High-risk coronary plaque refers to a distinct set of plaque characteristics prone to future coronary events. Coronary physiology represents a group of indexes reflective of the local physiological ...environment and hemodynamic changes in the macrovascular and microvascular system. Although a large body of evidence has supported the clinical relevance of these 2 factors, currently, identifying plaque morphology cannot reliably capture the lesion subset that causes hard events. Also, the guideline-directed approach based on physiological indexes cannot fully predict and prevent clinical events. In parallel, there is accumulating evidence that these 2 aspects of coronary artery disease influence each other with significant clinical implications, despite traditionally being considered to have separate effects on significances, treatments, and outcomes. In this state-of-the-art review, the authors explore the clinical evidence of pathophysiological interplay of physiological indexes related to local hemodynamics, epicardial stenosis, and microvascular dysfunction with plaque morphological characteristics that provide a better understanding of the nature of coronary events. Furthermore, the authors examine the emerging data on the complementary role between plaque morphology and coronary physiology in prognostication and how to apply this concept to overcome the limitations of individual assessment alone. Finally, they propose the potential benefit of integrative assessment of coronary anatomy, plaque quantity and quality, and physiological aspects of a target lesion and vessels for personalized risk profiling and optimized treatment strategy.
Objectives
We aimed to develop a novel wire‐ and adenosine‐free microcirculatory resistive index from functional angiography (angio‐IMR) to estimate coronary microcirculatory resistance, and to ...investigate how this method can improve clinical interpretation of physiological stenosis assessment with quantitative flow ratio (QFR).
Background
Hyperemic index of coronary microcirculatory resistance (IMR) is a widely used tool to assess microcirculatory dysfunction. However, the need of dedicated intracoronary wire and hyperemia limits its adoption in clinical practice.
Methods
We performed our study in two separate stages: (1) development of a formula (angio‐IMR) to estimate IMR from resting angiograms and aortic pressure (Pa), and (2) validation of the method in a clinical population using invasively measured IMR as reference. Additionally, QFR diagnostic performance was assessed considering angio‐IMR values.
Results
We developed the formula: angio‐IMR = (Pa–0.1*Pa)*QFR*e‐Tmn (where e‐Tmn is an estimation of hyperaemic mean transit time) and validated it in 115 vessels (104 patients). Angio‐IMR correlated well with IMR (Spearman's rho = 0.70, p < 0.001). Sensitivity, specificity, positive and negative predictive value, accuracy and area under the curve of angio‐IMR to predict IMR were 87.5% (73.2–95.8), 85.3% (75.3–92.4), 76.1% (64.5–84.8), 92.8% (84.9–96.7), 85% and 0.90 (0.83–0.95), respectively. False positive QFR measurements decreased from 19.5% to 8.5% when angio‐IMR was incorporated into the QFR interpretation workflow.
Conclusions
Estimation of IMR without physiology wire and adenosine is feasible. Coronary microcirculatory dysfunction causing high IMR can be ruled‐out with high confidence in vessels with low angio‐IMR. Awareness of angio‐IMR contributes to a better clinical interpretation of functional stenosis assessment with QFR.
A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest ...benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy.
HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium BARC criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971.
From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference −2·9%, pnon-inferiority<0·0001; hazard ratio 0·70 95% CI 0·52–0·92, pequivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 0·40–1·45; p=0·40), and the risk of bleeding events was significantly decreased (0·48 0·32–0·73; p=0·0007).
In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia.
Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.
Revascularization of coronary artery stenosis should be based on objective evidence of ischemia. Fractional flow reserve (FFR) is an invasive physiologic index that can be easily measured in the ...cardiac catheterization laboratory to assess the functional significance of coronary stenosis. FFR-guided revascularization strategy has been proven to be better than angiography-guided strategy in patients with coronary artery disease. Recent development of more convenient ways to induce hyperemia will reduce the barrier to measuring FFR and further expand its clinical applicability. Invasive physiologic indices without hyperemia are also under active investigation. Moreover, a novel noninvasive FFR measurement based on coronary CT angiography and computational fluid dynamics has been developed and will soon be incorporated into clinical practice. Given the rapid adoption of invasive and noninvasive physiologic indices in daily practice, a review of the current status of FFR and future perspectives is presented. (Circ J 2014; 78: 1048–1054)
Abstract Background The prognostic impact of microvascular status in patients with high fractional flow reserve (FFR) is not clear. Objectives The goal of this study was to investigate the ...implications of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients who underwent FFR measurement. Methods Patients with high FFR (>0.80) were grouped according to CFR (≤2) and IMR (≥23 U) levels: group A, high CFR with low IMR; group B, high CFR with high IMR; group C, low CFR with low IMR; and group D, low CFR with high IMR. Patient-oriented composite outcome (POCO) of any death, myocardial infarction, and revascularization was assessed. The median follow-up was 658 days (interquartile range: 503.8 to 1,139.3 days). Results A total of 313 patients (663 vessels) were assessed with FFR, CFR, and IMR. Correlation ( r = 0.201; p < 0.001) and categorical agreement (kappa value = 0.178; p < 0.001) between FFR and CFR were modest. Low CFR was associated with higher POCO than high CFR (p = 0.034). There were no significant differences in clinical and angiographic characteristics among groups. Patients with high IMR with low CFR had the highest POCO (p = 0.002). Overt microvascular disease (p = 0.008), multivessel disease (p = 0.033), and diabetes mellitus (p = 0.033) were independent predictors of POCO. Inclusion of a physiological index significantly improved the discriminant function of a predictive model (relative integrated discrimination improvement 0.467 p = 0.037; category-free net reclassification index 0.648 p = 0.007). Conclusions CFR and IMR improved the risk stratification of patients with high FFR. Low CFR with high IMR was associated with poor prognosis. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093 )
CONTEXT Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, ...fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFRCT) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date. OBJECTIVE To assess the diagnostic performance of FFRCT plus CT for diagnosis of hemodynamically significant coronary stenosis. DESIGN, SETTING, AND PATIENTS Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFRCT between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFRCT were interpreted in blinded fashion by independent core laboratories. Accuracy of FFRCT plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFRCT of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA. MAIN OUTCOME MEASURES The primary study outcome assessed whether FFRCT plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%. RESULTS Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve AUC, 0.68; 95% CI, 0.62-0.74), FFRCT was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001). CONCLUSION Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFRCT plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.
Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery ...Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial.
From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group).
During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 95% CI, 0.63-0.86;
<0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 95% CI, 0.55-0.79;
<0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 95% CI, 0.57-0.94;
=0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 95% CI, 0.82-1.31;
=0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period.
During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents.
URL: https://www.
gov; Unique identifier: NCT02044250.
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