Reducing length of stay after transfemoral transcatheter aortic valve implantation: the FAST-TAVI II trial.

BACKGROUND AND AIMS: The length of stay (LOS) after transcatheter aortic valve implantation (TAVI) remains extremely variable whereas early discharge has been shown to be feasible and safe. The study objective was to evaluate the efficacy and safety of an intervention aimed at reducing LOS after transfemoral TAVI. METHODS: FAST-TAVI II is a prospective, multicentre, cluster, randomized, controlled study including patients with severe symptomatic aortic stenosis, who had transfemoral TAVI. The intervention consisted in a dedicated training programme to implement 10 quality of care measures to reduce LOS with an implementation phase of eight weeks. The primary endpoint was the proportion of patients discharged early within 3 days. Secondary endpoints included: LOS, 30-day mortality and 30-day incidence of readmission for cardiovascular events. RESULTS: During the study period, 969 patients were enrolled in the intervention group and 860 patients in the control group. Mean age was 81.9 ± 6.6 years and mean EuroSCORE II was 4.4 ± 4.5%. Early discharge was achieved in 563 (58.1%) patients in the intervention group vs. 364 (42.3%) patients in the control group (P < .0001). Median LOS was significantly reduced in the intervention group compared to the control group [3 (IQR: 3) vs. 4 days (IQR: 3), P < .0001]. Thirty-day mortality was low and similar in the two groups (0.5% vs. 0.9%, P = .30), as were 30-day readmissions (4.6% vs. 2.8%, P = .28). CONCLUSIONS: The intervention was simple and fast to implement, and was effective and safe to reduce LOS and increase the proportion of patients discharged early after TAVI (NCT04503655).

In-Hospital and 1-Year Clinical Results from the French Registry Using Polymer-Free Sirolimus-Eluting Stents in Acute Coronary Syndrome and Stable Coronary Artery Disease.

Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies. Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.

Rhabdomyolysis with Co-Administration of Statins and Antiplatelet Therapies-Analysis of the WHO Pharmacovigilance Database.

PURPOSE: While statins and antiplatelet therapies are largely prescribed together worldwide, limited information is available on the safety of their association regarding rhabdomyolysis occurrence. We aimed to assess the reporting of rhabdomyolysis in patients treated with a combination of statin and antiplatelet therapy, compared to statin alone. METHODS: We used the World Health Organization pharmacovigilance database (VigiBase®) to compare the rhabdomyolysis reporting between statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) plus antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor) groups versus statin alone groups, for each statin and antiplatelet therapy. Study setting was restricted to patients aged 45 or older, including reports up until 1st September, 2021. We computed reporting Odds-Ratio (ROR) and their 95% confidence interval (CI) to quantify the disproportionality between groups, adjusted on age and sex. RESULTS: Among the 11,431,708 reports of adverse reactions, we extracted 9,489 cases of rhabdomyolysis in patients treated with statins, of whom 2,464 (26%) were also treated with antiplatelet therapy. The reporting of rhabdomyolysis was increased when ticagrelor was associated with atorvastatin (ROR 1.30 [1.02-1.65]) or rosuvastatin (ROR 1.90 [1.42-2.54]) compared to the respective statin alone but did not change when aspirin, clopidogrel or prasugrel were considered. CONCLUSION: Rhabdomyolysis reporting was increased when ticagrelor -but not other antiplatelet agents- was notified with the most prescribed statins in practice. This finding needs to be considered by physicians especially in high-risk patients.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis.

AIM: To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). METHODS AND RESULTS: In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. CONCLUSION: In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

Left atrial strain quantified after myocardial infarction is associated with early left ventricular remodeling.

BACKGROUND: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow-up in STEMI patients. METHODS: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow-up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end-diastolic volume compared to baseline at follow-up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. RESULTS: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow-up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p < .001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (-7.4% [-10.1, -6.5] vs. -9.9% [-12.8, -8.1], p < .01), both on univariate and baseline LV volumes-adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow-up. Intra- and interobserver analysis showed good reproducibility of LA strain. CONCLUSIONS: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management.

Effectiveness and Safety of P2Y12 Inhibitors Pretreatment in Primary Percutaneous Coronary Intervention with Long Transfer Times.

