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

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

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

J Am Coll Cardiol: 04 Oct 2021; 78:1407-1417

Assessing Microvascular Dysfunction in Angina With Unobstructed Coronary Arteries: JACC Review Topic of the Week.

Jansen TPJ, Konst RE, Elias-Smale SE, van den Oord SC, ... van Royen N, Damman P
Coronary microvascular dysfunction is a highly prevalent condition of both structural and functional coronary disorders in patients with angina and nonobstructive coronary artery disease (ANOCA). Current diagnostic modalities to assess microvascular function are related to prognosis, but these modalities have several technical shortcomings and lack the opportunity to determine true coronary blood flow and microvascular resistance. Intracoronary continuous thermodilution assessment of absolute coronary flow (Q) and microvascular resistance (R) was recently shown to be safe and feasible in ANOCA. Further exploration and implementation could lead to a better understanding and treatment of patients with ANOCA. This review discuss the coronary pathophysiology of microvascular dysfunction, provides an overview of noninvasive and invasive diagnostics, and focuses on the novel continuous thermodilution method. Finally, how these measurements of absolute Q and R could be integrated and how this would affect future clinical care are discussed.

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

J Am Coll Cardiol: 04 Oct 2021; 78:1471-1479

Coronary Microvascular Dysfunction Across the Spectrum of Cardiovascular Diseases: JACC State-of-the-Art Review.

Del Buono MG, Montone RA, Camilli M, Carbone S, ... Niccoli G, Crea F
Coronary microvascular dysfunction (CMD) encompasses several pathogenetic mechanisms involving coronary microcirculation and plays a major role in determining myocardial ischemia in patients with angina without obstructive coronary artery disease, as well as in several other conditions, including obstructive coronary artery disease, nonischemic cardiomyopathies, takotsubo syndrome, and heart failure, especially the phenotype associated with preserved ejection fraction. Unfortunately, despite the identified pathophysiological and prognostic role of CMD in several conditions, to date, there is no specific treatment for CMD. Due to the emerging role of CMD as common denominator in different clinical phenotypes, additional research in this area is warranted to provide personalized treatments in this \"garden variety\" of patients. The purpose of this review is to describe the pathophysiological mechanisms of CMD and its mechanistic and prognostic role across different cardiovascular diseases. We will also discuss diagnostic modalities and the potential therapeutic strategies resulting from recent clinical studies.

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

J Am Coll Cardiol: 27 Sep 2021; 78:1352-1371

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

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

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

Eur Heart J: 06 Oct 2021; epub ahead of print

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

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

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

Eur Heart J: 30 Sep 2021; 42:3844-3852

Bridging Antiplatelet Therapy After Percutaneous Coronary Intervention: JACC Review Topic of the Week.

Sullivan AE, Nanna MG, Wang TY, Bhatt DL, ... Rao SV, Ohman EM
Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal antiplatelet strategy in patients who cannot discontinue dual antiplatelet therapy (DAPT) before surgery is unclear. Current guidelines, based on surgical and clinical characteristics, provide risk stratification for bridging therapy with intravenous antiplatelet agents, but management is guided primarily by expert opinion. This review summarizes perioperative risk factors to consider before discontinuing DAPT and reviews the data for intravenous bridging therapies. Published reports have included bridging options such as small molecule glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) and cangrelor, an intravenous P2Y₁₂ inhibitor. However, optimal management of these complex patients remains unclear in the absence of randomized controlled data, without which an argument can be made both for and against the use of perioperative intravenous bridging therapy after discontinuing oral P2Y₁₂ inhibitors. Multidisciplinary risk assessment remains a critical component of perioperative care.

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

J Am Coll Cardiol: 11 Oct 2021; 78:1550-1563

Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function: JACC Technology Corner.

De Bruyne B, Pijls NHJ, Gallinoro E, Candreva A, ... Collet C, Fearon WF
The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10 mL/min (rest) and 20 mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r = 0.88; 95% confidence interval: 0.72-0.93; P < 0.001). MRR was independent from the epicardial resistance, the lower the FFR value, the greater the difference between MRR and CFR. Therefore, MRR is proposed as a specific, quantitative, and operator-independent metric to quantify coronary microvascular dysfunction.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 11 Oct 2021; 78:1541-1549

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

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

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

Eur Heart J: 17 Oct 2021; epub ahead of print

Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial.

Kim CJ, Park MW, Kim MC, Choo EH, ... Chang K, TALOS-AMI investigators
Background
In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.
Methods
In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.
Findings
From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (p_{non-inferiority}<0·001; HR 0·55 [95% CI 0·40-0·76], p_superiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42-1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35-0·77, p=0·0012).
Interpretation
In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.
Funding
ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 08 Oct 2021; 398:1305-1316

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

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



Circulation: 04 Oct 2021; 144:1120-1129

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

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



Circulation: 11 Oct 2021; 144:1196-1211

Prognostication of Asymptomatic Penetrating Aortic Ulcers: A Modern Approach.

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



Circulation: 04 Oct 2021; 144:1091-1101

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

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



Circulation: 27 Sep 2021; 144:1024-1038

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

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

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

BMJ: 28 Sep 2021; 374:n2106

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

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

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

Heart: 29 Sep 2021; 107:1398-1406

MRI and CT coronary angiography in survivors of COVID-19.

Singh T, Kite TA, Joshi SS, Spath NB, ... Dweck M, McCann GP
Objectives
To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.
Methods
In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis.
Results
In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15.29%) were admitted to intensive care and a fifth (n=11.21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8.35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms.
Conclusions
Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities.
Trial registration number
NCT04625075.

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

Heart: 05 Oct 2021; epub ahead of print

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

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

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

Heart: 21 Oct 2021; epub ahead of print

Trends, Predictors and In-Hospital Outcomes of the Next Day Discharge Approach After Transcatheter Mitral Valve Repair.

Grant JK, Vincent L, Ebner B, Singh H, ... Braghiroli J, De Marchena E
Early discharge strategies are associated with lower cost and resource utilization during hospitalization, as such we sought to evaluate trends, predictors and outcomes of the next day discharge (NDD) approach after transcatheter mitral valve repair (TMVR) procedures with the MitraClip device. The National Inpatient Sample (NIS) was queried between 2013 and 2018 for patients undergoing TMVR using the International Classification of Diseases (ICD) 9 procedure code \'3597\' and ICD-10 procedure code \'02UG3JZ\'. Patients undergoing TMVR were stratified into two groups, determined by hospital length of stay (LOS) [≤1 day, NDD versus >1-day, non-NDD]. Overall, 22,035 patients underwent TMVR with 35.7% (n  = 7,870) belonging to the NDD group (mean age 78.1 ± 9.7 years, women 45%). From 2013 to 2018, the proportion of patients being discharged using the NDD approach trended upward from 18.3% to 46.0%. Amongst demographic and social factors, female sex, black race, and low median household income were predictive of non-NDD (p <0.05 for all). Amongst clinical factors, anemia, iron deficiency anemia, major depressive disorder, thrombocytopenia, obesity and end stage renal disease were some predictors of non-NDD (p <0.05 for all). In the non-NDD group there was a downward trend of pooled post-procedure complications, post procedure cardiogenic shock, vascular complications, acute kidney injury, mechanical circulatory support use, acute respiratory distress and postoperative ischemic stroke and (p for trend <0.001 for all). Despite the overall downward trend, complications began increasing in 2017-18. In conclusion, these trends may reflect improving operator experience, advancement in vascular access device closures and techniques, and prioritization of decreasing length of stay. Ideally, the feasibility and safety of this approach should be confirmed in larger-sized multicenter, randomized trials.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:93-100

Risk Markers for Limited Coronary Artery Calcium in Persons With Significant Aortic Valve Calcium (From the Multi-ethnic Study of Atherosclerosis).

Razavi AC, Cardoso R, Dzaye O, Budoff M, ... Blaha MJ, Whelton SP
The early stages of aortic valve calcification (AVC) and coronary artery calcification (CAC) include shared ASCVD risk factors, yet there is considerable heterogeneity between the burden of AVC, and CAC. We sought to identify the markers associated with limited CAC among persons with significant AVC. There were 325 participants from the Multi-Ethnic Study of Atherosclerosis without clinical ASCVD and with AVC ≥100 Agatston units (AU) at Visit 1. Multivariable-adjusted prevalence ratios for limited CAC (0 to 99 AU) were calculated using modified Poisson regression. Participants had a mean age of 72.1 years, median AVC score of 209, and 34% were women. A total of 133 (41%) participants had CAC <100, of whom 46/133 had CAC = 0. Younger age (PR = 1.40, 95% CI: 1.22 to 1.62, per 10-years), female gender (PR = 1.68, 95% CI: 1.28 to 2.20), and low 10-year ASCVD risk (PR = 2.30, 95% CI: 1.85 to 2.85) were most strongly associated with limited CAC. Neither a normal lipoprotein(a) nor normal measures of inflammation were significantly associated with limited CAC. Lower serum phosphate (PR = 1.15, 95% CI: 1.01 to 1.31; per 0.5 mg/dl lower) and calcium-phosphate product (PR = 1.16, 95% CI: 1.02 to 1.34; per SD lower) were associated with an approximately 15% higher prevalence of limited CAC. In conclusion, more than 40% of persons with significant AVC had CAC. Beyond traditional risk factors, lower serum phosphate, and lower calcium-phosphate product were associated with a higher prevalence of limited CAC.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:58-64

Cost-effectiveness of Radial Access Percutaneous Coronary Intervention in Acute Coronary Syndrome.

Lee P, Liew D, Brennan A, Stub D, ... Reid CM, Zomer E
Clinical trials have shown that radial access percutaneous coronary intervention (PCI) is associated with improved patient outcomes compared to femoral artery access. However, few studies have evaluated the cost-effectiveness of radial access PCI. This analysis sought to evaluate the cost-effectiveness of transradial versus transfemoral access PCI for patients with acute coronary syndrome (ACS) using data from the Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) trial. A decision analytic Markov model was constructed from an Australian health care perspective with a 2 year time horizon. The model simulated recurrent cardiovascular disease and death post PCI among a hypothetical cohort of 1000 individuals with ACS. Population and efficacy data were based on the MATRIX trial. Cost and utility data were drawn from published sources. Over a 2-year time horizon, radial access was predicted to save 12 (discounted) quality adjusted life years (QALYs) compared with femoral access PCI. Cost savings (discounted) amounted to AUD $51,305. Hence from a health economic point of view, radial access PCI was dominant over femoral access PCI. Sensitivity analyses supported the robustness of these findings. Radial access PCI is likely to be associated with both better outcomes and lower costs compared to femoral access PCI over 2 years post procedure. In conclusion, these findings support radial access being the preferred approach in PCI for ACS.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:44-51

Comparison of Outcomes of Patients With Versus Without Chronic Liver Disease Undergoing Percutaneous Coronary Intervention.

Istanbuly S, Matetic A, Mohamed MO, Panaich S, ... Alkhouli M, Mamas MA
There are limited data on the outcomes of chronic liver disease (CLD) patients admitted for percutaneous coronary intervention (PCI). All PCI hospitalizations from the Nationwide Inpatient Sample (2004 to 2015) were analyzed and stratified by the presence, cause and severity of CLD, as well as the indication for PCI. Multivariable logistic regression analysis was performed to determine the adjusted odds ratios (aOR) of in-hospital adverse outcomes in patients with CLD compared with those without CLD. Among 7,296,679 PCI admissions, 54,368 (0.7%) had a CLD diagnosis. Among patients with CLD, 36,853 (67.8%) had severe CLD. Patients with CLD had higher likelihood of adverse outcomes including major adverse cardiovascular and cerebrovascular events (MACCE) (aOR 1.25, 95%CI 1.20 to 1.30), mortality (aOR 1.43, 95%CI 1.35 to 1.51), major bleeding (aOR 2.22, 95%CI 2.12 to 2.32). When accounting for severity, only severe CLD subgroup was more likely to have MACCE and all-cause mortality compared to no-CLD patients (p <0.001). Among CLD etiologic subgroups, those with \'alcohol-related liver disease\' and \'other CLD\' were consistently more likely to develop MACCE, all-cause mortality and major bleeding in comparison to no-CLD patients, while \'chronic viral hepatitis\' subgroup had only increased odds of major bleeding (p <0.001). In conclusion, CLD patients admitted for PCI are more likely to have worse in-hospital outcomes, particularly in the severe CLD subgroup and \'alcohol-related liver disease\' and \'other CLD\' etiologic subgroups.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:32-38

Prevalence and Long-term Outcomes of Patients with Coronary Artery Ectasia Presenting with Acute Myocardial Infarction.

Wang X, Montero-Cabezas JM, Mandurino-Mirizzi A, Hirasawa K, ... Bax JJ, Delgado V
Coronary artery ectasia (CAE) is described in 5% of patients undergoing coronary angiography. Previous studies have shown controversial results regarding the prognostic impact of CAE. The prevalence and prognostic value of CAE in patients with acute myocardial infarction (AMI) remain unknown. In 4788 patients presenting with AMI referred for coronary angiography the presence of CAE (defined as dilation of a coronary segment with a diameter ≥1.5 times of the adjacent normal segment) was confirmed in 174 (3.6%) patients (age 62 ± 12 years; 81% male), and was present in the culprit vessel in 79.9%. Multivessel CAE was frequent (67%). CAE patients were more frequently male, had high thrombus burden and were treated more often with thrombectomy and less often was stent implantation. Markis I was the most frequent angiographic phenotype (43%). During a median follow-up of 4 years (1-7), 1243 patients (26%) experienced a major adverse cardiovascular event (MACE): 282 (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) presented with a stroke. Patients with CAE showed higher rates of MACE as compared to those without CAE (36.8% versus 25.6%; p <0.001). On multivariable analysis, CAE was associated with MACE (HR 1.597; 95% CI 1.238-2.060; p <0.001) after adjusting for risk factors, type of AMI and number of narrowed coronary arteries. In conclusion, the prevalence of CAE in patients presenting with AMI is relatively low but was independently associated with an increased risk of MACE at follow-up.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:9-15

Trends in the Outcomes of High-risk Percutaneous Ventricular Assist Device-assisted Percutaneous Coronary Intervention, 2008-2018.

