A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

No Differences in Levels of Circulating Progenitor Endothelial Cells or Circulating Endothelial Cells Among Patients Treated With Ticagrelor Compared With Clopidogrel During Non- ST -Segment-Elevation Myocardial Infarction.

Background Ticagrelor use during acute coronary syndromes demonstrated a decrease in all-cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non-platelet-derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non-ST-segment-elevation myocardial infarction. Methods and Results In this multicenter, randomized study ( NCT 02244710), patients were considered for inclusion after non-ST-segment-elevation myocardial infarction whenever they were P2Y12-inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28-64), 50 (33-63), and 38 (23-62) cells/mL, respectively, for clopidogrel and 38 (29-60), 45 (32-85), and 35 (24-71) cells/mL, respectively, for ticagrelor ( P=0.6). Endothelial progenitor cell levels were 29 (15-47), 27 (15-33), and 18 (10-25) cells/mL, respectively, for clopidogrel and 20 (11-33), 22 (12-32), and 18 (11-29) cells/mL, respectively, for ticagrelor ( P=0.9). No differences in intraindividual changes were found. Conclusions Patients treated with ticagrelor during non-ST-segment-elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02244710.

Percutaneous paravalvular leak closure after CoreValve transcatheter aortic valve implantation using an arterio-arterial loop.

Significant periprosthetic aortic regurgitation after transcatheter aortic valve implantation has become a major concern of this technique given its association with impaired survival. We report the successful closure of such defect using a vascular occlusion device with the creation of an arterio-arterial loop to gain enough support to advance the delivery sheath into de the left ventricle.

Double Guide Catheter Technique for Sealing an Iatrogenic Coronary Perforation.

INTRODUCTION: Coronary vessel perforation is one of the most feared complications of coronary angioplasty. The treatment of this complication relies mostly on the implantation of covered stents. However, due to their design, covered stents are difficult to advance in a tortuous or calcified vessel. CASE PRESENTATION: We present a case of a grade III coronary perforation in which the double guiding catheter technique helped us to deliver the graft stent. CONCLUSIONS: The double-guiding technique is useful in emergency situations to increase the safety and efficacy of sealing a coronary perforation.

Third CoreValve™ insertion for treatment of a severe paravalvular leak after a failed valve-in-valve procedure.

An 83-year-old high-risk gentleman diagnosed with severe symptomatic aortic stenosis was scheduled for TAVR. A 31 mm CoreValve was implanted but severe paravalvular leak was noted. A valve-in-valve procedure was performed. However, the valve frame was partially dislodged into de ascending aorta. We report our strategy to solve this severe leak after a failed valve-in-valve procedure.

Timely reperfusion for ST-segment elevation myocardial infarction: Effect of direct transfer to primary angioplasty on time delays and clinical outcomes.

Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy for patients presenting with ST-segment elevation myocardial infarction (STEMI) when it can be performed expeditiously and by experienced operators. In spite of excellent clinical results this technique is associated with longer delays than thrombolysis and this fact may nullify the benefit of selecting this therapeutic option. Several strategies have been proposed to decrease the temporal delays to deliver PPCI. Among them, prehospital diagnosis and direct transfer to the cath lab, by-passing the emergency department of hospitals, has emerged as an attractive way of diminishing delays. The purpose of this review is to address the effect of direct transfer on time delays and clinical events of patients with STEMI treated by PPCI.

Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial.

BACKGROUND: The effect of ß-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). METHODS AND RESULTS: Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). CONCLUSIONS: In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

Techniques and material used in the percutaneous treatment of chronic coronary occlusions. Data from the CIBELES study.

