pharmaco-invasive strategy in ST-segment elevation myocardial infarction in Norway.

Jortveit J, Pripp AH, Halvorsen S
Aims
Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) provided it can be performed within 120 min from diagnosis. However, it is unclear whether pPCI or a pharmaco-invasive (P-I) strategy is the best choice in patients who cannot receive timely pPCI. The aim of the present study was to compare outcomes after delayed and late pPCI vs. a P-I strategy in STEMI patients who did not receive timely pPCI.
Methods and results
All patients with STEMI registered in the Norwegian Myocardial Infarction Registry (NORMI) between 2013 and 2019, with ≤12 h from symptom onset to first medical contact and available timelines were included in the study. The primary outcome was all-cause mortality, and follow-up was through 2019. A total of 21 121 (27% of 78 368) STEMI patients were registered in the NORMI. Among patients who met the inclusion criteria, 7238 (54%) patients underwent timely pPCI, 1537 (11%) delayed pPCI (121-180 min), 1012 (7%) late pPCI (>180 min), and 2338 (17%) patients were treated with a P-I strategy. After a median follow-up time of 2.5 years, mortality was higher in the delayed pPCI [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.5] and in the late pPCI group (adjusted HR 1.4, 95% CI 1.1-1.7) compared to the P-I strategy group, but bleeding complications were more frequent after P-I strategy.
Conclusions
In STEMI patients who did not receive timely percutaneous coronary intervention, a P-I strategy seemed to be associated with better long-term survival compared to delayed/late pPCI.

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

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:442-451

Concerns about the use of digoxin in acute coronary syndromes.

Bugiardini R, Cenko E, Yoon J, van der Schaar M, ... Badimon L, Manfrini O
Aims
The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases.
Methods and results
Of the 25 187 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes Archives (NCT04008173) registry, 4722 (18.7%) received digoxin on hospital admission. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it [33.8% vs. 29.2%; relative risk (RR) ratio: 1.24; 95% confidence interval (CI): 1.12-1.37]. Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio: 1.20; 95% CI: 1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratio: 1.26; 95% CI: 1.10-1.45 in women and RR ratio: 1.21; 95% CI: 1.06-1.39 in men) and those in sinus rhythm at admission (RR ratio: 1.34; 95% CI: 1.15-1.54 in women and RR ratio: 1.26; 95% CI: 1.10-1.45 in men).
Conclusion
Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.

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

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:474-482

Incidence, associated outcomes, and predictors of upper gastrointestinal bleeding following acute myocardial infarction: a SWEDEHEART-based nationwide cohort study.

Sarajlic P, Simonsson M, Jernberg T, Bäck M, Hofmann R
Aims
Of all spontaneous bleeding complications in patients with acute myocardial infarction (MI), upper gastrointestinal bleeding (UGIB) is common and of specific interest since it could be prevented by several prophylactic measures. We aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI.
Methods and results
All patients with acute MI enrolled in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry from January 2007 to June 2016 and discharged alive on any antithrombotic therapy (n = 149 477) were followed regarding UGIB for 1 year. Associated outcomes were determined by Cox proportional hazards regression with UGIB as a time-dependent covariate, adjusting for baseline characteristics, invasive treatment, and medical treatment at discharge. Predictors of UGIB were determined by logistic regression and machine learning models.At 1 year, UGIB had occurred in 2230 patients (cumulative incidence 1.5%) and was significantly associated with an increased risk of all-cause death [hazard ratio (HR) 2.86, 95% confidence interval (CI) 2.58-3.16] and stroke (HR 1.80, 95% CI 1.32-2.45) but not with recurrent MI (HR 1.17, 95% CI 0.97-1.42). The most important predictors of UGIB were haemoglobin, age, systolic blood pressure, blood glucose, smoking status, previous upper gastrointestinal bleeding, and antithrombotic and gastroprotective treatment.
Conclusion
After acute MI, readmission because of UGIB is common and significantly associated with poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified.

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

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:483-491

Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis.

Tavenier AH, Mehran R, Chiarito M, Cao D, ... Sharma SK, Dangas G
Aim
Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI.
Methods and results
PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies.
Conclusion
De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

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

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:492-502

Clinical outcomes of drug-coated balloon in coronary lesions: a real-world, all-comers study.

Pan L, Lu W, Han Z, Pan S, ... Huang Z, Qiu C
Backgrounds
Although drug-eluting stents are the most common interventional devices for patients with coronary disease, drug-coated balloons (DCBs) represent a novel therapeutic alternative in certain scenarios. This prospective, observational all-comers study explored the clinical outcomes of DCB use in patients with coronary lesions.
Methods and results
All patients treated with DCBs were enrolled in this study, including patients with in-stent restenosis (ISR) or de novo lesions. The primary outcome was the target lesion revascularization (TLR) rate at one year. We enrolled 2306 patients with 2660 lesions and performed DCB angioplasty in 399 patients (17.3%) with ISR and 1907 patients (82.7%) with de novo lesions. During follow-up (366 ± 46 days), the TLR rate was lower in the de novo lesion group (1.31%) compared to the ISR group (7.02%) [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.101-0.305, p < 0.001]. Patients with de novo lesions had a lower yearly incidence of MACE compared to ISR patients (2.73 vs. 9.27%, respectively, OR 0.274, 95% CI 0.177-0.424, p < 0.001) and a lower incidence of any revascularization (5.09 vs. 13.03%, OR 0.358, 95% CI 0.251-0.510, p < 0.001). No significant differences between groups were observed in the rates of cardiac death (OR 0.783, 95% CI 0.258-2.371, p = 0.655) or MI (OR 0.696, 95% CI 0.191-2.540, p = 0.573).
Conclusions
DCB angioplasty in this all-comers, real-world, prospective study was safe and efficient with low TLR and MACE rates. Thus, DCB appears to be an attractive alternative for the stent-less treatment of de novo coronary lesions. ISR in-stent restenosis; OR odds ratio; CI confidence interval; TLR target lesion revascularization; MACE major adverse cardiovascular events; MI myocardial infraction. MACE defined as the composite outcome of cardiac death, myocardial infarction, and target vessel revascularization. Any revascularization includes any percutaneous coronary intervention, and coronary artery bypass grafting.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 01 Jul 2022; 111:732-741

Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany.

Stachon P, Kaier K, Hehn P, Peikert A, ... Bode C, von Zur Mühlen C
Background
Recent randomized controlled trials have sparked debate about the optimal treatment of patients suffering from left main coronary artery disease. The present study analyzes outcomes of left main stenting versus coronary bypass grafting (CABG) in a nationwide registry in patients with chronic coronary syndrome (CCS).
Methods
All cases suffering from CCS and left main coronary artery disease treated either with CABG or stent, were identified within the database of the German bureau of statistics. Logistic or linear regression models were used with 20 baseline patient characteristics as potential confounders to compare both regimens.
Results
In 2018, 1318 cases with left main stenosis were treated with CABG and 8,920 with stent. Patients assigned for stenting were older (72.58 ± 9.87 vs. 68.63 ± 9.40, p < 0.001) and at higher operative risk, as assessed by logistic EuroSCORE (8.77 ± 8.45 vs. 4.85 ± 4.65, p < 0.001). After risk adjustment, no marked differences in outcomes were found for in-hospital mortality and stroke (risk adjusted odds ratio (aOR) for stent instead of CABG: aOR mortality: 1.08 [95% CI 0.66; 1.78], p = 0.748; aOR stroke: 0.59 [0.27; 1.32], p = 0.199). Stent implantation was associated with a reduced risk of relevant bleeding (aOR 0.38 [0.24; 0.61], p < 0.001), reduced prolonged ventilation time (aOR 0.54 [0.37 0.79], p = 0.002), and postoperative delirium (aOR 0.16 [0.11; 0.22], p < 0.001). Furthermore, stent implantation was associated with shorter hospital stay (- 6.78 days [- 5.86; - 7.71], p < 0.001) and lower costs (- €10,035 [- €11,500; - €8570], p < 0.001).
Conclusion
Left main stenting is a safe and effective treatment option for CCS-patients suffering from left main coronary artery disease at reasonable economic cost. Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany. All cases with chronic coronary syndrome and left main stenosis treated in 2018 in Germany either with left main stenting or coronary bypass grafting were extracted from a nation-wide database. In-hospital outcomes were compared after logistic regression analysis.

