Usefulness of the Hybrid RFR-FFR Approach: Results of a Prospective and Multicenter Analysis of Diagnostic Agreement between RFR and FFR-The RECOPA (REsting Full-Cycle Ratio Comparation versus Fractional Flow Reserve (A Prospective Validation)) Study.

BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.

Impact of anaemia on mortality and its causes in elderly patients with acute coronary syndromes.

BACKGROUND: Prognostic impact of anaemia in the elderly with acute coronary syndromes has not been specifically analysed, and little information exists about causes of mortality in this setting. METHODS: We prospectively included consecutive patients with acute coronary syndromes. Anaemia was defined as haemoglobin < 130 g/L in men, and < 120 g/L in women. Primary outcome was mid-term mortality and its causes. Analyses were performed by Cox regression method. RESULTS: We included 2128 patients, of whom 394 (18.6%) were aged 75 years or older. Anaemia was more common in the elderly (40.4% vs 19.5%, p <0.001). Mean follow-up was 386 days. Anaemia independently predicted overall mortality (HR 1.47, 95% CI 1.05-2.06), cardiac mortality (HR 1.76, 95% CI 1.06-2.94) and non-cardiac mortality (HR 1.59, 95% CI 1.03-2.45) in the overall cohort. In young patients the association between anaemia and mortality was significant only for non-cardiac causes. The association between anaemia and mortality was not significant in the elderly (HR 1.08, 95% CI 0.71-1.63, p 0.736). CONCLUSIONS: The impact of anaemia on cause specific of mortality seem to be different according to age subgroup. The association between anaemia and mortality was not observed in elderly patients from our series.

MGuard mesh-covered stent for treatment of ST-segment elevation myocardial infarction with high thrombus burden despite manual aspiration.

OBJECTIVES: To assess the usefulness of the MGuard stent in patients with ST-segment elevation myocardial infarction (STEMI) in whom a high thrombus burden persists after manual aspiration. BACKGROUND: In some patients with STEMI, a high thrombus burden may persist after manual aspiration. These patients may be at high risk of distal embolization and therefore impaired myocardial reperfusion. The MGuard is a novel mesh-covered stent designed to minimize thrombus embolization. METHODS: Single-arm, prospective registry of patients with STEMI and high thrombus burden after aggressive thrombus aspiration treated with the MGuard stent. High thrombus burden was defined as thrombus burden grade 4 or 5 according to the TIMI score. Lesions with a side branch ≥2 mm and patients with cardiogenic shock were not included. The study end-points were proportion of final TIMI 3 flow, normal myocardial blush, and complete ST-segment resolution. RESULTS: Fifty-six patients were included. After MGuard stent implantation >85% of cases had thrombus score = 0. Final TIMI 3 flow was achieved in 82% of cases, normal myocardial blush in 55%, and complete ST-segment resolution in 59%. Occlusion of a side branch (<2 mm) occurred in 2 cases (3.5%), embolization to a distal branch in 5 cases (8.9%), and transient no-reflow in 4 cases (7.1%). Major adverse cardiac events rate at 9 months was 3.6%, including 1 definite acute stent thrombosis and 1 target-vessel revascularization. CONCLUSIONS: The MGuard stent may be useful to prevent distal embolization in patients with STEMI and high thrombus burden despite mechanical aspiration.

Preserved endothelial vasomotor function after everolimus-eluting stent implantation.

AIMS: To compare the degree of endothelial dysfunction (ED) in patients treated with everolimus-eluting stent (EES) versus bare metal stent (BMS) implantation. METHODS AND RESULTS: This is an observational study. A total of 30 elective patients (15 treated with EES and 15 with BMS) were recruited. All patients underwent coronary angiography and intracoronary acetylcholine (Ach) test at different doses at six months after stent implantation. Quantitative coronary angiography analysis was performed to evaluate the changes in mean luminal diameter (MLD) of the segments distal to the distal stent edge after increasing doses of Ach. Both EES and BMS groups had similar baseline characteristics except for stent length (18.6±2.5 vs. 16.5±2.5 mm; p=0.033) and diameter (3.1±0.2 vs. 3.4±0.3 mm; p=0.007). The vasomotion test showed that EES had 3.14% of MLD decrease after Ach infusion and BMS had 2.35% of vasoconstriction (p=0.62). After adjustment for baseline characteristics, no statistical difference was observed between groups. CONCLUSIONS: In our study EES implantation was associated with a low degree of ED and had a similar vasomotion response as compared to BMS. Prospective randomised investigations are warranted to confirm these findings.

