Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.

Background: The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). Objectives: The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. Methods: A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. Results: From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. Conclusions: Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Ischemia With Nonobstructive Coronary Artery Disease: Concept, Assessment, and Management.

In daily clinical practice, physicians often encounter patients with angina or those with evidence of myocardial ischemia from noninvasive tests but not having obstructive coronary artery disease. This type of ischemic heart disease is referred to as ischemia with nonobstructive coronary arteries (INOCA). INOCA patients often suffer from recurrent chest pain without adequate management and are associated with poor clinical outcomes. There are several endotypes of INOCA, and each endotype should be treated based on its specific underlying mechanism. Therefore, identifying INOCA and discriminating its underlying mechanisms are important issues and of clinical interest. Invasive physiologic assessment is the first step in the diagnosis of INOCA and discriminating the underlying mechanism; additional provocation tests help physicians identify the vasospastic component in INOCA patients. Comprehensive information acquired from these invasive tests can provide a template for mechanism-specific management for patients with INOCA.

Physiologic Assessment after Coronary Stent Implantation.

The presence of myocardial ischemia is a prerequisite for the benefit of coronary revascularization. In the cardiac catheterization laboratory, fractional flow reserve and non-hyperemic pressure ratios are used to define the ischemia-causing coronary stenosis, and several randomized studies showed the benefit of physiology-guided coronary revascularization. However, physiology-guided revascularization does not necessarily guarantee the relief of ischemia. Recent studies reported that residual ischemia might exist in up to 15-20% of cases after angiographically successful percutaneous coronary intervention (PCI). Therefore, post-PCI physiologic assessment is necessary for judging the appropriateness of PCI, detecting the lesions that may benefit from additional PCI, and risk stratification after PCI. This review will focus on the current evidence for post-PCI physiologic assessment, how to interpret these findings, and the future perspectives of physiologic assessment after PCI.

Role of Post-Stent Physiological Assessment in a Risk Prediction Model After Coronary Stent Implantation.

OBJECTIVES: The aim of this study was to develop a risk model incorporating clinical, angiographic, and physiological parameters to predict future clinical events after drug-eluting stent implantation. BACKGROUND: Prognostic factors after coronary stenting have not been comprehensively investigated. METHODS: A risk model to predict target vessel failure (TVF) at 2 years was developed from 2,200 patients who underwent second-generation drug-eluting stent implantation and post-stent fractional flow reserve (FFR) measurement. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. A random survival forest model with automatic feature selection by minimal depth analysis was used for risk model development. RESULTS: During 2 years of follow-up, the cumulative incidence of TVF was 5.9%. From clinical, angiographic, and physiological parameters, 6 variables were selected for the risk model in order of importance within the model as follows: total stent length, post-stent FFR, age, post-stent percentage diameter stenosis, reference vessel diameter, and diabetes mellitus. Harrell's C index of the random survival forest model was 0.72 (95% confidence interval [CI]: 0.62 to 0.82). This risk model showed better prediction ability than models with clinical risk factors alone (Harrell's C index = 0.55; 95% CI: 0.41 to 0.59; p for comparison = 0.005) and with clinical risk factors and angiographic parameters (Harrell's C index = 0.65; 95% CI: 0.52 to 0.77; p for comparison = 0.045). When the patients were divided into 2 groups according to the median of total stent length (30 mm), post-stent FFR and total stent length showed the highest variable importance in the short- and long-stent groups, respectively. CONCLUSIONS: A risk model incorporating clinical, angiographic, and physiological predictors can help predict the risk for TVF at 2 years after coronary stenting. Total stent length and post-stent FFR were the most important predictors. (International Post PCI FFR Registry; NCT04012281).

Sex Differences in Long-Term Outcomes in Patients With Deferred Revascularization Following Fractional Flow Reserve Assessment: International Collaboration Registry of Comprehensive Physiologic Evaluation.

Background Sex-specific differences may influence prognosis after deferred revascularization following fractional flow reserve (FFR) measurement. This study sought to investigate the sex differences in long-term prognosis of patients with deferred revascularization following FFR assessment. Methods and Results A total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and coronary flow reserve measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long-term outcomes were assessed in 649 men and 230 women by the patient-oriented composite outcome (POCO, a composite of any death, any myocardial infarction, and any revascularization). We applied inverse-probability weighting based on propensity scores to account for differences at baseline between women and men (age, hyperlipidemia, diabetes mellitus, diameter stenosis, lesion length, multivessel disease, FFR, coronary flow reserve. The median follow-up duration was 1855 days (745-1855 days). Median FFR values were 0.88 (0.83-0.93) in men and 0.89 (0.85-0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% versus 4.2%, P=0.007). Kaplan-Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX proportional hazards regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of males for POCO was 2.07 (95% CI, 1.07-4.04, P=0.032). Conclusions This large multinational study reveals that long-term outcome differs between women and men in favor of women after FFR-guided revascularization deferral. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02186093.

Influence of Sex on Relationship Between Total Anatomical and Physiologic Disease Burdens and Their Prognostic Implications in Patients With Coronary Artery Disease.

Background Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined. Methods and Results A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3-vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per-vessel FFR (0.89±0.10 versus 0.87±0.11, P<0.001) and 3-vessel FFR (2.72±0.13 versus 2.69±0.15, P<0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2-year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes. Conclusions Despite similar angiographic disease severity, both per-vessel and per-patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Physiological and Clinical Assessment of Resting Physiological Indexes.

BACKGROUND: Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels. RESULTS: Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by 13N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels. CONCLUSIONS: All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Physiologic Assessment of Coronary Artery Disease: Focus on Fractional Flow Reserve.

The presence of myocardial ischemia is the most important prognostic factor in patients with ischemic heart disease. Fractional flow reserve (FFR) is a gold standard invasive method used to detect the stenosis-specific myocardial ischemia. FFR-guided revascularization strategy is superior to angiography-guided strategy. The recently developed hyperemia-free index, instantaneous wave free ratio is being actively investigated. A non-invasive FFR derived from coronary CT angiography is now used in clinical practice. Due to rapid expansion of invasive and non-invasive physiologic assessment, comprehensive understanding of the role and potential pitfalls of each modality are required for its application. In this review, we focus on the basic and clinical aspects of physiologic assessment in ischemic heart disease.