© 2021. The Author(s).

Clin Res Cardiol: 01 Jul 2022; 111:742-749

Pregnancy-related acute myocardial infarction: a review of the recent literature.

Merlo AC, Rosa GM, Porto I
Pregnancy-related acute myocardial infarction is a rare and potentially life-threatening cardiovascular event, the incidence of which is growing due to the heightened prevalence of several risk factors, including increased maternal age. Its main aetiology is spontaneous coronary artery dissection, which particularly occurs in pregnancy and may engender severe clinical scenarios. Therefore, despite frequently atypical and deceptive presentations, early recognition of such a dangerous complication of gestation is paramount. Notwithstanding diagnostic and therapeutic improvements, pregnancy-related acute myocardial infarction often carries unfavourable outcomes, as emergent management is difficult owing to significant limitations in the use of ionising radiation-e.g. during coronary angiography, potentially harmful to the foetus even at low doses. Notably, however, maternal mortality has steadily decreased in recent decades, indicating enhanced awareness and major medical advances in this field. In our paper, we review the recent literature on pregnancy-related acute myocardial infarction and highlight the key points in its management.

© 2021. The Author(s).

Clin Res Cardiol: 01 Jul 2022; 111:723-731

Human coronary microvascular contractile dysfunction associates with viable synthetic smooth muscle cells.

Dora KA, Borysova L, Ye X, Powell C, ... Smart N, Ascione R
Aims
Coronary microvascular smooth muscle cells (SMCs) respond to luminal pressure by developing myogenic tone (MT), a process integral to the regulation of microvascular perfusion. The cellular mechanisms underlying poor myogenic reactivity in patients with heart valve disease are unknown and form the focus of this study.
Methods and results
Intramyocardial coronary micro-arteries (IMCAs) isolated from human and pig right atrial (RA) appendage and left ventricular (LV) biopsies were studied using pressure myography combined with confocal microscopy. All RA- and LV-IMCAs from organ donors and pigs developed circa 25% MT. In contrast, 44% of human RA-IMCAs from 88 patients with heart valve disease had poor (<10%) MT yet retained cell viability and an ability to raise cytoplasmic Ca2+ in response to vasoconstrictor agents. Comparing across human heart chambers and species, we found that based on patient medical history and six tests, the strongest predictor of poor MT in IMCAs was increased expression of the synthetic marker caldesmon relative to the contractile marker SM-myosin heavy chain. In addition, high resolution imaging revealed a distinct layer of longitudinally aligned SMCs between ECs and radial SMCs, and we show poor MT was associated with disruptions in these cellular alignments.
Conclusion
These data demonstrate the first use of atrial and ventricular biopsies from patients and pigs to reveal that impaired coronary MT reflects a switch of viable SMCs towards a synthetic phenotype, rather than a loss of SMC viability. These arteries represent a model for further studies of coronary microvascular contractile dysfunction.

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

Cardiovasc Res: 29 Jun 2022; 118:1978-1992

Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications.

Margaritis M, Saini F, Baranowska-Clarke AA, Parsons S, ... Sheppard MN, Adlam D
Aims 
Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndromes and in rare cases sudden cardiac death (SCD). Connective tissue abnormalities, coronary inflammation, increased coronary vasa vasorum (VV) density, and coronary fibromuscular dysplasia have all been implicated in the pathophysiology of SCAD but have not previously been systematically assessed. We designed a study to investigate the coronary histological and dermal collagen ultrastructural findings in SCAD.
Methods and results
Thirty-six autopsy SCAD cases were compared with 359 SCAD survivors. Coronary and myocardial histology and immunohistochemistry were undertaken. Transmission electron microscopy (TEM) of dermal extracellular matrix (ECM) components of n = 31 SCAD survivors and n = 16 healthy volunteers were compared. Autopsy cases were more likely male (19% vs. 5%; P = 0.0004) with greater proximal left coronary involvement (56% vs. 18%; P < 0.0001) compared to SCAD survivors. N = 24 (66%) of cases showed no myocardial infarction on macro- or microscopic examination consistent with arrhythmogenic death. There was significantly (P < 0.001) higher inflammation in cases with delayed-onset death vs. sudden death and significantly more inflammation surrounding the dissected vs. non-dissected vessel segments. N = 17 (47%) cases showed limited intimal fibro-elastic thickening but no features of fibromuscular dysplasia and no endothelial or internal elastic lamina abnormalities. There were no differences in VV density between SCAD and control cases. TEM revealed no general ultrastructural differences in ECM components or markers of fibroblast metabolic activity.
Conclusions 
Assessment of SCD requires careful exclusion of SCAD, particularly in cases without myocardial necrosis. Peri-coronary inflammation in SCAD is distinct from vasculitides and likely a reaction to, rather than a cause for SCAD. Coronary fibromuscular dysplasia or increased VV density does not appear pathophysiologically important. Dermal connective tissue changes are not common in SCAD survivors.

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

Cardiovasc Res: 22 Jun 2022; 118:1835-1848

Risk predicting for acute coronary syndrome based on machine learning model with kinetic plaque features from serial coronary computed tomography angiography.

Wang Y, Chen H, Sun T, Li A, ... Wang X, Cao F
Aims
More patients with suspected coronary artery disease underwent coronary computed tomography angiography (CCTA) as gatekeeper. However, the prospective relation of plaque features to acute coronary syndrome (ACS) events has not been previously explored.
Methods and results
One hundred and one out of 452 patients with documented ACS event and received more than once CCTA during the past 12 years were recruited. Other 101 patients without ACS event were matched as case control. Baseline, follow-up, and changes of anatomical, compositional, and haemodynamic parameters [e.g. luminal stenosis, plaque volume, necrotic core, calcification, and CCTA-derived fractional flow reserve (CT-FFR)] were analysed by independent CCTA measurement core laboratories. Baseline anatomical, compositional, and haemodynamic parameters of lesions showed no significant difference between the two cohorts (P > 0.05). While the culprit lesions exhibited significant increase of luminal stenosis (10.18 ± 2.26% vs. 3.62 ± 1.41%, P = 0.018), remodelling index (0.15 ± 0.14 vs. 0.09 ± 0.01, P < 0.01), and necrotic core (4.79 ± 1.84% vs. 0.43 ± 1.09%, P = 0.019) while decrease of CT-FFR (-0.05 ± 0.005 vs. -0.01 ± 0.003, P < 0.01) and calcium ratio (-4.28 ± 2.48% vs. 4.48 ± 1.46%, P = 0.004) between follow-up CCTA and baseline scans in comparison to that of non-culprit lesion. The XGBoost model comprising the top five important plaque features revealed higher predictive ability (area under the curve 0.918, 95% confidence interval 0.861-0.968).
Conclusions
Dynamic changes of plaque features are highly relative with subsequent ACS events. The machine learning model of integrating these lesion characteristics (e.g. CT-FFR, necrotic core, remodelling index, plaque volume, and calcium) can improve the ability for predicting risks of ACS events.

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

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:800-810

Aortic enlargement and coronary artery calcification in a general population cohort.

