Glycoprotein IIb/IIIa inhibitors use in the setting of primary percutaneous coronary intervention for ST elevation myocardial infarction in patients pre-treated with newer P2Y12 inhibitors.

OBJECTIVES: We sought to investigate the safety and potential benefit of administrating glycoprotein IIb-IIIa inhibitors (GPIs) on top of more potent P2Y12 inhibitors. BACKGROUND: A number of clinical trials, performed at a time when pretreatment and potent platelet inhibition was not part of routine clinical practice, have documented clinical benefits of GPI in ST-segment elevation myocardial infarction (STEMI) patients at the cost of a higher risk of bleeding. METHODS: We used the data of a prospective, ongoing registry of patients admitted for STEMI in our center. For the purpose of this study only patients presenting for primary percutaneous coronary intervention and pretreated with new P2Y12 inhibitors (prasugrel or ticagrelor) were included. We compared patients who received GPI with those who did not. RESULTS: Eight hundred twenty-four STEMI patients were included in our registry; GPIs were used in 338 patients (41%). GPI patients presented more often with cardiogenic shock and Thrombolysis in myocardial infarction (TIMI) flow grade <3. GPI use was not associated with an increase in in-hospital or 3-month mortality. Bleeding endpoints were similar in both groups. CONCLUSIONS: Our study suggests that GPI may be used safely in combination with recent P2Y12 inhibitors in STEMI patients in association with modern primary percutaneous coronary intervention strategies (radial access and anticoagulation with enoxaparin) with similar bleeding and mortality rates at hospital discharge and 3-month follow-up.

Evaluation of Left Main Coronary Artery Using Optical Frequency Domain Imaging and Its Pitfalls.

OBJECTIVES: We aimed to assess the quality of optical frequency domain imaging (OFDI) of the left main (LM) arterial wall and describe and analyse potential artefacts in this setting. BACKGROUND: OFDI is increasingly used to assess ambiguous lesions and optimize LM percutaneous coronary intervention. However, its ability to provide artefact-free high-quality images of coronary ostia and large segments such as the LM remains uncertain. METHODS: We included 42 consecutive patients who underwent OFDI, including LM imaging. Each OFDI frame was subdivided into four quadrants and analysed. The number of quadrants with artifacts was calculated within the proximal, mid, and distal LM and the first 5 mm of the left anterior descending artery (LAD) and/or left circumflex artery (LCX). RESULTS: The quadrants analysis showed an overall artifact rate of 8.9%, mostly out-of-field (45.1%) or residual blood (44.7%) artefacts. Most artifacts were located in the proximal LM (18.6%) with a stepwise reduction of artifact rates towards distal segments (mid LM 5.8%; distal LM 3.6%, ostial LAD 2.6%, and ostial LCX 0%; p < 0.001). While 20 (48.8%) patients had angiographically visible plaques, OFDI showed plaques in 32 patients (76.2%; p=0.007). CONCLUSION: OFDI can accurately evaluate the LM and detect and assess angiographically unvisualized atherosclerotic plaques providing accurate assessment of >90% of the quadrants of the LM and the ostia of its bifurcation branches. However, artifacts mainly located in the proximal LM and decreasing distally in a stepwise fashion should be considered in the interpretation of OFDI in this setting.

Residual platelet reactivity, thrombus burden and myocardial reperfusion in patients treated by PCI after successful pre-hospital fibrinolysis compared to primary PCI.

We compared residual platelet reactivity and post PCI atherothrombotic burden using OFDI in patients successfully treated by primary PCI versus pharmacoinvasive approach (PI) defined as PCI after successful pre-hospital fibrinolysis. Despite pre-hospital P2Y12-inhibitor loading dose, high rates of high on-treatment platelet reactivity were found at the time of PCI in both groups. Primary PCI patients had higher post stenting thrombus burden and lower rates of final normal myocardial blush grade compared to PI. These findings support the use of a pharmacoinvasive reperfusion strategy especially when primary PCI cannot be timely performed.

Systematic review and meta-analysis of the prognostic impact of cancer among patients with acute coronary syndrome and/or percutaneous coronary intervention.