Efficacy of bleeding risk scores in elderly patients with acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: The incidence of acute coronary syndromes is high in the elderly population. Bleeding is associated with a poorer prognosis in this clinical setting. The available bleeding risk scores have not been validated specifically in the elderly. Our aim was to assess predictive ability of the most important bleeding risk scores in patients with acute coronary syndrome aged ≥ 75 years. METHODS: We prospectively included consecutive acute coronary syndromes patients. Baseline characteristics, laboratory findings, and hemodynamic data were collected. In-hospital bleeding was defined according to CRUSADE, Mehran, ACTION, and BARC definitions. CRUSADE, Mehran, and ACTION bleeding risk scores were calculated for each patient. The ability of these scores to predict major bleeding was assessed by binary logistic regression, receiver operating characteristic curves, and area under the curves. RESULTS: We included 2036 patients, with mean age of 62.1 years; 369 patients (18.1%) were ≥ 75 years. Older patients had higher bleeding risk (CRUSADE, 42 vs 22; Mehran, 25 vs 15; ACTION, 36 vs 28; P<.001) and a slightly higher incidence of major bleeding events (CRUSADE bleeding, 5.1% vs 3.8%; P=.250). The predictive ability of these 3 scores was lower in the elderly (area under the curve, CRUSADE: 0.63 in older patients, 0.81 in young patients; P=.027; Mehran: 0.67 in older patients, 0.73 in younger patients; P=.340; ACTION: 0.58 in older patients, 0.75 in younger patients; P=.041). CONCLUSIONS: Current bleeding risk scores showed poorer predictive performance in elderly patients with acute coronary syndromes than in younger patients.

Lumen enlargement of the coronary segments located distal to chronic total occlusions successfully treated with drug-eluting stents at follow-up.

AIMS: Chronic total occlusions (CTO) are the final stage of atherosclerosis. Occluded coronary arteries have large plaque burden and negative remodelling. The aim of this study was to assess lumen and vessel changes of segments located distal to successfully recanalised CTO. METHODS AND RESULTS: Ninety-one CTO treated with drug-eluting stents underwent quantitative coronary angiography (QCA) at baseline and at 12-18 months; 31 underwent serial intravascular ultrasound (IVUS) imaging. Angiographic changes were assessed with QCA as differences in minimal, mean and maximal lumen diameter (MinLD, MeanLD and MaxLD, respectively). Vessel changes were assessed with IVUS as changes in plaque and vessel volume. At follow-up, angiographic MinLD increased 23.9% (from 0.88±0.32 to 1.09±0.35 mm; p<0.01), MeanLD 16.4% (from 1.59±0.44 to 1.85±0.45 mm; p<0.01) and MaxLD 11.7% (from 2.39±0.67 to 2.67±0.70 mm; p<0.01). Lumen enlargement was greater in non-restenotic lesions, small lumen area at the end of the index procedure and low LDL-cholesterol levels during the study. By IVUS, lumen volume increased 26.9% (from 108.1±89.2 to 137.3±115.3 mm3; p<0.01), vessel volume increased 12.1% (from 207.1±170.2 to 232.2±196.0 mm3; p<0.01) and plaque volume tended to decrease 3.9% (from 98.9±88.7 to 94.9±89.3 mm3; p=0.07). Small lumen at baseline was related to greater lumen enlargement. CONCLUSIONS: Segments distal to recanalised CTO showed a notable lumen and vessel enlargement with a trend toward mild plaque regression. Low LDL-cholesterol levels increase lumen enlargement.

Prognostic impact of chronic total occlusion in a nonculprit artery in patients with acute myocardial infarction undergoing primary angioplasty.

