Three-year outcomes of A Randomized Multicentre Trial Comparing Revascularization and Optimal Medical Therapy for Chronic Total Coronary Occlusions (EuroCTO).

BACKGROUND: Percutaneous coronary intervention (PCI) for chronic total coronary occlusions (CTO) improves clinical symptoms and quality of life. The longer-term safety of PCI compared to optimal medical therapy (OMT) remains uncertain. AIMS: We sought to evaluate the long-term safety of PCI for CTO in a randomised trial as compared to OMT. METHODS: A total of 396 patients with a symptomatic CTO were enrolled into a randomised, multicentre clinical trial comparing PCI and OMT. Half of the patients had a single CTO; the others had multivessel disease. Non-CTO lesions were treated prior to randomisation (2:1 ratio). During follow-up, crossover from OMT to PCI occurred in 7.3% (1 year) and 17.5% (3 years) of patients. RESULTS: At 3 years, the incidence of cardiovascular death or nonfatal myocardial infarction was not significantly different between the groups (OMT 3.7% vs PCI 6.2%; p=0.29). By per-protocol analysis, the difference remained non-significant (OMT 5.7% vs PCI 4.7%; p=0.67). Overall, major adverse cardiovascular events (MACE) were more frequent with OMT (OMT 21.2% vs PCI 11.2%), largely because of ischaemia-driven revascularisation. The rates of stroke or hospitalisation for bleeding were not different between the groups. CONCLUSIONS: At 3 years there was no difference in the rate of cardiovascular death or myocardial infarction between PCI or OMT among patients with a remaining single coronary CTO. The MACE rate was higher in the OMT group due largely to ischaemia-driven revascularisation. CTO PCI appears to be a safe option for patients with a single remaining significant coronary CTO. CinicalTrials.gov: NCT01760083.

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.

Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation.

Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. Materials and methods: In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 µM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02457130].

Improved prediction of electrical storm in patients with prior myocardial infarction and implantable cardioverter defibrillator.

AIMS: To evaluate predictors of electrical storm (ES), including chronic total occlusion in an infarct-related coronary artery (infarct-related artery CTO, IRACTO), in a cohort of patients with prior myocardial infarction (MI) and implantable cardioverter-defibrillators (ICD). METHODS: Multicenter observational cohort study including 643 consecutive patients with prior MI and a first ICD implanted between 2005 and 2018 at three tertiary hospitals. All the patients included in the study had undergone a diagnostic coronary angiography before ICD implantation. The variable prior ventricular arrhythmias (VA+) was positive in patients with secondary prevention ICDs and in those with at least one appropriate ICD therapy after primary prevention implantation. RESULTS: During a median follow-up of 42 months 59 patients (9%) suffered ES. The presence of at least one IRACTO not revascularized (IRACTO-NR) was associated with a significantly higher cumulative incidence of ES (14.5% vs 4.8%, p < 0.001). IRACTO-NR maintained a significant association with ES after adjustment for potential confounders (HR 2.3, p = 0.005) and was an independent predictor of ES together with VA+ and LVEF. The best cut-off of LVEF to predict ES was ≤38%. A risk-prediction model based on IRACTO-NR, VA+ and LVEF≤38% identified three categories of ES risk (low, intermediate and high), with progressively increasing cumulative incidence of ES (2.2%, 9% and 20%). CONCLUSION: In a cohort of patients with prior MI and ICD, IRACTO-NR is an independent predictor of ES. A new risk-prediction model allowed the identification of three categories of risk, with potentially important clinical implications.

Impact of operators experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry.

BACKGROUND: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. METHODS: Prospective, multicenter, "real-world" registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. RESULTS: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centers previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. CONCLUSIONS: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operators experience with its previous device iteration or the number of Watchman FLX devices implanted.

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).

Coronary endothelial and microvascular function distal to polymer-free and endothelial cell-capturing drug-eluting stents. The randomized FUNCOMBO trial.

INTRODUCTION AND OBJECTIVES: The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months. METHODS: Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion. RESULTS: Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P=.913). Mean lumen diameter decreased by 16.0 ±20.2% vs 16.1 ±21.6% during acetylcholine infusion (P=.983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ±1.77 vs 3.23±1.62 (P=.992) and the index of microcirculatory resistance was 24.8±16.8 vs 21.3±12.0 (P=.440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P=.466), malapposed struts (0.1% vs 0.3%; P=.519) and major evaginations (7.1% vs 5.6%; P=.708) were observed in few cases. CONCLUSIONS: Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172.