Ballegaard CR, Pham MHC, Sigvardsen PE, Kühl JT, ... Køber LV, Kofoed KF
Aims
The role of atherosclerosis in the pathogenesis of aortic enlargement is uncertain. We aimed to evaluate the relationship between the diameters of the ascending, descending and abdominal aorta, and coronary artery calcification.
Methods and results
Individuals in the Copenhagen General Population Study underwent thoracic and abdominal computed tomography. Maximal aortic diameters were measured in each aortic segment and coronary artery calcium scores (CACS) were calculated. Participants were stratified into five predefined groups according to CACSs and compared to aortic dimensions. The relation between aortic diameter and CACS was adjusted for risk factors for aortic dilatation in a multivariable model. A total of 2678 eligible individuals were included. In all segments of the aorta, aortic diameter was associated to CACSs, with mean increases in aortic diameters ranging from 0.7 to 3.5 mm in individuals with calcified coronary arteries compared to non-calcified subjects (P-value < 0.001). After correction for risk factors, individuals with CACS above 400 had larger ascending, descending and abdominal aortic diameter than the non-calcified reference group (P-value < 0.01).
Conclusion
Enlarged thoracic and abdominal aortic vascular segments are associated with co-existing coronary artery calcification in the general population.

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

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:855-862

Anxa1 in smooth muscle cells protects against acute aortic dissection.

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

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

Cardiovasc Res: 06 May 2022; 118:1564-1582

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

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

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

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:291-301

Impact of HAS-BLED Score on outcome after percutaneous left atrial appendage closure: insights from the German Left Atrial Appendage Occluder Registry LAARGE.

Ledwoch J, Franke J, Brachmann J, Lewalter T, ... Krapivsky A, Sievert H
Aim
Percutaneous left atrial appendage (LAA) closure has been established as alternative stroke prophylaxis in patients with non-valvular atrial fibrillation (AF) and high bleeding risk. However, little is known regarding the outcome after LAA closure depending on the HAS-BLED score.
Methods
A sub-analysis of the prospective, multicenter, Left-Atrium-Appendage Occluder Register-GErmany (LAARGE) registry was performed assessing three different groups with respect to the HAS-BLED score (0-2 [group 1] vs. 3-4 [group 2] vs. 5-7 [group 3]).
Results
A total of 633 patients at 38 centers were enrolled. Of them, 9% (n = 59) were in group 1, 63% (n = 400) in group 2 and 28% (n = 174) in group 3. The Kaplan-Meier estimated 1-year composite of death, stroke and systemic embolism was 3.4% in group 1 vs. 10.4% in group 2 vs. 20.1% in group 3, respectively (p log-rank < 0.001). The difference was driven by death since stroke and systemic embolism did not show a significant difference between the groups. The rate of major bleeding at 1 year was 0% vs. 0% vs. 2.4%, respectively (p = 0.016).
Conclusion
The present data show that patients had similarly low rates of ischemic complications 1 year after LAA closure irrespective of the baseline bleeding risk. Higher HAS-BLED scores were associated with increased mortality due to higher age and more severe comorbidity of these patients.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 01 May 2022; 111:541-547

Safety and feasibility of intravascular ultrasound guided zero-contrast percutaneous coronary intervention-A prospective study.

Nandhakumar V, Pakshirajan B, Chopra A, Anandan H, ... Victor SM, Ajit MS
Background
There are published reports of safety and feasibility of percutaneous coronary intervention (PCI) without contrast, using intravascular ultrasound (IVUS) and coronary physiology guidance in chronic kidney disease population. We prospectively evaluated the safety and feasibility of zero-contrast PCI technique.
Methods
In this prospective study, we hypothesized that PCI is feasible without contrast, using IVUS guidance alone without mandatory coronary physiology to rule out slow-flow or no-flow at the end of PCI in a population at risk of contrast-induced acute kidney injury (CI-AKI). In this study, we included 31 vessels in 27 patients at risk of CI-AKI and assessed the primary outcome of technical success at the end of PCI. Major adverse cardio-cerebro vascular events (MACCE) and percent change in estimated glomerular filtration rate(eGFR) one month after PCI were the secondary outcomes of the study.
Results
The primary outcome was met in 87.1%(n = 27) of the procedures. Technical failure was seen in 12.9%(n = 4) of the procedures. None of the patients developed MACCE at one-month follow-up. The median percent change in eGFR at one-month follow-up was -8.19%(-24.40%, +0.92%). There was no newer initiation of renal replacement therapy at one-month follow-up.
Conclusions
Zero-contrast PCI is safe and feasible in selective coronary anatomies with IVUS guidance. Coronary physiology is not mandatory to rule out slow-flow or no-flow at the end of procedure. Contrast may be needed to tide over the crisis during the possible complications, namely slow-flow, geographical miss and intraprocedural thrombus.

Copyright © 2022 Elsevier B.V. All rights reserved.

Int J Cardiol: 15 Apr 2022; 353:22-28

Remote ischemic preconditioning can extend the tolerance to extended drug-coated balloon inflation time by reducing myocardial damage during percutaneous coronary intervention.

Zhao Z, Shi Q, Guo Q, Peng L, ... Rao L, Li M
Background
Remote ischemic preconditioning (RIPC) alleviates myocardial ischemia-reperfusion injury (IRI) that occurs during percutaneous coronary intervention (PCI) and increases the myocardial tolerance to ischemia and hypoxia. Prolonged inflation time of drug-coated balloons (DCBs) can improve the treatment effects of PCI and the long-term prognosis of patients. This study investigated whether preoperative RIPC improves the tolerance to extended DCB inflation time.
Methods and results
Overall, 345 patients with coronary artery disease (CAD) were enrolled; 90, 96, 83, and 76 of these were randomized into the upper limb RIPC, lower limb RIPC, upper limb control, and lower limb control groups, respectively. Their baseline data were collected. Data on cardiac markers were analyzed. The DCB inflation time was recorded. The baseline data and cardiac marker levels before operation did not differ between RIPC and control groups. The post-PCI high-sensitivity troponin-T levels were lower in the RIPC groups (35.81 ± 14.02 and 34.65 ± 14.86 pg/mL) than in the control groups (41.63 ± 18.31 and 42.24 ± 14.38 pg/mL) (P = 0.001). The DCB inflation tolerance time was higher in the lower limb RIPC group (120 s [120,120]) than in the upper limb RIPC group (120 s [110,120]), and was the lowest in the upper limb control (100 s [90, 120]) and the lower limb control (100 s [90, 115]) groups (P < 0.001).
Conclusions
RIPC reduces the level of myocardial damage that occurs during PCI and prolongs tolerance to increased DCB inflation time. The larger the ischemic area in RIPC, the better the improvement in the tolerance to extended DCB inflation time.

Copyright © 2022. Published by Elsevier B.V.

Int J Cardiol: 15 Apr 2022; 353:3-8

Computed tomography-based selection of transseptal puncture site for percutaneous left atrial appendage closure.

Fukutomi M, Fuchs A, Bieliauskas G, Wong I, ... Søndergaard L, De Backer O
Background
An inferoposterior transseptal puncture (TSP) is generally recommended for percutaneous left atrial appendage (LAA) closure. However, the LAA is a highly variable anatomical structure. This may have an impact on the preferred TSP site.
Aims
This study aimed to determine the optimal TSP site for percutaneous LAA closure in different LAA morphologies.
Methods
In this prospective study, 182 patients undergoing percutaneous LAA closure were included. The spatial relationship of the LAA to the fossa ovalis and its consequence for TSP was assessed at preprocedural cardiac computed tomography (CCT).
Results
Based on CCT analysis, it was predicted that coaxial alignment between the delivery sheath and the LAA would be obtained by an inferoposterior, inferocentral, or inferoanterior TSP in 75%, 16% and 8% of cases, respectively. This was also confirmed by procedural LAA angiogram in 175 cases (96%) with <30° angle between the delivery sheath and the LAA central axis. Multivariate logistic regression analysis identified reverse chicken wing LAA (odds ratio [OR] 6.36 [1.85-29.3]; p=0.005) and posterior bending of the proximal LAA (OR 17.2 [3.3-96.2]; p<0.001) as independent predictors of a central or anterior TSP - this to increase the chance of obtaining coaxial alignment between the delivery sheath and the LAA.
Conclusions
An inferoposterior TSP is recommended in the majority of percutaneous LAA closure procedures in order to obtain coaxial alignment between the delivery sheath and the LAA. An inferior but more central/anterior TSP should be recommended in case of a reverse chicken wing LAA or posterior bending of the proximal LAA, which occurs in 20-25% of cases.