Lemor A, Basir MB, Truesdell AG, Tamis-Holland JE, ... Pinto DS, O\'Neill W
Percutaneous ventricular assist devices (pVAD) are frequently utilized in high-risk percutaneous coronary intervention (HR-PCI) to provide hemodynamic support in patients with complex cardiovascular disease and/or multiple comorbidities who are poor candidates for surgical revascularization. Using the National Inpatient Sample we identified pVAD-assisted PCI (excluding intra-aortic balloon pump) in patients without cardiogenic shock from January 2008 to December 2018. We evaluated the trends in patient and procedural characteristics, and complication rates across the 11-year study period. A total of 26,661 pVAD-PCI was performed. From 2008 to 2018 there has was a 27-fold increase in the number of pVAD-PCIs performed annually. There has also been an increase in the proportion of procedures performed in small to medium sized hospitals. The use of atherectomy, image-guided PCI, FFR/iFR, drug-eluting stents, and multi-vessel intervention has significantly increased. Patients undergoing pVAD-PCI had a higher burden of comorbidities, without a significant difference in mortality over time. There were decreased rates of acute stroke and blood transfusions over time, while vascular complications and acute kidney injury (AKI) requiring dialysis remained mostly unchanged. In conclusion, the use of pVAD for HR-PCI has increased significantly, along with adjunctive PCI techniques such as atherectomy, intravascular imaging, and physiologic lesion assessment. With increasing use of this device, there appeared to be lower rates of peri-procedural stroke, and blood transfusions. Despite a higher burden of comorbidities, adjusted mortality remained stable over time.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:65-71

Effect of once-weekly exenatide on hospitalization for acute coronary syndrome or coronary revascularization in patients with type 2 diabetes mellitus.

Barbery CE, Giczewska A, White J, Lokhnygina Y, ... Hernandez AF, Jones WS
Cardiovascular (CV) outcome studies of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shifted the paradigm of type 2 diabetes management given their benefits regarding a reduction in major adverse CV events. However, the relationship between GLP-1 RAs and coronary revascularization remains poorly understood. In this EXSCEL post-hoc analysis, we used univariate Cox proportional models and Kaplan Meier survival analysis to evaluate the effect of once-weekly exenatide (EQW) on a composite outcome of hospitalization for acute coronary syndrome (ACS) or coronary revascularization. Similar models were utilized to evaluate the relationship between significant participant characteristics within the entire study population and the composite outcome. Of the 14,736 participants in EXSCEL with complete follow-up data, 1642 (11.1%) experienced an ACS or coronary revascularization event during a median follow-up of 3.3 years (interquartile range, 2.3-4.4). EQW had no effect on hospitalization for ACS or coronary revascularization (HR 1.00, 95% CI 0.91-1.10). Among EXSCEL participants, enrollment in Latin America (HR 0.51, 95% CI 0.43-0.60) and a history of peripheral artery disease (HR 0.79, 95% CI 0.70-0.90) were associated with a reduced risk for coronary revascularization, whereas enrollment in North America (HR 1.92, 95% CI 1.74-2.12), a history of CV disease (HR 3.24, 95% CI 2.78-3.78), and a previous myocardial infarction (HR 1.54, 95% CI 1.39-1.71) were associated with increased risk for study end points. EQW had no association with hospitalization for ACS or coronary revascularization. Participant enrollment location and CV disease burden may play a role in the variable CV efficacy of GLP-1 RAs that has been observed in trials thus far.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Sep 2021; 239:59-63

The Definition of \"Acute Kidney Injury\" Following Percutaneous Coronary Intervention and Cardiovascular Outcomes.

Skalsky K, Levi A, Bental T, Vaknin-Assa H, ... Kornowski R, Perl L
Acute kidney injury (AKI) is a complication of percutaneous coronary intervention (PCI), known to increase rates of adverse medical events. We aimed to identify the optimal definition of AKI in predicting adverse cardiovascular outcomes and mortality post PCI. From a large registry of patients undergoing PCI between 2006-2018 (n = 25,690) at our medical center, consecutive patients were assessed for the presence of AKI according to four different definitions: a relative elevation of ≥25% or ≥50%; or an absolute elevation of ≥0.3 mg/dL or ≥0.5 mg/dL in serum creatinine at 48 hours post PCI. We assessed the calculated rates of AKI according to the different definitions. The discriminant capacity for 30-day and 1-year mortality and MACE (MACE: all-cause death, myocardial infarction, target-vessel revascularization and coronary artery bypass graft surgery) of each definition was calculated using ROC curves and AUCs. Data of 15,153 patients was available for the final analysis. Rates of AKI were 12.1%, 3.2%, 8.1% and 3.9% according to the four definitions, respectively. The discriminant capacity of adverse outcomes was highest among those defined as AKI according to the third definition - an absolute elevation of ≥0.3 mg/dL in serum creatinine with an AUC of 0.82 (95% CI 0.80-0.84) for 30-day mortality (P value = 0.036) and an AUC of 0.78 (CI 0.76-0.79) for 30-day MACE. In conclusion, an absolute elevation of ≥ 0.3 mg/dL in serum creatinine 48 hours post PCI predicts overall mortality and MACE most accurately.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:39-43

Long-term (≥15 years) Follow-up of Percutaneous Coronary Intervention of Unprotected Left Main (From the GRAVITY Registry).

D\'Ascenzo F, Elia E, Marengo G, Wańha W, ... Sheiban I, Ferrari GM
Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF <35% (HR 4.71, 95%CI 1.90 to 11.66) to CV death. Repeated PCI on ULMCA occurred in 91 (28%) patients during the course of follow up and did not significantly impact on freedom from all-cause or CV mortality. In conclusion, in a large, unselected population treated with PCI on ULMCA, 47% died after 15 years, 17% due to CV causes. Age, number of vessels treated during index PCI and depressed LVEF increased risk of all cause death, while re-PCI on ULMCA did not impact survival.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:72-78

A Novel Two-Dimensional Echocardiography Method to Objectively Quantify Aortic Valve Calcium and Predict Aortic Stenosis Severity.

Slostad B, Twing A, Lee K, Hubbard C, ... Frazin L, Kansal M
Aortic valve calcium (AVC) is a strong predictor of aortic stenosis (AS) severity and is typically calculated by multidetector computed tomography (MDCT). We propose a novel method using pixel density quantification software to objectively quantify AVC by two-dimensional (2D) transthoracic echocardiography (TTE) and distinguish severe from non-severe AS. A total of 90 patients (mean age 76 ± 10 years, 75% male, mean AV gradient 32 ± 11 mmHg, peak AV velocity 3.6 ± 0.6 m/s, AV area (AVA) 1.0 ± 0.3 cm², dimensionless index (DI) 0.27 ± 0.08) with suspected severe aortic stenosis undergoing 2D echocardiography were retrospectively evaluated. Parasternal short axis aortic valve views were used to calculate a gain-independent ratio between the average pixel density of the entire aortic valve in short axis at end diastole and the average pixel density of the aortic annulus in short axis (2D-AVC ratio). The 2D-AVC ratio was compared to echocardiographic hemodynamic parameters associated with AS, MDCT AVC quantification, and expert reader interpretation of AS severity based on echocardiographic AVC interpretation. The 2D-AVC ratio exhibited strong correlations with mean AV gradient (r = 0.72, p < 0.001), peak AV velocity (r = 0.74, p < 0.001), AVC quantified by MDCT (r = 0.71, p <0.001) and excellent accuracy in distinguishing severe from non-severe AS (area under the curve = 0.93). Conversely, expert reader interpretation of AS severity based on echocardiographic AVC was not significantly related to AV mean gradient (t = 0.23, p = 0.64), AVA (t = 2.94, p = 0.11), peak velocity (t = 0.59, p = 0.46), or DI (t = 0.02, p = 0.89). In conclusion, these data suggest that the 2D-AVC ratio may be a complementary method for AS severity adjudication that is readily quantifiable at time of TTE.

Published by Elsevier Inc.

Am J Cardiol: 30 Sep 2021; 156:108-113

Increased Rate of New-onset Left Bundle Branch Block in Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation (From a National Registry).

Shiyovich A, Kornowski R, Plakht Y, Aviv Y, ... Perlman GY, Hamdan A
There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:101-107

Incidence and Predictors of Stent Thrombosis in Patients Treated with Stents for Coronary Bifurcation Narrowing (From the BIFURCAT Registry).

Franchin L, Kang J, De Filippo O, Gwon HC, ... Koo BK, D\'Ascenzo F
Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.

Copyright © 2021. Published by Elsevier Inc.

Am J Cardiol: 30 Sep 2021; 156:24-31

Benefit of Extended Dual Antiplatelet Therapy Duration in Acute Coronary Syndrome Patients Treated with Drug Eluting Stents for Coronary Bifurcation Lesions (from the BIFURCAT Registry).

Filippo O, Kang J, Bruno F, Han JK, ... Koo BK, D\'Ascenzo F
Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2021; 156:16-23

Changes in Global Left Ventricular Myocardial Work Indices and Stunning Detection 3 Months After ST-Segment Elevation Myocardial Infarction.

Lustosa RP, Fortuni F, van der Bijl P, Mahdiui ME, ... Delgado V, Bax JJ
Global left ventricular (LV) myocardial work (MW) indices (GLVMWI) are derived from speckle tracking echocardiographic strain data in combination with non-invasive blood pressure measurements. Changes in global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) after ST-segment elevation myocardial infarction (STEMI) have not been explored. The aim of present study was to assess the evolution of GLVMWI in STEMI patients from baseline (index infarct) to 3 months\' follow-up. Three-hundred and fifty patients (265 men; mean age 61 ± 10 years) with STEMI treated with primary percutaneous coronary intervention (PCI) and guideline-based medical therapy were retrospectively evaluated. Clinical variables, conventional echocardiographic measures and GLVMWI were recorded at baseline within 48 hours post-primary PCI and 3 months\' follow-up. LV ejection fraction (from 54 ± 10% to 57 ± 10%, p < 0.001), GWI (from 1449 ± 451 mm Hg% to 1953 ± 492 mm Hg%, p < 0.001), GCW (from 1624 ± 519 mm Hg% to 2228 ± 563 mm Hg%, p < 0.001) and GWE (from 93% (interquartile range (IQR) 86%-95%) to 95% (IQR 91%-96%), p < 0.001) improved significantly at 3 months\' follow-up with no significant difference in GWW (from 101 mm Hg% (IQR 63-155 mm Hg%) to 96 mm Hg% (IQR 64-155 mm Hg%); p = 0.535). On multivariable linear regression analysis, lower values of troponin T at baseline, increase in systolic blood pressure and improvement in LV global longitudinal strain were independently associated with higher GWI and GCW at 3 months\' follow-up. In conclusion, the evolution of GWI, GCW and GWE in STEMI patients may reflect myocardial stunning, whereas the stability in GWW may reflect permanent myocardial damage and the development of non-viable scar tissue.

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

Am J Cardiol: 14 Oct 2021; 157:15-21

Spleen Size and Thrombocytopenia After Transcatheter Aortic Valve Implantation.

Sugiura A, Treiling L, Al-Kassou B, Shamekhi J, ... Nickenig G, Sedaghat A
The pathophysiology of thrombocytopenia after transcatheter aortic valve implantation (TAVI) thrombocytopenia is still poorly understood. We assessed the association of spleen size with acquired thrombocytopenia in patients undergoing TAVI. We included 732 patients who underwent TAVI with new generation transcatheter heart valves (THVs) at our center from February 2016 to July 2019. We measured splenic volume index in consecutive patients derived from multidetector row computed tomographic datasets. Patients were stratified according to post-TAVI thrombocytopenia, which was defined as a decline in platelet count (DPC) ≥50% at nadir, and evaluated regarding baseline characteristics and outcome parameters. After the procedure, platelet counts declined from 212.9 ± 67.4 × 10⁹/L at baseline to 138.8 ± 49.8 × 10⁹/L at nadir after a median of 2 days (interquartile range [IQR] 2 to 3). Of all patients, 10.1% showed a DPC ≥50%. Compared with patients with DPC <50%, patients with DPC ≥50% had significantly lower splenic volume index (95.5 ml/m² [IQR 78.0 to 123.7] vs 85.8 ml/m² [IQR 71.4 to 102.6], p = 0.008). A multivariable analysis revealed that the splenic volume index was negatively associated with a DPC ≥50% (OR 0.89, 95% CI 0.82 to 0.97, p = 0.005), independent of the type of THV (balloon-expandable THV: OR 2.06, 95% CI 1.13 to 3.76, p = 0.02), major bleeding (OR 13.40, 95% CI 3.58 to 50.40, p <0.001), blood transfusion (OR 3.63, 95% CI 1.54 to 8.56, p = 0.003), or postprocedural paravalvular leakage ≥moderate (OR 5.48, 95% CI 1.23 to 24.40, p = 0.03). Furthermore, DPC ≥50% was independently associated with 1-year mortality (HR 3.36, 95% CI 1.66 to 6.81, p <0.001). In conclusion, acquired thrombocytopenia remains prevalent in modern TAVI patients. Spleen size appears to be associated with the occurrence of thrombocytopenia after TAVI, which is independently correlated with 1-year mortality.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:85-92

Comparison of Outcomes of Asymptomatic Moderate Aortic Stenosis With Preserved Left Ventricular Ejection Fraction in Patients ≥80 Years Versus 70-79 Years Versus <70 Years.

Chew NW, Kong G, Ngiam JN, Phua K, ... Tan HC, Poh KK
Aortic stenosis (AS) is increasingly diagnosed in the aging population with more studies focused on the prognostic outcomes of severe asymptomatic AS. However, little is known about the outcomes of moderate asymptomatic AS in the elderly population. From 2001 to 2020, 738 consecutive patients with asymptomatic moderate AS with preserved left ventricular ejection fraction were studied. They were allocated according to the age group at the index echocardiography: very elderly (≥80 years), elderly (70 to 79 years) and control group (<70 years). The primary study outcomes were aortic valve replacement (AVR), congestive cardiac failure (CCF) and all-cause mortality. Overall, about one-third of the subjects were in the very elderly, elderly and control groups each. The median follow-up duration was 114.2 (interquartile range, 27.0 to 183.7) months. There was significantly higher all-cause mortality in the very elderly group (47.9%) followed by elderly (34.8%) and control group (21.9%). Similarly, there was significantly higher CCF rates in the very elderly group (5.8%) compared to elderly (5.1%) and control group (2.8%). There were significantly lower rates of AVR offered and completed in the very elderly group compared to control group. Multivariable logistic regression demonstrated that age ≥80 years remained an independent predictor of mortality after adjusting for important prognostic cofounders (Adjusted HR 2.424, 95% CI 1.728 to 3.400, p < 0.001). Cox regression showed no significant difference in mortality between patients ≥80 years with moderate AS compared to a younger age-group ≥70 years with severe AS. In conclusion, very elderly patients of ≥80 years of age with moderate AS have worse prognostic outcomes than their younger counterparts. They share similar unfavorable prognostic outcomes as those of a younger age-group ≥70 years with severe AS. Closer surveillance are warranted in this group of at-risk elderly patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:93-100

Characteristics and Outcomes of Patients Admitted With Type 2 Myocardial Infarction.

