Combined Assessment of Fractional Flow Reserve and Coronary Flow Velocity Reserve after Drug-Eluting Stent Implantation.

BACKGROUND: Coronary flow velocity reserve (CFVR) can be measured noninvasively using stress transthoracic Doppler echocardiography (S-TDE). The prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to investigate the prognostic value of post-PCI CFVR and its additional efficacy to fractional flow reserve (FFR) in patients undergoing elective PCI. METHODS: A retrospective study was conducted involving 187 consecutive patients with chronic coronary syndrome who underwent elective PCI guided by FFR for the left anterior descending coronary artery. Pre- and post-PCI wire-based FFR and CFVR assessments of the left anterior descending coronary artery using S-TDE were performed in all patients. The association between post-PCI clinical and physiologic parameters and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, heart failure, and unplanned remote target vessel revascularization, was evaluated. RESULTS: Three-quarters of patients exhibited CFVR increase after PCI, while all patients showed FFR improvement. During a median follow-up period of 1.5 years, MACE occurred in 21 patients (11.2%). Among clinical demographics, patients with MACE had higher levels of N-terminal pro-brain natriuretic peptide compared with those without MACE (median, 615 pg/mL [interquartile range, 245-1,500 pg/mL] vs 180 pg/mL [interquartile range, 70-559 pg/mL]; P = .010). Post-PCI S-TDE-derived CFVR was lower in patients with MACE, while post-PCI FFR showed a nonsignificant tendency to be lower in patients with MACE. In a multivariable analysis, higher NT-proBNP (adjusted hazard ratio, 1.33; 95% CI, 1.02-1.74; P = .038), post-PCI CFVR ≤ 2.0 (adjusted hazard ratio, 2.93; 95% CI, 1.16-7.40; P = .023), and post-PCI FFR ≤ 0.82 (adjusted hazard ratio, 3.93; 95% CI, 1.52-10.18; P = .005) were independently associated with MACE. CONCLUSIONS: In patients with chronic coronary syndrome who underwent successful elective PCI for left anterior descending coronary artery, the combined assessment of S-TDE-derived post-PCI CFVR and post-PCI FFR provided a significant association with the occurrence of MACE.

Coronary Reactivity Assessment Is Associated With Lower Health Care-Associated Costs in Patients Presenting With Angina and Nonobstructive Coronary Artery Disease.

BACKGROUND: The financial burden linked to the diagnosis and treatment of patients with chest pain on the health care system is considerable. Angina and nonobstructive coronary artery disease (ANOCA) is common, associated with adverse cardiovascular events, and may lead to repeat testing or hospitalizations. Diagnostic certainty can be achieved in patients with ANOCA using coronary reactivity testing (CRT); however, its financial effect on the patient has not been studied. Our goal was to assess the effect of CRT on health care-related cost in patients with ANOCA. METHODS: Patients with ANOCA who underwent diagnostic coronary angiography (CAG) and CRT (CRT group) were matched to controls who had similar presentation but only underwent a CAG without CRT (CAG group). Standardized inflation-adjusted costs were collected and compared between the 2 groups on an annual basis for 2 years post the index date (CRT or CAG). RESULTS: Two hundred seven CRT and 207 CAG patients were included in the study with an average age of 52.3±11.5 years and 76% females. The total cost was significantly higher in the CAG group as compared with the CRT group ($37 804 [$26 933-$48 674] versus $13 679 [$9447-$17 910]; P<0.001). When costs are itemized and divided based on the Berenson-Eggers Type of Service categorization, the largest cost difference occurred in imaging (any type, including CAG; P<0.001), procedures (eg, percutaneous coronary intervention/coronary artery bypass grafting/thrombectomy) (P=0.001), and test (eg, blood tests, EKG; P<0.001). CONCLUSIONS: In this retrospective observational study, assessment of CRT in patients with ANOCA was associated with significantly reduced annual total costs and health care utilization. Therefore, the study may support the integration of CRT into clinical practice.

Association between patient age, microcirculation, and coronary stenosis assessment with fractional flow reserve and instantaneous wave-free ratio.