EuroIntervention: 01 Apr 2022; 17:e1435-e1444

Mechanical thrombectomy with retrievable stents and aspiration catheters for acute ischaemic stroke: a meta-analysis of randomised controlled trials.

Rajkumar CA, Ganesananthan S, Ahmad Y, Seligman H, ... Malik I, Shun-Shin MJ
Background
Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke.
Aims
The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and long-term neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke.
Methods
A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis.
Results
Twelve trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (odds ratio [OR] 0.52, 95% credible interval [CrI] 0.46 to 0.61, probability_{(control better)}<0.0001). Furthermore, thrombectomy reduced the odds of functional dependence at 90 days, indicated by an mRS score >2 (OR 0.44, CrI 0.37 to 0.52, p<0.0001). Thrombectomy reduced all-cause mortality at 90 days (16.1% vs 19.2%, OR 0.81, 95% CrI 0.66 to 0.99, p=0.024). The frequency of symptomatic intracranial haemorrhage was similar between thrombectomy (4.2%) and control (4.0%) (OR 1.12, 95% CrI 0.76 to 1.68, p=0.72).
Conclusions
In patients with an acute anterior circulation stroke, modern device thrombectomy significantly reduces death and subsequent disability. The magnitude of these effects suggests that universal access to this treatment strategy should be the standard of care.



EuroIntervention: 01 Apr 2022; 17:e1425-e1434

Unraveling the Multitude of Etiologies in Myocardial Infarction With Nonobstructive Coronary Arteries.

Pustjens TFS, Vranken NPA, Hermanides RS, Rasoul S, Ottervanger JP, Van\'t Hof AWJ
Although recent studies revealed suboptimal outcomes in patients with myocardial infarction with nonobstructive coronary arteries (MINOCAs), the underlying etiology remains unknown in most patients. Therefore, adequate treatment modalities have not yet been established. We aimed to assess demographics, treatment strategies, and long-term clinical outcome in MINOCA subgroups. We retrospectively analyzed data from a large, prospective observational study of patients with acute coronary syndrome admitted to the Isala hospital in Zwolle, The Netherlands between 2006 and 2014. Patients with MINOCA were divided into subgroups based on the underlying cause of the event. From 7,693 patients, 402 patients (5%) concerned MINOCA. After the exclusion of missing cases (n = 47), 5 subgroups were distinguished: \"true\" acute myocardial infarction (10%), perimyocarditis (13%), cardiomyopathy (including Takotsubo cardiomyopathy) (19%), miscellaneous causes (21%), and an indeterminate group (38%). Patients with cardiomyopathy were predominantly women (78%) and showed the highest incidence of major adverse cardiovascular events at 30 days follow-up (7%; p = 0.012), 1 year (19%; p = 0.004), and mortality at long-term follow-up (27%; p = 0.010) compared with any other MINOCA subgroup. The cardiomyopathy group was followed by the indeterminate group, with major adverse cardiovascular events rates of 1% and 5%, respectively, and 17% long-term all-cause mortality. In conclusion, long-term prognosis in MINOCA depends on the underlying etiology. Prognosis is worst in the cardiomyopathy group followed by the indeterminate group. This underlines the importance of revealing the diagnosis to ultimately optimize treatment.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:17-21

Relation of Iron Status to Prognosis After Acute Coronary Syndrome.

Gürgöze MT, Kardys I, Akkerhuis KM, Oemrawsingh RM, ... Manintveld OC, Boersma E
Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:22-30

Early Resolution of New-Onset Left Bundle Branch Block After Transcatheter Aortic Valve Implantation With the SAPIEN 3 Valve.

Isogai T, Dykun I, Agrawal A, Shekhar S, ... Kapadia SR, Puri R
New-onset left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) but can resolve in the post-TAVI period. We sought to examine the incidence, predictors, and outcomes of early resolution of new-onset LBBB among TAVI recipients with a SAPIEN 3 (S3) valve. Among 1,203 S3-TAVI recipients without a pre-existing pacemaker or wide QRS complex at our institution between 2016 and 2019, we identified 143 patients who developed new-onset LBBB during TAVI and divided them according to the resolution or persistence of LBBB by the next day post-TAVI to compare high-degree atrioventricular block (HAVB) and permanent pacemaker (PPM) rates. Patients with resolved LBBB (n = 74, 52%), compared with those with persistent LBBB, were more often women and had a shorter QRS duration at baseline and post-TAVI, with a smaller S3 size and a shallower implantation depth. A multivariable logistic regression model demonstrated significant associations of post-TAVI QRS duration (per 10 ms increase, odds ratio = 0.60 [95% confidence interval = 0.44 to 0.82]) and implantation depth (per 1-mm-depth-increase, 0.77 [0.61 to 0.97]) with a lower likelihood of LBBB resolution. No patient with resolved LBBB developed HAVB within 30 days post-TAVI. Meanwhile, 8 patients (11.6%) with persistent LBBB developed HAVB. The 2-year PPM rate was significantly higher after persistent LBBB than after resolved LBBB (30.3% vs 4.5%, log-rank p <0.001), mainly driven by higher 30-day PPM rate (18.8% vs 0.0%). In conclusion, about half of new-onset LBBBs that occurred during S3-TAVI resolved by the next day post-TAVI without HAVB. In contrast, new-onset persistent LBBB may need follow-up with ambulatory monitoring within 30 days because of the HAVB risk.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:117-127

Effect of Elevated C-Reactive Protein on Outcomes After Complex Percutaneous Coronary Intervention for Angina Pectoris.

Camaj A, Giustino G, Kocovic N, Cao D, ... Sharma SK, Mehran R
Inflammation and procedural complexity are individually associated with adverse outcomes after percutaneous coronary intervention (PCI). We aimed to evaluate the association of high sensitivity C-reactive protein (hsCRP) with adverse events according to PCI complexity. We included patients with available hsCRP levels who underwent PCI at our center from 2012 to 2017. We compared patients with hsCRP ≥3 versus <3 mg/L. Complex PCI was defined as having ≥1 of the following: ≥3 different target vessels, ≥3 lesions treated, ≥3 stents implanted, bifurcation lesion treated with 2 stents, chronic total occlusion as target lesion, or total stent length >60 mm. The primary end point was major adverse cardiac events (MACEs) (composite of all-cause death, myocardial infarction, or target vessel revascularization) at 1 year. A total of 11,979 patients were included, of which 2,840 (24%) underwent complex PCI. In those, 767 (27%) had hsCRP ≥3 mg/L. The 1-year incidence of MACE was 6% (noncomplex PCI, low hsCRP), 10% (noncomplex PCI, high hsCRP), 10% (complex PCI, low hsCRP), and 15% (complex PCI, high hsCRP). Overall, hsCRP ≥3 mg/L was associated with an increased risk of MACE compared with hsCRP <3 mg/L; this was independent of the number of complex PCI features: 0 (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.27 to 1.86), 1 (adjusted HR 1.77; 95% CI 1.21 to 2.60), or ≥2 (adjusted HR 1.21; 95% CI 0.80 to 1.83) (p_interaction = 0.42). In conclusion, in patients who underwent PCI, elevated hsCRP is associated with an increased risk of ischemic events. The effect of elevated hsCRP on cardiovascular risk is consistent regardless of PCI complexity.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:47-54