INTRODUCTION: In recent years, various specific techniques and materials have been developed for the treatment of coronary chronic total occlusions (CTO). OBJECTIVE: To evaluate the current situation in the treatment of CTO (techniques and material) in our setting. METHODS: We evaluated data on techniques and material used in the CIBELES (ChronIc coronary occlusion treated By EveroLimus Eluting Stent) trial, a randomized comparison of sirolimus- and everolimus-eluting stents in 207 patients with CTO in 13 centers in Spain and Portugal. RESULTS: A radial approach was used in 23% of patients, and retrograde techniques were used in only 5%. A high number of balloons were used (2.2±0.9 per patient). Microcatheters were used in 33% of patients, and post-dilatation balloons in only 25%. The mean number of stents implanted per patient was 2.1±1.0, with a mean total stent length of 49±24 mm. Other devices and techniques used were: Tornus penetration catheter in 4% of patients, rotational atherectomy in 2%, and cutting balloon in 1%. Intracoronary ultrasound was used in only 6% of patients. In 34% of cases, operators used guidewires that were not specifically for CTO. Considerable variability between centers was detected in the use of different techniques, the highest and lowest variability being observed in the use of intracoronary ultrasound and the use of CTO guidewires, respectively. CONCLUSIONS: In the CIBELES trial, techniques and devices specifically designed for the treatment of CTO were used in a relatively low proportion of patients. Considerable variability between centers was detected.

Preclinical evaluation of coronary stents: focus on safety issues.

In recent years, we have witnessed a revolution in the treatment of coronary artery disease. The development and improvement of drug eluting stents (DES) have lowered the incidence of restenosis to one-digit figures. In the search for a superior efficacy, animal models have played a key role. The classical swine model of coronary stenting remains the preferred model to measure restenosis, although the rabbit iliac artery stenting has become an accepted alternative. After widespread clinical use of DES, an unforeseen complication arose: late stent thrombosis. In a back-to-bench step, some data from animal models helped to explain the phenomenon. A delayed and incomplete vascular healing was detected. Toxic and hypersensitivity reactions to polymers and/or drugs seem to be the underlying causes. So, translational research focused on the safety aspect of these devices: development of better drug carriers as absorbable polymers or fully bioresorbable scaffolds, selection of different drugs and assessment of the re-endothelialization process. We review and evaluate the efficacy and safety of coronary stents in different animal models. Further improvements in this field such as, the selection of better animal models (e.g. hyperlipidemic, diabetic, atherosclerotic) that closely mimic the clinical setting and longer follow-up periods to detect late complications are also discussed.

Vasomotor response to different endothelium-dependent vasodilators in an animal model.

BACKGROUND AND OBJECTIVES: Incomplete re-endothelialization of stents can be revealed as paradoxical vasoconstriction with endothelium-dependent vasodilators. As no consensus exists about the best method or agent, our objective is to analyze the response to different drugs in a coronary swine model. METHODS: Twenty-seven stents were implanted in 9 domestic swine. The vessel diameter of proximal and distal segments (≥5 mm) was assessed immediately post implantation. Different endothelium-dependent vasodilators were used: intracoronary (IC) acetylcholine, 20 µg (A2) and 40 µg (A4), IC serotonin (S), 100 µg, and isoproterenol (I), intravenous infusion. The results are presented as constriction (%) compared with maximal vasodilation with IC nitroglycerin (N, 200 µg). RESULTS: In 10 vessels (37%), A4 provoked an occlusive spasm. Acetylcholine induced a higher degree of vasoconstriction (A4, 42 ± 39%; A2, 16 ± 14%) than the rest of the agonists (S, 6 ± 12%; I, 6 ± 11%; P<.01). The constriction rate was not related to the induced hemodynamic changes. CONCLUSIONS: After focal endothelial denudation in a coronary swine model, the constriction rate induced by different endothelium-dependent vasodilators is highly variable. The highest value is observed after IC acetylcholine bolus. The constriction rate does not correlate with the observed hemodynamic changes.

P2Y12 platelet reactivity after thrombolytic therapy for ST-segment elevation myocardial infarction.