BACKGROUND: Early initiation of a new P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients prior to primary percutaneous coronary intervention (PCI) is recommended over clopidogrel. However, comparative data remain limited, especially in semi-rural regions with subsequent longer transfer times. OBJECTIVES: We aimed to assess the determinants, effectiveness, and safety of pretreatment with new P2Y12 inhibitors compared with clopidogrel in a primary PCI regional network. METHODS: Outcomes of 1235 primary PCI patients pretreated with new P2Y12 inhibitors (n = 1050) or clopidogrel (n = 185) were evaluated using a prospective registry. Primary effectiveness endpoint was the composite of death, recurrent myocardial infarction, stroke, or new revascularization. Serious bleedings were defined as Bleeding Academic Research Consortium ≥ 2. RESULTS: Clopidogrel was more likely to be used in older and female patients with more comorbidities. Mean transfer time was longer in the clopidogrel group (123.3 ± 67.3 vs. 102.3 ± 57.2 min; p < 0.01). The primary endpoint was less frequent with new P2Y12 inhibitors compared with clopidogrel (14.9 vs. 30.3%; odds ratio 0.58, 95% confidence interval [CI] 0.39-0.87; p < 0.01), mostly driven by a reduced rate of death (4.5 vs. 26% respectively; hazard ratio 0.25, 95% CI 0.16-0.38; p < 0.01). Bleeding rates did not differ between groups (1 vs. 0.5%, respectively; p = 0.96). CONCLUSION: Compared with clopidogrel, pretreatment with new P2Y12 inhibitors seems to be associated with lower risks of mortality and ischemic outcomes, and similar risks of bleeding in a real-world registry. Our results are in line with the guidelines recommending the preferential pre-PCI administration of new P2Y12 inhibitors in STEMI patients referred for primary PCI.

Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial.

BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI. METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290. FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070). INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI. FUNDING: ACTION Study Group and AstraZeneca.

Safety and efficacy of very short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy in older patients undergoing percutaneous coronary intervention: meta-analysis of randomised controlled trials.

BACKGROUND: older patients undergoing percutaneous coronary intervention (PCI) represent a growing population sharing both a high ischemic and bleeding risk. Dual antiplatelet therapy (DAPT) reduces the incidence of thrombotic events but exposes patients to an increased risk of bleeding and subsequent mortality. Its optimal duration after PCI remains unclear. OBJECTIVE: to assess the impact of short-duration DAPT on both bleeding and ischemic events in the specific population of older patients undergoing PCI. METHODS: we performed a meta-analysis of randomised controlled trials comparing the safety and efficacy of standard versus very short duration (≤ 3 months, followed by P2Y12 inhibitor monotherapy) DAPT after PCI with a drug-eluting stent in older patients. RESULTS: four studies, representing 8,961 older patients, were finally included. Compared with standard duration, short-duration DAPT was associated with similar rates of major bleeding (relative risks, RR 0.70 [0.47; 1.05]) and the composite efficacy endpoint (RR 0.85 [0.63; 1.14]). There was a high level of heterogeneity between the studies (I2 = 68%) regarding major bleeding. CONCLUSION: our meta-analysis suggests that short DAPT may be a valid option in older patients after PCI but it also highlights the need for specific studies in such patients on optimal duration of antiplatelet therapy.

Impaired left atrial stiffness in patients with corrected congenital left ventricular outflow obstructions.

OBJECTIVE: We examined the left atrial stiffness index (LA Stiff) on echocardiography and its determinants in adults and adolescents with repaired congenital left ventricular outflow obstructions (c-LVOOs), including isolated subaortic stenosis (SAS), stenotic bicuspid aortic valve (BAV), and aortic coarctation (CoA). METHODS: Seventy-two patients (43 males, age: 31 ± 15 years) with repaired c-LVOOs (SAS: n = 12; BAV: n = 27; CoA: n = 33) were compared to 72 age- and sex-matched controls. 2D strain imaging was performed to assess left ventricular (LV) and LA function, including peak positive longitudinal LA strain (LAS), late diastolic LA strain (LDS), and LV global longitudinal strain (GLS). The (E/Ea)/LAS ratio was used to calculate LA Stiff. RESULTS: LA Stiff was significantly higher in the c-LVOO group than in the control group. Among the c-LVOO patients, the CoA group had the lowest GLS and the highest LA Stiff; no significant differences were found with respect to sex, hypertension history, smoking status, or repeated repair among c-LVOO subtypes. Multivariable regression analysis with the variables "BMI" and "c-LVOO subtype" revealed that BMI and c-LVOO subtypes were independently associated with LA Stiff (b = 0.290, P = .009 and b = 0.353, P = .002, respectively). CONCLUSIONS: We documented abnormal LA Stiff values in adults and adolescents after c-LVOO repair. Patients with CoA demonstrated the most impaired LA Stiff values. Overweight may contribute to worse LA Stiff values. Further studies are required to determine the prognostic implications of LA Stiff in patients with repaired c-LVOOs.