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

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

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

J Hypertens: 31 Mar 2022; 40:692-698

Single center experience in the treatment of hemodynamically significant diffuse coronary artery disease of the left anterior descending.

van Beek KAJ, van Steenbergen GJ, Vervaat FE, Mulders BCJH, ... van Nunen LX, Wijnbergen IF
Introduction
To date there are no recommendations on how to treat patients with an FFR positive but diffusely diseased left anterior descending coronary artery (LAD). Benefit of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is not so evident due to doubts regarding longevity and patency.
Methods
This retrospective single-center study assessed clinical outcomes in patients presenting with symptomatic single vessel coronary artery disease of a diffusely diseased, hemodynamically significant LAD treated by coronary artery bypass grafting (CABG) or optimal medical therapy (OMT) between 2015 and 2020. Primary outcome of this study was the composite endpoint of all-cause mortality, myocardial infarction and repeat revascularization during 2-year follow-up. Secondary endpoints consisted of the individual components of the primary endpoint. Change in angina severity grade based on the Canadian Cardiovascular Society (CCS) class between baseline and 2-year follow-up was assessed.
Results
Fifty-nine patients were included of which 25 patients underwent CABG and 34 patients were treated by OMT. There was a statistically significant difference in FFR value at baseline between the treatment groups (CABG 0.70 ± 0.04; OMT 0.75 ± 0.04; p < 0.001). After 2-year follow-up, there were no statistically significant differences with regard to the primary endpoint (CABG 16% (n = 4); OMT 17.6% (n = 6); p = 1.00) and secondary endpoints between the groups over 2-year follow-up.
Conclusion
In patients with hemodynamically significant diffuse single vessel coronary artery disease of the left anterior descending, there was no difference between OMT and CABG in terms of mortality, myocardial infarction, revascularization and symptom reduction after two years of follow-up.

Copyright © 2022 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2022; 352:40-44

Physiological and angiographic outcomes of PCI in calcified lesions after rotational atherectomy or intravascular lithotripsy.

Gallinoro E, Monizzi G, Sonck J, Candreva A, ... De Bruyne B, Collet C
Background
Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL.
Methods
Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90.
Results
From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669).
Conclusions
Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL.

Copyright © 2022. Published by Elsevier B.V.

Int J Cardiol: 31 Mar 2022; 352:27-32

Incidence, clinical impact and predictors of thrombocytopenia after transcatheter aortic valve replacement.

Tirado-Conte G, Salazar CH, McInerney A, Cruz-Utrilla A, ... Macaya C, Nombela-Franco L
Background
Thrombocytopenia is a common, yet poorly understood, complication after transcatheter aortic valve replacement (TAVR). Balloon-expandable transcatheter heart valve has been associated with higher incidence of thrombocytopenia, compared with self-expandable valves. The aim of this study was to analyze the incidence, clinical impact and predictors of acquired thrombocytopenia in patients undergoing TAVR.
Methods
We performed an observational study from consecutive patients with severe aortic stenosis undergoing TAVR (n = 679) in a single center. Association and best cut-off point of platelet decrease with early mortality was analyzed. Patients were classified according to postprocedural percentage decrease in platelet count (PDPC), comparing clinical outcomes and analyzing predictors of platelet decrease.
Results
The median PDPC was 37.1 [IQR: 27.4-46.9]. PDPC was associated with early mortality (OR: 2.1, 95%IC: 1.7-2.5 for each 10% decrease, AUC:0.81, 95%CI:0.72-0.89) with an optimal cut-off point of 46%. PDPC≥46% and late nadir (≥4 days) were both independent predictors of early mortality (OR: 6.0 [IQR: 2.4-14.9] and OR: 5.1 [IQR: 2.2-11.6], respectively). The combination of both factors (PDPC≥46% and nadir ≥4 day) was associated with higher 2-year mortality (55.7%) compared to an early significant nadir (PDPC≥46% and nadir <4 day, 28.9%) and non-significant nadir (PDPC<46%, 21.0%), p < 0.001. Independent predictors of PDPC≥46% were baseline platelet count, Portico™, Abbott valve, intraprocedural major vascular complication and residual aortic regurgitation ≥grade 2.
Conclusion
The platelet count decreased almost 40% after TAVR. Late nadir and PDPC≥46% predicted short-term clinical outcomes. Concomitant late and significant platelet decrease was associated with mid-term mortality.

Copyright © 2022 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2022; 352:21-26

Image-based biomechanical modeling for coronary atherosclerotic plaque progression and vulnerability prediction.

Lv R, Wang L, Maehara A, Guo X, ... Stone GW, Tang D
Atherosclerotic plaque progression and rupture play an important role in cardiovascular disease development and the final drastic events such as heart attack and stroke. Medical imaging and image-based computational modeling methods advanced considerably in recent years to quantify plaque morphology and biomechanical conditions and gain a better understanding of plaque evolution and rupture process. This article first briefly reviewed clinical imaging techniques for coronary thin-cap fibroatheroma (TCFA) plaques used in image-based computational modeling. This was followed by a summary of different types of biomechanical models for coronary plaques. Plaque progression and vulnerability prediction studies based on image-based computational modeling were reviewed and compared. Much progress has been made and a reasonable high prediction accuracy has been achieved. However, there are still some inconsistencies in existing literature on the impact of biomechanical and morphological factors on future plaque behavior, and it is very difficult to perform direct comparison analysis as differences like image modality, biomechanical factors selection, predictive models, and progression/vulnerability measures exist among these studies. Encouraging data and model sharing across the research community would partially resolve these differences, and possibly lead to clearer assertive conclusions. In vivo image-based computational modeling could be used as a powerful tool for quantitative assessment of coronary plaque vulnerability for potential clinical applications.

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2022; 352:1-8

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

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

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

Heart: 30 Mar 2022; 108:500-506

Coronary revascularisation outcomes in patients with cancer.

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

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

Heart: 30 Mar 2022; 108:507-516

Challenges of long-term dual antiplatelet therapy use following acute coronary syndromes.

Sidhu MS, Lyubarova R, Bangalore S, Bonaca MP
An acute coronary syndrome (ACS) event is associated with a high risk of recurrent ACS, stroke, and death. To ameliorate the risk of subsequent events, current guidelines for ST-segment elevation myocardial infarction and non-ST-segment elevation ACS recommend long-term management strategies for secondary prevention including risk factor modification and anti-ischemic and antiplatelet therapies. Dual antiplatelet therapy (DAPT), comprising aspirin plus a P2Y₁₂ inhibitor, is a critical component of secondary prevention therapy following ACS. However, despite the importance of DAPT for secondary prevention after ACS, questions remain over the optimal duration of therapy. Clinical evidence is emerging that maintenance DAPT >12 months lowers the risk of recurrent ACS events; however, this benefit must be considered against any potential risks of prolonged DAPT such as bleeding. Several tools for bleeding risk assessment have shown promise; however, their limited accuracy and discriminative power necessitates further development. Assessment of patient ischemic risk should consider the complexity of the percutaneous coronary intervention (PCI) procedure, anatomic burden of coronary artery disease, and additional underlying risk factors. Consequently, identifying patients in whom the risk:benefit ratio favors prolonged DAPT may prove invaluable for clinicians in deciding which patients should continue or stop taking DAPT at 12 months after PCI, or consider P2Y₁₂ inhibitor monotherapy as an option. This article reviews the most recent information about the risks and benefits of DAPT continued for >12 months after ACS and provides critical guidance to assist physicians in identifying patients most likely to benefit from a secondary prevention strategy with DAPT.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:44-64

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

Bagiella E, Puskas JD, Moskowitz AJ, Gelijns AC, ... Mack MJ, Goldstein DJ
Background
Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery.
Methods
The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization.
Conclusions
The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:12-20

Association between race/ethnicity and income on the likelihood of coronary revascularization among postmenopausal women with acute myocardial infarction: Women\'s health initiative study.