BACKGROUND: Patients with cancer admitted for an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) represent a growing and high-risk population. The influence of co-existing cancer on mortality remains unclear in such patients. We aimed to assess the impact of cancer on early and late, all-cause and cardiac mortality in the setting of ACS and/or PCI. METHODS: We performed a systematic review and meta-analysis of studies comparing outcomes of patients with and without a history of cancer admitted for ACS and/or PCI. RESULTS: Six studies including 294,528 ACS patients and three studies including 39,973 PCI patients were selected for our meta-analysis. Patients with cancer had increased rates of in-hospital all-cause death (RR 1.74 [1.22; 2.47]), cardiac death (RR 2.44 [1.73; 3.44]) and bleeding (RR 1.64 [1.35; 1.98]) as well as one-year all-cause death (RR 2.62 [1.2; 5.73]) and cardiac death (RR 1.89 [1.25; 2.86]) in ACS studies. Rates of long term all-cause (RR 1.96 [1.52; 2.53]) but not cardiac death were higher in cancer patients admitted for PCI. CONCLUSION: Cancer patients represent a high-risk population both in the acute phase and at long-term after an ACS or PCI. The magnitude of the risk of mortality should however be tempered by the heterogeneity among studies. Early and long term optimal management of such patients should be promoted in clinical practice.

Residual atherothrombotic burden after primary percutaneous coronary intervention and myocardial reperfusion-An optical frequency domain imaging study.

OBJECTIVES: We aimed to assess the relationship between residual in-stent atherothrombotic burden (ATB) after primary percutaneous coronary intervention (PCI) measured by optical frequency domain imaging (OFDI) using different measurement methods and myocardial blush grade (MBG). BACKGROUND: The impact of residual ATB after primary PCI on myocardial reperfusion remains unclear. METHODS: We prospectively included 60 ST-elevation myocardial infarction patients pretreated with aspirin and ticagrelor. OFDI volumetric quantification using planimetry (with intervals every frame or every millimeter) and semiquantitative score were used to determine ATB. Patients were divided into two groups according to final MBG 3 or <3. RESULTS: The mean ATB was 10.08 ± 5.21%. ATB was lower in patients with final MBG 3 compared to those with impaired MBG, regardless of the measurement method (8.15 ± 5.58 vs. 11.77 ± 4.28%; p = .007 for quantification per frame; 7.8 ± 5.19 vs. 11.07 ± 4.07%; p = .009 for quantification per mm and 11.21 ± 11.75 vs. 22.91 ± 17.35; p = .003 for the semiquantitative thrombus score, respectively). CONCLUSION: Residual post-stenting ATB remains substantial after primary PCI in STEMI patients, even when pretreated with ticagrelor and aspirin. ATB appears as a significant correlate of suboptimal myocardial reperfusion, a known surrogate of clinical outcome.

A head-to-head comparison of three coronary fractional flow reserve measurement technologies: The fractional flow reserve-device study.

OBJECTIVES: To compare three FFR technologies: the electric-sensor Pressurewire® (P), the optic-sensor Comet® (C) guidewire, and the optic-sensor Navvus® (N) microcatheter. BACKGROUND: Different technologies are used to measure fractional flow reserve (FFR) for the functional assessment of coronary lesions with potential discrepancies. METHODS: Sixty-six FFR measurements performed on 32 lesions using each technology were used for a paired comparison of FFR on simultaneous measurements and in clinically relevant conditions (guidewires alone, N on a guidewire). RESULTS: Simultaneous measurements of FFR were significantly (p < .0001) correlated between systems (ρ = 0.88, 0.81 and 0.86 for P and N, P and C and, C and N, respectively). The presence of the N microcatheter, led to reduced values of FFR measured by P or C guidewires (p < .0001). The concomitant presence of P and C guidewires led to significantly lower FFR values (p < .0001) measured by P but not by C. In clinically relevant conditions, values of FFR measured by the optic-sensor C guidewire and N catheter were similar and lower than those measured by the P guidewire (p < .0001). The agreement between the three technologies (FFR ≤ 0.80) was 94%. CONCLUSIONS: FFR values simultaneously measured by three different technologies, are strongly correlated, and provide strongly concordant results. However, significant differences are found between values of FFR. The presence of N, but also C lead to a decrease of FFR measured by P. In clinically relevant conditions, the two optic-sensor technologies provide similar FFR measurements, lower than those measured by the piezo-electric technology suggesting a sensor-technology-related measurement variability. CLINICAL TRIAL REGISTRATION: NCT#03052803.

Residual platelet reactivity after pre-treatment with ticagrelor prior to primary percutaneous coronary intervention is associated with suboptimal myocardial reperfusion.