INTRODUCTION AND OBJECTIVES: The prognostic value of chronic total occlusion in nonculprit coronary arteries in patients with myocardial infarction undergoing primary angioplasty remains controversial. Several publications have described different methodologies and conflicting findings. In addition, causes of death were not reported. Our aim is to analyze the prognostic impact of chronic total occlusion in nonculprit coronary arteries and the role of left ventricular ejection fraction in this analysis. METHODS: Prospective inclusion of consecutive patients with ST-segment elevation myocardial infarction who underwent primary angioplasty. We recorded baseline characteristics, in-hospital clinical course, and mortality and its causes during follow-up. We assessed the impact of chronic total occlusion on mortality using Cox regression analysis. RESULTS: Chronic total occlusion in nonculprit arteries was present in 125 of 1176 patients (10.6%); in 79 of these 125 patients, chronic total occlusion was present in the proximal segments. The mean follow-up was 339 days; 64 (5.8%) patients died during the first 6 months. Patients with chronic total occlusions had more comorbidities, poorer ventricular function, and higher mortality (hazard ratio=2.79; 95% confidence interval, 1.71-4.56). Chronic total occlusion was also associated with noncardiac death (hazard ratio=3.83; 95% confidence interval, 2.10-7.01). Chronic total occlusion in proximal segments was associated with both cardiac (hazard ratio=3.22; 95% confidence interval, 1.42-7.30) and noncardiac deaths (hazard ratio=3.43; 95% confidence interval, 1.67-7.06). The multivariate analysis performed without including left ventricular ejection fraction showed a significant association between chronic total occlusion and mortality. However, when left ventricular ejection fraction was included in the analysis, this association was nonsignificant (hazard ratio=1.76; 95% confidence interval, 0.85-3.65; P=.166). CONCLUSIONS: Chronic total occlusion in this clinical setting identified patients at higher risk with more comorbidities and higher mortality, but did not behave as an independent predictor of mortality when left ventricular ejection fraction was included in the analysis.

Impact of mild hypothermia on platelet responsiveness to aspirin and clopidogrel: an in vitro pharmacodynamic investigation.

UNLABELLED: The combination of percutaneous coronary intervention (PCI) and therapeutic hypothermia in comatose patients after cardiac arrest due to an acute coronary syndrome has been reported to be safe and effective. However, recent investigations suggest that hypothermia may be associated with impaired response to clopidogrel and greater risk of thrombotic complications after PCI. This investigation aimed to evaluate the effect of hypothermia on the pharmacodynamic response of aspirin and clopidogrel in patients (n = 20) with ST elevation myocardial infarction undergoing primary PCI. Higher platelet reactivity (ADP stimulus) was observed in samples incubated at 33 °C compared with those at 37 °C (multiple electrode aggregometry, 235.2 ± 31.4 AU×min vs. 181.9 ± 30.2 AU×min, p < 0.001; VerifyNow P2Y12, 172.9 ± 20.3 PRU vs. 151.0 ± 19.3 PRU, p = 0.004). Numerically greater rates of clopidogrel poor responsiveness were also observed at 33 °C. No differences were seen in aspirin responsiveness. In conclusion, mild hypothermia was associated with reduced clopidogrel-mediated platelet inhibition with no impact on aspirin effects. CLINICAL RELEVANCE: Mild therapeutic hypothermia is associated with impaired response to clopidogrel therapy, which might contribute to increase the risk of thrombotic events in ACS comatose patients undergoing PCI.

Clopidogrel pretreatment in primary percutaneous coronary intervention: prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery.

To date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.

CRUSADE bleeding risk score validation for ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