OBJECTIVES: To investigate the effect of aging on coronary stenosis functional assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND: Limited data exist regarding the impact of patient age on these coronary pressure indices. METHODS: We analyzed 514 patients with coronary stenosis interrogated with intravascular physiology. The influence of patient age on FFR, iFR, and microcirculation-related indices was investigated. Vessel-oriented composite outcome (VOCO) was assessed in the FFR-based deferred population according to iFR, coronary flow reserve (CFR), and age. RESULTS: FFR increased (r = 0.128, p = 0.004), iFR remained unchanged (r = -0.001, p = 0.980), and CFR decreased (r = -0.095, p = 0.001) with patient age. Relationship between FFR and CFR differed across age groups (r = 0.263 in <60 years old vs. r = 0.124 in ≥60 years old, p = 0.0056), whereas iFR correlated to CFR similarly regardless age (r = 0.283 in <60 years old vs. r = 0.219 in ≥60 years old, p = 0.3781). No differences were found on angiographic stenosis severity (%DS 47.4 in <60 years old and 49.8 in ≥60 years old, p = 0.317). At 5 years, FFR-based revascularisation deferral in patients ≥60 years old was associated with more VOCO when either iFR (25%) or CFR (16.9%) were abnormal, compared to patients with normal iFR (6.3%) or normal CFR (4.6%) (log-rank p < 0.001). This difference in clinical outcomes was not observed in younger patients. CONCLUSIONS: FFR values increased progressively with patient age, potentially associated with age-related changes in the coronary microcirculation. Conversely, iFR values remained unchanged across the patient age spectrum. In ≥60 years old patients with revascularisation deferral based on FFR, both abnormal iFR and CFR values were associated with worse long-term patient outcomes.

Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.

OBJECTIVES: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. METHODS: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. RESULTS: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. CONCLUSION: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Serial Assessment of Pericoronary Adipose Tissue Inflammation in a Patient With MINOCA Potentially Complicated With Vasospasm.

Vascular inflammation is linked with the pathogenesis of vasospastic angina (VSA). Recent studies reported the potential of pericoronary adipose tissue attenuation as shown on coronary computed tomography angiography to detect coronary inflammation. This report presents a case of myocardial infarction with nonobstructive coronary arteries potentially complicated with VSA that demonstrated reduction of inflammation after symptom improvement with calcium channel-blocker treatment as assessed by serial examination of pericoronary adipose tissue attenuation. This case highlighted the feasibility of a noninvasive assessment of pericoronary adipose tissue attenuation to evaluate the disease activity of VSA and guide patient management.

L'inflammation vasculaire est liée à la pathogenèse de l'angine vasospastique (AVS). De récentes études ont révélé le potentiel de l'atténuation du tissu adipeux péricoronaire qui était observée à l'angiographie coronarienne par tomodensitométrie pour détecter l'inflammation coronarienne. Le présent rapport porte sur un cas d'infarctus du myocarde sans obstruction coronaire potentiellement compliqué par l'AVS qui selon l'examen en série de l'atténuation du tissu adipeux péricoronaire a démontré une réduction de l'inflammation après l'amélioration des symptômes à l'aide d'un traitement par bloqueurs des canaux calciques. Ce cas a illustré la faisabilité d'un examen non effractif de l'atténuation du tissu adipeux péricoronaire pour évaluer l'activité de l'AVS et orienter la prise en charge du patient.

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.

Coronary physiological assessment combining fractional flow reserve and index of microcirculatory resistance in patients undergoing elective percutaneous coronary intervention with grey zone fractional flow reserve.