Impaired left atrial function in adults and adolescents with corrected aortic coarctation.

This study examined the left atrial (LA) function using two-dimensional (2D) strain analysis after aortic coarctation (CoA) repair, as well as relationships between LA function and patient characteristics, especially aortic arch anatomy. 56 patients (34 males, age: 31 ± 16 years) with CoA repair (46 post 'end-to-end anastomosis/subclavian flap') and 56 controls were studied. 2D strain imaging was performed to assess left ventricular (LV) and LA functions including peak-positive LA strain, early and late diastolic LA strains, and global longitudinal (LV-GLS) and circumferential (LV-GCS) strains. LA dysfunction (LAD) was defined as a peak-positive LA strain value lower than the mean value of the control group minus 2 SDs. Peak-positive LA strain, early and late diastolic LA strains, and LV-GLS were significantly lower in the CoA group while LV-GCS did not differ. No significant correlation was found between LA strain and either current age, age at initial repair, or blood pressure; Ea and LV-GLS were moderately correlated to peak-positive LA strain (r = 0.49, p < 0.001 and r = - 0.55, p < 0.001, respectively). 23 CoA patients (41%) presented LAD (abnormal peak-positive LA strain < 25%). Among patients who underwent end-to-end anastomosis/subclavian flap, those with a non-romanesque aortic arch anatomy exhibited a significantly lower peak-positive LA strain. Ischemic stroke and atrial arrhythmia were more frequent in CoA patients with LAD. Our findings suggest that LAD may be prevalent late after CoA repair. Postoperative aortic arch anatomy may impact peak-positive LA strain.

EMERGEncy versus delayed coronary angiogram in survivors of out-of-hospital cardiac arrest with no obvious non-cardiac cause of arrest: Design of the EMERGE trial.

BACKGROUND: In adults, the most common cause of out-of-hospital cardiac arrests (OHCA) is acute coronary artery occlusion. If an immediate coronary angiogram (CAG) is recommended for survivors presenting a ST segment elevation on the electrocardiogram (ECG) performed after resuscitation, there is still a debate regarding the best strategy in patients without ST segment elevation. HYPOTHESIS: Performing an immediate CAG after an OHCA without ST segment elevation on the post-resuscitation ECG and no obvious non-cardiac cause of arrest could lead to a better 180-day survival rate with no or minimal neurological sequel as compared with a delayed CAG performed 48 to 96 hours after the arrest. DESIGN: The EMERGE trial is a prospective national, randomized, open and parallel group trial, in which 970 survivors of OHCA will be randomized (1:1) to either immediate (as soon as possible after return of spontaneous circulation) or delayed (48 to 96 h) CAG. Participants will be OHCA patients with no ST segment elevation on the post resuscitation ECG and no obvious non-cardiac cause of arrest. The primary endpoint of the study is the 180-day survival rate with no or minimal neurological sequel corresponding to Cerebral Performance Category (CPC) 1 or 2. The secondary endpoints are: occurrence of shock during the first 48 hours, ventricular tachycardia and/or fibrillation during the first 48 hours, change in left ventricular ejection fraction between baseline and 180 days assessed by echocardiogram, neurological status evaluated by the CPC score at intensive care unit (ICU) discharge and day 90 neurological status assessed by the Glasgow Outcome Scale Extended score (GOSE) at 90 and 180 days, overall survival rate, and hospital length of stay. SUMMARY: The EMERGE trial is a prospective, multicenter, randomized, controlled trial that will assess the 180-day survival rate with no or minimal neurologic sequel in patients resuscitated from an OHCA without ST segment elevation and who will be managed with either immediate or delayed CAG.

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study.

BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

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.

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.

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.

Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

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.