Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study.

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Sex Differences in 10-Year Outcomes Following STEMI: A Subanalysis From the EXAMINATION-EXTEND Trial.

BACKGROUND: Short-term outcomes following ST-segment elevation myocardial infarction (STEMI) in women are worse than in men, with a higher mortality rate. It is unknown whether sex plays a role in very long term outcomes. OBJECTIVES: The aim of this study was to assess whether very long term outcomes following STEMI treatment are influenced by sex. METHODS: EXAMINATION-EXTEND (10-Year Follow-Up of the EXAMINATION Trial) was an investigator-driven 10-year follow-up of the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction) trial, which randomly 1:1 assigned 1,498 patients with STEMI to receive either everolimus-eluting stents or bare-metal stents. The present study was a subanalysis according to sex. The primary endpoint was the composite patient-oriented endpoint (all-cause death, any myocardial infarction, or any revascularization) at 10 years. Secondary endpoints were individual components of the primary endpoint. All endpoints were adjusted for age. RESULTS: Among 1,498 patients with STEMI, 254 (17%) were women. Overall, women were older, with more arterial hypertension and less smoking history than men. At 10 years, no difference was observed between women and men for the patient-oriented composite endpoint (40.6% vs 34.2%; adjusted HR: 1.14; 95% CI: 0.91-1.42; P = 0.259). There was a trend toward higher all-cause death in women vs men (27.6% vs 19.4%; adjusted HR: 1.30; 95% CI: 0.99-1.71; P = 0.063), with no difference in cardiac death or other endpoints. CONCLUSIONS: At very long term follow-up, there were no differences in the combined patient-oriented endpoint between women and men, with a trend toward higher all-cause death in women not driven by cardiac death. The present findings underline the need for focused personalized medicine in women after percutaneous revascularization aimed at both cardiovascular and sex-specific risk factor control and targeted treatment. (10-Years Follow-Up of the EXAMINATION Trial [EXAMINAT10N]; NCT04462315).

Long-Term Vascular Function in CTO Recanalization: A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel.

BACKGROUND: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). METHODS: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. RESULTS: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). CONCLUSION: The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066).

ST-Segment Elevation Myocardial Infarction Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk. OBJECTIVES: The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR. METHODS: This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (interquartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries. RESULTS: Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate <60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class ≥2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk. CONCLUSIONS: STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to-balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes.

Ticagrelor versus clopidogrel for recovery of vascular function immediately after successful chronic coronary total occlusion recanalization: A randomized clinical trial.

Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor. We sought if ticagrelor may augment adenosine-induced coronary blood flow vs. clopidogrel immediately after successful CTO percutaneous coronary intervention (PCI).

TIcaGrEloR and Absorb bioresorbable vascular scaffold implantation for recovery of vascular function after successful chronic total occlusion recanalization (TIGER-BVS trial): Rationale and study design.

OBJECTIVES: To explore the role of ticagrelor versus clopidogrel in coronary blood flow normalization immediately after chronic coronary total occlusion (CTO) recanalization. BACKGROUND: Coronary vascular function of a CTO immediately after recanalization is demonstrated to be poor. METHODS: The TIGER BVS is a prospective, double-randomized, open-label, two parallel-group controlled clinical trial to evaluate efficacy of ticagrelor versus clopidogrel in improving vascular function of coronary segment distal to CTO immediately after CTO recanalization. A total of 50 patients who receive CTO PCI will be randomized 1:1 to receive ticagrelor versus clopidogrel at least 3 days before the procedure. Immediately after CTO recanalization with Absorb BVS implantation, a specific study of vascular function under adenosine infusion will be performed. Patients will be therefore randomized 1:1 to receive angiographic follow-up with vascular function and optical coherence tomography analyses at 1- or 3-year follow-up. This study is registered on ClinicalTrials.gov with number NCT02211066. CONCLUSIONS: The TIGER BVS trial will provide the first randomized comparison between ticagrelor versus clopidogrel in recovering vascular function in CTO patients. It will also provide important data on vascular restoration therapy of Absorb BVS in this scenario.

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.

Drug-eluting stents for off-label indications in real clinical world: evidence based or 'intuition' based clinical practice?

BACKGROUND: The use of drug-eluting stents (DES) is an example of the disparity between recommendations given by regulatory agencies and the real clinical world. Such disparity might lead cardiologists to adopt different routines in the use of DES. We aimed to assess variability of off-label DES use between hospitals and to what extent it can be explained by differences in patient or hospital characteristics. METHODS: Characteristics of consecutive patients receiving DES in 29 hospitals were recorded. Individual and hospital determinants of receiving DES for off-label indications were assessed by multilevel logistic regression. RESULTS: 1903 patients were recruited and 1188 (62.4%) received DES for off-label indications. Individual variables associated with off-label use were age (OR 1.01 (1-1.02)), previous percutaneous (OR 2.24 (1.68-2.97)) or surgical (2.41 (1.52-3.84)) revascularization, repeated procedure at the same admission (OR 4.66 (2.7-8.05)), receiving two (OR 4.17 (3.24-5.37)) or three or more DES (OR 14.12 (9.08-21.96)) vs one. Adjusting for individual variables, the Odds of receiving DES for off-label indication was higher in public funding hospitals with surgery availability vs private hospitals: 1.49 (0.86-2.6), and in public hospitals without surgery vs public with surgery availability: OR 1.76 (1.02-3.03). Interhospital variability reminded significant after adjustment for individual and contextual variables. CONCLUSION: Off-label DES use is highly variable between centers. Although this variability is partially determined by hospital type of funding and cardiac surgery availability, the substantial interhospital variability after multilevel adjustment suggests heterogeneity in the process of care.

Long-term follow-up after percutaneous treatment of the unprotected left main stenosis in high risk patients not suitable for bypass surgery.

INTRODUCTION AND OBJECTIVES: Percutaneous coronary intervention is recommended in patients with unprotected left main stenosis non suitable for coronary artery bypass graft. Long-term follow-up of those patients remains uncertain. METHODS: All patients with de novo unprotected left main stenosis treated with stent implantation were consecutively enrolled. Percutaneous coronary intervention was indicated according to the standards of care, taking into account clinical and anatomical conditions unfavorable for coronary artery bypass graft. The primary end point was the occurrence of major adverse cardiac events, a composite of death, nonfatal acute myocardial infarction, or target lesion revascularization. RESULTS: Of 226 consecutive patients included, 202 (89.4%) were treated with drug-eluting stents. Mean age was 72.1 years, 41.1% had renal dysfunction, and mean Syntax score and EuroSCORE were 28.9 and 7.4, respectively. Angiographic and procedural success was achieved in 99.6% and 92.9% of patients. At 3 years, the rates of major adverse cardiac events, death, nonfatal acute myocardial infarction and target lesion revascularization were 36.2%, 25.2%, 8.4%, 8.0%, respectively. Target lesion revascularization was more frequently observed when ≥ 2 stents were implanted rather than a single stent (18.5% vs 5.8%, P=.03); and with bare metal stents rather than drug-eluting stents (13.0% vs 7.9%, P=.24). Definite stent thrombosis was observed in 2 patients (0.9%) and probable stent thrombosis in 7 (3.1%). Female sex, impaired left ventricular function, and use of bare metal stents were significantly related with all-cause mortality. CONCLUSIONS: High-risk patients with unprotected left main stenosis treated with percutaneous coronary intervention presented with a high rate of major adverse cardiac events at long-term follow-up. Female sex, impaired left ventricular function, and use of bare metal stents were predictors of poor prognosis.

Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial.

AIMS: Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial. METHODS AND RESULTS: The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group. CONCLUSION: SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.