BACKGROUND: The evidence of a clinical benefit of P2Y12 inhibitor pre-treatment in primary percutaneous coronary intervention (PCI) and the relation between the level of platelet inhibition and myocardial reperfusion with newer potent P2Y12 inhibitors remain unclear. We aimed to assess the relationship between platelet reactivity at the time of primary PCI after pre-treatment with aspirin and ticagrelor and the post-PCI myocardial blush grade (MBG). METHODS: We prospectively included 61 patients. Platelet reaction units for ticagrelor (PRU) and aspirin reaction units (ARU) were measured using the point-of-care test VerifyNow before PCI. The high on-ticagrelor (PRU >208) and on-aspirin (ARU ⩾ 550) platelet reactivity (HPR and HaPR) were assessed. Patients were divided into two groups according to MBG 3 or <3. RESULTS: MBG 3 was identified in 28 (46%) patients. Mean PRU was lower in such patients as compared with those with MBG <3 (155.82 ± 90.91 vs. 227.42 ± 65.18; p=0.001) while mean ARU was similar between groups. HPR and HaPR were observed in 30 (49.2%) and 11 patients (18%), respectively. HPR but not HaPR was more frequent in the group with impaired MBG (66.7 vs. 28.6%; p=0.003 and 21.2 vs. 14.3%; p=0.48 respectively). CONCLUSION: Our study shows that higher PRU and the subsequent HPR at the time of primary PCI, after pretreatment with ticagrelor, are the only correlates of post PCI MBG. These findings support the earliest possible loading with ticagrelor prior to primary PCI.

Vitamin K antagonist vs direct oral anticoagulants with antiplatelet therapy in dual or triple therapy after percutaneous coronary intervention or acute coronary syndrome in atrial fibrillation: Meta-analysis of randomized controlled trials.

BACKGROUND: The combination of vitamin K antagonists (VKA) for atrial fibrillation (AF) and antiplatelet agents following percutaneous coronary intervention (PCI) is associated with an increased bleeding risk. HYPOTHESIS: Direct oral anticoagulants (DOAC) are associated with a greater safety profile but the optimal antithrombotic treatment strategy, especially when considering ischemic events, is unclear. METHODS: We performed a meta-analysis of randomized controlled trials comparing outcomes in AF patients following PCI and/or acute coronary syndrome (ACS) when treated with DOAC vs VKA, both in combination with one (dual) or two (triple) antiplatelet regimens. A systematic review was performed by searches of electronic databases MEDLINE (source PubMed) and the Cochrane Controlled Clinical Trials Register Database as well as Cardiology annual meetings. Three studies were finally included. RESULTS: Compared to VKA triple therapy, the use of DOAC was associated with a decreased risk of any bleeding (relative risk [RR] 0.68 [0.62; 0.74]), major bleeding (RR 0.61 [0.51; 0.75]) and intracranial bleeding (RR 0.33 [0.17; 0.66]) and similar rates of the composite efficacy endpoint (RR 1.0 [0.87; 1.14]) and its components. Similar and consistent results were observed with both dual and triple therapy including a DOAC compared to VKA. CONCLUSION: Our meta-analysis supports the use of dual therapy combining a DOAC and clopidogrel as the default regimen in most AF patients after PCI and/or ACS.

Bedside mental status and outcome in elderly patients admitted for acute coronary syndromes.

OBJECTIVE: We investigated whether mental status assessed by simple bedside tests in elderly patients admitted for acute coronary syndromes (ACS) was associated with higher risk of mortality. METHODS: We used the data from a prospective, open, ongoing cohort of patients≥75 years old admitted for ACS to a tertiary centre. Cognitive impairment (CogI) was defined by delirium detected by the Confusion Assessment Method or an abnormal Mini Mental State Examination score. A Cox model adjusted on predefined correlates of mortality was used to assess the relationship between CogI and 1-year mortality. RESULTS: Six-hundred consecutive patients with mental status assessment within 48 hours after admission were included. CogI was identified in 172 (29%) patients among whom 153 (25.5%) had an abnormal Mini Mental State Evaluation and 19 (3.2%) delirium. Death occurred in 49 (28.6%) patients with and 43 (10.5%) patients without CogI at 1 year. There was a significant association between CogI and 1-year mortality (adjusted-HR 2.4, 95% CI 1.53 to 3.62), p<0.001) independent of other covariables. CogI was also independently associated with higher rates of in-hospital bleeding and mortality as well as 3-month rates of all-cause, cardiovascular-related and heart failure-related rehospitalisation. CONCLUSIONS: CogI detected by simple bedside tests in patients≥75 admitted for ACS is associated with an increased risk of 1-year mortality and 3 month rehospitalisation independent of other correlates of poor outcome.