Tripathi B, Tan BE, Sharma P, Gaddam M, ... Deshmukh A, Klein J
Type 2 myocardial infarction (Type 2 MI) is a common problem and carries a high diagnostic uncertainty. Large studies exploring outcomes in type 2 MI are lacking. Nationwide Readmission Database (2017) was queried using the International Classification of Diseases codes (ICD-10-CM) to identify type 2 MI patients. Characteristics, in-hospital outcomes, 30-day readmissions, and predictors of in-hospital mortality as well as 30-day readmissions were explored. We identified 21,738 patients with a diagnosis of type 2 MI. Most common primary diagnosis at presentation included infection/sepsis (27.5%), hypertensive heart disease (15.3%) and pulmonary diseases (8.5%). Overall, in-hospital mortality and 30-day readmission for patients with type 2 MI were 9.0% and 19.1% respectively. On multivariable analysis, significant predictors of increased in-hospital mortality included male gender, coexisting atrial fibrillation/flutter, peripheral vascular disease, coagulopathy, malignancy, and fluid/electrolyte abnormalities. Significant predictors of 30-day readmission were coexisting diabetes mellitus, atrial fibrillation/ flutter, carotid artery stenosis, anemia, COPD, CKD and prior history of myocardial infarction, A primary diagnosis of sepsis, pulmonary issues including respiratory failure, neurological conditions including stroke carried highest risk of mortality however readmission risk was not influenced by primary diagnosis at presentation. In conclusion, approximately 1 in 10 patients admitted for type 2 MI died during admission, and nearly 1 in 5 patients were readmitted at 30 days after discharge. In-hospital mortality varied based on associated primary diagnosis at presentation. Proposed predictive model for mortality and 30-day readmission in our study can help to target high risk patients for post-Type 2 MI care.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:33-41

Risk of Ischemic Stroke in Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patients With Prior Stroke.

Ando T, Ashraf S, Briasoulis A, Takagi H, Grines CL, Malik AH
It has not been well studied whether transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) have lower risk of ischemic stroke (IS) in those with prior history of IS. From the Nationwide Readmission Database from October 2015 to November 2017, TAVI and SAVR above age 50 were identified with the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System codes. Transapical TAVI and SAVR with concomitant bypass, mitral, or tricuspid surgery were excluded. The primary outcome was in-hospital IS. A total of 92,435 TAVI (13,292 with prior stroke) and 68,651 SAVR (5,365 with prior stroke) were identified. In-hospital IS was significantly lower in TAVI compared with SAVR (3.7% vs 8.0%, adjusted odds ratio 0.65, 95% confidence interval 0.47 to 0.89, p <0.01) with prior stroke whereas it was similar between TAVI and SAVR (1.7% vs 2.1%, adjusted odds ratio 0.97, 95% confidence interval 0.78 to 1.19, p = 0.75) in those without prior stroke (P _interaction < 0.001). In-hospital mortality, acute kidney injury, and bleeding were lower in TAVI compared with SAVR in patients with and without prior stroke (P _interaction > 0.05 for all). This analysis of a national claims database showed that TAVI was associated with a lower risk of in-hospital IS compared with SAVR among patients with prior stroke.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:79-84

Meta-Analysis of Transradial Versus Transfemoral Access for Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease.

Latif A, Ahsan MJ, Mirza MM, Aurit S, ... Bhatt DL, Velagapudi P
Data comparing outcomes of transradial (TR) versus transfemoral (TF) access for percutaneous coronary intervention (PCI) in chronic kidney disease (CKD) including patients with eGFR< 30 ml/min/1.73m² and patients with end-stage renal disease on dialysis (ESRD) are lacking. This meta-analysis compares the outcomes of TR versus TF approach for PCI in patients with CKD. PubMed, Embase, Cochrane, ClinicalTrials.gov, and Google Scholar were searched for studies including adults with CKD undergoing PCI via a TR versus TF approach from January 1, 2000, until January 15, 2021. The primary outcome was in-hospital all-cause mortality and secondary outcomes included major bleeding, stroke, myocardial infarction (MI), blood transfusion, contrast volume, and fluoroscopy time. The analysis was performed using a random-effects-model using the Mantel-Haenszel method. Five observational studies met inclusion criteria, including 1,156 and 6,156 patients in the TR and TF arms, respectively. The mean age of included patients was 70.5 years, 66% were male and 90% had ESRD. In patients with CKD, TR access for PCI was associated with lower all-cause mortality (RR = 0.48; 95% CI: 0.32 to 0.73), major bleeding (RR = 0.51; 95% CI: 0.36 to 0.73), blood transfusion (RR = 0.53, 95% CI: 0.42 to 0.68) and contrast volume (SMD -0.34 [-0.60 to -0.08]) with no difference in stroke, MI, or fluoroscopy time compared with TF access. In conclusion, in patients with CKD undergoing PCI, the TR approach was associated with a lower risk of in-hospital mortality, post-procedural bleeding, and blood transfusion compared with TF access.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:8-14

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.

Povsic TJ, Henry TD, Ohman EM, Pepine CJ, ... Answini GA, Mokadam NA
Background
Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect.
Methods
The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 10⁹, 1 × 10¹⁰, 4 × 10¹⁰, and 1 × 10¹¹ viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency.
Conclusions
The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation.
Clinical trial registration
NCT04125732.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Oct 2021; 241:38-49

Effect of Polypharmacy on Long-Term Mortality After Percutaneous Coronary Intervention.

Yamamoto K, Natsuaki M, Morimoto T, Shiomi H, ... Kimura T, CREDO-Kyoto PCI/CABG Registry Cohort-3 investigators
Polypharmacy was reported to be associated with increased mortality in various populations. However, there is a scarcity of data on status of polypharmacy and association with long-term mortality in patients who underwent percutaneous coronary intervention (PCI). Among 12,291 patients who underwent first PCI in the CREDO-Kyoto PCI/CABG registry Cohort-3, we evaluated the number of medications at discharge from index PCI hospitalization, and compared long-term mortality across the 3 groups divided by the tertiles of the number of medications. The median number of medications was 6 (interquartile range: 5 to 8), and 88.0% of the patients were on >=5 medications. Most of medications were those related to cardiovascular disease. Patients taking more medications were older and more often had co-morbidities and guideline-indicated medications. The cumulative 5-year incidence of all-cause death increased incrementally with increasing number of medications (Tertile 1 [<=5]: 13.1%, Tertile 2 [6 to 7]: 13.9%, and Tertile 3 [>=8]: 18.0%, log-rank p <0.001). After adjusting confounders, the mortality risks of Tertile 2 and Tertile 3 relative to Tertile 1 were no longer significant (Tertile 2: hazard ratio 0.93; 95% confidence interval 0.84 to 1.04; p = 0.23, and Tertile 3: hazard ratio 0.91; 95% confidence interval 0.81 to 1.03; p = 0.14, respectively). In conclusion, in a real-world population of patients who underwent PCI, approximately 90% of patients were on >=5 medications. Increasing medications was associated with higher crude incidence of all-cause death, whereas adjusted mortality risks were similar regardless of the number of medications. These data might suggest that achievement of optimal medical therapy would be preferred, even if it might increase the number of medications used.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:19-29

High-Risk Percutaneous Coronary Intervention of Native Coronary Arteries Without Mechanical Circulatory Support in Acute Coronary Syndrome Without Cardiogenic Shock.

Khalid N, Zhang C, Shea C, Shlofmitz E, ... Satler LF, Waksman R
Widespread utilization of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI) remains controversial, with a lack of randomized supporting evidence and associated risk of device-related complications. We investigated whether high-risk PCI of native coronary arteries without elective MCS in patients with acute coronary syndrome (ACS) is safe and feasible. We performed a single-center, retrospective analysis for ACS patients meeting American College of Cardiology high-risk criteria: unprotected left main disease, last remaining conduit, ejection fraction <35%, 3-vessel coronary artery disease, severe aortic stenosis, or severe mitral regurgitation. Patients with cardiogenic shock and those undergoing PCI of the bypass grafts were excluded. Major in-hospital and 30-day cardiovascular outcomes were assessed. From 2003 through 2018, 499 patients (847 lesions) with unstable angina pectoris (UAP), 1218 patients (1807 lesions) with non-ST-elevation myocardial infarction (NSTEMI), and 868 patients (1260 lesions) with ST-segment elevation myocardial infarction (STEMI) underwent high-risk PCI. Procedural success was achieved in 97.2% of UAP, 98.3% of NSTEMI, and 96.6% of STEMI patients. In-hospital and 30-day all-cause mortality were as follows: UAP, 2%; NSTEMI, 2.1%; and STEMI 4.7%. Bailout intra-aortic balloon pump was required in 1.6% of UAP, 3.1% of NSTEMI, and 10.3% of STEMI patients. Major complications for UAP, NSTEMI, and STEMI were, respectively: target lesion revascularization (2.3%, 1.4%, and 1.5%), stroke or transient ischemic attack (0.8%, 0.6%, and 1.3%), acute renal failure (8.2%, 7.2%, and 10.2%), major bleeding (1.6%, 3.1%, and 8.5%). In conclusion, our results show that high-risk PCI without elective MCS is safe and feasible in most ACS patients, challenging professional societies\' current recommendations. A randomized trial comparing unprotected versus protected high-risk PCI for non-shock ACS patients is warranted.

Copyright © 2021. Published by Elsevier Inc.

Am J Cardiol: 31 Oct 2021; 158:37-44

Frequency and Significance of Right Bundle Branch Block and Subclinical Coronary Atherosclerosis in Asymptomatic Individuals.

Lee H, Jeon YJ, Kang BJ, Lee TY, ... Choi SH, Park GM
Limited data exist regarding the association between right bundle branch block (RBBB) and subclinical coronary atherosclerosis. This study investigated the influence of RBBB on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. We retrospectively analyzed 7,205 asymptomatic individuals (mean age 54.4 ± 7.9 years and 4,695 men [65.2%]) with no prior history of coronary artery disease who voluntarily underwent CCTA and 12-lead electrocardiographic evaluation as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA, and ≥50% diameter stenosis was defined as significant. The association between RBBB and subclinical coronary atherosclerosis was determined by logistic regression and propensity score matching analyses. Of study participants, 116 (1.6%) had RBBB. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of RBBB for any atherosclerotic plaque (0.87, 95% confidence interval [CI] 0.57 to 1.32), calcified plaque (0.78, 95% CI 0.51 to 1.19), noncalcified plaque (1.44, 95% CI 0.77 to 2.69), mixed plaque (1.12, 95% CI 0.52 to 2.39), and significant coronary artery stenosis (0.92, 95% CI 0.48 to 1.74). Similarly, in the 5: 1 propensity score-matched population (n = 696), there were no statistically significant differences in the odds ratios for any subclinical coronary atherosclerosis between participants with and without RBBB (p for all >0.05). In conclusion, through this large cross-sectional study of asymptomatic individuals who underwent CCTA and electrocardiography evaluation, individuals with RBBB were not associated with an increased risk of subclinical coronary atherosclerosis compared with those without RBBB.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Oct 2021; 158:30-36

Relation of Left Ventricular Assist Device Infections With Cardiac Transplant Outcomes.

Parikh A, Halista M, Raymond S, Feinman J, ... Lala A, Pinney S
Left ventricular assist device (LVAD)-specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

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

Am J Cardiol: 02 Oct 2021; epub ahead of print

Incidence and Outcomes of Pericardial Effusion and Cardiac Tamponade Following Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation.

Bansal A, Kalra A, Puri R, Saliba W, ... Kapadia SR, Reed GW
Permanent pacemaker (PPM) implantation is required in 5% to 10% of patients following transcatheter aortic valve implantation (TAVI). However, there are limited data on the impact of PPM implantation on the incidence of pericardial effusion, cardiac tamponade, and outcomes after TAVI. We identified all hospitalizations in patients ≥18 years of age who underwent TAVI in the years 2016 to 2017 in the Nationwide Readmission Database. The endpoints of the study were pericardial effusion, cardiac tamponade, and percutaneous or surgical drainage of the pericardial cavity in patients that required PPM implantation after TAVI. Multivariable logistic regression determined associations of PPM implantation, pericardial effusion, and tamponade with patient outcomes. A total of 54,317 unweighted hospitalizations for TAVI were identified, of which 5,639 (10.4%) required PPM. The risk of pericardial effusion was significantly greater in patients who required PPM (2.4% vs 1.6%, adjusted odds ratio (aOR) 1.39 (1.15 to 1.70), p <0.001)), and risk of cardiac tamponade nearly doubled (1.6% vs 0.8%, p <0.001; aOR: 1.90 (1.48 to 2.40), p <0.001). Female gender was independently associated with increased risk of pericardial effusion and cardiac tamponade whereas history of previous  CABG was associated with decreased risk of both. Pericardial complications following PPM implantation were associated with increased in-hospital mortality, length of stay (LOS), hospital costs, and risk of 30-day readmission following TAVI (p <0.01 for all comparisons). In conclusion, although common, PPM implantation post-TAVI carries increased risks of pericardial effusion and associated cardiac tamponade. Patients developing these pericardial complications are at particularly high-risk for in-hospital mortality, greater LOS, and 30-day readmission.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:135-139

Mitral Regurgitation Following Acute Myocardial Infarction Treated by Percutaneous Coronary Intervention-Prevalence, Risk factors, and Predictors of Outcome.

Sharma H, Radhakrishnan A, Nightingale P, Brown S, ... Adnan Nadir M, Steeds RP
Mitral regurgitation (MR) following acute myocardial infarction (AMI) worsens prognosis and reports of prevalence vary significantly. The objective was to determine prevalence, risk factors, and outcomes related to MR following AMI. We identified 1000 consecutive patients admitted with AMI in 2016/17 treated by percutaneous coronary intervention with pre-discharge transthoracic echocardiography. MR was observed in 294 of 1000 (29%), graded as mild (n = 224 [76%]), moderate (n = 61 [21%]) and severe (n = 9 [3%]). Compared with patients without MR, patients with MR were older (70 ± 12 vs 63 ± 13 years; p <0.001), with worse left ventricular ejection fraction (LVEF) (52 ± 15% vs 55 ± 11%; p <0.001) and creatinine clearance (69 ± 33 ml/min vs 90 ± 39 ml/min; p <0.001). They also had higher rates of hypertension (64% vs 55%; p = 0.012), heart failure (3.4% vs 1.1%; p = 0.014), previous MI (28% vs 20%; p = 0.005) and severe flow-limitation in the circumflex (50% vs 33%; p <0.001) or right coronary artery (51% vs 42%; p = 0.014). Prevalence and severity of MR were unaffected by AMI subtype. Revascularization later than 72 hours from symptom-onset was associated with increased likelihood of MR (33% vs 25%; p = 0.036) in patients with non-ST elevation myocardial infarction (NSTEMI). After a mean of 3.2 years, 56 of 288 (19%) patients with untreated MR died. Age and LVEF independently predicted mortality. The presence of even mild MR was associated with increased mortality (p = 0.029), despite accounting for confounders. In conclusion, MR is observed in over one-quarter of patients after AMI and associated with lower survival, even when mild. Prevalence and severity are independent of MI subtype, but MR was more common with delayed revascularization following NSTEMI.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2021; 157:22-32

Long-Term Outcomes After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents or Coronary Artery Bypass Grafting for Multivessel Coronary Disease.

