Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

[Clopidogrel versus prasugrel in acute coronary syndrome treated with coronary angioplasty]. / Clopidogrel versus prasugrel en síndrome coronario agudo tratado con angioplastia.

Greater antithrombotic potency new antiplatelet agents have been added such as prasugrel (PR) and ticagrelor to the traditional use of clopidogrel (CL) in the treatment of acute coronary syndrome (ACS). This study was aimed at comparing the incidence of long term ischemic and hemorrhagic events in patients treated with CL or PR during hospitalization. Retrospective ACS data base analysis performed by our cardiology service was completed prospectively. There were consecutively included all patients with percutaneous coronary intervention (PCI) during hospitalization due to ACS from December 2011 thru December 2012. A total of 398 ACS patients who underwent PCI with stent implantation were recruited. No differences in cardiovascular related deaths were observed in both groups (PR 2.9% vs. CL 2.5%, p=0.48). PR group showed less re-infraction (1.9% vs. 6.8%, p=0.01) with more total bleedings (18.5% vs. 8.5%, p=0.001) and minor bleedings (12.4% vs. 3.4%, p<0.001) with no differences in major and life threatening bleedings (p=ns). Multivariate analysis showed that independent predictors of cardiovascular mortality were age (OR 1.08, CI 95% 1.02-1.16) and renal failure (OR 6.98, CI 95% 1.23-39.71). Independent predictors for total bleeding were age (OR 1.06, CI 95% 1.02-1.09),ST segment elevation myocardial infarction (OR 1.99, CI 95% 1.05-3.79), renal failure (OR 3.32, CI 95% 1.62-6.78) and prasugrel use (OR 3.97, CI 95% 1.87-8.41). Use of prasugrel, in the ACS that requires PCI with stent, is associated with a lower myocardial infarction a year after follow-up, and it also leads to an increase of milder hemorrhage. No significant differences were observed in the cardiovascular mortality of both groups.

Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin­Coronary Artery Disease Trial.

BACKGROUND: Thrombin is a key mediator of platelet activation. Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects. The phase II Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease (LANCELOT-CAD) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD. METHODS AND RESULTS: Subjects with a qualifying history were randomized in a double-blind fashion to 3 dosing regimens of atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks and followed up for an additional 4 weeks. The key safety end points were bleeding according to the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Thrombolysis in Myocardial Infarction (TIMI) classifications. Secondary objectives included platelet aggregation and major adverse cardiac events. Seven hundred and twenty subjects were randomized. Overall bleeding rates tended to be higher with atopaxar compared with placebo by CURE criteria (placebo, 0.6%; atopaxar, 3.9%; relative risk, 6.82, P=0.03; 50 mg, 3.9%; 100 mg, 1.7%; 200 mg, 5.9%; P for trend=0.01) and TIMI criteria (placebo, 6.8%; atopaxar, 10.3%; relative risk, 1.52, P=0.17; 50 mg, 9.9%; 100 mg, 8.1%; 200 mg, 12.9%; P for trend=0.07). There was no difference in major bleeding. Major adverse cardiac events were numerically lower in the atopaxar subjects. All atopaxar regimens achieved high levels of platelet inhibition. A transient elevation in liver transaminases and dose-dependent QTc prolongation without apparent complications were observed in higher-dose atopaxar treatment groups. CONCLUSIONS: In this dose-ranging study of patients with CAD, treatment with atopaxar resulted in platelet inhibition, more minor bleeding, and numerically but not statistically fewer ischemic events. Larger-scale trials are needed to determine whether these patterns translate into clinically meaningful effects. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00312052.

Intravenous platelet blockade with cangrelor during PCI.