Tertulien T, Roberts MB, Eaton CB, Cene CW, ... Nassir R, Breathett K
Background
Historically, race, income, and gender were associated with likelihood of receipt of coronary revascularization for acute myocardial infarction (AMI). Given public health initiatives such as Healthy People 2010, it is unclear whether race and income remain associated with the likelihood of coronary revascularization among women with AMI.
Methods
Using the Women\'s Health Initiative Study, hazards ratio (HR) of revascularization for AMI was compared for Black and Hispanic women vs White women and among women with annual income <$20,000/year vs ≥$20,000/year over median 9.5 years follow-up(1993-2019). Proportional hazards models were adjusted for demographics, comorbidities, and AMI type. Results were stratified by revascularization type: percutaneous coronary intervention and coronary artery bypass grafting(CABG). Trends by race and income were compared pre- and post-2010 using time-varying analysis.
Results
Among 5,284 individuals with AMI (9.5% Black, 2.8% Hispanic, and 87.7% White; 23.2% <$20,000/year), Black race was associated with lower likelihood of receiving revascularization for AMI compared to White race in fully adjusted analyses [HR:0.79(95% Confidence Interval:[CI]0.66,0.95)]. When further stratified by type of revascularization, Black race was associated with lower likelihood of percutaneous coronary intervention for AMI compared to White race [HR:0.72(95% CI:0.59,0.90)] but not for CABG [HR:0.97(95%CI:0.72,1.32)]. Income was associated with lower likelihood of revascularization [HR:0.90(95%CI:0.82,0.99)] for AMI. No differences were observed for other racial/ethnic groups. Time periods (pre/post-2010) were not associated with change in revascularization rates.
Conclusion
Black race and income remain associated with lower likelihood of revascularization among patients presenting with AMI. There is a substantial need to disrupt the mechanisms contributing to race, sex, and income disparities in AMI management.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:82-92

Same day discharge following non-elective PCI for non-ST elevation acute coronary syndromes.

Hariri E, Kassas I, Hammoud MA, Hansra B, ... Smith CS, Barringhaus KG
Background:
and aim
Timing of discharge after percutaneous coronary intervention (PCI) is a crucial aspect of procedural safety and patient turnover. We examined predictors and outcomes of same-day discharge (SDD) after non-elective PCI for non-ST elevation acute coronary syndromes (NSTE-ACS) in comparison with next-day discharge (NDD).
Methods
Baseline demographic, clinical, and procedural data were collected as were in-hospital outcomes and post-PCI length of stay (LOS) for all patients undergoing non-elective PCI for NSTE-ACS between 2011 and 2014 at a central tertiary care center. Thirty day and 1-year mortality and bleeding as well as 30-day readmission rates were determined from social security record and medical chart review. Logistic regression was performed to identify predictors of SDD, and propensity-matched analysis was done to examine the differences in outcomes between NDD and SDD.
Results
Out of 2,529 patients who underwent non-elective PCI for NSTE-ACS from 2011 to 2014, 1,385 met the inclusion criteria (mean age = 63 years; 26% women) and were discharged either the same day of (N = 300) or the day after (N = 1,085) PCI. Thirty-day and one-year mortality and major bleeding rates were similar between the 2 groups. Logistic regression identified male sex, radial access, negative troponin biomarker status, and procedure start time as predictors of SDD. In propensity-matched analyses, there was no difference in 30-day mortality and readmission between SDD and NDD groups.
Conclusions
SDD after non-elective PCI for NSTE-ACS may be a reasonable alternative to NDD for selected low-risk patients with comparable mortality, bleeding, and readmission rates.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:125-135

One-year outcome after percutaneous coronary intervention in nonagenarians: Insights from the J-PCI OUTCOME registry.

Otowa K, Kohsaka S, Sawano M, Matsuura S, ... Nakamura M, Ikari Y
Background
Nonagenarian patients who undergo percutaneous coronary intervention (PCI) are increasing, and a few previous studies have reported their long-term outcomes. However, differences in their long-term outcomes between generations remain unclear. This study aimed to investigate 1-year all-cause and cardiovascular (CV) mortality, and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke) of nonagenarian patients who underwent PCI compared with the other elder patients, using a nationwide registration system.
Methods
The patient-level data registered between January 2017 and December 2017 was extracted from the J-PCI OUTCOME Registry endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT). The one-year all-cause and cardiovascular (CV) mortality, MACE, and major bleeding events were identified.
Results
Out of 40,722 patients over 60 years of age, 880 (2.1%) were nonagenarians. For nonagenarians, the 1-year mortality rate was substantial (13.5%). The MACE and CV death rates were also high (8.1%, and 6.8%, respectively) for nonagenarians, and these event rates were approximately 1.5 times higher in nonagenarians than octogenarians. Multivariate regression analysis showed that presentation with cardiogenic shock [hazard ratio (HR) 2.32; 95 confidence intervals (CI): 1.22-4.41], or cardiac arrest (HR 2.91; 90% CI: 1.28-6.62), and use of oral anticoagulants (HR 2.10; 90% CI: 1.07-4.12) were the predictors of 1-year MACE.
Conclusions
Even in the contemporary era, nonagenarians who have undergone PCI still face a considerably increased risk for adverse cardiovascular events that reduces long-term survival. In addition to having poorer lesion characteristics, adverse events, including death, MACEs, and major bleeding, occurred 1.5 times more frequently in nonagenarians than in octogenarians.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:105-116

Long-term clinical outcomes of everolimus-eluting bioresorbable scaffolds versus everolimus-eluting stents: final five-year results of the AIDA randomised clinical trial.

Kerkmeijer LSM, Renkens MPL, Tijssen RYG, Hofma SH, ... de Winter RJ, Wykrzykowska JJ
Background
Absorb bioresorbable vascular scaffold (BVS)-related events have been reported between 1 and 3 years - the period of active scaffold bioresorption. Data on the performance of the Absorb BVS in daily clinical practice beyond this time point are scarce.
Aims
This report aimed to provide the final five-year clinical follow-up of the Absorb BVS in comparison with the XIENCE everolimus-eluting stent (EES). In addition, we evaluated the effect of prolonged dual antiplatelet therapy (DAPT) administration on events in the scaffold group.
Methods
AIDA was a multicentre, investigator-initiated, non-inferiority trial, in which 1,845 unselected patients with coronary artery disease were randomly assigned to either the Absorb BVS (n=924) or the XIENCE EES (n=921). Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction or target vessel revascularisation, was the primary endpoint. Scaffold thrombosis cases were matched with controls and tested for the effect of prolonged DAPT.
Results
Up to five-year follow-up, there was no difference in TVF between the Absorb BVS (17.7%) and the XIENCE EES (16.1%) (hazard ratio [HR] 1.31, 95% confidence interval [CI]: 0.90-1.41; p=0.302). Definite or probable device thrombosis (DT) occurred in 43 patients (4.8%) in the scaffold group compared to 13 patients (1.5%) in the stent group (HR 3.32, 95% CI: 1.78-6.17; p<0.001). DT between 3 and 4 years occurred six times in the Absorb arm versus three times in the XIENCE arm. Between 4 and 5 years, the incidence was three versus two, respectively. Of those three DT in the scaffold group, two occurred in XIENCE EES-treated lesions. The odds ratio of scaffold thrombosis in patients on DAPT compared to off DAPT throughout five-year follow-up was 0.36 (95% CI: 0.15-0.86).
Conclusions
The excess risk of the Absorb BVS on late adverse events, in particular device thrombosis, in routine PCI continues up to 4 years and seems to plateau afterwards. Clinical
Trial registration:
ClinicalTrials.gov: NCT01858077.