Kim TO, Ahn JM, Kang DY, Park H, ... Park DW, Asan-Multivessel Registry Investigators
More evidence is required with respect to the comparative effectiveness of percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DESs) versus coronary artery bypass grafting (CABG) in contemporary clinical practice. This prospective observational registry-based study compared the outcomes of 6,647 patients with multivessel disease who underwent PCI with second-generation DES (n = 3,858) or CABG (n = 2,789) between January 2006 and June 2018 and for whom follow-up data were available for at least 2 to 13 years (median 4.8). The primary outcome was a composite of death, spontaneous myocardial infarction, or stroke. Baseline differences were adjusted using propensity scores and inverse probability weighting. In the overall cohort, there were no significant between-group differences in the adjusted risks for the primary composite outcome (hazard ratio [HR] for PCI vs CABG 1.03, 95% confidence interval [CI] 0.86 to 1.25, p = 0.73) and all-cause mortality (HR 0.95, 95% CI 0.76 to 1.20, p = 0.68). This relative treatment effect on the primary outcome was similar in patients with diabetes (HR 1.15, 95% CI 0.91 to 1.46, p = 0.25) and without diabetes (HR 0.95, 95% CI 0.73 to 1.22, p = 0.67) (p for interaction = 0.24). The adjusted risk of the primary outcome was significantly greater after PCI than after CABG in patients with left main involvement (HR 1.39, 95% CI 1.01 to 1.90, p = 0.044), but not in those without left main involvement (HR 0.94, 95% CI 0.76 to 1.16, p = 0.56) (p = 0.03 for interaction). In this prospective real-world long-term registry, we observed that the risk for the primary composite of death, spontaneous myocardial infarction, or stroke was similar between PCI with contemporary DES and CABG.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Oct 2021; epub ahead of print

Impact of Active and Historical Cancer on Short- and Long-Term Outcomes in Patients With Acute Myocardial Infarction.

Matsumoto T, Saito Y, Yamashita D, Sato T, ... Sano K, Kobayashi Y
Patients with cancer have an increased risk of cardiovascular events including myocardial infarction (MI) and vice versa, and are at high risks of ischemic and bleeding events after MI. However, short- and long-term clinical outcomes in patients with acute MI based on cancer status are not fully understood. This bi-center registry included 903 patients with acute MI undergoing primary percutaneous coronary intervention in a contemporary setting. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrent MI, and stroke, and major bleedings were evaluated. Of 903 patients, 49 (5.4%) and 65 (7.2%) had active cancer and a history of cancer, and 87 (9.6%) patients died during the hospitalization. In-hospital MACE was not significantly different among the 3 groups (16.3% vs 10.8% vs 10.9%, p = 0.48), whereas the rate of major bleeding events during the index hospitalization was significantly higher in patients with active cancer than their counterpart (20.4% vs 6.2% vs 5.8%, p = 0.002). After discharge, patients with active cancer had an increased risk of MACE and major bleedings compared with those with a history of cancer and no cancer during the mean follow-up period of 853 days. In conclusions, active cancer rather than a history of cancer and no cancer had significant impact on in-hospital bleeding events, and MACE and major bleedings after discharge in patients with acute MI undergoing primary percutaneous coronary intervention.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:59-64

Meta-Analysis Comparing Valve Durability Among Different Transcatheter and Surgical Aortic Valve Bioprosthesis.

Ueyama H, Kuno T, Takagi H, Kobayashi A, ... Søndergaard L, Attizzani GF
Durability of transcatheter heart valve (THV) is critical as the indication of transcatheter aortic valve implantation (TAVI) expands to patients with longer life-expectancy. We aimed to compare the durability of different THV systems (balloon-expandable [BE] and self-expandable [SE]) and surgical aortic valve replacement (SAVR) prosthesis. PUBMED and EMBASE were searched through February 2021 for randomized trials investigating parameters of valve durability after TAVI and/or SAVR in severe aortic stenosis. A network meta-analysis using random-effect model was performed. Synthesis was performed with 5-year follow-up data for echocardiographic outcomes and the longest available follow-up data for clinical outcomes. Ten trials with a total of 9,388 patients (BE-THV: 2,562; SE-THV: 2,863; SAVR: 3,963) were included. Follow-up ranged from 1 to 6 years. SE-THV demonstrated significantly larger effective orifice area, lower mean aortic valve gradient (AVG), and less increase in mean AVG at 5-year compared with BE-THV and SAVR. Structural valve deterioration (SVD) was less frequent in SE-THV compared with BE-THV and SAVR (HR 0.14, 95% CI 0.07 to 0.27; HR 0.34, 95% CI 0.24 to 0.47, respectively). Total moderate-severe aortic regurgitation and reintervention was more frequent in BE-THV (HR 4.21, 95% CI 2.40 to 7.39; HR 2.22, 95% CI 1.16 to 4.26, respectively), and SE-THV (HR 7.51, 95% CI 3.89 to 14.5; HR 2.86, 95% CI 1.59 to 5.13, respectively) compared with SAVR. In conclusion, TAVI with SE-THV demonstrated favorable forward-flow hemodynamics and lowest risk of SVD compared with BE-THV and SAVR at mid-term. However, both THV systems suffer an increased risk of AR and re-intervention, and long-term data from newer generation valves is warranted.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Oct 2021; 158:104-111

Impact of Low Body Mass Index on Features of Coronary Culprit Plaques and Outcomes in Patients With Acute Coronary Syndrome.

Kobayashi N, Shibata Y, Kurihara O, Todoroki T, ... Asai K, Miyauchi Y
The mechanisms behind poorer cardiac outcomes in underweight patients with acute coronary syndrome (ACS) are not understood and features of coronary culprit lesions in underweight ACS patients have not been fully examined. A total of 1,683 patients with ACS were divided into 4 groups according to body mass index (BMI): <18.5 (n = 73), 18.5 to 24.9 (n = 995), 25 to 29.9 (n = 488), and ≥30 (n = 117). Angiography and optical coherence tomography (OCT) images were analyzed for 1,428 of these patients who had primary percutaneous coronary intervention (PCI) and 838 who had primary PCI with OCT guidance, respectively. Diabetes (p <0.001), hypertension (p <0.001), and dyslipidemia (p <0.001) were less prevalent in BMI <18.5. Statin prescription at discharge was less frequent in the BMI <18.5 group (p <0.001). Quantitative coronary angiography analyses revealed smaller reference vessel (p = 0.001) and minimum lumen diameters after PCI (p = 0.019) and OCT revealed longer lipidic plaque length (p = 0.029) in the BMI <18.5 group. Kaplan-Meier analyses revealed higher rates of cardiac mortality (p <0.001) and major bleeding (p = 0.034) during the 2-year follow-up in the BMI <18.5 group. After adjusting for traditional cardiovascular risk factors, BMI <18.5 independently predicted 2-year cardiac mortality (hazard ratio 1.917 [95% confidence interval [1.082 to 3.397], p = 0.026). In conclusion, being underweight contributed to poorer cardiac outcomes in established ACS population. Smaller minimum lumen diameter after PCI and further progressed atherosclerosis at the culprit lesions despite their lower prevalence of comorbid metabolic risk factors may be related partly to poorer cardiac outcomes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Oct 2021; 158:6-14

Plaque Character and Progression According to the Location of Coronary Atherosclerotic Plaque.

Bax AM, Yoon YE, Gianni U, Ma X, ... Shaw LJ, Chang HJ
Although acute coronary syndrome culprit lesions occur more frequently in the proximal coronary artery, whether the proximal clustering of high-risk plaque is reflected in earlier-stage atherosclerosis remains unclarified. We evaluated the longitudinal distribution of stable atherosclerotic lesions on coronary computed tomography angiography (CCTA) in 1,478 patients (mean age, 61 years; men, 58%) enrolled from a prospective multinational registry of consecutive patients undergoing serial CCTA. Of 3,202 coronary artery lesions identified, 2,140 left lesions were classified (based on the minimal lumen diameter location) into left main (LM, n = 128), proximal (n = 739), and other (n = 1,273), and 1,062 right lesions were classified into proximal (n = 355) and other (n = 707). Plaque volume (PV) was the highest in proximal lesions (median, 26.1 mm³), followed by LM (20.6 mm³) and other lesions (15.0 mm³, p <0.001), for left lesions, and was lager in proximal (25.8 mm³) than in other lesions (15.2 mm³, p <0.001) for right lesions. On both sides, proximally located lesions tended to have greater necrotic core and fibrofatty components than other lesions (left: LM, 10.6%; proximal, 5.8%; other, 3.4% of the total PV, p <0.001; right: proximal, 8.4%; other 3.1%, p <0.001), with less calcified plaque component (left: LM, 18.3%; proximal, 30.3%; other, 37.7%, p <0.001; right: proximal, 23.3%, other, 36.6%, p <0.001), and tended to progress rapidly (adjusted odds ratios: left: LM, reference; proximal, 0.95, p = 0.803; other, 0.64, p = 0.017; right: proximal, reference; other, 0.52, p <0.001). Proximally located plaques were larger, with more risky composition, and progressed more rapidly.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Oct 2021; 158:15-22

Prognostic Implications of Bicuspid and Tricuspid Aortic Valve Phenotype on Progression of Moderate Aortic Stenosis and Ascending Aorta Dilatation.

Chew NWS, Phua K, Ho YJ, Zhang A, ... Kong WKF, Poh KK
Studies on the impact of aortic valve anatomy (bicuspid aortic valve [BAV] or tricuspid aortic valve [TAV]) on the progression of moderate aortic stenosis (AS) and ascending aorta (AA) dilatation and its prognostic implications are limited. From 1991 to 2016, 288 asymptomatic patients with moderate AS detected during index echocardiography with at least 1 year of echocardiographic follow-up were retrospectively studied. Baseline clinical and echocardiographic characteristics were compared between patients with BAV (n = 80) and patients with TAV (n = 208). Co-primary outcomes were 1-year hemodynamic and anatomic progression of AS and AA dilatation. Secondary end points were the incidence of AA rapid progressors, all-cause mortality, aortic valve replacement, and congestive heart failure. Determinants of AS progression, AA diameters, AA dilatation, and prognostic outcomes were evaluated. Similar 1-year progression of the aortic valve peak velocity, V_max (9 ± 18 vs 9 ± 23 cm/s), mean gradient (1.5 ± 2.3 vs 1.3 ± 3.2 mm Hg), and aortic valve area (AVA) (-0.04 ± 0.09 vs -0.05 ± 0.10 cm²) were noted for BAV and TAV groups, respectively. One-year progressions of AA were similar at Valsalva (0.11 ± 0.88 vs 0.14 ± 1.10 mm) and tubular levels (0.12 ± 0.68 vs 0.30 ± 1.51 mm) in BAV and TAV groups, respectively. A trend toward increased rapid AA progression in patients with BAV (31.3%) was observed compared with patients with TAV (14.8%, p = 0.099). BAV was associated with progression of V_max (β = 0.17, p = 0.036), the dimensionless index (β = -0.17, p = 0.008), and AVA (β = -0.14, p = 0.048), but not mean gradient after adjusting for age, baseline severity indexes, gender, hypertension, diabetes, and body surface area. Although BAV was a determinant of larger baseline AA diameter, there was no significant association between BAV and AA rapid progressors. Adjusted Kaplan-Meier curves demonstrated no differences in congestive heart failure, aortic valve replacement, or mortality between valve morphology. In conclusion, there was a similar 1-year disease progression in terms of AVA, V_max, mean gradient, and AA diameters between patients with BAV and patients with TAV. BAV was associated with a significant increase in V_max, dimensionless index, and AVA after adjusting for important confounders. Close and prolonged follow-up is warranted in both groups of patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 05 Oct 2021; epub ahead of print

Predictors of Recurrent Ischemic Events in Patients With ST-Segment Elevation Myocardial Infarction.

Galasso G, De Angelis E, Silverio A, Di Maio M, ... Parodi G, Vecchione C
Little is known about the predictors recurrent ischemic events in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed at investigating the predictors of recurrent myocardial infarction (MI) at long-term follow-up in a real-world STEMI cohort. All consecutive STEMI patients who underwent emergent coronary angiography and primary percutaneous coronary intervention between February 2013 and June 2019 at our institution were included. The primary outcome was recurrent MI; secondary outcomes were all-cause death, target vessel revascularization (TVR), in-stent restenosis, definite stent thrombosis (ST) and non-TVR. The study population included 724 STEMI patients; at median follow-up of 803 (324 to 1,394) days, the primary outcome was reported in 70 patients (10.1%). All-cause death occurred in 6.8%, TVR in 4.2%, in-stent restenosis in 2.5%, and ST in 1.9% of cases. At multivariable analysis, diabetes (hazard ratio [HR] = 1.18), serum level of lipoprotein(a) [Lp(a), HR = 1.01], and angiographic evidence of restenotic lesion (HR = 2.98) resulted independent predictors of recurrent MI. Kaplan-Meier analysis confirmed that diabetes, restenotic lesion, and differential Lp(a) risk range values, identified patients with lower long-term survival free from recurrent MI. Lp(a) level ≥ 30 mg/dL had an incremental prognostic stratification capability in patients with diabetes (HR = 5.34), and in patients with both diabetes and restenotic lesion (HR = 17.07). In conclusion, in this contemporary cohort of STEMI patients, diabetes, Lp(a) serum levels and restenotic lesions were independently associated with recurrent MI at long term. The coexistence of Lp(a) level ≥ 30 mg/dL showed an incremental risk stratification capability, supporting its implementation for long-term prognostic assessment in this high-risk clinical setting.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:44-51

Computerized technologies informing cardiac catheterization and guiding coronary intervention.