Revascularization of coronary chronic total occlusions in an infarct-related artery and recurrence of ventricular arrhythmias among patients with secondary prevention implantable cardioverter defibrillator.

OBJECTIVES: To evaluate whether the revascularization of a coronary chronic total occlusion in an infarct-related artery (IRACTO) may be associated with lower recurrence of ventricular arrhythmias (VA) among patients with a secondary prevention implantable cardioverter defibrillator (ICD). BACKGROUND: IRACTO is increasingly recognized as an independent predictor of VA. It is unknown whether IRACTO revascularization can reduce the burden of VA. METHODS: Multicenter observational cohort study that included consecutive patients with prior myocardial infarction and secondary prevention ICD. The primary endpoint was any appropriate ICD therapy. RESULTS: Among the 460 patients included, 269 (58%) had at least one IRACTO at the coronary angiogram performed before ICD implantation; of these, 20 (7%) had their IRACTO successfully revascularized (IRACTO-R) afterwards. During a median follow-up of 48 months, 229 patients (49%) had at least one appropriate ICD therapy. Patients with IRACTO not revascularized (IRACTO-NR) had the highest incidence of ICD therapies (65%) while patients with IRACTO-R had the lowest (10%, p < .001). In the entire cohort, IRACTO-NR was an independent predictor of appropriate ICD therapies (HR 2.85, p < .001) and appropriate ICD shocks (HR 2.94, p < .001). Among patients with IRACTO at baseline, IRACTO-R was independently associated with a marked reduction of appropriate ICD therapies (HR 0.12, p = .002) and appropriate ICD shocks (HR 0.21, p = .03). CONCLUSIONS: In patients with prior myocardial infarction and secondary prevention ICD, IRACTO revascularization was independently associated with a markedly lower incidence of appropriate ICD therapies and shocks. These results should be corroborated by larger prospective studies.

Association of fractalkine with functional severity of heart failure and impact on clopidogrel efficacy in patients with ischemic heart disease.

INTRODUCTION: Patients with heart failure (HF) display elevated levels of soluble fractalkine, a chemokine involved in inflammation processes, atherosclerosis and platelet activation. Further, fractalkine has been associated with reduced pharmacodynamic (PD) responsiveness to clopidogrel. The aim of this study was to investigate the association of fractalkine with the severity of HF and its impact on platelet activation and clopidogrel response in patients with coronary artery disease (CAD) with and without HF. MATERIALS AND METHODS: This prospective PD study included 116 stable CAD patients on DAPT with aspirin and clopidogrel. Subjects were classified in two groups: patients with HF and reduced (<40%) left ventricular ejection fraction (HFrEF group, n = 56) and patients without HF (no HF group, n = 60). Clinical severity of HF was graded according to NYHA classification. Platelet function assays included vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry and light transmittance aggregometry. Fractalkine and P-selectin concentrations were determined by ELISA. RESULTS: Fractalkine levels progressively increased with the severity of the disease in the HFrEF group (NYHA I: 471.2 ± 52.4 pg/ml, NYHA II: 500.5 ± 38.4 pg/ml, NYHA III: 638.9 ± 54.3 pg/ml, p for linear trend 0.023). Numerically higher concentrations of fractalkine were observed in the HFrEF group compared to the no HF group with borderline significance (p = 0.052). No significant differences in clopidogrel-induced platelet inhibition according to fractalkine values were observed in any of the groups. CONCLUSIONS: Fractalkine levels were increased in patients with HFrEF and positively associated with the functional severity of the disease. No evident impact of fractalkine on clopidogrel PD efficacy was found.

Coronary vasomotor function and myocardial flow with bioresorbable vascular scaffolds or everolimus-eluting metallic stents: a randomised trial.

