Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study.

BACKGROUND: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. METHODS: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. RESULTS: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was ≥6 mm2 in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). CONCLUSIONS: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03767621.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

BACKGROUND: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. METHODS: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. RESULTS: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. CONCLUSIONS: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Global Geriatric Assessment and In-Hospital Bleeding Risk in Elderly Patients with Acute Coronary Syndromes: Insights from the LONGEVO-SCA Registry.

BACKGROUND: Bleeding risk scores have shown a limited predictive ability in elderly patients with acute coronary syndromes (ACS). No study explored the role of a comprehensive geriatric assessment to predict in-hospital bleeding in this clinical setting. METHODS: The prospective multicentre LONGEVO-SCA registry included 532 unselected patients with non-ST segment elevation ACS (NSTEACS) aged 80 years or older. Comorbidity (Charlson index), frailty (FRAIL scale), disability (Barthel index and Lawton-Brody index), cognitive status (Pfeiffer test) and nutritional risk (mini nutritional assessment-short form test) were assessed during hospitalization. CRUSADE score was prospectively calculated for each patient. In-hospital major bleeding was defined by the CRUSADE classification. The association between geriatric syndromes and in-hospital major bleeding was assessed by logistic regression method and the area under the receiver operating characteristic curves (AUC). RESULTS: Mean age was 84.3 years (SD 4.1), 61.7% male. Most patients had increased troponin levels (84%). Mean CRUSADE bleeding score was 41 (SD 13). A total of 416 patients (78%) underwent an invasive strategy, and major bleeding was observed in 37 cases (7%). The ability of the CRUSADE score for predicting major bleeding was modest (AUC 0.64). From all aging-related variables, only comorbidity (Charlson index) was independently associated with major bleeding (per point, odds ratio: 1.23, p = 0.021). The addition of comorbidity to CRUSADE score slightly improved the ability for predicting major bleeding (AUC: 0.68). CONCLUSION: Comorbidity was associated with major bleeding in very elderly patients with NSTEACS. The contribution of frailty, disability or nutritional risk for predicting in-hospital major bleeding was marginal.

An Easy Assessment of Frailty at Baseline Independently Predicts Prognosis in Very Elderly Patients With Acute Coronary Syndromes.

BACKGROUND: Information about the impact of frailty in patients with acute coronary syndromes (ACS) is scarce. No study has assessed the prognostic impact of frailty as measured by the FRAIL scale in very elderly patients with ACS. METHODS: The prospective multicenter LONGEVO-SCA registry included unselected patients with ACS aged 80 years or older. A comprehensive geriatric assessment was performed during hospitalization, including frailty assessment by the FRAIL scale. The primary endpoint was mortality at 6 months. RESULTS: A total of 532 patients were included. Mean age was 84.3 years, 61.7% male. Most patients had positive troponin levels (84%) and high GRACE risk score values (mean 165). A total of 205 patients were classified as prefrail (38.5%) and 145 as frail (27.3%). Frail and prefrail patients had a higher prevalence of comorbidities, lower left ventricle ejection fraction, and higher mean GRACE score value. A total of 63 patients (11.8%) were dead at 6 months. Both prefrailty and frailty were associated with higher 6-month mortality rates (P < .001). After adjusting for potential confounders, this association remained significant (hazard ratio [HR] 2.71; 95% confidence interval [CI] 1.09-6.73 for prefrailty and HR 2.99; 95% CI 1.20-7.44 for frailty, P = .024). The other independent predictors of mortality were age, Charlson Index, and GRACE risk score. CONCLUSIONS: The FRAIL scale is a simple tool that independently predicts mortality in unselected very elderly patients with ACS. The presence of prefrailty criteria also should be taken into account when performing risk stratification of these patients.

Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

Clinical outcomes after intravascular ultrasound and fractional flow reserve assessment of intermediate coronary lesions. Propensity score matching of large cohorts from two institutions with a differential approach.

AIMS: Assessment of intermediate coronary lesions can be done with fractional flow reserve (FFR) and intravascular ultrasound (IVUS). There are no randomised trials and only a small registry from one centre is available but this is subject to important bias. We sought to evaluate the clinical outcomes of an FFR strategy compared with an IVUS strategy for intermediate lesion assessment. METHODS AND RESULTS: We compared the outcome of patients assessed with FFR and IVUS in two centres with a differential approach. After propensity score matching 400 pairs of patients were included. Revascularisation was done when FFR was <0.75 or minimum lumen area was <4 mm2 in vessels >3 mm, and <3.5 mm2 in vessels 2.5-3 mm, along with plaque burden >50%. After FFR and IVUS, 72% and 51.2% of lesions, respectively, were left untreated (p<0.001). At one and two years no significant differences in MACE-free survival were observed in overall groups (97.7% at one year and 93.1% at two years in the FFR group and 97.7% at one year and 95.6% at two years in the IVUS group; p=0.35) and among those with deferred intervention (97.9% at one year and 94.2% at two years in the FFR group and 96.5% at one year and 93.6% at two years in the IVUS group; p=0.7). CONCLUSIONS: IVUS and FFR may be safely used to defer revascularisation of intermediate lesions. IVUS induces a higher degree of revascularisation but much lower than previously reported and does not affect the clinical outcome.