BACKGROUND: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI). METHODS: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI, followed by 600 mg of clopidogrel. The primary end point was a composite of death, myocardial infarction, or ischemia-driven revascularization at 48 hours. Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point. RESULTS: The primary end point occurred in 185 of 2654 patients receiving cangrelor (7.0%) and in 210 of 2641 patients receiving placebo (8.0%) (odds ratio in the cangrelor group, 0.87; 95% confidence interval [CI], 0.71 to 1.07; P=0.17) (modified intention-to-treat population adjusted for missing data). In the cangrelor group, as compared with the placebo group, two prespecified secondary end points were significantly reduced at 48 hours: the rate of stent thrombosis, from 0.6% to 0.2% (odds ratio, 0.31; 95% CI, 0.11 to 0.85; P=0.02), and the rate of death from any cause, from 0.7% to 0.2% (odds ratio, 0.33; 95% CI, 0.13 to 0.83; P=0.02). There was no significant difference in the rate of blood transfusion (1.0% in the cangrelor group and 0.6% in the placebo group, P=0.13), though major bleeding on one scale was increased in the cangrelor group, from 3.5% to 5.5% (P<0.001), because of more groin hematomas. CONCLUSIONS: The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point. The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group, with no significant increase in the rate of transfusion. Further study of intravenous ADP blockade with cangrelor may be warranted. (ClinicalTrials.gov number, NCT00385138.)

Surgical Risk Scoring in TAVR: Still Needed? A Metaregression Analysis.

Several randomized controlled trials evaluating the effectiveness of transcatheter aortic valve replacement (TAVR) against surgical aortic valve replacement have been published to date. The fact that higher risk populations were implemented first does not necessarily mean that they benefit more from a TAVR procedure. We performed meta-analysis of the 8 randomized clinical trials performing TAVR for both mortality and stroke outcomes. Meta-regression was used to evaluate the association between mean surgical risk using the Society of Thoracic Surgeons (STS) score and hazard ratio observed in each of the trials. Overall, TAVR was associated with a significant reduction of both mortality and stroke across the whole spectrum of patients enrolled, with no evidence of significant heterogeneity. Metaregression analysis does not suggest a statistically significant association between STS score and hazard ratio for both mortality and stroke. This observation suggests reconsidering the use of risk scores to prioritize TAVR utilization in higher risk patients, while more focus should be done on patient's life expectancy related to TAVR durability.

Clinical practice guideline for transcatheter versus surgical valve replacement in patients with severe aortic stenosis in Latin America.

In elderly (75 years or older) patients living in Latin America with severe symptomatic aortic stenosis candidates for transfemoral approach, the panel suggests the use of transcatheter aortic valve implant (TAVI) over surgical aortic valve replacement (SAVR). This is a conditional recommendation, based on moderate certainty in the evidence (⨁⨁⨁Ο).This recommendation does not apply to patients in which there is a standard of care, like TAVI for patients at very high risk for cardiac surgery or inoperable patients, or SAVR for non-elderly patients (eg, under 65 years old) at low risk for cardiac surgery. The suggested age threshold of 75 years old is based on judgement of limited available literature and should be used as a guide rather than a determinant threshold.The conditional nature of this recommendation means that the majority of patients in this situation would want a transfemoral TAVI over SAVR, but some may prefer SAVR. For clinicians, this means that they must be familiar with the evidence supporting this recommendation and help each patient to arrive at a management decision integrating a multidisciplinary team discussion (Heart Team), patient's values and preferences through shared decision-making, and available resources. Policymakers will require substantial debate and the involvement of various stakeholders to implement this recommendation.

Incidence, Predictor, and Clinical Outcomes of Multiple Resheathing With Self-Expanding Valves During Transcatheter Aortic Valve Replacement.

Background No study has evaluated the impact of the additional manipulation demanded by multiple resheathing (MR) in patients undergoing transcatheter aortic valve replacement with repositionable self-expanding valves. Methods and Results This study included a real-world, multicenter registry involving 16 centers from Canada, Germany, Latin America, and Spain. All consecutive patients who underwent transcatheter aortic valve replacement with the Evolut R, Evolut PRO, and Portico valves were included. Patients were divided according to the number of resheathing: no resheathing, single resheathing (SR), and MR. The primary end point was device success. Secondary outcomes included procedural complications, early safety events, and 1-year mortality. In 1026 patients, the proportion who required SR and MR was 23.9% and 9.3%, respectively. MR was predicted by the use of Portico and moderate/severe aortic regurgitation at baseline (both with P<0.01). Patients undergoing MR had less device success (no resheathing=89.9%, SR=89.8%, and MR=80%; P=0.01), driven by more need for a second prosthesis and device embolization. At 30 days, there were no differences in safety events. At 1 year, more deaths occurred with MR (no resheathing=10.5%, SR=8.0%, and MR=18.8%; P=0.014). After adjusting for baseline differences and center experience by annual volume, MR associated with less device success (odds ratio, 0.42; P=0.003) and increased 1-year mortality (hazard ratio, 2.06; P=0.01). When including only the Evolut R/PRO cases (N=837), MR continued to have less device success (P<0.001) and a trend toward increased mortality (P=0.05). Conclusions Repositioning a self-expanding valve is used in a third of patients, being multiple in ≈10%. MR, but not SR, was associated with more device failure and higher 1-year mortality, regardless of the type of valve implanted.