Bajaj R, Parasa R, Ramasamy A, Makariou N, ... Baumbach A, Bourantas CV
Advances in image processing and computer hardware have enabled the development of user-friendly software which operate in real-time and can be used in the catheterization laboratory to facilitate percutaneous coronary intervention (PCI). The two dimensional-(2D) quantitative coronary angiography (QCA) systems that have traditionally been used to assess lesion severity have been replaced by 3D-QCA systems, enabling more reliable evaluation of vessel geometry and lesion dimensions. This also allows 3D reconstruction of coronary bifurcation anatomy and generation of models that can be processed by computational fluid dynamic techniques to reliably detect flow-limiting lesions. More recently, software has been introduced that has the capability of generating a digital silhouette of the coronary arteries superimposed onto X-ray angiography to facilitate wire crossing and stent placement, and potentially reduce contrast use. In parallel, methodologies have been developed that operate with an accessible interface and can process intravascular imaging data, reliably quantify lesion severity and co-register intravascular and X-ray angiographic data to comprehensively assess plaque distribution and guide PCI. The above advances are used in daily practice to improve procedural results and outcomes. This review aims to provide an overview of the developments in the field - it presents the computer-based technologies that have been designed to accurately assess lesion severity, summarizes the advantages and limitations of the systems introduced to co-register imaging data and discusses the potential value of the existing and emerging software in the catheterization laboratory.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Sep 2021; 240:28-45

Lipid-rich plaques detected by near-infrared spectroscopy predict coronary events irrespective of age: A Lipid Rich Plaque sub-study.

Bambagioni G, Di Mario C, Torguson R, Demola P, ... Mintz GS, Waksman R
Background:
and aims
In this Lipid Rich Plaque (LRP) sub-study, 1551 patients undergoing coronary angiography for acute coronary syndromes or stable angina were examined with near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). We aimed to assess the correlation of patient age with the presence of high-risk plaques, defined as maximum 4-mm Lipid Core Burden Index (maxLCBI_4mm) >400 and plaque burden >70%, and 2-year incidence of non-culprit major adverse cardiovascular events (NC-MACE).
Methods
The study population was divided into four groups according to age: <50 years (122), 50-64 years (700), 65-74 years (502), and ≥75 years (227). The primary outcome was NC-MACE from index procedure to event or the end of the study. Cox regression and mixed-effects Cox regression models were used to assess the effect of age on the association between LCBI and NC-MACE at the patient and plaque levels.
Results
Average maxLCBI_4mm and percentage of patients with at least one segment with maxLCBI_4mm > 400 were similar across the four age groups at both the patient and coronary segment levels. Having at least one segment with maxLCBI_4mm > 400 was strongly associated with NC-MACE, and that association did not differ significantly across age subgroups. Although less common (prevalence of 0.8%-1.3%), a similar trend toward greater NC-MACE rates was seen in patients with plaque burden >70% at the maximum LCBI site across age subgroups.
Conclusions
Lipid-rich plaques were as frequent in older as in younger patients and predicted a higher incidence of NC-MACE over 2-year follow-up irrespective of age.

Copyright © 2021. Published by Elsevier B.V.

Atherosclerosis: 29 Sep 2021; 334:17-22

Evolution of Management and Outcomes of Patients with Myocardial Injury During the COVID-19 Pandemic.

Case BC, Abramowitz J, Shea C, Rappaport H, ... Weintraub WS, Waksman R
Cardiac involvement in coronavirus disease 2019 (COVID-19) has been established. This is manifested by troponin elevation and associated with worse patient prognosis. We evaluated whether patient outcomes improved as experience accumulated during the pandemic. We analyzed COVID-19-positive patients with myocardial injury (defined as troponin elevation) who presented to the MedStar Health system (11 hospitals in Washington, DC, and Maryland) during the \"Early Phase\" of the pandemic (March 1 - June 30, 2020) and compared their characteristics and outcomes to the COVID-19-positive patients with the presence of troponin elevation in the \"Later Phase\" of the pandemic (October 1, 2020 - January 31, 2021). The cohort included 788 COVID-19-positive admitted patients for whom troponin was elevated, 167 during the \"Early Phase\" and 621 during the \"Later Phase.\" Maximum troponin-I in the \"Early Phase\" was 13.46±34.72 ng/mL versus 11.21±20.57 ng/mL in the \"Later Phase\" (p = 0.553). In-hospital mortality was significantly higher in the \"Later Phase\" (50.3% vs. 24.6%; p<0.001), as were incidence of intensive-care-unit admission (77.8% vs. 46.1%; p<0.001) and need for mechanical ventilation (61.7% versus 28%; p<0.001). In addition, more \"Early Phase\" patients underwent coronary angiography (6% vs. 2.3%; p=0.013). Finally, 3% of \"Early Phase\" and 0.8% of \"Later Phase\" patients underwent percutaneous coronary intervention (p=0.025). In conclusion, treatment outcomes have significantly improved since the beginning of the pandemic in COVID-19-positive patients with troponin elevation. This may be attributed to awareness, severity of the disease, improvements in therapies, and provider experience.

Copyright © 2021. Published by Elsevier Inc.

Am J Cardiol: 14 Oct 2021; 157:42-47

Impact of the Geriatric Nutritional Risk Index in Patients Undergoing Transcatheter Aortic Valve Implantation.

Koseki K, Yoon SH, Kaewkes D, Koren O, ... Komuro I, Makkar R
Several studies have shown that nutritional indexes are associated with cardiovascular events; however, limited studies have investigated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to evaluate the clinical impact of GNRI in patients undergoing TAVI. This single-center retrospective study analyzed consecutive patients treated with TAVI, stratified into groups according to their median baseline GNRI. The primary endpoint was 2-year all-cause mortality. In total, 968 patients with a mean age of 82.1 years and a median Society of Thoracic Surgeons (STS) score of 4.8% who underwent TAVI were included. The median GNRI was 103. Compared with the high-GNRI group (GNRI≥103, n = 451), the low-GNRI group (GNRI<103, n = 517) had higher STS scores and renal insufficiency rates. The 2-year all-cause mortality was significantly higher in the low-GNRI group than in the high-GNRI group (24.9% vs. 9.3%, p<0.001), despite no significant differences in procedural and clinical outcomes between the groups. On multivariable analysis, lower GNRI was independently associated with higher 2-year all-cause mortality (adjusted hazard ratio: 1.07; 95% confidence interval: 1.05-1.10; p<0.001). The GNRI retained its predictive value in subgroup analyses stratified by age (>75 vs. ≤75 years) and STS score (≥4 vs. <4). In conclusion, The GNRI is an important surrogate marker for predicting prognosis and mortality in patients undergoing TAVI.

Published by Elsevier Inc.

Am J Cardiol: 14 Oct 2021; 157:71-78

Lipoprotein(a) and subclinical coronary atherosclerosis in asymptomatic individuals.

Lee H, Park KS, Jeon YJ, Park EJ, ... Choi SH, Park GM
Background:
and aims
There are limited data regarding the association between lipoprotein(a) (Lp[a]) and subclinical coronary atherosclerosis. This study investigated the association between Lp(a) and subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population.
Methods
We retrospectively analyzed 7201 asymptomatic individuals (mean age 54.4 ± 7.9 years; 65.3% men with no prior history of coronary artery disease who voluntarily underwent CCTA as part of a general health examination). The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA. Study participants were stratified into quartiles according to their Lp(a) levels (<4.3, 4.3-8.9, 9.0-20.1, and ≥20.2 mg/dL).
Results
Of the study participants, any coronary plaque on CCTA was observed in 2557 (35.5%). Specifically, calcified, non-calcified, and mixed plaques were observed in 2411 (33.5%), 363 (5.0%) and 249 (3.5%) participants, respectively. After adjustment for the presence of cardiovascular risk factors, the fourth Lp(a) quartile was significantly associated with any coronary (odds ratio [OR] 1.212; 95% confidence interval [CI] 1.038-1.416), calcified (1.205, 95% CI 1.030-1.410), non-calcified (1.588, 95% CI 1.152-2.189), or mixed (1.674, 95% CI 1.172-2.391) plaque compared with the first Lp(a) quartile. In addition, 442 (6.1%) had significant coronary artery stenosis (≥50% diameter stenosis). The odds ratio for significant stenosis (1.537, 95% CI 1.153-2.048) was higher in the fourth quartile compared with the first quartile.
Conclusions
In this large cross-sectional study with asymptomatic individuals undergoing CCTA, higher Lp(a) level was associated with subclinical coronary atherosclerosis.

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

Atherosclerosis: 27 Sep 2021; epub ahead of print

Pericarditis Recurrence After Initial Uncomplicated Clinical Course.

Del Buono MG, Vecchié A, Damonte JI, Chiabrando JG, ... Gal TS, Abbate A
Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. However, the exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is unknown. We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the United States. We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis and selected only those with an uncomplicated course (without in-hospital death, large pericardial effusion [>20 mm] or tamponade, constriction, or incessant pericarditis) at the VCU Medical Center (Richmond, Virginia) from 2009 to 2018. A total of 240 patients met acute pericarditis criteria: of the 240 patients, 164 patients (68%) had an uncomplicated course (median age [interquartile range] in years: 50 [32 to 62], 43% females). The median follow-up time was 186 (19 to 467) days. Pericarditis was idiopathic in 84 patients (51%). Fifteen patients (9%) had at least 1 episode of recurrent pericarditis. Compared with those without recurrence, patients with recurrent pericarditis were younger (37 [25 to 59] vs 51 [34 to 62] years, p = 0.034), had a higher prevalence of subacute/delayed presentation (2 [13%] vs 1 [1%], p = 0.023), and less frequently received colchicine (6 [40%] vs 100 [67%], p = 0.036). At multivariate logistic regression analysis, subacute presentation and younger age remained predictors of recurrence at follow-up. In conclusion, 9% of patients with acute pericarditis experienced a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Younger age and subacute presentation were associated with a significantly increased risk of recurrence.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 27 Sep 2021; epub ahead of print

Frequency of Lipid-Rich Coronary Plaques in Stable Angina Pectoris versus Acute Coronary Syndrome (from the Lipid Rich Plaque Study).

Torguson R, Shlofmitz E, Mintz GS, Mario CD, ... Garcia-Garcia HM, Waksman R
The multicenter prospective Lipid Rich Plaque (LRP) registry showed that nonculprit (NC) lipid-rich plaques identified by near-infrared spectroscopy (maxLCBI_4mm >400) with an intravascular ultrasound plaque burden (PB) >70% and/or minimum lumen area (MLA) <4 mm² within the maxLCBI_4mm segment were more frequently associated with major adverse cardiac events (MACE) within 2 years. The aim of this sub-study was to report the relationship between initial clinical presentation and subsequent NC-MACE. Patients enrolled in the LRP study were stratified post hoc as having a stable angina pectoris or silent ischemia presentation versus acute coronary syndrome, excluding patients presenting with acute ST-elevation myocardial infarction. Among the 1552 patients, 717 presented with stable angina pectoris or silent ischemia. Patients presenting with acute coronary syndrome were more likely to be younger and Black, current smokers, and have less chronic kidney disease. Of the scanned nonculprit vessels, there was no difference between the 2 clinical presentation groups regarding lipidic content, and the rate of lipid-rich plaques (maxLCBI_4mm >400) was 31.9% in both groups. Finally, there was no difference in NC-MACE at 2 years\' follow-up, although within each group (stable versus acute coronary syndrome), the NC-MACE rate associated with maxLCBI_4mm >400 was significantly higher than maxLCBI_4mm ≤400 (stable 13.8% vs 6.5%; acute patients 11.6% vs 6.3%, respectively). In conclusion, in patient groups that present with stable angina pectoris or silent ischemia versus acute coronary syndrome, the NC lipidic content was similar, as was NC-MACE, through 2 years of follow-up.

Copyright © 2021. Published by Elsevier Inc.

Am J Cardiol: 31 Oct 2021; 158:1-5

Length of Preprocedure Fasting Was Associated With Contrast Associated-Acute Kidney Injury in High-Risk Patients Undergoing Coronary Angiography.

Shah A, Bazemore T, Wolf H, Yang H, Liu Y, Stouffer GA
Hydration is recommended to prevent contrast associated-acute kidney injury (CA-AKI) but interactions between blood pressure, left ventricular end diastolic pressure (LVEDP) and hydration status on CA-AKI are incompletely understood. This analysis presents the results of a single-center prospective study of patients undergoing coronary angiography with a predicted risk of CA-AKI >14%. 146 patients were enrolled with a mean (±SD) age of 71 ± 11 years; 94 (64.4%) were men, 142 (97.3%) had hypertension, 96 (65.8%) had diabetes mellitus and the mean (SD) serum creatinine was 1.21 ± 0.36 mg/dl. CA-AKI occurred in 31 (21%) patients. There were no significant differences in demographics, comorbidities, renal function, LVEDP, systolic blood pressure, diastolic blood pressure, heart rate, mean arterial pressure or pulse pressure in patients who developed versus those who did not develop CA-AKI. There was no association between the amount of peri-procedure intravenous fluids and change in creatinine postprocedure. In multivariate analysis, hemoglobin, the time that the patient was fasting from solids (NPO time), and contrast volume were associated with the development of CA-AKI. There was a highly significant interaction (p = 0.0028) between the amount of intravenous fluids, NPO time and contrast volume and changes in postprocedure creatinine. In summary, hemoglobin, NPO time and contrast volume, but not hemodynamic variables, correlated with worsening renal function following coronary angiography in this population of high-risk patients. Results suggested that intravenous hydration is important in subgroups of patients depending on NPO time and contrast volume.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:1-7

Temporal Trends in the Characteristics, Treatment, and Outcomes of Conservatively Managed Patients With Non-ST Elevation Acute Coronary Syndrome (from the ACSIS Registry 2000 to 2016).

Aviv Y, Shechter A, Richter I, Kornowski R, ... Pereg D, Eisen A
Despite advances in percutaneous coronary interventions (PCI), a subgroup of acute coronary syndrome (ACS) patients are still managed medically by a conservative approach. We sought to characterize a contemporary, large-scale, real-world cohort of ACS patients treated conservatively via pharmacological management, without PCI. Data was gathered from the ACS Israeli Survey (ACSIS) between 2000 and 2016, encompassing all consecutive patients admitted to cardiology wards with an ACS diagnosis. Included were 3,543 conservatively managed patients with non-ST elevation ACS (NSTE-ACS). Patients with ST elevation MI or those who underwent any coronary revascularization (PCI or bypass surgery) were excluded. Primary endpoints were 30-day major adverse cardiovascular events (MACE) and 1-year mortality. The study cohort was divided to 4 time-periods. Over 2 decades, medically managed NSTE-ACS patients remained of similar age (67 ± 13 years, p = 0.78), but had more atherosclerotic risk-factors and comorbidities. During time, patients were more often referred to diagnostic angiography and treated with statins, ACE-I/ARBs, and P2Y12 inhibitors (p < 0.001 for each). Over time, there were less in-hospital complications such as kidney injury and heart failure. The rate of 30-day MACE decreased (from 20.7% to 10.3%, earliest to latest period, p < 0.001). Compared with the earliest period, the latest period was associated with a reduction in 1-year mortality (14.7% to 11.6%; adjusted HR 0.65, 95% CI 0.47 to 0.90). In conclusion, Over 2 decades, in medically managed NSTE-ACS patients, short term prognosis has significantly improved while 1-year mortality demonstrated improvement only recently, likely due to incremental benefits of medical management.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:52-58

Predictors, Treatments, and Outcomes of Do-Not-Resuscitate Status in Acute Myocardial Infarction Patients (from a Nationwide Inpatient Cohort Study).