Comparison of effectiveness of high-dose intracoronary adenosine versus intravenous administration on the assessment of fractional flow reserve in patients with coronary heart disease.

Intravenous adenosine is considered the drug of choice to obtain maximum hyperemia in the measurement of the fractional flow reserve (FFR). However, comparative studies performed between intravenous and intracoronary administration have not used high doses of intracoronary adenosine. The present study compared the efficacy and safety of high doses of intracoronary adenosine to intravenous administration when calculating the FFR. Intracoronary bolus doses of 60, 180, 300, and 600 µg adenosine were compared to an intravenous administration of 140 µg/kg/min, 200 µg/kg/min, and 140 µg/kg/min plus an intracoronary bolus of 120 µg. All the cases were performed using the radial approach. FFR was assessed in 102 patients with 108 intermediate lesions by an intracoronary pressure wire. The intracoronary dose of 60 µg was associated with a significantly greater FFR compared to the intravenous infusion (0.02 ± 0.03, p = 0.001). The intracoronary doses of 300 (-0.01 ± 0.00; p = 0.006) and 600 µg (-0.02 ± 0.00; p <0.0005) were significantly associated with a smaller FFR compared to the intravenous infusion. An intracoronary dose of 600 µg revealed a significantly greater percentage of lesions with an FFR <0.80 compared to intravenous infusion at 140 µg/kg/min (37.6 vs 31.5%; p <0.05) and 200 µg/kg/min (37.6 vs 32.4%; p <0.05) and compared to intracoronary doses of 60 (26.9%) and 180 µg (31.5%). In conclusion, an intracoronary bolus dose >300 µg can be equal to or more effective than an intravenous infusion of adenosine in achieving maximum hyperemia when calculating the FFR. Its use could simplify these procedures without having an effect on safety.

Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study.

OBJECTIVES: This study is a prospective validation of 6 mm(2) as a minimum lumen area (MLA) cutoff value for revascularization of left main coronary artery (LMCA) lesions. BACKGROUND: Lesions involving the LMCA are prognostically relevant. Angiography has important limitations in the evaluation of LMCA lesions with intermediate severity. An MLA of 6 mm(2) assessed by intravascular ultrasound has been proposed as a cutoff value to determine lesion severity, but there are no large studies evaluating the prospective application and safety of this approach. METHODS: We have designed a multicenter, prospective study. Consecutive patients with intermediate lesions in unprotected LMCA were evaluated with intravascular ultrasound. An MLA <6 mm(2) was used as criterion for revascularization. RESULTS: A total of 354 patients were included in 22 centers. LMCA revascularization was performed in 90.5% (152 of 168) of patients with an MLA <6 mm(2) and was deferred in 96% (179 of 186) of patients with an MLA of 6 mm(2) or more. A large scatter was observed between both groups regarding angiographic parameters. In a 2-year follow-up period, cardiac death-free survival was 97.7% in the deferred group versus 94.5% in the revascularized group (p = 0.5), and event-free survival was 87.3% versus 80.6%, respectively (p = 0.3). In the 2-year period, only 8 (4.4%) patients in the deferred group required subsequent LMCA revascularization, none with an infarction. CONCLUSIONS: Angiographic measurements are not reliable in the assessment of intermediate LMCA lesions. An MLA of 6 mm(2) or more is a safe value for deferring revascularization of the LMCA, given the application of the clinical and angiographic inclusion criteria used in this study.

[Detection of angiographic lesions in the left anterior descending coronary artery by transthoracic Doppler echocardiography: usefulness of non-invasive assessment of coronary flow reserve]. / Detección de estenosis angiográfica de la arteria coronaria descendente anterior mediante ecocardiografía Doppler transtorácica: utilidad de la medida no invasiva de la reserva del flujo coronario.

INTRODUCTION: We evaluated the feasibility of detecting blood flow in the left anterior descending coronary artery and the usefulness of measuring coronary flow reserve to diagnose significant coronary artery disease, both by means of transthoracic Doppler echocardiography using a high-frequency transducer and echo-contrast agent. PATIENTS AND METHOD: We studied 107 patients who were scheduled for coronary arteriography for known or suspected ischemic heart disease. A Doppler signal was recorded by a pulsed wave in the distal left anterior descending artery at baseline and after dipyridamole infusion. An echo-contrast agent was administered to all patients. A coronary flow reserve equal to or higher than 1.7 was considered normal. RESULTS: We recorded Doppler signals in the left anterior descending coronary artery of 83 patients (78%). Significant stenosis of the left anterior descending coronary artery was observed in 24 out of 83 patients (29%). The prevalence of significant stenosis was higher (62 vs 29%; p = 0.006) in patients in which no Doppler signal was detected. The sensitivity, specificity, and accuracy of abnormal coronary flow reserve in detecting significant stenosis of the left anterior descending coronary artery were 87, 74 and 78%, respectively. CONCLUSIONS: The measurement of coronary flow reserve by transthoracic Doppler echocardiography using a high-frequency transducer and echo-contrast agent is a feasible, widely available, and accurate method for detecting significant stenosis of the left anterior descending coronary artery.