Impacto de un Heart Team en pacientes con estenosis aórtica candidatos a reemplazo percutáneo / Impact of a Heart Team in patients with aortic stenosis who are candidates for transcatheter aortic valve replacement

RESUMEN La difusión del reemplazo valvular aórtico percutáneo (TAVI) en la estenosis aórtica (EAo) generó la creación de un Heart Team (HT), para elegir el mejor tratamiento. Existen pocos reportes sobre su utilidad. Objetivos: analizar los resultados del tratamiento de los pacientes con EAo evaluados por un HT durante 10 años Material y métodos: Inclusión consecutiva de todos los pacientes con EAo candidatos a TAVI entre enero del 2012 y julio del 2021 para seleccionar el mejor tratamiento, incluyendo además Cirugía de reemplazo valvular aórtico (CRVA) y Tratamiento médico conservador (TMC). Resultados: De 841 pacientes, se asignaron a TAVI 455 (53%), CRVA 213 (24%) y TMC 183 (23%). El porcentaje asignado a TAVI aumentó con el tiempo de 48 a 62% (p < 0,05). Los pacientes que fueron a TAVI, con respecto a los enviados a CRVA, eran mayores (86 ± 7 vs 83 ± 7 años), con mayor EUROSCORE II (6,2, IC95% 5,7-6,6 vs 5,6, IC95% 4,4-6,5) y más frágiles (1,62 ± 1 vs 0,91 ± 1), en todos los casos p <0,01. La sobrevida actuarial (IC 95%) a 1 y a 2 años fue, para TAVI 88% (84-91%) y 82% (77-86%), para CRVA 83% (76-88%) y 78% (70-84%) y para TMC 70% (60-87%) y 59% (48-68%) respectivamente (p <0,001). Conclusiones: Durante los primeros 10 años de establecido un Heart Team para la toma de decisiones en EAo, se asignaron a TAVI aproximadamente la mitad y el resto se asignó por mitades a cirugía u observación. La sobrevida de los pacientes intervenidos fue similar a 2 años y mayor que la de los no intervenidos.

ABSTRACT As transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) became widespread, the need for a Heart Team (HT) arose to choose the best treatment. There are few reports regarding its usefulness. Objectives: To analyze treatment outcomes in patients with AS evaluated by a HT for 10 years. Methods: Consecutive enrollment of all patients with AS who were candidates for TAVI between January 2012 and July 2021 to choose the best treatment, including surgical aortic valve replacement (SAVR) and conservative medical management (CMM). Results: Out of 841 patients, 455 were assigned to TAVI (53%), 213 to SAVR (24%), and 183 to CMM (23%). The percentage assigned to TAVI has increased from 48% to 62% over time (p <0.05). Patients who underwent TAVI versus those who underwent SAVR were older (86 ± 7 vs. 83 ± 7 years), had a higher EUROSCORE II (6.2, 95% CI 5.7-6.6 vs. 5.6; 95% CI 4.4-6.5) and were frailer (1.62 ± 1 vs. 0.91 ± 1), in all cases p <0.01. Actuarial survival (95% CI) at 1 and 2 years was 88% (84-91%) and 82% (77-86%) for TAVI, 83% (76-88%) and 78% (70-84%) for SAVR, and 70% (60-87%) and 59% (48-68%) for CMM, respectively (p <0.001). Conclusions: For the first 10 years after a Heart Team was established for AS decision-making, approximately half of the patients were assigned to TAVI, and the rest were equally assigned in halves to either surgery or observation. Survival for patients who received interventions was similar at 2 years and higher than in those who did not.

Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction (PREMIAR).

Distal embolization may decrease myocardial reperfusion after primary percutaneous coronary intervention (PCI). Nonetheless, results of previous trials assessing the role of distal protection during primary PCI have been controversial. The Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction Trial (PREMIAR) was a prospective, randomized, controlled study designed to evaluate the role of filter-based distal protection during PCI in patients with acute ST-segment elevation myocardial infarction at high risk of embolic events (including only baseline Thrombolysis In Myocardial Infarction grade 0 to 2 flow). The primary end point was continuous monitoring of ST-segment resolution. Secondary end points included core laboratory analysis of angiographic myocardial blush, ejection fraction measured by cardiac ultrasound, and adverse cardiac events at 6 months. From a total of 194 enrolled patients, 140 subjects were randomized to PCI with or without embolic protection, and 54 were included in a registry arm due to the presence of angiographic exclusion criteria. Baseline characteristics were comparable between arms. The rate of complete ST-segment resolution (>or=70%) at 60 minutes was similar in patients treated with or without distal protection (61.2% vs 60.3%, respectively, p = 0.85). Angiographic myocardial blush (67% vs 70.7%, p = 0.73), in-hospital ejection fraction (47.4 +/- 9.9% vs 45.3 +/- 7.3%, p = 0.29), and combined end point of death, heart failure, or reinfarction at 6 months (14.3% vs 15.7%, p = 0.81) were consistently achieved in a similar proportion in the 2 groups. In conclusion, the use of filter-based distal protection is safe and effectively retrieves debris; however, such use does not translate into an improvement of myocardial reperfusion, left ventricular performance, or clinical outcomes.

Clinical outcome in nonagenarians undergoing transcatheter valve replacement.

BACKGROUND: Nonagenarians are mostly denied from different therapeutic strategies due to high preoperative risk. We present the results of nonagenarians with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: Our retrospective analysis include baseline and procedural data along with clinical outcome. Clinical follow-up was performed in all patients after TAVR. RESULTS: Out of 689 patients, 33 nonagenarians with a mean age of 90.9±1.4years suffering from severe AS and elevated comorbidity index (logistic EuroSCORE of 16.3±9.6%, STS score 11.1±9.9%) underwent TAVR between September 2009 and July 2016 using self-expanding prosthesis. Baseline transthoracic echocardiography reported a mean aortic valve area (AVA) of 0.64±0.12cm2 with a mean pressure gradient of 56.1±16.1mmHg. Five (16.2%) patients had postprocedural moderate/severe aortic regurgitation. One patient died intraoperally due to ventricular perforation during predilatation, while two patients died within the first 30days, one due to cardiogenic shock and the other due to pneumonia. No patient experienced a myocardial infarction or a stroke, while ten (30.3%) required permanent pacemaker placement. At follow-up (mean 20.3 months, range 1-78 months), all cause and cardiovascular mortality was 24.2% and 15.1%, respectively. Two patients presented heart failure and 12 (40%) had exertional dyspnea. By echo, mean valve area was 1.72±0.12cm2 and mean gradient 11.2±1.4mmHg. Two patients (16.7%) presented moderate aortic regurgitation. CONCLUSION: Our case series demonstrate that even with elevated comorbidity index, clinical endpoints and valve-associated results are relatively favorable in nonagenarians treated with TAVR.

Clinical practice guideline for transcatheter versus surgical valve replacement in patients with severe aortic stenosis in Latin America

In elderly (75 years or older) patients living in Latin America with severe symptomatic aortic stenosis candidates for transfemoral approach, the panel suggests the use of transcatheter aortic valve implant (TAVI) over surgical aortic valve replacement (SAVR). This is a conditional recommendation, based on moderate certainty in the evidence. This recommendation does not apply to patients in which there is a standard of care, like TAVI for patients at very high risk for cardiac surgery or inoperable patients, or SAVR for non-elderly patients (eg, under 65 years old) at low risk for cardiac surgery. The suggested age threshold of 75 years old is based on judgement of limited available literature and should be used as a guide rather than a determinant threshold. The conditional nature of this recommendation means that the majority of patients in this situation would want a transfemoral TAVI over SAVR, but some may prefer SAVR. For clinicians, this means that they must be familiar with the evidence supporting this recommendation and help each patient to arrive at a management decision integrating a multidisciplinary team discussion (Heart Team), patient's values and preferences through shared decision-making, and available resources. Policymakers will require substantial debate and the involvement of various stakeholders to implement this recommendation.