Plaque erosion versus rupture characterization by optical frequency domain imaging before and after coronary stenting following successful fibrinolysis for ST-segment elevation myocardial infarction.

Intracoronary thrombus burden affects the quality of myocardial reperfusion in the setting of ST-elevation myocardial infarction (STEMI). We aimed to study the characteristics of the plaque and thrombus assessed by intracoronary optical frequency domain imaging (OFDI) according to the presence of plaque rupture or erosion in STEMI patients treated with successful fibrinolysis. Pre-stenting thrombus and post-stenting atherothrombotic burden were compared between plaque rupture and erosion. Twenty-seven consecutive patients were included: 17 (63%) had OFDI-plaque rupture and 10 (37%) had OFDI-erosion. Thrombus volume and burden were significantly higher in case of rupture compared to erosion at baseline (13.4 ± 18.4 vs 2.8 ± 2.3 mm3; p = 0.03 and 33.8 ± 17.5 vs 17.5 ± 9.9%; p = 0.007, respectively). In the rupture group, the core of the thrombus consisted dominantly of red thrombus evenly distributed along the entire culprit plaque. In the erosion group, it consisted dominantly of white thrombus with a focal distribution near the minimal lumen area zone. After stenting, the atherothrombotic volume, burden and its distribution, as well as angiographic estimators of myocardial reperfusion were similar between groups. Our study showed that pre-PCI thrombus amount, typesetting and distribution are mainly linked to the underlying mechanism of STEMI. After stenting, the atherothrombotic burden and its distribution were similar between the groups.

Residual platelet reactivity after pre-treatment with ticagrelor prior to primary percutaneous coronary intervention is associated with suboptimal myocardial reperfusion.

BACKGROUND: The evidence of a clinical benefit of P2Y12 inhibitor pre-treatment in primary percutaneous coronary intervention (PCI) and the relation between the level of platelet inhibition and myocardial reperfusion with newer potent P2Y12 inhibitors remain unclear. We aimed to assess the relationship between platelet reactivity at the time of primary PCI after pre-treatment with aspirin and ticagrelor and the post-PCI myocardial blush grade (MBG). METHODS: We prospectively included 61 patients. Platelet reaction units for ticagrelor (PRU) and aspirin reaction units (ARU) were measured using the point-of-care test VerifyNow before PCI. The high on-ticagrelor (PRU >208) and on-aspirin (ARU ⩾ 550) platelet reactivity (HPR and HaPR) were assessed. Patients were divided into two groups according to MBG 3 or <3. RESULTS: MBG 3 was identified in 28 (46%) patients. Mean PRU was lower in such patients as compared with those with MBG <3 (155.82 ± 90.91 vs. 227.42 ± 65.18; p=0.001) while mean ARU was similar between groups. HPR and HaPR were observed in 30 (49.2%) and 11 patients (18%), respectively. HPR but not HaPR was more frequent in the group with impaired MBG (66.7 vs. 28.6%; p=0.003 and 21.2 vs. 14.3%; p=0.48 respectively). CONCLUSION: Our study shows that higher PRU and the subsequent HPR at the time of primary PCI, after pretreatment with ticagrelor, are the only correlates of post PCI MBG. These findings support the earliest possible loading with ticagrelor prior to primary PCI.

Occluded or Not?: A Subtle Electrocardiographic Answer.

This report describes the case of a 48-year-old man whose electrocardiogram after cardiopulmonary resuscitation showed up-sloping ST-segment depression at the J point in precordial leads combined with tall symmetrical T waves. This electrocardiographic pattern corresponded to de Winter syndrome and is related to proximal left anterior descending coronary artery occlusion. (Level of Difficulty: Beginner.).

Point of Care Tests VerifyNow P2Y12 and INNOVANCE PFA P2Y Compared to Light Transmittance Aggregometry After Fibrinolysis.