AIMS: The aim of this study was to compare the hyperaemic flow and vasomotor response to endothelium-dependent stimuli between bioresorbable vascular scaffolds (BVS) and metallic everolimus-eluting stents (EES) at 13 months. METHODS AND RESULTS: Seventy non-diabetic patients aiming to achieve complete revascularisation were randomised 1:1 to BVS or EES implantation. At 13 months, invasive coronary angiography was performed using intracoronary pressure and Doppler ultrasound measurements at rest and maximal hyperaemia. A vasomotor test to endothelium-dependent (acetylcholine) and independent (nitroglycerine) stimuli and optical coherence tomography (OCT) were also performed. Fifty-nine patients (30 BVS and 29 EES) underwent 13-month examination. Doppler ultrasound average peak velocity (49.0±17.5 vs 49.3±18.3 cm/sec; p=0.95), coronary blood flow (97.4±53.5 vs 88.3±46.7 ml/min; p=0.51), coronary flow reserve (2.6±0.9 vs 2.7±0.8; p=0.84) and fractional flow reserve (0.92±0.06 vs 0.94±0.04; p=0.17) were similar between the groups. The vasomotor test showed vasoconstriction response to acetylcholine in 75.6% proximal and 72.2% distal peri-scaffold segments without differences between study devices. BVS had larger in-scaffold vasoconstriction than EES (60.0% vs 27.6%; p=0.01) despite similar neointima response as assessed by OCT. CONCLUSIONS: BVS and EES had similar microcirculatory response to hyperaemia and predominant vasoconstrictive response in the peri-scaffold segments to endothelium-dependent stimuli. However, BVS exhibited larger vasoconstriction to endothelium-dependent stimuli in the scaffold segment.

Resultados inmediatos e impacto funcional y pronóstico tras la recanalización de oclusiones coronarias crónicas. Resultados del Registro Ibérico / Procedural, functional and prognostic outcomes following recanalization of coronary chronic total occlusions. Results of the Iberian Registry

Introducción y objetivos: El impacto de la intervención coronaria percutánea (ICP) sobre oclusiones coronarias crónicas totales (OCT) presenta controversias. Se analizan los resultados agudos y al seguimiento en nuestro entorno. Métodos: Registro prospectivo de ICP sobre OCT en 24 centros durante 2 años. Resultados: Se realizaron 1.000 ICP sobre OCT en 952 pacientes. La mayoría tenía síntomas (81,5%) y cardiopatía isquémica previa (59,2%), y hubo intentos de desobstrucción previos en un 15%. El SYNTAX anatómico fue 19,5 +/- 10,6 y tenía J-score > 2 el 17,3%. El procedimiento fue retrógrado en 92 pacientes (9,2%). La tasa de éxito fue del 74,9%, mayor en aquellos sin ICP previa (el 82,2 frente al 75,2%; p = 0,001), con J-score ≤ 2 (el 80,5 frente al 69,5%; p = 0,002) y con el uso de ecografía intravascular (el 89,9 frente al 76,2%; p = 0,001), que fue predictor independiente del éxito. Por el contrario, lesiones calcificadas, > 20 mm o con muñón proximal romo lo fueron de fracaso. El 7,1% tuvo complicaciones, como perforación (3%), infarto (1,3%) o muerte (0,5%). Al año de seguimiento, el 88,2% mejoró clínicamente en caso de ICP exitosa (frente al 34,8%; p < 0,001). Dicha mejoría se asoció con menor mortalidad. La tasa de mortalidad al año fue del 1,5%. Conclusiones: Los pacientes del Registro Ibérico con OCT tratados con ICP presentan complejidad clínico-anatómica, tasas de éxito y complicaciones similares a los de otros registros nacionales e importante impacto de la recanalización exitosa en la mejoría funcional, que a su vez se asoció con menor mortalidad