Use of drug-eluting stents for the treatment of in-stent restenosis in routine clinical practice.

BACKGROUND: Although target lesion revascularization (TLR) has been dramatically decreased by using drug-eluting stents (DESs) in de-novo lesions, their efficacy for in-stent restenosis (ISR) has not yet been well established. METHODS: We retrospectively analysed patients treated for ISR with DESs from three referral hospitals. RESULTS: Eighty-seven consecutive patients, from June 2002 to April 2004, were included, with a mean age of 64+/-11 years; 83% were men, 32% had diabetes, 47% had had a previous myocardial infarction and 16% had low left ventricular ejection fraction. Angiographic characteristics were as follows: mean vessel diameter, 3.05+/-0.4 mm; lesion length, 17.8+/-7.7 mm; diameter stenosis, 84.0+/-10.7%; and complex lesion, 81%. The restenosis was focal in 45%, diffuse/proliferative in 51.3% and total occlusion in 3.7% of the cases. Sirolimus- and paclitaxel-eluting stents were used in 42 and 58% of the patients, respectively. Stent diameter was 3.1+/-0.3 mm and the length was 26.1+/-5.8 mm. Angiographic success was achieved in all patients, with one patient experiencing a post-procedural non-Q-wave myocardial infarction. At 6-month clinical follow-up, two patients had died from non-cardiac deaths, five had experienced a new TLR (5.7%, four percutaneous and one coronary artery bypass graft) and eight (9.2%) had had major adverse cardiac events. A stress test was performed in 60% of the population; target vessel ischemia was observed in one patient (3.3%). CONCLUSION: In this non-select cohort of patients, the use of DESs is a safe and effective strategy for ISR lesions.

Experiencia multicéntrica de implante valvular aórtico percutáneo discriminada por riesgo en centros de Latinoamérica / Multicenter Experience of Transcatheter Aortic Valve Implantation Stratified by Risk in Latin American Centers

RESUMEN Introducción: El implante valvular aórtico percutáneo ha sido valorado en diferentes escenarios del amplio espectro de la población portadora de estenosis aórtica grave sintomática. La elección del tipo de tratamiento parte de una evaluación del riesgo de un equipo multidisciplinario. Objetivos: El objetivo de este estudio fue analizar las características y conocer los resultados de los pacientes sometidos a IVAP en Latinoamérica según el riesgo. Material y métodos: Se incluyeron a partir de marzo de 2009 a diciembre de 2018 pacientes en forma continua del registro multicéntrico latinoamericano de implante valvular aórtico percutáneo. La indicación de implante valvular aórtico percutáneo fue realizada en cada caso por un equipo multidisciplinario local. Se estratifica la población en función del riesgo quirúrgico evaluado por el puntaje STS-PROM. Se definieron tres grupos en función de los puntos de corte del STS -PROM establecidos: riesgo alto (RA, mayor del 8%), riesgo intermedio (RI, entre el 4% y el 8%) y riesgo bajo (RB, menordel 4%). Resultados: Se incluyeron en el análisis 770 pacientes; la mitad era de sexo femenino (50,2%) con una mediana de edad de 81 años (RIC 75,6-85,7). Del total, 230 pacientes (29,8%) fueron incluidos en el grupo AR (STS-PROM medio 11 [9,3-16,7]); 339 pacientes (44%), al riesgo intermedio (STS-PROM medio 6 [4,8-6,71]); y los restantes 201 (26,1%), al bajo riesgo (STS-PROM medio 2,7 [2-3,24]). La proporción de pacientes de bajo riesgo se incrementó a lo largo del período del registro (ptrend 0,011). Se utilizó acceso femoral (95%), y fue percutáneo en el 69% de los pacientes. Se implantaron en el 80% válvulas autoexpandibles. Del total de válvulas implantadas, el 23% (n = 177) resultaron ser reposicionables sin diferencias a través de los grupos. No se evidenciaron diferencias en mortalidad a los 30 días (RA 10,4%, RI 6,48%, RB 5,9%, p: 0,154) Tanto en el RA como en el de RB se observó una reducción de la mortalidad (RA 13,7%-4,1%, p: 0,001; RB 11,7%-0%; p: 0,0023). Conclusiones: La estratificación de riesgo mediante puntajes quirúrgicos continúa representando una guía de gran utilidad, sin embargo la indicación de implante valvular percutáneo en el mundo real incorpora otros factores no contemplados en la puntuación clásica, que modifica nuestras decisiones en la práctica diaria.