INTRODUCTION: The CRUSADE bleeding risk score (CBRS) accurately predicts major bleeding in non-ST segment elevation myocardial infarction NSTEMI patients. However, little information exists about its application in ST segment elevation myocardial infarction STEMI. We aimed to assess the ability of CBRS to predict in-hospital major bleeding in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). MATERIALS AND METHODS: We prospectively analyzed consecutive STEMI patients undergoing PPCI. Baseline characteristics, in-hospital complications and mid term mortality were recorded. Major bleeding was defined by the CRUSADE definition. Predictive ability of the CBRS was assessed by logistic regression method and the area under the ROC curve (AUC). RESULTS: We included 1064 patients (mean age 63years). Mean CBRS value was 24. Most of patients (740/1064 (69.6%)) were in the two lowest risk quintiles of CBRS. Incidence of in-hospital major bleeding was 33/1064 (3.1%). The rates of in-hospital bleeding across the quintiles of risk groups were 0.4% (very low risk), 2.6% (low), 4.6% (moderate), 7.2% (high), and 13.4% (very high) (p 0.001). AUC was 0.80 (95% CI 0.73-0.87 p 0.001). In patients with radial access angiography (n=621) AUC was 0.81 (95% CI: 0.65-0.97). Mean follow up was 344days. Patients with bleeding events had higher mortality during follow up (HR 6.91; 95% CI 3.72-12.82; p 0.001). CONCLUSIONS: Our patients had a significantly lower bleeding risk as compared to CRUSADE NSTEMI population. CBRS accurately predicted major in-hospital bleeding in this different clinical scenario, including patients with radial artery approach.

Global risk score for choosing the best revascularization strategy in patients with unprotected left main stenosis.

BACKGROUND: Coronary artery bypass graft (CABG) is recommended for patients with unprotected left main stenosis (ULMS). Percutaneous coronary intervention (PCI) is only recommended in specific anatomic conditions as in patients with low/mid SYNTAX score (SS). The aim of this study was to assess if the clinical and anatomic global risk classification (GRC) can enhance the indication of both revascularization therapies. METHODS: A total of 407 patients with ULMS treated with CABG (n = 285) or PCI (n = 122) were prospectively collected. The decision to treat with CABG or PCI was dependent on patient and physician's choice. Patients with ST-elevation myocardial infarction, shock, or valve disease were excluded. Clinical follow-up was obtained at 3 years. RESULTS: Patients with low GRC (n = 151) treated with CABG vs those with PCI had similar cardiac mortality (5.9% vs 0%, respectively; P=.17) and major adverse cardiac events (MACE; 18.5% vs 12.5%, respectively; P=.40). Patients classified as mid GRC (n = 175) had similar cardiac death (11.1% vs 10.3%; P=.85) and MACE rates (20.7% vs 22.4%; P=.92) with CABG or PCI, respectively. Patients with high GRC (n = 81) treated with CABG had numerically fewer cardiac deaths (16.3% vs 28.1%; P=.16) and lower MACE rates (24.5% vs 40.6%; P=.048) than with PCI. Statistical models using the GRC as a predictor of cardiac death showed better goodness-of-fit than the SS. CONCLUSION: Patients with low/mid GRC have similar mid-term outcomes with either CABG or PCI; patients with high GRC seem to benefit from CABG. Although further investigations are required, GRC is a better predictor of outcomes than SS.

Characterization of coronary plaques with combined use of intravascular ultrasound, virtual histology and optical coherence tomography.

According to post-mortem studies, luminal thrombosis occurs from plaque rupture, erosion and calcified nodules. In vivo studies have found thin cap fibroatheroma (TCFA) as the main vulnerable lesion, prone to rupture. Few data about other post-mortem lesions have been reported in vivo. Our main objective is to characterize in vivo the coronary plaques with intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT), in order to detect not only thin cap fibroatheroma (TCFA), but also other possible vulnerable lesions. The secondary objective is to correlate these findings with clinical and analytical data. Twenty-five patients (18 stable) submitted to coronary angiography were included in this pilot study. After angiography, the three vessels were studied (when possible) with IVUS-VH and OCT. Plaque characteristics were correlated with clinical and analytical data. Forty-six lesions were analyzed. IVUS-VH detected significant necrotic core in 15 (3 were definite TCFA). OCT detected TCFA in 10 lesions, erosion in 6, thrombus in 5 and calcified nodule in 8. Possible vulnerable lesion was found in 61% of stable and 57% of unstable patients. Erosions and calcified nodules were only found in stable patients. Those with significant necrotic core had higher body mass index (P=0.016), higher levels of hs-CRP (P=0.019) and triglycerides (P=0.040). The higher the levels of hs-CRP, the larger the size of the necrotic core (r=0.69, P=0.003). Lesions with characteristics of vulnerability were detected by IVUS-VH and OCT in more than 50% of stable and unstable coronary patients. A significant necrotic core was mainly correlated with higher hs-CRP.