Kobo O, Moledina SM, Slawnych M, Sinnarajah A, ... Mohamed MO, Mamas MA
Little is known about how frequently do-not-resuscitate (DNR) orders are placed in patients with acute myocardial infarction (AMI), the types of patients in which they are placed, treatment strategies or clinical outcomes of such patients. Using the United States (US) National Inpatient Sample (NIS) database from 2015 to 2018, we identified 2,767,549 admissions that were admitted to US hospitals and during the hospitalization received a principle diagnosis of AMI, of which 339,270 (12.3%) patients had a DNR order (instigated both preadmission and during in-hospital stay). Patients with a DNR status were older (median age 83 vs 65, p < 0.001), more likely to be female (53.4% vs 39.3%, p < 0.001) and White (81.0% vs 73.3%, p < 0.001). Predictors of DNR status included comorbidities such as heart failure (OR: 1.47, 95% CI: 1.45 to 1.48), dementia (OR: 2.53, 95% CI: 2.50 to 2.55), and cancer. Patients with a DNR order were less likely to undergo invasive management or be discharged home (13.5% vs 52.8%), with only 1/3 receiving palliative consultation. In hospital mortality (32.7% vs 4.6%, p < 0.001) and MACCE (37.1% vs 8.8%, p < 0.001) were higher in the DNR group. Factors independently associated with in-hospital mortality among patients with a DNR order included a STEMI presentation (OR: 2.90, 95% CI: 2.84 to 2.96) and being of Black (OR: 1.29, 95% CI: 1.26 to 1.33), Hispanic (OR: 1.36, 95% CI: 1.32 to 1.41) or Asian/Pacific Islander (OR: 1.56, 95% CI:1.49-race. In conclusion, AMI patients with a DNR status were older, multimorbid, less likely to receive invasive management, with only one third of patients with DNR status referred for palliative care.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:8-18

Distal versus conventional radial access for coronary angiography and intervention: design and rationale of DISCO RADIAL Study.

Aminian A, Sgueglia GA, Wiemer M, Gasparini GL, ... Borovicanin V, Saito S
Background
Transradial access (TRA) has become the default access method for coronary diagnostic and interventional procedures. As compared to transfemoral access, TRA has been shown to be safer, cost-effective and more patient-friendly. Radial artery occlusion (RAO) represents the most frequent complication of TRA, and precludes future coronary procedures through the radial artery, the use of the radial artery as a conduit for coronary artery bypass grafting or as arteriovenous fistula for patients on hemodialysis. Recently, distal radial access (DRA) has emerged as a promising alternative to TRA, yielding potential for minimizing the risk of RAO. However, an international multicenter randomized comparison between DRA and conventional TRA with respect to the rate of RAO is still lacking.
Trial design
DISCO RADIAL is a prospective, multicenter, open-label, randomized, controlled, superiority trial. A total of 1300 eligible patients will be randomly allocated to undergo coronary angiography and/or percutaneous coronary intervention (PCI) through DRA or TRA using the 6 Fr Glidesheath Slender sheath introducer. Extended experience with both TRA and DRA is required for operators\' eligibility and optimal evidence-based best practice to reduce RAO systematically implemented by protocol. The primary endpoint is the incidence of forearm RAO assessed by vascular ultrasound at discharge. Several important secondary endpoints will also be assessed, including access-site cross-over, hemostasis time and access-site related complications.
Summary
The DISCO RADIAL trial will provide the first large-scale multicenter randomized evidence comparing DRA to TRA in patients scheduled for coronary angiography or PCI with respect to the incidence of RAO at discharge.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 15 Oct 2021; epub ahead of print

Translocator protein imaging with F-FEDAC-positron emission tomography in rabbit atherosclerosis and its presence in human coronary vulnerable plaques.

Maekawa K, Tsuji AB, Yamashita A, Sugyo A, ... Yoshinaga K, Asada Y
Background:
and aims
This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[¹⁸F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (¹⁸F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques.
Methods
¹⁸F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and balloon injury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of ¹⁸F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically. TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI).
Results
¹⁸F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi.
Conclusions
¹⁸F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques.

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

Atherosclerosis: 11 Oct 2021; 337:7-17

Long-term outcome of left atrial appendage occlusion with multiple devices.

Radinovic A, Falasconi G, Marzi A, D\'Angelo G, ... Bella PD, Mazzone P
Background
To evaluate long-term efficacy of left atrial appendage occlusion with multiple devices.
Methods
All consecutive patients who underwent left atrial appendage occlusion (LAAO) with a follow-up of at least 4 years, were included in this single center, retrospective registry. No specific exclusion criteria were applied. LAA occlusion was performed with the Watchman, Watchman FLX, Amplatzer Cardiac plug or Amplatzer Amulet occluder devices.
Results
A total of 224 consecutive patients underwent LAAO occlusion. Mean age was 72.5 ± 9.0 years. A history of stroke was present in 29%, TIA in 8.5% and a previous episode of bleeding in 64.7% of patients. In 63% there was a contraindication to oral anticoagulants. The average CHADS-VASc was 4.0 ± 1.6 and the average HAS-BLED was 3.4 ± 1.3. There was a reduction of strokes of 72.9%, thromboembolic events of 59.7% and major bleeding events of 70.9% compared to historic data. During follow-up, 48.3% of the ischemic and major bleeding events occurred within the first year. The annual mortality rate of 7.5 deaths/ 100 patients years. There were no significant differences in terms of outcome between the devices used and there were no late events associated with any device. The main antithrombotic regimen in the long term was with single antiplatelet therapy and the second one was no therapy.
Conclusion
LAAO is a safe and effective procedure, that reduces ischemic and bleeding events in the long-term, regardless of the type of device used, in AF patients at high risk of ischemic stroke and major bleeding, without the need of anticoagulation.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 28 Sep 2021; epub ahead of print

Percutaneous closure of a post-surgical ascending aortic pseudoaneurysm with an amplatzer septal occluder device and steerable guiding sheath.

McClure GR, Ratnayake G, Chan A, Gagnon J
Thoracic pseudoaneurysm in the ascending aorta is an uncommon condition associated with significant risk of morbidity and mortality. Treatment is recommended in all cases regardless of symptoms as the mortality rate if left untreated has been documented to be as high as 61%. The current standard of care for managing these lesions is open surgical repair. However, this is associated with significant morbidity. In-hospital mortality reported for patients undergoing surgical repair of an ascending aortic pseudoaneurysm ranges from 6.7% to 41%. When anatomically suitable, a less invasive approach using amplatzer vascular plug or septal occluder is an attractive approach. We present a case report of repair of a post-surgical ascending aortic false aneurysm using an amplatzer septal occluder with an Oscor ™ steerable guiding sheath; a novel approach to increase platform stability when engaging an aneurysm neck. Endovascular occluder deployment for closure of aortic false aneurysms remains a relatively novel technique. It is limited by the requirement to develop a stable endovascular platform to deliver the device and avoid system prolapse, particularly when accessing challenging lesions on the inner aortic curvature. We present the first case to utilize a steerable guiding sheath system to improve system stability and facilitate successful device delivery. Given the significant morbidity associated with open repair of these lesions we hope this will further expand the range of lesions viewed as appropriate for endovascular repair.

© 2021 Wiley Periodicals LLC.

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

Intracardiac echocardiography for guidance of transcatheter left atrial appendage occlusion: An expert consensus document.

Berti S, Pastormerlo LE, Korsholm K, Saw J, ... Santoro G, Nielsen-Kudsk JE
Transcatheter left atrial appendage occlusion (LAAO) is an increasingly used alternative to oral anticoagulation in selected patients with atrial fibrillation. Intraprocedural imaging is a crucial for a successful intervention, with transesophageal echocardiography (TEE) as the current gold standard. Since some important limitations may affect TEE use, intracardiac echocardiography (ICE) is increasingly used as an alternative to TEE for guiding LAAO. The lack of a standardized imaging protocol has slowed the adoption of ICE into clinical practice. On the basis of current research and expert consensus, this paper provides a protocol for ICE support of left atrial appendage occlusion.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 Sep 2021; 98:815-825

Prognosis of patients with acute pulmonary embolism and discordant right ventricle strain serum biomarkers.

Seropian IM, Chiabrando JG, Damonte JI, Halsband AL, ... Berrocal DH, Bluro IM
Background
Right ventricle strain serum biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-proBNP), are prognostic in patients with pulmonary embolism (PE). Prognosis accuracy in patients with discordancy between serum biomarkers remains, however, unknown.
Methods
We performed a retrospective analysis in patients with intermediate or high risk PE and discordant serum biomarkers of RV strain as follows: high hs-cTnT and low NT-proBNP (\'high troponin discordance\'), compared to patients with low hs-cTnT and high NT-proBNP (\'high NT-proBNP discordance\'). Cut-off values for high hs-cTnT were ≥14 pg/mL in patients <75 years and ≥45 pg/mL in patients >75-year. Cut-off values for high NT-proBNP were ≥600 pg/mL. The primary end-point was a composite of death, resuscitated cardiac arrest, mechanical ventilation, and inotrope use at one month. \'High troponin discordance\', age, sex and body mass index (BMI) were included in a logistic regression model. Time to event analysis was performed using Kaplan Meier curves and Log-rank test.
Results
73 patients were included. \'High troponin discordance\' patients (n=41) were younger, presented with a higher heart rate, more frequent bilateral PE, and received more thrombolytics as treatment compared with \'high NT-proBNP discordance\' patients (n = 32). Primary end-point was significantly higher in the \'high troponin discordance\' patients (29.3% vs 9.4%, p=0.045). \'High troponin discordance\' was independently associated with the primary end-point after adjusting for age, sex and BMI. Log rank test confirmed worse outcome in the high troponin discordance group (p=0.037).
Conclusions
High troponin discordance\' patients with intermediate/high risk PE, had worse outcomes than patients with high BNP discordance.

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

Int J Cardiol: 30 Sep 2021; 340:88-93

Impact of major infections on 10-year mortality after revascularization in patients with complex coronary artery disease.

Ono M, Kawashima H, Hara H, Mancone M, ... Serruys PW, SYNTAX Extended Survival Investigators
Background
The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear.
Methods and results
This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62-1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057).
Conclusions
Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years.
Trial registration
SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Oct 2021; 341:9-12

Outcomes of distal versus conventional transradial access for coronary angiography and intervention: An updated systematic review and meta-analysis.

Mhanna M, Beran A, Nazir S, Al-Abdouh A, ... Malhas SE, Eltahawy EA
Introduction
Distal transradial artery access (DTRA) has recently gained attention due to potential benefits in terms of local complications. In this meta-analysis, we aimed to evaluate the utility of DTRA compared to conventional transradial artery access (CTRA) for coronary angiography and intervention.
Method
Multiple databases were searched from inception through May 2021 for all the studies that evaluated the efficacy and safety of DTRA in the coronary field. The primary outcome was the access success rate. The secondary outcomes were periprocedural local complications (site hematoma, radial artery occlusion, and spasm) and procedural characteristics (cannulation, fluoroscopy, procedure, and radial artery compression times). All meta-analyses were conducted using a random-effect model.
Results
A total of 12 studies (including four randomized control trials) with 1634 patients who underwent DTRA vs. 1657 with CTRA were included in the final analysis. The access success rate was similar between the two groups (odds ratio (OR):0.62; 95% confidence interval (CI):0.30-1.26; P = 0.18; I² = 61%). DTRA was associated with a statistically significant lower rate of radial artery occlusion (OR:0.36; 95% CI: 0.22-0.59; P < 0.001; I² = 0%) but similar rates of radial artery spasm and site hematoma when compared to CTRA. Regarding the procedural characteristics, despite having a longer canulation time (mean difference (min.) [MD] 0.89, 95% CI 0.36-1.42; P < 0.0001), DTRA was associated with shorter compression time and comparable fluoroscopy and procedure times.
Conclusions
Our meta-analysis demonstrates that the DTRA is effective and safe with superiority in preventing radial artery occlusion when compared to CTRA.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 05 Oct 2021; epub ahead of print

Assessment of independent clinical predictors of early readmission after percutaneous endoluminal left atrial appendage closure with the Watchman device using National Readmission Database.

Rahman MU, Amritphale A, Kumar S, Trice C, Awan GM, Omar BA
Background
Percutaneous endoluminal left atrial appendage closure (pLAAC) procedure has been used to prevent strokes in patients who are not eligible for long-term prophylactic anticoagulation. Since its approval, multiple studies have looked at its efficacy with comparable outcomes to anticoagulation, the current standard of care.
Objectives
To assess the readmission rate and determine the factors associated with readmission after the endocardial pLAAC procedure using the Watchman device.
Methods
Data was obtained from the National Readmission Database (NRD), and we used SPSS software to determine statistically significant clinical predictors affecting readmission after implantation of the Watchman device at 30 days.
Results
The rate of readmission was found to be 9.2%. The true median cost of index hospitalization for the total population in the study was found to be [median (interquartile range = IQR), p] USD 24594 (USD 18883-31,041), whereas the true median cost of admission for those who were getting readmitted after 30 days was [median (IQR)] USD 7699 (USD 4955-14,243). Multivariate analysis of all clinically relevant predictors showed adjusted ratio for [adjusted odds ratio (OR), 95% confidence interval (95% CI), p-value] female genders (1.288, 1.104-1.503, p = 0.001), discharge to home health care (6.155, 1.509-25.096, p = 0.01), chronic kidney disease (CKD) (1.847,1.511-2.258, p < 0.001), chronic lung disease (1.419, 1.194-1.686, p < 0.001), heart failure (1.280, 1.040-1.574, p = 0.02), pericardial disorders (1.485, 1.011-2.179, p = 0.04), fluid and electrolyte disorders (1.456,1.050-2.018, p = 0.02) in those who were getting readmitted at 30-days compared to those who were not readmitted. The median length of stay for the index hospitalization was found to be one day, whereas the median length of stay at the 30-day readmission was reported to be [Median (IQR)] 4 days (2-6 days). Major cardiac reasons for readmission were heart failure, arrhythmias, and pericardial disorders.
Conclusion
Our study aims to assess 30-day outcomes in the US population after pLAAC using a Watchman device. Our analysis showed that one in ten patients were getting readmitted. In addition, chronic kidney disease, chronic obstructive pulmonary disease, heart failure, and pericardial disorders were associated with higher readmission rates. These findings will help us assess clinical correlations and predict which patients are more at risk of readmission after a Watchman procedure.