Detection of high on-treatment platelet reactivity (HPR) by point-of-care tests has not been validated after successful fibrinolysis for ST-elevation myocardial infarction. We assessed the validity of the point-of-care VerifyNow P2Y12 (VN) and INNOVANCE PFA P2Y (PFA) tests on HPR compared to light transmittance aggregometry (LTA) in these patients. The HPR was identified in 10 (34.5%) patients, 15 (51.7%) patients, and 14 (50%) patients using LTA, VN, and PFA, respectively. Discrepancies were observed between the tests despite significant correlations between platelet reactivity measures by LTA and VN ( r = 0.74; P < .0001) and LTA and PFA ( r = .75; P < .0001). Compared to LTA, VN and PFA were associated with a 92% and 53% and 92% and 64% positive predictive value (PPV) and negative predictive value (NPV), respectively, in detecting HPR. When combined, VN and PFA results yielded 90% and 100% PPV and NPV values if discrepancies between the 2 tests were considered as non-HPR. The VN or PFA identify patients without HPR correctly but overestimate the proportion of HPR patients. The association of the 2 tests, in case of HPR, improves the accuracy of the detection of HPR.

Safety and efficacy of IIb/IIIa inhibitors in combination with highly active oral antiplatelet regimens in acute coronary syndromes: A meta-analysis of pivotal trials.

The risk and benefit of GP-IIb/IIIa Inhibition (GPI) in combination with recent antiplatelet regimens in acute coronary syndromes (ACS) remain unassessed. The advent of fast-acting highly active oral P2Y12 inhibitors questions the additional value and risk of their association with GPI. We studied the effect of GPI in combination with prasugrel and ticagrelor, compared to clopidogrel on major bleeding in pivotal randomized controlled trials in the setting of ACS, using a meta-analytic approach. A similar analysis, further including the comparison of a double versus standard dose clopidogrel regimen, was performed for the risk of the primary efficacy endpoint. The combination of GPI and recent P2Y12 inhibitors was associated with a similar risk of bleeding as compared with GPI and the standard clopidogrel regimen (RR 0.92 [0.74; 1.13]). The benefit of recent regimens, including double dose clopidogrel, in reducing the primary ischemic endpoint (RR 0.86 [0.78; 0.94]) persisted in those treated with GPI. Although GPI use was associated with a consistent increase in the risk of bleeding in both recent (RR 1.27 [1.05-1.55]) and standard regimens (RR 2.01 [1.64-2.47]), the relative magnitude of such an increase was lower in association with prasugrel or ticagrelor as compared with clopidogrel. The risk of bleeding using a combination of GPI and oral antiplatelet regimens is mainly related to the use of GPI and not the oral antiplatelet regimen. Considering the absence of increased risk of bleeding and the persistence of the benefit of recent P2Y12 regimens in combination with GPI as compared with the standard clopidogrel regimen, the use of such a combination within the guidelines is supported by our findings.

Prehospital fibrinolysis versus primary percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with ST-elevation myocardial infarction (STEMI), but its benefit over prehospital fibrinolysis (FL) is not clear. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in which outcomes of patients with STEMI managed with FL early in the prehospital setting versus PPCI were compared. RESULTS: Compared with PPCI, FL was consistently associated with similar rates of short-term (30-90 days) death (relative risk [RR] 0.94, 95 % CI 0.67-1.31) and cardiovascular death (RR 0.95, 95 % CI 0.64-1.4), a decreased risk of cardiogenic shock (RR 0.67, 95 % CI 0.48-0.95), and an increased risk of any stroke (RR 3.57, 95 % CI 1.39-9.17) and hemorrhagic stroke (RR 4.37, 95 % CI 1.25-15.26). FL was also associated with similar rates of 1-year mortality (RR 1.01, 95 % CI 0.75-1.34) and major bleeding (RR 1.31, 95 % CI 0.96-1.78) in comparison with PPCI, but with a notable level (I 2 index 30.5 % and 59.8 %) of heterogeneity among studies. CONCLUSIONS: Our study suggests that, compared with PPCI, FL performed in the early prehospital setting is associated with similar mortality rates, lower rates of cardiogenic shock, and higher rates of stroke in patients with STEMI. Although the number of studies comparing the two strategies is relatively low, our results support prehospital FL and transfer to hub percutaneous coronary intervention (PCI) centers as a valid alternative to PPCI, allowing potential limitation of resources allocated to developing proximity 24/7 PCI facilities.