Introduction and objectives: There is current controversy regarding the benefits of percutaneous recanalization (PCI) of chronic total coronary occlusions (CTO). Our aim was to determine acute and follow-up outcomes in our setting. Methods: Two-year prospective registry of consecutive patients undergoing PCI of CTO in 24 centers. Results: A total of 1000 PCIs of CTO were performed in 952 patients. Most were symptomatic (81.5%), with chronic ischemic heart disease (59.2%). Previous recanalization attempts had been made in 15%. The mean SYNTAX score was 19.5 +/- 10.6 and J-score was > 2 in 17.3%. A retrograde procedure was performed in 92 patients (9.2%). The success rate was 74.9% and was higher in patients without previous attempts (82.2% vs 75.2%; P = .001), those with a J-score ≤ 2 (80.5% vs 69.5%; P = .002), and in intravascular ultrasound-guided PCI (89.9% vs 76.2%, P = .001), which was an independent predictor of success. In contrast, severe calcification, length > 20mm, and blunt proximal cap were independent predictors of failed recanalization. The rate of procedural complications was 7.1%, including perforation (3%), myocardial infarction (1.3%), and death (0.5%). At 1-year of follow-up, 88.2% of successfully revascularized patients showed clinical improvement (vs 34.8%, P < .001), which was associated with lower mortality. At 1-year of follow-up, the mortality rate was 1.5%. Conclusions: Compared with other national registries, patients in the Iberian registry undergoing PCI of a CTO showed similar complexity, success rate, and complications. Successful recanalization was strongly associated with functional improvement, which was related to lower mortality

Procedural, Functional and Prognostic Outcomes Following Recanalization of Coronary Chronic Total Occlusions. Results of the Iberian Registry.

INTRODUCTION AND OBJECTIVES: There is current controversy regarding the benefits of percutaneous recanalization (PCI) of chronic total coronary occlusions (CTO). Our aim was to determine acute and follow-up outcomes in our setting. METHODS: Two-year prospective registry of consecutive patients undergoing PCI of CTO in 24 centers. RESULTS: A total of 1000 PCIs of CTO were performed in 952 patients. Most were symptomatic (81.5%), with chronic ischemic heart disease (59.2%). Previous recanalization attempts had been made in 15%. The mean SYNTAX score was 19.5 ± 10.6 and J-score was > 2 in 17.3%. A retrograde procedure was performed in 92 patients (9.2%). The success rate was 74.9% and was higher in patients without previous attempts (82.2% vs 75.2%; P = .001), those with a J-score ≤ 2 (80.5% vs 69.5%; P = .002), and in intravascular ultrasound-guided PCI (89.9% vs 76.2%, P = .001), which was an independent predictor of success. In contrast, severe calcification, length > 20mm, and blunt proximal cap were independent predictors of failed recanalization. The rate of procedural complications was 7.1%, including perforation (3%), myocardial infarction (1.3%), and death (0.5%). At 1-year of follow-up, 88.2% of successfully revascularized patients showed clinical improvement (vs 34.8%, P < .001), which was associated with lower mortality. At 1-year of follow-up, the mortality rate was 1.5%. CONCLUSIONS: Compared with other national registries, patients in the Iberian registry undergoing PCI of a CTO showed similar complexity, success rate, and complications. Successful recanalization was strongly associated with functional improvement, which was related to lower mortality.

Frailty in elderly patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The prevalence of frailty, cognitive impairment and disability and its prognostic impact in patients with myocardial infarction undergoing primary percutaneous coronary intervention is unknown. AIMS: The aim of this study was to assess the prevalence of frailty and other ageing-related variables and their association with inhospital mortality in consecutive elderly ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention in a tertiary care hospital. METHODS: We prospectively included patients aged 75 years or older with STEMI undergoing primary percutaneous coronary intervention. The nursing team provided pre-discharge, standardised questionnaires and tests to each patient to study the presence of frailty (FRAIL scale), comorbidity (Charlson index), disability (Barthel test, Lawton-Brody index), nutritional risk (MNA-SF test) and cognitive status (Pfeiffer test). The association between ageing-related variables and mortality was assessed by binary logistic regression. RESULTS: A total of 259 patients were included with a mean age of 82.6±6 years, 57.9% men. A total of 51 patients (19.7%) were frail, 26 presented with moderate or severe disability (10%), and 82 were at risk of malnutrition (31.7%). Frailty was associated with a higher prevalence of diabetes, hypertension and previous stroke, and a higher inhospital mortality (21.6% vs. 3.4%; P<0.001). After adjusting for potential confounders, this association remained significant (odds ratio 3.96; 95% confidence interval 1.16-13.56; P=0.028). CONCLUSION: A not negligible proportion of elderly patients with STEMI fulfilled the frailty criteria. Frailty was independently associated with mortality. A very simple, feasible geriatric assessment by trained nurses can contribute to predict mortality.