INTRODUCTION: Thrombolysis, as reperfusion therapy for ST segment elevation myocardial infarction (STEMI), induces a pro-thrombotic status with enhanced platelet activity; this study aims to evaluate P2Y12 platelet reactivity and response to clopidogrel in the post-thrombolysis scenario. MATERIALS AND METHODS: Observational, prospective study, including consecutive patients with elective angiography after thrombolytic therapy for STEMI. Every patient received antiplatelet therapy with loading doses of 250 mg aspirin and 300 mg clopidogrel on admission followed by 100mg aspirin and 75 mg clopidogrel daily. P2Y12-dependent platelet reactivity (expressed in P2Y12-Reaction Units, PRU) was assessed with VerifyNow® device on admission, daily after thrombolysis and pre-angiography. RESULTS: 41 patients fulfilled the inclusion criteria. Median time between thrombolysis and angiography was 2,5 days (IQR 1,8-4,1). Post-treatment platelet reactivity (PPR) showed poor correlation with time on clopidogrel treatment (r2=0.04) and reached a maximum value of 274 ± 84 PRU during the first 24h after thrombolysis (Day +1 determination). After this, values showed a progressive reduction until the point of angiography (249 ± 82 PRU), without significant differences between consecutive time-points (p=0,549). Inhibition of platelet aggregation (IPA) assessed as a percentage of P2Y12 receptor blockage was poor, increasing gradually from 0 ± 4% on admission to 11 ± 6% the day of the angiography (p=0,001). 71,4% of patients showed PPR ≥ 208 PRU during angiography. CONCLUSIONS: Platelet reactivity, as assessed by post-treatment P2Y12 mediated reactivity, is heightened after thrombolytic therapy during STEMI management. In this scenario, standard doses of clopidogrel did not achieve significant inhibition of ADP-mediated platelet reactivity.

La reestenosis en el stent depende del daño vascular inducido. ¿Son válidos los modelos experimentales actuales de análisis de los stents farmacoactivos? / Instent restenosis related to vessel injury score degree. Are current experimental models valid for drug-eluting stents analysis?

Introducción y objetivos. Los stents farmacoactivos son una herramienta útil para prevenir la reestenosis, pero los mecanismos involucrados en la respuesta proliferativa tras su implante aún no son conocidos en su totalidad. El objetivo de este estudio es comparar la histomorfometría vascular coronaria tras el implante de stents sin recubrir o stents farmacoactivos en un modelo porcino. Métodos. En 20 hembras de cerdos de la raza Large White de 2 meses de edad se implantó de forma aleatoria un total de 60 stents distribuidos en dos grupos: convencionales (n=20) y farmacoactivos (paclitaxel) (n=40). A los 28 días se procedió a eutanasia y análisis histomorfométrico. Se clasificó el grado de daño vascular en función de integridad o rotura de la túnica limitante elástica interna. Resultados. En el grupo de integridad de lámina elástica interna no se encontraron diferencias significativas entre stents farmacoactivos y stents convencionales para las variables área de neoíntima y porcentaje de reestenosis (1,3 [1,1-2,2] frente a 2 [1,3-2,5] mm2; p=0,6; y 14 [12,1-20,8] frente a 22,2 [14,1-23,3] %; p=0,5). En cambio, en el grupo de rotura de la lámina elástica interna sí se encontraron diferencias significativas (área de neoíntima, 1,2 [0,8-2] frente a 2,9 [2,3-3,7] mm2; p=0,001 y porcentaje de reestenosis, 16,63 [11,2-23,5] frente a 30,4 [26,4-45,7] %; p=0,001). Conclusiones. En el modelo porcino de coronarias sanas, la integridad de la lámina elástica interna no permite apreciar diferencias en la respuesta proliferativa entre stent farmacoactivo y convencional; la diferencia se establece sólo cuando el daño vascular es más profundo (AU)