SUMMARY Introduction: Transcatheter aortic valve implantation (TAVI) has been evaluated in different scenarios of the broad spectrum of patients with severe symptomatic aortic stenosis. The choice of treatment starts through a risk assessment guided by a multidisciplinary team. Purpose: The aim of this study was to analyze the population undergoing TAVI in Latin America according to their risk. Methods: From March 2009 to December 2018, consecutive TAVI procedures registered in the Latin American multicenter registry were included. The indication of TAVI was made in each case by a multidisciplinary team set up by each center. The population is stratified according to the surgical risk evaluated by the STS-PROM score. Three groups were defined, based on the established STS-PROM cut-off points: high risk (RA, higher 8%), intermediate risk (IR, between 4%-8%) and low risk (RB, lower 4%). Results: 770 patients were included in the analysis, resulting 50,2% female, with a mean age of 81 y/o (IQR 75.6-85.7). 29.8% were included in the AR group (STS-PROM 11 (9.3-16.7), 44% at intermediate risk (STS-PROM 6 (4.8-6.71) and 26.1% at low risk (STS-PROM 2.7 (2-3.24). The proportion of low-risk patients has increased significantly over the period of inclusion (ptrend 0.011). Femoral access (95%), being percutaneous in 69% of patients. Self-expanding valves were implanted in 80%. 23% of the valves were repositionable without differences across the groups. There was no differences in 30-day mortality (RA 10.4%, IR 6.48%, RB 5.9%, p 0.154). Reduction in mortality were observed (RA 13, 7-4.1%, p0.001; RB 11.7-0%; p 0.0023) during the analyzed period. Conclusions: Risk stratification through surgical "scores" continues to represent a very useful guide, however the indication of TAVI in the real world incorporates other factors not contemplated in the classical score, which modifies our decisions in daily practice.

ST-segment resolution 60 minutes after combination treatment of abciximab with reteplase or reteplase alone for acute myocardial infarction (30-day mortality results from the resolution of ST-segment after reperfusion therapy substudy).

The combination of abciximab with thrombolytic therapy when treating acute ST-elevation myocardial infarction has been hypothesized to enhance microvascular perfusion. Resolution of ST-segment elevation after thrombolytic therapy is believed to be a marker of myocardial reperfusion and to predict mortality rate. Among 16,588 patients enrolled in the Fifth Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction trial, 1,764 consecutive patients from selected centers had their study electrocardiograms evaluated by a core laboratory for ST-segment deviation resolution 60 minutes after treatment. Patients were categorized into 4 groups: complete resolution (>70%), partial resolution (<70% to 30%), no resolution (<30%), and worsening ST-segment deviation. Patients treated with reteplase or a combination of reteplase plus abciximab had similar rates of complete resolution (32% vs 34%), partial resolution (29% vs 27%), no resolution (15% vs 16%), and worsening ST-segment elevation (23 vs 23%; p = 0.59). The 30-day mortality rates in these 4 groups were 2.1%, 5.2%, 5.5%, and 8.1% (p <0.001). Even after accounting for baseline variables, incomplete ST-segment resolution (<70%) was associated with an increased risk of death within 30 days (adjusted hazard ratio 2.41, 95% confidence interval 1.25 to 4.63, p <0.008). Thus, ST-segment resolution at 60 minutes was no different in patients treated with full-dose reteplase from those treated with a combination of abciximab and reteplase. Patients with >70% ST-segment resolution within 60 minutes had markedly decreased mortality rates, irrespective of treatment.