Evaluación del efecto sinérgico de la metformina y los inhibidores mTOR sobre la endotelización de los stents farmacoactivos en pacientes diabéticos / In vivo evaluation of the synergic effect of metformin and mTOR inhibitors on the endothelial healing of drug-eluting stents in diabetic patients

Introducción y objetivos: Estudios recientes en animales han demostrado que la metformina (MF) perjudica la endotelización de los stents farmacoactivos (SFA). Se evaluó el efecto de la MF en el recubrimiento neointimal de los SFA en pacientes diabéticos por tomografía de coherencia óptica (OCT). Métodos: El ensayo RESERVOIR aleatorizó 116 lesiones en 112 pacientes con diabetes mellitus a stents liberadores de amphilimus o everolimus, a los que se realizó una OCT a los 9 meses. Los pacientes se dividieron en 3 grupos según el tratamiento hipoglucemiante recibido: a) no MF; b) MF sin insulina, y c) MF con insulina. El objetivo primario fue el porcentaje de struts no recubiertos. Resultados: Diecisiete pacientes (19 lesiones) al grupo sin MF; 53 pacientes (54 lesiones) al grupo MF sin insulina y 28 pacientes (28 lesiones) al grupo MF con insulina. Las características basales fueron comparables, aunque los pacientes del grupo MF sin insulina tuvieron un mejor control glucémico (p < 0,01). Por OCT la frecuencia relativa de struts no recubiertos fue comparable entre grupos (3,07 ± 4,80% frente a 2,23 ± 4,73% frente a 3,43 ± 6,69% respectivamente, p = 0,48). El análisis multivariante confirmó que la MF no altera el recubrimiento de los SFA (OR = 1,49; IC95%, 0,71-3,08, p = 0,29). La angiografía cuantitativa tampoco mostró efecto de la MF sobre la pérdida luminal tardía, mientras que el tratamiento con insulina si se asoció a una mayor pérdida luminal tardía (p = 0,02). Conclusiones: El uso de MF no perjudica el recubrimiento neointimal de los SFA en diabéticos independientemente de que reciban o no tratamiento con insulina. De acuerdo a nuestros resultados, el uso de MF parece no estar desaconsejado en estos pacientes

Introduction and objectives: Recent animal studies have shown metformin (MF) to impair endothelialization of drug-eluting stents (DES). The aim of this study was to evaluate the effect of MF on the healing of DES in human coronary arteries of patients with diabetes mellitus by optical coherence tomography (OCT). Methods: The RESERVOIR trial randomized 116 lesions in 112 patients with diabetes mellitus to amphilimus- or everolimus-eluting stents and included mandatory OCT at 9 months of follow-up. Patients were divided in 3 groups according to the glucose-lowering agents received: a) no MF; b) MF in noninsulin treated patients, and c) MF in insulin-treated patients. The primary safety endpoint was the rate of uncovered stents. Results: Seventeen patients with 19 lesions did not receive MF, whereas MF was administered to 53 noninsulin treated patients (54 lesions) and 28 insulin-treated patients (28 lesions). Baseline characteristics were comparable, although noninsulin treated patients who received MF had better glycemic control (P < .01). By OCT, rates of uncovered struts were comparable between groups (3.07 ± 4.80% vs 2.23 ± 4.73% vs 3.43 ± 6.69%, respectively; P = .48). Multivariate models confirmed that MF had no effect on the healing of DES (OR, 1.49, 95%CI, 0.71-3.08; P = .29). Similarly, quantitative angiography showed no effect of MF on late lumen loss, whereas patients treated with exogenous insulin had greater late lumen loss (P = .02). Conclusions: Metformin use does not impair endothelial healing of DES in patients with both insulin- and noninsulin-treated diabetes mellitus. According to these results, MF should not be discouraged in these patients

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).

One-year optical coherence tomography findings in patients with late and very-late stent thrombosis treated with intravascular imaging guided percutaneous coronary intervention.