EuroIntervention: 18 Mar 2022; 17:1340-1347

Transcatheter edge-to-edge mitral valve repair in patients with mitral annulus calcification.

Fernández-Peregrina E, Pascual I, Freixa X, Tirado-Conte G, ... Nombela-Franco L, Arzamendi D
Background
MAC is commonly found in patients affected with MR, and it is associated with high morbidity, mortality and worse cardiac surgical outcomes. Transcatheter edge-to-edge repair could be an alternative treatment, although there is little evidence in this population.
Aims
The aim of this study was to analyse the safety, efficacy and durability of MitraClip implantation in patients affected with mitral regurgitation (MR) and mitral annulus calcification (MAC).
Methods
We analysed the outcomes of 61 suitable patients affected with severe MR and moderate or severe MAC (the \"MAC\" group) and 791 patients with no or mild MAC (the \"NoMAC\" group) treated with the MitraClip device.
Results
Procedural success was similar (91.8% vs 95.1%, p=0.268, in MAC and NoMAC, respectively), with a very low rate of complications. At one-year follow-up, 90.6% of MAC and 79.5% of NoMAC patients had MR grade ≤2 (p=0.129), 80% in both groups remained in NYHA Functional Class ≤II, and a significant reduction in cardiac readmissions was observed (65% vs 78% in MAC vs NoMAC, p=0.145). One-year mortality tended to be higher in MAC patients (19.7% vs 11.3%, p=0.050), with no difference in cardiovascular mortality (15.3% vs 9.2%, p=0.129).
Conclusions
MitraClip use in selected patients with moderate or severe MAC is safe, feasible and achieves good clinical and echocardiographic results at one-year follow-up.



EuroIntervention: 18 Mar 2022; 17:1300-1309

Prevalence, predictors, and outcomes of in-stent restenosis with calcified nodules.

Tada T, Miura K, Ikuta A, Ohya M, ... Fuku Y, Kadota K
Background
Calcified nodules (CN) have been reported as being associated with stent failure including in-stent restenosis (ISR). However, there is no systematic study of this condition.
Aims
We aimed to clarify the prevalence, predictors, and midterm results of ISR lesions with CN.
Methods
We examined the clinical characteristics of 651 ISR lesions in patients who underwent percutaneous coronary intervention (PCI) with optical coherence tomography (OCT) between October 2008 and July 2016, and their 6- to 8-month follow-up angiography results. CN was defined as a high backscattering mass with small nodular calcium depositions which protruded into the vessel lumen.
Results
Thirty-two ISR lesions (4.9%) had CN. Multivariable analysis showed that calcified lesion (odds ratio [OR] 12.441, p<0.001), incomplete stent apposition (OR 3.228, p=0.005), haemodialysis (OR 3.633, p=0.024), and female gender (OR 3.212, p=0.036) were independently associated with ISR lesions with CN. Midterm follow-up was performed on 612 ISR lesions. Both ISR and target lesion revascularisation (TLR) rates were significantly higher in lesions with CN compared with those without CN (43.8% vs 25.0%, p=0.023; 37.5% vs 18.8%, p=0.020, respectively). However, multivariate analysis did not show the presence of CN as an independent predictor of re-TLR (OR 1.690, p=0.286).
Conclusions
The prevalence of ISR lesions with CN was 4.9%. Calcified lesions, incomplete stent apposition, haemodialysis, and female gender are probably associated with CN formation. ISR lesions with CN may have poor midterm outcomes compared with ISR lesions without CN.



EuroIntervention: 18 Mar 2022; 17:1352-1361

Temporal trends in clinical outcomes after percutaneous coronary intervention: a systematic review of 66,327 patients from 25 all-comers trials.

Asano T, Ono M, Dai Z, Saito A, ... Yoneoka D, Komiyama N
Background
With the improvements of percutaneous coronary intervention (PCI) technology and post-PCI patient management, several registry studies reported temporal trends in post-PCI clinical outcomes. However, their results are inconclusive, potentially reflecting region-specific trends, based on site-reported events without external validity.
Aims
This study aimed to investigate temporal trends in post-PCI clinical outcomes in all-comers randomised controlled trials (RCTs) involving coronary stents.
Methods
We performed a systematic review identifying RCTs comparing a clinical outcome as a primary endpoint among different coronary stents with an all-comers design and independent clinical event adjudication, extracting the study start year, patient baseline characteristics, and one- and five-year clinical outcomes. Temporal trends in clinical outcomes (cardiac death, myocardial infarction [MI], target lesion revascularisation [TLR], stent thrombosis [ST]) were assessed using random-effects meta-regression analyses, estimating the relationship between clinical outcomes and study start year.
Results
Overall, 25 all-comers trials (51 device arms, 66,327 patients) conducted between 2003 and 2018 fulfilled the eligibility criteria. Random-effects meta-regression analysis revealed significant decreasing trends in one- and five-year cardiac death, one-year TLR, and five-year ST incidences (relative risk per 10-year increase: 0.69 [0.51-0.92], 0.66 [0.44-0.98], 0.60 [0.41-0.88], and 0.18 [0.07-0.44], respectively). There was no significant trend in myocardial infarction incidences.
Conclusions
This is the first attempt to clarify and quantify the temporal trends of post-PCI outcome incidence. The 15-year improvements in PCI therapy and post-therapeutic patient management are associated with reduced incidences of cardiac death and PCI-related adverse events.



EuroIntervention: 18 Mar 2022; 17:1318-1329

Clinical outcomes of transcatheter aortic valve implantation in patients younger than 70 years rejected for surgery: the AMTRAC registry.

Witberg G, Landes U, Codner P, Barbanti M, ... Finkelstein A, Kornowski R
Background
The mean age of transcatheter aortic valve implantation (TAVI) patients is steadily decreasing.
Aims
The aim of the study was to describe the characteristics, the indications for and the outcomes of TAVI in patients <70 years old.
Methods
All patients undergoing TAVI (n=8,626) from the 18 participating centres between January 2007 and June 2020 were stratified by age (</>70). For patients <70, the indications for TAVI were extracted from Heart Team discussions and the baseline characteristics and mortality were compared between the two groups.
Results
Overall, 640 (7.4%) patients were <70 (9.1% during 2018-2020, p<0.001); the mean age was 65.0±2.3 years. The younger patients were more often male, with bicuspid valves or needing valve-in-valve procedures. They had a higher prevalence of lung disease and diabetes. In 80.7% of cases, the Heart Team estimated an increased surgical risk and TAVI was selected, reflected by an STS score >4% in 20.4%. Five-year mortality was similar (29.4 vs 29.8%, HR 0.95, p=0.432) in the <70 and >70 groups. In the <70 group, mortality was higher for those referred for TAVI due to an increased surgical risk compared to those referred for other reasons (31.6 vs 24.5%, HR 1.23, p=0.021). Mortality was similar regardless of the STS stratum in patients judged by the Heart Team to be at increased surgical risk (32.6 vs 30.4%, HR 0.98, p=0.715).
Conclusions
Use of TAVI in patients <70 is becoming more frequent. The main reason for choosing TAVI is due to an increased surgical risk not adequately represented by the STS score. The outcomes for these patients are similar to those for older TAVI patients. Dedicated trials of TAVI/SAVR in younger patients are needed to guide decisions concerning expansion of TAVI indications. ((ClinicalTrials.gov: NCT04031274).



EuroIntervention: 18 Mar 2022; 17:1289-1297

Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study.