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

Int J Cardiol: 14 Nov 2021; 343:21-26

In vitro Doppler versus catheter transvalvular pressure gradients in balloon-expandable versus self-expanding transcatheter aortic valves.

Stanová V, Rieu R, Côté N, Salaun E, Rodés-Cabau J, Pibarot P
Objectives
The objective of this in vitro study was to compare Doppler versus catheter transvalvular pressure gradients (TPG) in third generations balloon-expandable (BE) versus self-expanding (SE) transcatheter heart valves (THV).
Background
TPG is a key parameter to assess and follow valve hemodynamic function following transcatheter aortic valve implantation (TAVI). It remains uncertain and debated whether, and to which extent, TPGs differ according to the type of THV, that is, BE versus SE and to the method used for TPG measurement, that is, Doppler echocardiography versus cardiac catheterization.
Methods
The CoreValve EVOLUT PRO 26 mm and the SAPIEN 3 23 mm THVs were tested in a left heart simulator using a 21 mm aortic annulus under following conditions: heart rate: 70 bpm, mean aortic pressure: 100 mmHg, stroke volume: 30, 70 and 100 ml. Mean TPGs were measured by continuous-wave Doppler and by micro-tip pressure catheters positioned in the left ventricle and at 50 mm downstream to the tip of the THV leaflets.
Results
Doppler TPGs (9.5 ± 3.9 mmHg) were on average 40.5 ± 13.9% higher (p < 0.001) than catheter TPGs (6.3 ± 3.4 mmHg). Both Doppler and catheter TPGs were lower (p = 0.003) in the SE versus BE THVs (Doppler: 8.7 ± 3.5 vs. 10.7 ± 4.6; catheter: 5.0 ± 1.7 mmHg vs. 7.1 ± 2.2). The Doppler versus catheter difference in TPG increased with the higher flow conditions. The Doppler versus catheter difference in TPG was similar in BE versus SE THVs (3.6 ± 1.1 vs. 3.7 ± 1.4 mmHg or 42 ± 9 vs. 47 ± 9%; p = 0.58) overall and in each flow conditions.
Conclusion
The Doppler TPGs are, on average, 40% higher than the catheter TPGs for both BE and SE THVs. The SE THV had lower Doppler and catheter TPGs compared to the BE THV, at normal and high flow states. The absolute and percent differences between Doppler versus catheter TPGs were similar in BE versus SE THVs.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 10 Oct 2021; epub ahead of print

Conventional versus modified delivery system technique in commissural alignment from the Evolut low-risk CT substudy.

Tang GHL, Sengupta A, Alexis SL, Zaid S, ... Kini A, Reardon MJ
Objectives
We assessed the impact of conventional delivery system (DS) insertion technique on \"Hat-marker\" orientation/commissural alignment in patients who underwent transcatheter aortic valve replacement (TAVR) in the Evolut Low Risk Trial CT substudy versus a modified technique.
Background
Unlike surgical aortic valve replacement, where alignment of the surgical valve commissures with native commissures can be achieved virtually 100% of the time, commissural alignment during TAVR is not achieved consistently. This may subsequently impact the feasibility of both coronary access and reintervention after TAVR.
Methods
\"Hat-marker\" orientations during deployment were characterized as outer curve (OC), center front (CF), inner curve, and center back. Severe commissure-to-CA overlap was 0-20°. \"Hat-marker\" orientations and CA overlap were compared to 240 patients from a single center using the modified 3-o\'clock flush port DS technique.
Results
In the CT substudy in which conventional DS insertion was performed (flush port at 12 o\'clock); 154/249 had both analyzable CT and procedural fluoroscopy to validate \"Hat-marker\" to C-tab/commissural orientation. On post-TAVR CT, Evolut valve commissural orientation and coronary artery (CA) ostia were identified. Compared to conventional DS technique in the CT substudy, the modified technique had higher rates of \"Hat-marker\" at OC/CF orientation, improved commissural alignment and reduced severe CA overlap; (left main, 14.2 vs. 27.9%; right coronary artery, 11.7 vs. 27.3% both, 5.0 vs. 13.6%; 1 or both CA, 20.8 vs. 41.6%, all p < 0.01).
Conclusions
The modified technique improved initial \"Hat-marker\" orientation during Evolut deployment and resulted in better commissural alignment and reduced CA overlap.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 08 Oct 2021; epub ahead of print

Instantaneous wave-free ratio compared with fractional flow reserve in PCI: A cost-minimization analysis.

Berntorp K, Persson J, Koul SM, Patel MR, ... Fröbert O, Götberg M
Background
Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization.
Methods
In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result.
Results
The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions.
Conclusions
IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 29 Sep 2021; epub ahead of print

Pretreatment With P2Y12 Inhibitors in Patients With Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Report From the Swedish Coronary Angiography and Angioplasty Registry.

Jurga J, Szummer KE, Lewinter C, Mellbin L, ... Jernberg T, Venetsanos D
Background
In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors\' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population.
Methods
In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding.
Results
We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel.
Conclusions
In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care.



Circ Cardiovasc Interv: 30 Sep 2021:CIRCINTERVENTIONS121010849; epub ahead of print

Finding sideline benefits-Of pandemics and same-day-discharge following rotational atherectomy.

Hawamdeh H, Moliterno DJ
The occurrence of same-day discharge following elective rotational atherectomy cases in England and Wales during 2007-2014 increased from approximately 7 to 36%. High-volume centers and transradial approach were associated with more likelihood of same-day discharge. As compared with patients who stayed for overnight observation following elective rotational atherectomy, those discharged the same day as the procedure had a similar rate of 30-day mortality (0.35 and 0.50%, respectively; p = 0.409).

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 Sep 2021; 98:689-690

Thirty-day outcomes and predictors of mortality following acute myocardial infarction in northern Tanzania: A prospective observational cohort study.

Goli S, Sakita FM, Kweka GL, Tarimo TG, ... Limkakeng AT, Hertz JT
Objective
There is a rising burden of myocardial infarction (MI) within sub-Saharan Africa. Prospective studies of detailed MI outcomes in the region are lacking.
Methods
Adult patients with confirmed MI from a prospective surveillance study in northern Tanzania were enrolled in a longitudinal cohort study after baseline health history, medication use, and sociodemographic data were obtained. Thirty days following hospital presentation, symptom status, rehospitalizations, medication use, and mortality were assessed via telephone or in-person interviews using a standardized follow-up questionnaire. Multivariate logistic regression was performed to identify baseline predictors of thirty-day mortality.
Results
Thirty-day follow-up was achieved for 150 (98.7%) of 152 enrolled participants. Of these, 85 (56.7%) survived to thirty-day follow-up. Of the surviving participants, 71 (83.5%) reported persistent anginal symptoms, four (4.7%) reported taking aspirin regularly, seven (8.2%) were able to identify MI as the reason for their hospitalization, and 17 (20.0%) had unscheduled rehospitalizations. Self-reported history of diabetes at baseline (OR 0.32, 95% CI 0.10-0.89, p = 0.04), self-reported history of hypertension at baseline (OR 0.34, 95% CI 0.15-0.74, p = 0.01), and antiplatelet use at initial presentation (OR 0.19, 95% CI 0.04-0.65, p = 0.02) were all associated with lower odds of thirty-day mortality.
Conclusions
In northern Tanzania, thirty-day outcomes following acute MI are poor, and mortality is associated with self-awareness of comorbidities and medication usage. Further investigation is needed to develop interventions to improve care and outcomes of MI in Tanzania.

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

Int J Cardiol: 31 Oct 2021; 342:23-28

The impact of computed tomography-derived aortic atheroma volume on prognosis after transcatheter aortic valve replacement.

Fujita H, Toba T, Miwa K, Suzuki M, ... Kono A, Hirata KI
Background
The impact of the extent of aortic atheroma on patients\' prognosis after transcatheter aortic valve replacement (TAVR) has not been completely evaluated. This study aimed to evaluate the prognostic value of the aortic atheroma volume (AAV) derived from computed tomography, and the effect of its differences among the segments of the aorta, in patients undergoing TAVR.
Methods
In total, 143 patients with symptomatic severe aortic stenosis who underwent pre-procedural computed tomography before TAVR procedure indication were evaluated. AAV was calculated by measuring the aortic lumen and vessel volume using every 1-mm axial image and was further divided into thoracic (TAAV) and abdominal segments (AbAAV).
Results
During a median follow-up of 651 days, 24 all-cause and 14 cardiac deaths occurred. In the Kaplan-Meier analysis, the high AAV group had significantly higher all-cause and cardiac mortalities than the low AAV group (p = 0.016 and 0.023, respectively). Regarding segmental AAV, all-cause and cardiac mortalities did not have significant differences between the high and low TAAV groups. Moreover, all-cause and cardiac mortalities were significantly higher in the high AbAAV group than in the low AbAAV group (p = 0.0043 and 0.023, respectively). The multivariable analysis showed that only AbAAV was an independent predictor for all-cause mortality (hazard ratio: 1.06, p = 0.046).
Conclusion
AAV was significantly associated with the mortality after TAVR. The current study suggests the pre-procedural assessment of AAV is valuable in predicting prognosis after TAVR. However, further investigation with a larger sample size is needed to validate our findings.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 29 Sep 2021; epub ahead of print

Ticagrelor versus prasugrel in patients with acute myocardial infarction.

Park S, Kim YG, Ann SH, Park HW, ... Han S, Park GM
Background
Ticagrelor and prasugrel are the mainstay of antithrombotic therapy for patients with acute myocardial infarction (MI). However, direct comparative data on clinical outcomes of potent P2Y12 inhibitors are limited, especially in East Asian populations. We aimed to evaluate the effect of ticagrelor versus prasugrel on clinical outcomes in patients with acute MI.
Methods
From the Korean nationwide National Health Insurance database, 10,797 patients with acute MI who received either ticagrelor or prasugrel in combination with aspirin after percutaneous coronary intervention (PCI) were enrolled. The primary outcome was net clinical benefit, defined as a composite of death, MI, stroke, or major bleeding. Secondary outcomes included the individual components of the primary outcome as effectiveness and safety measures.
Results
Among 10,797 patients, 9591 (88.8%) received ticagrelor and 1206 (11.2%) received prasugrel. During a median follow-up of 1.8 years, the primary outcome occurred in 1051 (16.6%) and 131 (14.4%) patients in the ticagrelor and prasugrel groups, respectively. In the propensity score matched cohort (n = 5979), the risk for the primary outcome was similar between the two groups (hazard ratio [HR] 0.949 for prasugrel; 95% confidence interval [CI]: 0.780-1.154). The risks for the composite of death, MI, or stroke (HR 0.938; 95% CI: 0.752-1.169) and major bleeding (HR 1.022; 95% CI: 0.709-1.472) were also comparable.
Conclusions
In patients with acute MI undergoing PCI, ticagrelor and prasugrel appeared to have similar net clinical benefits. The risks for death, MI, or stroke and major bleeding were not significantly different between the two groups.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 03 Oct 2021; epub ahead of print

Impact of intravascular ultrasound on Outcomes following PErcutaneous coronary interventioN for In-stent Restenosis (iOPEN-ISR study).

Shlofmitz E, Torguson R, Zhang C, Mintz GS, ... Garcia-Garcia HM, Waksman R
Background
Percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) remains common. Intravascular imaging allows for the determination of the mechanism of ISR, potentially guiding appropriate therapy. Intravascular ultrasound (IVUS)-guided stent implantation is associated with a reduction in adverse events after PCI, but its impact on treatment of ISR is not clear.
Methods
All patients with 1-year follow-up after ISR treatment from 2003 through 2016 were included and stratified by IVUS use. The primary endpoint was the rate of major adverse cardiac events (MACE) at 1 year, defined as the composite of all-cause mortality, Q-wave myocardial infarction, and target vessel revascularization (TVR).
Results
The final analysis included 1522 ISR patients, 65.9% of whom were treated with IVUS guidance. The primary endpoint occurred in 18.0% of patients treated with IVUS guidance vs. 24.5% of patients treated with angiography guidance (p = 0.0014). Post-dilatation was used more often with IVUS (18.6% vs. 14.1%, p < 0.001), with a larger diameter of new stents (3.04 ± 0.35 mm vs. 2.94 ± 0.47 mm, p = 0.001). At 1 year, TVR occurred in 14.5% with IVUS guidance and 19.2% with angiography guidance (p = 0.021).
Conclusions
The use of IVUS is associated with decreased MACE at 1 year following PCI for ISR. These results support routine IVUS for the treatment of ISR lesions.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2021; 340:17-21

Integrated coronary disease burden and patterns to discriminate vessels benefiting from percutaneous coronary intervention.

Dai N, Zhang R, Hu N, Guan C, ... Xu B, Ge J
Objective
To evaluate the prognostic implications of atherosclerosis functional pattern on ischemia-causing vessels received percutaneous coronary intervention (PCI) or conservative treatment.
Background
Quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) index is recently proposed to characterize atherosclerosis functional pattern, but its prognostic value remains unclear.
Methods
QFR-derived PPG index was retrospectively calculated in patients from the PANDA III trial. Vessels with low or high PPG treated by PCI or not were compared for the risk of 2-year vessel-oriented composite outcome (VOCO), which was a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death.
Results
A total of 1444 vessels were included while 94 (6.5%) VOCOs occurred within 2 years. Among physiologically ischemic vessels (QFR ≤ 0.80) treated by PCI, those with low PPG acquired higher VOCO risk than those with high PPG (8.4% vs. 3.8%; adjusted hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.18 to 3.86), and a similar VOCO risk (8.4% vs. 7.8%; adjusted HR 1.11, 95%CI 0.70-1.78) compared to those treated by conservatively. After multiple adjustment, PPG index was an independent predictor for VOCO (HR 1.30, 95% CI 1.05-1.62). The addition of PPG to the model of clinical risk factors substantially improved the predictions of VOCO (C-index 0.67 vs. 0.62, net reclassification index 0.42).
Conclusions
PCI treatment was associated with improved outcomes in vessels with high PPG, but not for those with low PPG, which acquired similar risk of VOCO compared to vessels treated conservatively. QFR-derived PPG might assist the treatment strategy selection in ischemia-causing vessels.

© 2021 Wiley Periodicals LLC.