Patients with late/very-late stent thrombosis (ST) are at high risk of recurrent-ST. The mechanisms of recurrent-ST are largely unknown. The objective is to describe the 1-year optical coherence tomography (OCT) findings of patients suffering from late/very-late ST treated with intravascular imaging guided percutaneous coronary intervention (PCI). All consecutive patients with late/very-late ST undergoing intravascular imaging guided PCI were screened to undergo coronary angiography and OCT examination at 1 year. Patients were classified according to the observation of stent malapposition as most contributing cause of the ST. Thirty-four patients were included. Stent malapposition was observed in 17 (50%) and the remaining 17 cases were classified as: neoatherosclerosis (n = 9), underexpansion (n = 3) and unknown mechanism (n = 5). Patients with malapposition had a remarkable reduction of the malapposition volume (from 6.4 to 1.3 mm3; p = 0.02) during the ST procedure, but this was not fully corrected in 13 (76.5%). At 12 months, two patients of the malapposition group presented with uneventful target vessel re-occlusion. Persistent malapposition was observed in nine patients (60.0%). Major coronary evaginations (46.7 vs. 0%; p = 0.001) and uncovered struts (6.3 vs. 1.0%; p < 0.001) were also more frequent in patients with malapposition than without malapposition. None of the patients had thin-cap fibroatheroma neoatherosclerosis. Contributing causes of late/very-late ST are diverse and have different healing patterns at 12 months. Patients with stent malapposition treated with intravascular imaging guided PCI showed poor re-healing; but patients with other causes of the ST showed optimal stent healing as assessed by OCT.

Long-Term Coronary Functional Assessment of the Infarct-Related Artery Treated With Everolimus-Eluting Bioresorbable Scaffolds or Everolimus-Eluting Metallic Stents: Insights of the TROFI II Trial.

OBJECTIVES: The study sought to compare the vasomotor and microcirculatory function of the infarct-related artery (IRA) between bioresorbable vascular scaffolds (BVS) and everolimus-eluting stents (EES) at 3 years. BACKGROUND: The ABSORB STEMI TROFI II study showed similar outcomes between BVS and EES in the context of ST-segment elevation myocardial infarction at 3 years. METHODS: Sixty-three consecutive event-free patients of the randomized TROFI II study were screened to undergo coronary angiography with vasomotor, microcirculatory, and optical coherence tomography (OCT) examination at 3 years. Vasomotion was defined as >4% change in mean lumen diameter to acetylcholine (ACH) and nitroglycerin as assessed by quantitative angiography. Microcirculatory examination was performed with pressure or thermodilution techniques. RESULTS: A total of 38 patients (20 BVS and 18 EES) were included. At 3 years, ≥60% of patients exhibited paradoxical vasoconstriction to ACH in the periscaffold or stent segments. Vasoconstriction to ACH and vasodilatation to nitroglycerin were more often observed in the scaffold or stent segment with BVS than with EES (77.8% vs. 25.0%; p = 0.008 and 61.1% vs. 18.8%; p = 0.018). The IRA-depending microcirculation showed similar index of resistance (23.8 vs. 22.4; p = 0.781), coronary flow reserve (2.4 vs. 1.9; p = 0.523), fractional flow reserve (0.91 vs. 0.93; p = 0.317), and absolute flow (135.5 ml/min vs. 147.3 ml/min; p = 0.791). OCT showed remaining strut footprints and larger number of intraluminal scaffold dismantling (26.3% vs. 0%; p = 0.049) in the BVS group. CONCLUSIONS: Both endothelium-dependent and -independent vasomotion of the IRA were more evident with BVS, as compared with EES, at 3 years. Functional microcirculatory parameters were mostly adequate and similar between BVS and EES. Clinical implications of these findings warrant further investigations.

A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.

Aims: The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. Method and results: Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. Conclusion: Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. Trial registration: NCT01760083.

Hallazgos por IVUS en trombosis de stent tardía y muy tardía. Comparación entre stents metálicos y farmacoactivos / IVUS findings in late and very late stent thrombosis. A comparison between bare-metal and drug-eluting stents