Clopidogrel is associated with better in-hospital and 30-day outcomes than ticlopidine after coronary stenting.

BACKGROUND: Recent reports of fatal ticlopidine-induced blood dyscrasias have led many interventional cardiologists to administer clopidogrel instead of ticlopidine for coronary stenting. Most studies have demonstrated similar outcomes and a more favourable safety profile supporting this change in practice patterns. OBJECTIVES: To assess the clinical outcomes in patients who received clopidogrel rather than ticlopidine after coronary stenting. METHODS: Between June 1996 and December 1998, 652 patients received a clopidogrel-based periprocedural regimen (300 mg loading dose followed by 75 mg daily in addition to acetylsalicylic acid 325 mg daily) and 1717 patients received a ticlopidine-based regimen (500 mg loading dose followed by 250 mg bid in addition to acetylsalicylic acid 325 mg daily). In-hospital and 30-day outcomes were assessed in the two groups. RESULTS: At 30 days, unadjusted mortality was 0.3% in the clopidogrel group versus 1.5% in the ticlopidine group, and myocardial infarction (MI) was also reduced in the clopidogrel group (4.0% versus 6.5%). No difference was found in the rate of repeat revascularization (1.4% versus 1.2%). The combination of death/MI/repeat revascularization at 30 days was reduced by 32%, an absolute difference of 2.9% (6.2% versus 9.1%). On multivariate analysis, clopidogrel was found to be an independent predictor of freedom from nonfatal MI (odds ratio [OR] 0.64, 95% CI 0.41 to 0.99, P=0.04), the composite of death or MI (OR 0.62, 95% CI 0.40 to 0.95, P=0.03) and the composite of death/MI/revascularization (OR 0.69, 95% CI 0.48 to 1.00, P=0.05). CONCLUSION: After coronary stenting, in a large, nonrandomized, consecutive patient experience, clopidogrel appears to be associated with more favourable clinical outcomes than ticlopidine, without increasing the risk of bleeding or peripheral vascular complications.

Eficiencia y seguridad del acceso radial versus el acceso femoral en la angioplastia coronaria / Efficiency and Safety of Radial Access versus Femoral Access in Percutaneous Coronary Intervention

RESUMEN Introducción: El acceso radial se ha asociado a numerosos beneficios en angioplastia coronaria en comparación con el acceso femoral. Sin embargo, múltiples registros internacionales han reportado una escasa adherencia a esta técnica. Objetivos: Evaluar la seguridad, la eficacia y la eficiencia operativa de la angioplastia coronaria según la vía de acceso utilizada y el cuadro clínico del paciente. Métodos: Análisis de registro, unicéntrico y retrospectivo de los pacientes con enfermedad coronaria tratados con angioplastia coronaria desde marzo de 2009 a junio de 2018, según el acceso vascular. Se aplicó un modelo de regresión de Cox ajustado para evaluar la relación entre la vía de acceso y el riesgo de eventos cardiovasculares mayores y un modelo de regresión logística para evaluar la relación con el sangrado mayor y las complicaciones del acceso vascular. La eficiencia operativa se evaluó mediante la medición del tiempo de internación total y los costos totales asociados a esta. Resultados: Se incluyeron 8155 angioplastias coronarias (seguimiento promedio 1448,6 ± 714,1 días), mediante acceso radial (n = 5706) o acceso femoral (n = 2449). A los 30 días, el riesgo de eventos cardiovasculares mayores se redujo significativamente con el acceso radial (HR 0,66 [0,5-0,88], p = 0,004), a expensas de una reducción de la mortalidad total. A su vez, el acceso radial redujo significativamente el riesgo de sangrado mayor (HR 0,33 [0,16- 0,67], p = 0,002) y de complicaciones del acceso vascular (HR 0,72 [0,53-0,98], p = 0,038). Se observó una interacción significativa entre la vía de acceso y el riesgo de eventos según el cuadro clínico al ingreso. Se observó una reducción significativa del tiempo total de internación (≈30%) y de sus costos totales (≈15%) mediante el uso del acceso radial. Conclusiones: El uso del acceso radial en angioplastia coronaria es seguro y eficaz en comparación con el acceso femoral, con menores tasas de eventos cardiovasculares mayores a los 30 días, como, así también, un menor riesgo de sangrado mayor y complicaciones del acceso vascular. Asimismo, el acceso radial se asoció con una mayor eficiencia operativa durante la internación.