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

Midterm Outcomes Following Sutureless and Transcatheter Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis.

Vilalta V, Alperi A, Cediel G, Mohammadi S, ... Bayés-Genís A, Rodés-Cabau J
Background
Sutureless-surgical aortic valve replacement (SU-SAVR) has been proposed as a surgical alternative for treating aortic stenosis, which facilitates a minimally invasive approach. While some studies have compared the early outcomes of SU-SAVR versus transcatheter aortic valve replacement (TAVR), most data were obtained in high-risk patients and/or limited to in-hospital outcomes. This study aimed to compare in-hospital and midterm clinical outcomes following SU-SAVR and TAVR in low-risk patients with aortic stenosis.
Methods
A total of 806 consecutive low-risk (EuroSCORE II <4%) patients underwent TAVR or SU-SAVR between 2011 and 2020 in 2 centers. A 1:1 propensity score matching was performed and identified 171 pairs with similar characteristics that were included in the analysis. Baseline characteristics, in-hospital and follow-up events (defined according to Valve Academic Research Consortium-2) were collected.
Results
Baseline characteristics were well balanced between groups, with a median EuroSCORE II of 1.9% (1.3%-2.5%) in both SU-SAVR and TAVR groups (P=0.85). There were no statistically significant differences regarding in-hospital mortality (SU-SAVR: 4.1%, TAVR: 1.8%, P=0.199) and stroke (SU-SAVR: 2.3%, TAVR: 2.9%, P=0.736), but SU-SAVR recipients exhibited higher rates of bleeding and new-onset atrial fibrillation, higher residual transvalvular gradients (P<0.001), and a lower rate of pacemaker implantation (P=0.011). After a median follow-up of 2 (1-3) years, there were no differences between groups in all-cause mortality (hazard ratio, 0.97 [95% CI, 0.52-1.82], P=0.936) and stroke (hazard ratio, 0.83 [95% CI, 0.32-2.15], P=0.708), but SU-SAVR was associated with a higher risk of heart failure hospitalization (hazard ratio, 5.38 [95% CI, 1.88-15.38], P=0.002).
Conclusions
In low-risk patients with aortic stenosis, TAVR was associated with improved in-hospital outcomes (except for conduction disturbances) and valve hemodynamics, compared with SU-SAVR. Although similar mortality and stroke rates were observed at 2-year follow-up, the risk of heart failure hospitalization was higher among SU-SAVR patients. These results may contribute to reinforce TAVR over SU-SAVR for the majority of such patients.



Circ Cardiovasc Interv: 04 Oct 2021:CIRCINTERVENTIONS121011120; epub ahead of print

Impact of diabetes mellitus on outcome after transcatheter aortic valve replacement: Identifying high-risk diabetic population from the OCEAN-TAVI registry.

Matsumoto S, Ohno Y, Miyamoto J, Ikari Y, ... Hayashida K, OCEAN-TAVI Investigators
Objectives
To identify the vulnerable diabetic cohort in patients undergoing transcatheter aortic valve replacement (TAVR).
Backgrounds
Considerable controversy remains about whether specific cohort exists in which presence of diabetes mellitus (DM) carries adverse risk of mortality after TAVR.
Methods
Of the 2588 patients who were enrolled in the OCEAN-TAVI registry, 2526 patients with glycohemoglobin data were analyzed. The individuals were divided into DM and non-DM groups according to previous medical history of DM or using diabetic medicine, and increased HbA1c values (≥6.5%) at baseline. The primary endpoint of this study was 2-year all-cause mortality after TAVR.
Results
The follow up rate of clinical outcome at 1-year was 2514/2526 (99.5%) and median follow-up period was 22.5 months. DM group had 699 (27.7%) patients, in which 153 (21.9%) was diagnosed by increased HbA1c levels without previous medical history of DM. Kaplan-Meier curve of 2-year all-cause mortality presented significant difference between patients with and without DM (p = 0.029). In addition, patients with low-density lipoprotein cholesterol (LDL-C) levels > 100 mg/dl and left ventricular ejection fraction (LVEF) < 40% had great risk of mortality after TAVR (LDL-C: hazard ratio [HR] 1.82, p < 0.001; LVEF: HR 2.61, p = 0.002, respectively).
Conclusions
Presence of DM was significantly associated with poor outcome after TAVR and adverse effect of DM was remarkable in patients with relatively higher LDL-C levels and reduced LVEF under 40%. These subtypes may need intensive control of cardiovascular risk factors, including DM, before and after TAVR.

© 2021 Wiley Periodicals LLC.

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

Left atrial appendage closure for stroke prevention in atrial fibrillation: Final report from the French left atrial appendage closure registry.

Teiger E, Thambo JB, Defaye P, Hermida JS, ... Le Corvoisier P, French national Left Atrial Appendage Closure registry (FLAAC) investigators
Objectives
The French left atrial appendage (LAA) closure registry (FLAAC) aimed to assess the safety and efficacy of LAA closure in daily practice.
Background
LAA closure has emerged as an alternative for preventing thromboembolic events (TE) in patients with non-valvular atrial fibrillation (NVAF). Clinical data in this field remains limited and few investigator-initiated, real-world registries have been reported.
Methods
This nationwide, prospective study was performed in 36 French centers. The primary endpoint was the TE rate after successful LAA closure.
Results
The FLAAC registry included 816 patients with a mean age of 75.5 ± 0.3 years, mean follow-up of 16.0 ± 0.3 months, high TE (CHA₂ DS₂ -VASc score: 4.6 ± 0.1) and bleeding risks (HAS-BLED score: 3.2 ± 0.05) and common contraindications to long-term anticoagulation (95.7%). Procedure or device-related serious adverse events occurred in 49 (6.0%) patients. The annual rate of ischemic stroke/systemic embolism was 3.3% (2.4-4.6). This suggests a relative 57% reduction compared to the risk of stroke in historical NVAF populations without antithrombotic therapy. By multivariate analysis, history of TE was the only factor associated with stroke/systemic embolism during follow-up (HR, 3.3 [1.58-6.89], p = 0.001). The annual mortality rate was 10.2% (8.4-12.3). Most of the deaths were due to comorbidities or underlying cardiovascular diseases and unrelated to the device or to TE.
Conclusions
Our study suggests that LAA closure can be an option in patients with NVAF. Long-term follow-up mortality was high, mostly due to comorbidities and underlying cardiovascular diseases, highlighting the importance of multidisciplinary management after LAA closure.
Registration
NCT02252861.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 Sep 2021; 98:788-799

Finding the optimal access for proximal upper limb artery (PULA) interventions: Lessons learned from the PULA multicenter registry.

Nardai S, Zafirovska B, Pataki Á, Nemes B, ... Merkely B, Ruzsa Z
Objective
The multicenter proximal upper limb artery (PULA) Registry was created to study the optimal puncture sites for the interventions involving the subclavian, axillary, and innominate arteries.
Background
Little is known about the optimal vascular access for PULA interventions, despite the well-known technical complexity of these procedures.
Methods
We performed the retrospective analysis of consecutive patients treated for symptomatic steno-occlusive disease of the proximal upper limb arteries between January 2015 and December 2019 in three high-volume centers. Acute thrombotic occlusions were excluded from the study.
Results
Two hundred and seventy-two patients were treated for significant stenosis and 108 for total occlusion. The baseline patient\'s characteristics were similar, except for the higher median age of the stenotic patients: 68.5 years (31.1; 90.0) versus 64 years (38.0; 86.0) p = 0.0015. Successful revascularization rate was higher in the stenotic group 93.75% (255/272) versus 86.11% (93/108) p = 0.0230, while the procedure length 27 min (8; 133) versus 46 min (7; 140) p = 0.0001 and fluoroscopy times 439 s (92; 2993) versus 864 s (86; 4176) p = 0.0001 were higher in the occlusion group. The main adverse event rate was similarly low. Dual access was used more often to treat occlusions (60.19% (65/108) vs. 11.40% (31/272) p = 0.0001) without significantly increasing the complication rate. The safest access was ultrasound-guided distal radial artery puncture, significantly better than conventional radial access with 0% (0/31) versus 13.6% (18/131) p = 0.0253 complication.
Conclusions
The percutaneous revascularization of proximal upper limb arteries is a safe and effective. Dual access can be applied to increase treatment efficacy, without significantly compromising safety.

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

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

Safety and efficacy of dedicated guidewire, microcatheter, and guide catheter extension technologies for chronic total coronary occlusion revascularization: Primary results of the Teleflex Chronic Total Occlusion Study.

Kandzari DE, Alaswad K, Jaffer FA, Brilakis E, ... Buller C, Karmpaliotis D
Background
Description of procedural outcomes using contemporary techniques that apply specialized coronary guidewires, microcatheters, and guide catheter extensions designed for chronic total occlusion (CTO) percutaneous revascularization is limited.
Methods
A prospective, multicenter, single-arm study was conducted to evaluate procedural and in-hospital outcomes among 150 patients undergoing attempted CTO revascularization utilizing specialized guidewires, microcatheters and guide extensions. The primary endpoint was defined as successful guidewire recanalization and absence of in-hospital cardiac death, myocardial infarction (MI), or repeat target lesion revascularization (major adverse cardiac events, MACE).
Results
The prevalence of diabetes was 32.7%; prior MI, 48.0%; and previous bypass surgery, 32.7%. Average (mean ± standard deviation) CTO length was 46.9 ± 20.5 mm, and mean J-CTO score was 1.9 ± 0.9. Combined radial and femoral arterial access was performed in 50.0% of cases. Device utilization included: support microcatheter, 100%; guide catheter extension, 64.0%; and mean number of study guidewires/procedure was 4.8 ± 2.6. Overall, procedural success was achieved in 75.3% of patients. The rate of successful guidewire recanalization was 94.7%, and in-hospital MACE was 19.3%. Achievement of TIMI grade 2 or 3 flow was observed in 93.3% of patients. Crossing strategies included antegrade (54.0%), retrograde (1.3%) and combined antegrade/retrograde techniques (44.7%). Clinically significant perforation resulting in hemodynamic instability and/or requiring intervention occurred in 16 (10.7%) patients.
Conclusions
In a multicenter, prospective registration study, favorable procedural success was achieved despite high lesion complexity using antegrade and retrograde guidewire maneuvers and with acceptable safety, yet with comparably higher risk than conventional non-CTO PCI.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 27 Sep 2021; epub ahead of print

Optical coherence tomography, intravascular ultrasound or angiography guidance for distal left main coronary stenting. The ROCK cohort II study.

Cortese B, de la Torre Hernandez JM, Lanocha M, Ielasi A, ... Fineschi M, Burzotta F
Objectives
to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly.
Background
Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited.
Methods
ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS.
Results
A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93: p = 0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found.
Conclusions
Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 27 Sep 2021; epub ahead of print

Initial experience with the fourth generation MitraClip™: Outcomes, procedural aspects, and considerations for device selection.

Garcia-Sayan E, Raghunathan D, Li FM, Dhoble A, ... Smalling RW, Mackensen GB
Objectives
We present our initial experience with the fourth-generation MitraClip™ (G4) system and propose preliminary criteria for device selection.
Background
The MitraClip™ G4 system recently underwent a \"controlled release\" for transcatheter edge-to-edge mitral valve repair. The four new devices include technical improvements such as controlled gripper actuation (independent leaflet capture) and continuous left atrial pressure monitoring. To date, a patient-specific device selection algorithm, and the technology\'s impact on procedural times and success, have not been described.
Methods
We present an initial multi-center experience and short-term outcomes with the new system, suggest procedural and imaging considerations, and propose initial guidance for device selection.
Results
Sixty-one procedures performed by three operators at two centers between November 2019 and May 2020 were analyzed. At 30-day follow-up, there were three deaths (4.9%), four neurological events (6.6%), and seven re-hospitalizations (11.5%). Fifty-nine patients achieved device and procedural success (96.7%), and there was one device-related technical issue (1.6%). Compared to the same operators utilizing the third generation MitraClip™, the G4 system resulted in a significant reduction in the median number of clips used per patient (1 IQR 1-2 vs. 2 IQR 1-3, p = .023) and a trend toward shorter device times.
Conclusion
Based on our initial experience, we found that the MitraClip™ G4 system is associated with high procedural success and fewer devices needed per procedure. The expanded device options may allow a more targeted approach to the myriad of pathologic presentations of mitral regurgitation. This early experience should provide a foundational opportunity for further refinement.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 Sep 2021; 98:E626-E636

Percutaneous mitral valve repair with MitraClip device in hemodynamically unstable patients: A systematic review.

Martinez-Gomez E, McInerney A, Tirado-Conte G, de Agustin JA, ... Macaya C, Nombela-Franco L
Background
Very few data exist on percutaneous mitral valve repair (PMVr) in unstable patients with concomitant moderate-severe mitral regurgitation (MR). The purpose of this systematic review was to evaluate baseline characteristics, management and clinical outcomes of critically ill patients undergoing PMVr with MitraClip.
Methods
We conducted a systematic review of the published data on MitraClip from its first use in 2003 to December 2020. Studies referring to critically ill patients in cardiogenic shock or acute refractory pulmonary edema were included. A total of 40 publications including 254 patients with significant MR (Grade 4 in 91%) were included.
Results
Mean age was 70 ± 12 years with mean Euroscore II and STS of 21 ± 13 and 20.5 ± 16, respectively. Clinical presentation was with cardiogenic shock and acute myocardial infarction in 72.8 and 60.0% of patients, respectively. Device success was achieved in 238 (93.7%) patients with a significant reduction in MR (Grade ≤ 2 in 91.8%, p < .001). The median weaning time from the procedure, to discontinuation of mechanical circulatory or respiratory support, was 2 days (IQR 1-4), with an in-hospital mortality and non-fatal complication rate of 12.6 and 9.1%, respectively. Kaplan-Meier curves estimated an overall mortality rate of 39.1% at 12-month follow-up, with persistent reduction in MR severity for survivors (Grade ≤ 2 in 81.3%) and one case of mitral valve reintervention.
Conclusions
Percutaneous mitral valve repair with MitraClip device is a technically feasible and potentially viable management option in high-risk patients with cardiogenic shock or refractory pulmonary edema and concomitant moderate-severe MR. Prospective trials are required to confirm these findings, and definitively determine the value of MitraClip in hemodynamically unstable patients.

© 2021 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 Sep 2021; 98:E617-E625

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

Cook CM, Howard JP, Ahmad Y, Shun-Shin MJ, ... Francis DP, Davies JE
Objectives
Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis.
Methods
Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli.
Results
Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm^-1.sec^-1 vs 4.2 ± 1.7 mmHg.cm^-1.sec^-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all).
Conclusions
In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2021; 342:7-14