Dangas G, Baber U, Sharma S, Giustino G, ... Gibson CM, Mehran R
Background
In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Aims
The aim of this study was to evaluate the effects of ticagrelor monotherapy after three-month DAPT in patients undergoing PCI, according to DES type.
Methods
In the current sub-analysis from TWILIGHT, patients were stratified into three groups based on DES type: durable polymer everolimus-eluting stents (DP-EES), durable polymer zotarolimus-eluting stents (DP-ZES), and biodegradable polymer DES (BP-DES). Bleeding and ischaemic outcomes were assessed at one year after randomisation.
Results
Out of 5,769 patients, 3,014 (52.2%) had DP-EES, 1,350 (23.4%) had DP-ZES and 1,405 (24.4%) had BP-DES. Compared with ticagrelor plus aspirin, ticagrelor monotherapy had significantly lower BARC type 2, 3 or 5 bleeding compared with DAPT; DP-EES (3.8% vs 6.7%; HR 0.56, 95% CI: 0.41-0.78), DP-ZES (4.6% vs 6.9%; HR 0.66, 95% CI: 0.42-1.04) and BP-DES (4.2% vs 7.9%; HR 0.52, 95% CI: 0.33-0.81; p_interaction=0.76). Ticagrelor monotherapy resulted in similar rates of death, MI, or stroke: DP-EES (4.2% vs 4.3%; HR 0.97; 95% CI: 0.68-1.37); DP-ZES (4.1% vs 3.1%; HR 1.32; 95% CI: 0.75-2.33); BP-DES (3.9% vs 4.2%; HR 0.92; 95% CI: 0.54-1.55; p_interaction=0.60). In both unadjusted and covariate-adjusted analyses, DES type was not associated with any differences in ischaemic or bleeding complications.
Conclusions
As compared with ticagrelor plus aspirin, ticagrelor monotherapy after a short DAPT duration lowered bleeding complications without increasing the ischaemic risk, irrespective of DES type. We observed no significant differences among DES types.



EuroIntervention: 18 Mar 2022; 17:1330-1339

A new fastening system for temporary pacing with active-fixation leads: effectiveness and safety.

Vicente-Miralles R, Martín-Langerwerf DA, Núñez-Martínez JM, Marco-Juan A, ... Gil-Guillén VF, Bertomeu-Gonzalez V
Aims
Temporary cardiac pacing with active-fixation leads (TPAFL) using a reusable permanent pacemaker generator has been shown to be safer than lead systems without fixation. However, TPAFL requires the off-label use of pacemaker leads and generators. We designed a fastening system to ensure the safety and efficacy of the procedure: the KronoSafe System®. To demonstrate the safety and effectiveness of the KronoSafe System® for temporary pacing in a series of patients receiving TPAFL.
Methods and results
A prospective cohort of 20 patients undergoing TPAFL between August 2019 and June 2020 was recruited in a Spanish region. The temporary pacemaker was implanted through jugular access and secured with the KronoSafe System®. R-wave detection, lead impedance, and capture threshold were assessed every 48 h. Complications associated with the procedure or occurring during TPAFL were recorded. There were no complications associated with temporary pacing, and the therapy was effective in all cases. TPAFL was used for a mean of 7.6 days (maximum 25 days), and 84.56% of the time in a cardiology ward.
Conclusion
TPAFL secured using the KronoSafe system® provides safe and stable cardiac stimulation for patients requiring temporary cardiac pacing.

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

Eur Heart J Acute Cardiovasc Care: 16 Mar 2022; 11:224-229

Clinical outcomes of no stenting in patients with ST-segment elevation myocardial infarction undergoing deferred primary percutaneous coronary intervention.

Madsen JM, Kelbæk H, Nepper-Christensen L, Jacobsen MR, ... Engstrøm T, Lønborg JT
Background
ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted.
Aims
The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting.
Methods
Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR).
Results
Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting group, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rate of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively.
Conclusions
Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.



EuroIntervention: 15 Mar 2022; epub ahead of print

Association between obesity grade and the age of the first acute coronary syndrome: Prospective observational study.

Demirci D, Demirci DE, Chi G
Background
The study evaluates how obesity grade is associated with age during the first acute coronary syndrome (ACS) and examines the effect of cardiovascular (CV) risk factors and the age of first ACS in patients with severe obesity.
Methods
We enrolled consecutive patients diagnosed with first episode of ACS between 2014 and 2019, and categorized them by body mass indices (BMI). Severe obesity was defined as BMI ≥35 kg/m². Independent variables affecting the age of first ACS were examined by linear regression analysis.
Results
A total of 1005 patients (mean age, 57.5 ± 12.3 years; 19.3% female) were included. Approximately 6% and 12% of obese patients and normal weight patients had no other risk factors. Patients with ACS with severe obesity were younger than those with ACS in the grade-I obesity, overweight, and normal-weight groups (52.8 ± 9.9 vs. 55.3 ± 10.9, 56.8 ± 11.4, and 61.4 ± 14.2, respectively, p < 0.001). BMI had a strong, inverse linear relationship with earlier age of first ACS. The number of patients with no risk factors was significantly high in normal-weight individuals compared with patients with severe obesity (11.6% vs 5.6%, p = 0.037). After adjusting for CV risk factors, patients with overweight, grade-I obesity, and severe obesity may experience first ACS sooner than those with normal-weight by 3.9, 6.1, and 7.7 years, respectively (p < 0.001). However, males and females with severe obesity without CV risk factors experienced the first ACS episode 16 and 22 years later than those with the highest number of risk factors, respectively.
Conclusion
Patients with severe obesity experience first ACS episode 7.7 years earlier than those with normal-weight. Absence of CV risk factors in people with obesity can improve the potential negative effect of obesity on the ACS age.
Trial registration
NCT04578964, 08 October 2020.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Mar 2022; 351:93-99

Optimal low-density lipoprotein cholesterol target level in Korean acute myocardial infarction patients (<70 mg/dL vs. <55 mg/dL): Based on Korea acute myocardial infarction registry-National Institute of Health.

Ahn JH, Ahn Y, Jeong MH, Kim JH, ... Hur SH, Oh SK
Background
Current treatment guidelines for acute myocardial infarction (AMI) recommend lowering low density lipoprotein cholesterol (LDL-C). However, previous clinical studies among East Asian AMI patients failed to prove its clinical efficacy of lipid lowering therapy based on Western target LDL-C level. Thus, the purpose of this study is directly to compare the clinical outcomes of target LDL-C < 70 mg/dL and < 55 mg/dL and identify optimal target LDL-C level and in Korean AMI patients.
Methods and results
A total of 2198 AMI patients in Korea AMI Registry - National Institute of Health were enrolled. Patients were initially divided into LDL-C non-target group (n = 1115) and target group (n = 1083). Successful achievement of follow up target LDL-C was defined as <70 mg/dL and ≥ 50% reduction from baseline. Target group patients were additionally divided to <70 mg/dL group (n = 698) and <55 mg/dL group (n = 385). Propensity score matching analysis was done in non-target vs. target group and <70 mg/dL vs. <55 mg/dL group. In the matched population, the risk of 3 years major adverse cardiac event (MACE) (13.0% vs 9.8%, HR: 0.73; 95% CI: 0.56-0.96; p = 0.025) was higher in non-target group patients. However, the risk of MACE was similar in <70 mg/dL and < 55 mg/dL group patients (10.0% vs 8.1%, HR: 0.75, 95% CI: 0.46-1.22; p = 0.247).
Conclusion
In the present study, target LDL-C level of <70 mg/dL and ≥ 50% reduction from baseline level was associated with better clinical outcomes in Korean AMI patients. However, further lowering target LDL-C level of <55 mg/dL showed no additional benefits.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Mar 2022; 351:15-22

Early angiography in elderly patients with non-ST-segment elevation acute coronary syndrome: The cardio CHUS-HUSJ registry.

González Ferrero T, Álvarez Álvarez B, Cordero A, Martinón Martínez J, ... Gude Sampedro F, González Juanatey JR
Background
In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure.
Methods
This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS.
Results
Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)].
Concusions
In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up.
Brief summary
In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Mar 2022; 351:8-14