Introducción y objetivos: La trombosis de stent (TS) es una complicación grave tras la angioplastia coronaria, y la ecografía intravascular es una herramienta capaz de discernir las causas. El objetivo es comparar los hallazgos por ecografía intravascular entre stents metálicos (SM) y stents farmacoactivos (SFA) en pacientes con TS tardía (de 31 días a 1 año) o muy tardía (>1año). Métodos: Se incluyó a 114 pacientes (el 45,5% con SM y el 54,5% con SFA) de un total de 250 consecutivos con TS tardía o muy tardía en 7 hospitales españoles. Se realizó una ecografía intravascular, que se analizó posteriormente para detectar la presencia de malaposición, infraexpansión y neoateroesclerosis. Resultados: El tiempo hasta la TS fue de 4,0 años en los SM y 3,4 años en los SFA (p = 0,04). La malaposición fue similar en ambos grupos (el 36,5 frente al 46,8%; p = 0,18), aunque numéricamente menor en los SM con trombosis muy tardía (el 26,6 frente al 48,0%; p = 0,07). La infraexpansión se observó de manera similar en ambos grupos (el 13,5 frente al 11,3%; p = 0,47). La neoateroesclerosis solo se observó en TS muy tardías y fue más prevalente en los SM (22,9%) que en los SFA (6,0%; p = 0,02). A los 2,9 años de seguimiento, las muertes cardiacas eran 0 frente a 6,9% respectivamente (p = 0,06) y las recurrencias de TS se produjeron en el 4,0 frente al 5,2% (p = 0,60). Conclusiones: La malaposición es el hallazgo más frecuente en los pacientes con TS tardía y muy tardía, más prevalente en los SFA con TS muy tardías. Sin embargo, la neoateroesclerosis se observó únicamente en pacientes con TS muy tardías, y principalmente en SM

Introduction and objectives: Stent thrombosis (ST) is a life-threatening complication after stent implantation. Intravascular ultrasound is able to discern most causes of ST. The aim of this study was to compare intravascular ultrasound findings between bare-metal stents (BMS) and drug-eluting stents (DES) in patients with late (31 days to 1 year) or very late ST (> 1 year). Methods: Of 250 consecutive patients with late or very late ST in 7 Spanish institutions, 114 patients (45.5% BMS and 54.5% DES) were imaged with intravascular ultrasound. Off-line intravascular ultrasound analysis was performed to assess malapposition, underexpansion, and neoatherosclerosis. Results: The median time from stent implantation to ST was 4.0 years with BMS and 3.4 years with DES (P = .04). Isolated malapposition was similarly observed in both groups (36.5% vs 46.8%; P = .18) but was numerically lower with BMS (26.6% vs 48.0%; P = .07) in patients with very late ST. Isolated underexpansion was similarly observed in both groups (13.5% vs 11.3%; P = .47). Isolated neoatherosclerosis occurred only in patients with very late ST and was more prevalent with BMS (22.9%) than with DES (6.0%); P = .02. At 2.9 years' follow-up, there were 0% and 6.9% cardiac deaths, respectively (P = .06) and recurrent ST occurred in 4.0% and 5.2% of patients, respectively (P = .60). Conclusions: Malapposition was the most common finding in patients with late and very late ST and is more prevalent with DES in very late ST. In contrast, neoatherosclerosis was exclusively observed in patients with very late ST and mainly with BMS

Long-term prognostic impact of non-invasive follow-up with computed tomography angiography in patients with left main coronary artery stenting.

BACKGROUND: Left main coronary artery (LMCA) stenting is an evolving technique. Whether follow-up computed tomography angiography (CTA) might have clinical impact in these patients is controversial. The aim of present study is to compare clinical outcomes of patients with LMCA stenting followed with CTA versus patients with conventional clinical follow-up. METHODS: From 2003 to 2014 all consecutive patients with unprotected LMCA stenosis treated with single DES implantation were prospectively included. Since 2009 all patients underwent CTA at 6-month after LMCA stenting. Therefore, the non-CTA group included all patients treated from 2003 to 2009 and the CTA group included patients treated from 2009 to 2014. Patients with 6-month cardiac events, renal dysfunction or atrial fibrillation were excluded. All patients underwent at least 2-year clinical follow-up. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, and LMCA revascularization. RESULTS: A total of 236 patients were included (119 in the non-CTA and 117 in the CTA group). Nine event-free patients presented with in-stent restenosis as assessed by CTA at 6 months; 5 had angiographic confirmation and were revascularized. At 2 years, the primary end-point was observed in 15.1% and 7.3% of patients of the non-CTA and CTA groups, respectively (P=0.07). All-cause mortality was higher in the non-CTA group (8.4% vs. 2.6%; P=0.05). Euroscore and CTA were found independent predictors of the primary end-point in the multivariate analysis. CONCLUSIONS: Elective 6-month CTA after LMCA stenting is associated with better outcomes compared to conventional clinical follow-up.