Introduction and objectives. Drug-eluting stents are useful for preventing restenosis, but the patho-physiological processes involved in the proliferative response after implantation are still not known in detail. The aim of this study is to compare the coronary vascular histomorphometry after implanting drug-eluting stents and bare metal stents in a swine model. Methods. Sixty stents were randomly implanted in 20 Large White female pigs with a ratio of baremetal/drug-eluting stents of 1:2. After 28 days, euthanasia and histomorphometry were performed. We defined the vessel injury score in accordance to whether the internal elastic lamina was intact or ruptured. Results. There were no differences between drug-eluting stents and bare metal stents in the intact internal elastic lamina group regarding neointimal area or % restenosis (1.3 [1.1-2.2]) vs 2.0 [1.3-2.5] mm2; P=.6; and 14.0 [12.1-20.8] vs 22.2 [14.1-23.3] %; P=.5). We assessed statistically significant differences for the ruptured internal elastic lamina group, (neointimal area 1.2 [0.8-2.0] vs 2.9 [2.3-3.7] mm2; P=.001 and % restenosis 16.63 [11.2-23.5] vs 30.4 [26.4-45.7] %; P=.001). Conclusions. In our swine model, we did not find any differences between proliferative response of drug-eluting stents and bare metal stents when the internal elastic lamina is intact; differences are only found when vascular injury is deeper (AU)

[Instent restenosis related to vessel injury score degree. Are current experimental models valid for drug-eluting stents analysis?]. / La reestenosis en el stent depende del daño vascular inducido. ¿Son válidos los modelos experimentales actuales de análisis de los stents farmacoactivos?

INTRODUCTION AND OBJECTIVES: Drug-eluting stents are useful for preventing restenosis, but the patho-physiological processes involved in the proliferative response after implantation are still not known in detail. The aim of this study is to compare the coronary vascular histomorphometry after implanting drug-eluting stents and bare metal stents in a swine model. METHODS: Sixty stents were randomly implanted in 20 Large White female pigs with a ratio of baremetal/drug-eluting stents of 1:2. After 28 days, euthanasia and histomorphometry were performed. We defined the vessel injury score in accordance to whether the internal elastic lamina was intact or ruptured. RESULTS: There were no differences between drug-eluting stents and bare metal stents in the intact internal elastic lamina group regarding neointimal area or % restenosis (1.3 [1.1-2.2]) vs 2.0 [1.3-2.5] mm²; P=.6; and 14.0 [12.1-20.8] vs 22.2 [14.1-23.3] %; P=.5). We assessed statistically significant differences for the ruptured internal elastic lamina group, (neointimal area 1.2 [0.8-2.0] vs 2.9 [2.3-3.7] mm²; P=.001 and % restenosis 16.63 [11.2-23.5] vs 30.4 [26.4-45.7] %; P=.001). CONCLUSIONS: In our swine model, we did not find any differences between proliferative response of drug-eluting stents and bare metal stents when the internal elastic lamina is intact; differences are only found when vascular injury is deeper.

Cobalt-chromium stents in long lesions of large vessels: clinical and angiographic results.

Although drug-eluting stents have reduced the restenosis rate, some patients are not good candidates for prolonged double-antiplatelet therapy. Our goal was to learn the results of implanting cobalt-chromium stents in long lesions of large vessels.All consecutive patients with ≥1 lesion treated with a cobalt-chromium stent ≥28 mm in length and ≥3.5 mm in diameter during a 12-month period in 2 centers were monitored clinically and angiographically to determine the clinical status, restenosis rate, pattern of restenosis, and need for revascularization.The series comprised 78 patients with 81 lesions, mean age, 62.6 ± 15.2 yr; diabetes mellitus,19.2%; and primary or rescue intervention, 20.6%. Target vessels were the left anterior descending coronary artery, 12 (14.8%); left circumflex coronary artery, 12 (14.8%); and right coronary artery, 57 (70.4%). The mean lesion length was 35.18 ± 12.65 mm. The proximal reference diameter after percutaneous coronary intervention was 3.64 ± 0.54 mm; the distal, 3.2 ± 0.43 mm; and the mean, 3.42 ± 0.44 mm. The mean stent length was 38.05 ± 12.78 mm (range, 28-90 mm). The binary restenosis rate was 23% (15/64), with pattern IB in 2 cases, IC in 5, II in 7, and IV in 1. Revascularization was needed in 6 patients.In treating long lesions of large vessels, we found that cobalt-chromium stents achieved a moderate rate of target-vessel restenosis and a low rate of repeat revascularization. The pattern of restenosis was focal in almost half of the cases, and, in most remaining cases, restenosis affected short segments of the vessel.