OBJECTIVES: The aim of this study is to investigate the association between fractional flow reserve (FFR) values and change in coronary physiological indices after elective percutaneous coronary intervention (PCI). BACKGROUND: Decision making for revascularization when FFR is 0.75-0.80 is controversial. METHODS: A retrospective analysis was performed of 296 patients with stable angina pectoris who underwent physiological examinations before and after PCI. To investigate the differences of coronary flow improvement between territories with low-FFR (<0.75) and grey-zone FFR (0.75-0.80), serial changes in physiological indices including mean transit time (Tmn), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were compared between these two groups. RESULTS: Compared to low-FFR territories, grey-zone FFR territories showed significantly lower prevalence of Tmn shortening, CFR improvement, and decrease in IMR (Tmn shorting, 63.9% vs. 87.0%, P < .001; CFR improvement, 63.0% vs. 75.7%, P = .019; IMR decrease, 51.3% vs. 63.3%, P = .040) and lower extent of their absolute changes (Tmn shorting, 0.06 (-0.03 to 0.16) vs. 0.22 (0.07-0.45), P < .001; CFR improvement, 0.45 (-0.32 to 1.87) vs. 1.08 (0.02-2.44), P < .01; IMR decrease, 0.2 (-44.0 to 31.3) vs. 2.9 (-2.9 to 11.8), P = .022). Multivariate analysis showed that pre-PCI IMR predicted improved coronary flow profile in both groups, whereas pre-PCI FFR predicted increased coronary flow indices in low-FFR territories. CONCLUSIONS: Worsening of physiological indices after PCI was not uncommon in territories showing grey-zone FFR. Physiological assessment combining FFR and IMR may help identify patients who may benefit by PCI, particularly those in the grey zone.

Efficacy of Optical Coherence Tomography-derived Morphometric Assessment in Predicting the Physiological Significance of Coronary Stenosis: Head-to-Head Comparison with Intravascular Ultrasound.

AIMS: This study aimed to investigate the diagnostic efficacy of optical coherence tomography (OCT) in identifying functional significance via fractional flow reserve (FFR) compared with that of intravascular ultrasound (IVUS). METHODS AND RESULTS: We investigated 203 de novo intermediate coronary lesions of 186 patients who underwent frequency-domain OCT, IVUS and FFR measurements. Diagnostic efficacy of the minimal lumen area (MLA) obtained by OCT (OCT-MLA) and IVUS (IVUS-MLA) in predicting an FFR <0.75 was evaluated. Receiver operating characteristic curve analysis showed that OCT-MLA had significantly better diagnostic efficacy than IVUS-MLA in identifying functional ischaemia. OCT analysis revealed that the incidence of false positives (OCT-MLA ≤1.39 mm2 and FFR ≥0.75) was 46% (41/90), whereas the incidence of false negatives (OCT-MLA >1.39 mm2 and FFR <0.75) was 19% (22/113). Multivariate analysis showed that older age, non-left anterior descending artery and smaller angiographic reference diameter were independent predictors of false-positive results using the OCT-MLA criteria, whereas younger age and low left ventricular ejection fraction were independent predictors of false-negative results. CONCLUSIONS: Intravascular imaging is not interchangeable with FFR in clinical decision making. However, OCT may have superior efficacy to IVUS in detecting functional ischaemia. Discrepancies between OCT-MLA and FFR should be taken into account for OCT-guided decision making.

The influence of elective percutaneous coronary intervention on microvascular resistance: a serial assessment using the index of microcirculatory resistance.

This study investigates whether hyperemic microvascular resistance (MR) is influenced by elective percutaneous coronary intervention (PCI) by using the index of microcirculatory resistance (IMR). Seventy-one consecutive patients with stable angina pectoris undergoing elective PCI were prospectively studied. The IMR was measured before and after PCI and at the 10-mo follow-up. The IMR significantly decreased until follow-up; the pre-PCI, post-PCI, and follow-up IMRs had a median of 19.8 (interquartile range, 14.6-28.9), 16.2 (11.8-22.1), and 14.8 (11.8-18.7), respectively (P < 0.001). The pre-PCI IMR was significantly correlated with the change in IMR between pre- and post-PCI (r = 0.84, P < 0.001) and between pre-PCI and follow-up (r = 0.93, P < 0.001). Pre-PCI IMR values were significantly higher in territories with decreases in IMR than in those with increases in IMR [pre-PCI IMR: 25.4 (18.4-35.5) vs. 12.5 (9.4-16.8), P < 0.001]. At follow-up, IMR values in territories showing decreases in IMR were significantly lower than those with increases in IMR [IMR at follow-up: 13.9 (10.9-17.6) vs. 16.6 (14.0-21.4), P = 0.013]. The IMR decrease was significantly associated with a greater shortening of mean transit time, indicating increases in coronary flow (P < 0.001). The optimal cut-off values of pre-PCI IMR to predict a decrease in IMR after PCI and at follow-up were 16.8 and 17.0, respectively. In conclusion, elective PCI affected hyperemic MR and its change was associated with pre-PCI MR, resulting in showing a wide distribution. Overall hyperemic MR significantly decreased until follow-up. The modified hyperemic MR introduced by PCI may affect post-PCI coronary flow.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis in comparison with instantaneous wave-free ratio.

BACKGROUND: Despite evidence demonstrating the benefits of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to compare the diagnostic performances of instantaneous wave-free ratio (iFR) to a novel contrast medium-induced index in FFR prediction, hypothesizing that the latter parameter would offer superior diagnostic agreement with FFR. METHODS & RESULTS: We studied 132 intermediate stenoses in 97 patients prospectively. iFR was measured first, followed by intracoronary injection of 6 mL contrast medium at 3 mL/s to obtain end-diastolic instantaneous distal coronary pressure/aortic pressure ratio (Pd/Pa) 60 ms before the electrocardiographic R-wave (C-ED-Pd/Pa). Subsequently, conventional hyperemic FFR was measured as a reference standard. Of the 132 lesions, 120 were available for final analysis. The FFR values of 95/120 lesions (79.2%) were between 0.60 and 0.90. C-ED-Pd/Pa values (median 0.79 [interquartile range 0.69-0.87]) were significantly lower than FFR values (0.81 [0.75-0.88], P<0.01), whereas iFR values (0.91 [0.86-0.94], P<0.01) were significantly higher. Correlation coefficients with FFR were 0.78 (standard error of the estimate [SEE] 0.067, P<0.0001) and 0.93 (SEE 0.052, P<0.0001) for iFR and C-ED-Pd/Pa, respectively (P<0.001). The areas under the receiver operating characteristic curves were 0.88 and 0.96 for iFR and C-ED-Pd/Pa, respectively (P<0.01). Diagnostic accuracy was 85.0% and 92.5% for iFR and C-ED-Pd/Pa, respectively (P=0.06). CONCLUSIONS: C-ED-Pd/Pa is a novel, practical, and accurate measure for the physiological assessment of intermediate coronary stenosis compared to iFR.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis.

BACKGROUND: Despite evidence demonstrating the superiority of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to determine the diagnostic performance of baseline conditions and contrast medium-induced pressure indices in predicting FFR. We hypothesized that the contrast medium-induced end-diastolic pressure parameter would offer superior diagnostic agreement with FFR, compared to other indices. METHODS & RESULTS: Ninety-one intermediate stenoses in 75 patients were studied prospectively. The baseline distal coronary pressure to aortic pressure ratio (Pd/Pa) and end-diastolic instantaneous Pd/Pa 60 ms before the electrocardiographic R-wave (ED-Pd/Pa) were measured; then, after intracoronary injection of 6 mL contrast medium at 3 mL/s, Pd/Pa (C-Pd/Pa) and end-diastolic Pd/Pa (C-ED-Pd/Pa) were obtained. Subsequently, conventional FFR was measured as a reference standard. Of the 91 lesions, 11 (12.1%) were excluded because of suboptimal data acquisition, leaving 80 for final analysis. C-ED-Pd/Pa values (median 0.80 [interquartile range 0.70-0.88]) were significantly lower than conventional FFR (0.83 [0.75-0.89], P<0.01), whereas Pd/Pa (0.93 [0.90-0.96], P<0.01), ED-Pd/Pa (0.91 [0.87-0.93], P<0.01), and C-Pd/Pa (0.85 [0.79-0.90], P<0.05) were significantly higher. Correlation coefficients (R) with conventional FFR were 0.74 (standard error of the estimate [SEE] 0.067, P<0.0001), 0.78 (SEE 0.062, P<0.0001), 0.85 (SEE 0.052, P<0.0001), and 0.93 (SEE 0.037, P<0.0001) for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. Diagnostic accuracy was 81.2%, 83.8%, 87.5% and 93.8% for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. CONCLUSIONS: Among baseline indices and contrast-induced pressure parameters, C-ED-Pd/Pa is a novel, feasible, and high-performance measure for the physiological assessment of intermediate coronary stenosis.