ABSTRACT Background: Radial access has been associated with many advantages in percutaneous coronary intervention compared with femoral access. However, many international registries have reported poor adherence to this technique. Objectives: The aim of this study was to evaluate the safety, efficacy and operational efficiency of percutaneous coronary intervention according to the access site and the clinical presentation of the patient. Methods: A single-center, retrospective registry of patientis with coronary artery disease undergoing percutaneous coronary intervention was conducted from March 2009 to June 2018 according to the vascular access. A Cox proportional-hazards model was used to analyze the association between vascular access and risk of major cardiovascular eventis, and a logistic regression model was applied to assess the relationship between major bleeding and access site complications. Total hospital stay and total hospitalization costis were measured to evaluate the operational efficiency. Resultis: A total of 8,155 percutaneous coronary interventions (mean follow-up of 1,448.6±714.1 days), via radial access (n=5,706) or femoral access (n=2,449), were included in the study. At 30 days, the risk of major cardiovascular eventis was significantly lower with the radial access (HR 0.66 [0.5-0.88], p=0.004), at the expense of a reduction in all-cause mortal-ity In addition, radial access significantly reduced the risk of major bleeding (HR 0.33 [0.16-0.67], p=0.002) and access site complications (HR 0.72 [0.53-0.98], p=0.038). A significant interaction was observed between the vascular access site and the risk of eventis according to the clinical presentation at admission. Use of radial access was associated with a significant reduction in the length of total hospital stay (≈30%) and total hospitalization costis (≈15%). Conclusions: The use of radial access in percutaneous coronary intervention was safe and effective compared with the femoral access, with lower rates of major cardiovascular eventis at 30 days, lower risk of major bleeding and of access site complications. Moreover, radial access was associated with greater operational efficiency during hospitalization.

Impacto de la diabetes mellitus en pacientes tratados con angioplastia coronaria / Impact diabetes mellitus in patients undergoing percutaneous coronary intervention

RESUMEN Introducción: La diabetes mellitus (DM) se ha asociado a un incremento en los resultados adversos en pacientes tratados con angioplastia coronaria (ATC), en comparación con los pacientes no diabéticos. Objetivos: Evaluar el riesgo de eventos cardiovasculares mayores en los pacientes diabéticos, estratificados según el tratamiento recibido (no insulinorrequirientes o insulinorrequirientes), en una población de pacientes no seleccionada tratados con angioplastia coronaria. Material y métodos: Análisis de registro, unicéntrico y retrospectivo de pacientes con enfermedad coronaria tratados con ATC desde marzo 2009 a junio 2018, según la presencia de DM estratificada de acuerdo con el tratamiento establecido para el control del desorden metabólico en: DM insulino-requirientes (DM-IR) y DM no insulino-requirientes (DM-NIR). Se aplicó un modelo de regresión de Cox ajustado para evaluar la relación entre la presencia de diabetes y el riesgo de eventos cardiovasculares mayores. Resultados: Se incluyeron 6.313 pacientes (seguimiento promedio 4,1 ± 1,8 años), con una prevalencia global de DM del 22,8% (DM-NIR 19,1%; DM-IR 3,8%). Los pacientes diabéticos presentaron un perfil de riesgo elevado, particularmente los DM-IR. Al seguimiento promedio, el riesgo ajustado de eventos cardiovasculares mayores fue similar entre los pacientes No-DM y los DM-NIR (HR 1,02 [0,81-1,27], p 0,85). En relación con los pacientes DM-IR, se observó un riesgo elevado comparados con los No-DM (HR 1,73 [1,20-2,49], p 0,003) y con los DM-NIR (HR 1,65 [1,10-2,48], p 0,015). Se observó una interacción significativa entre el estado diabético y el riesgo de eventos según la indicación de la angioplastia coronaria al ingreso (pint 0,045). Conclusiones: En nuestra serie de pacientes tratados con angioplastia coronaria y con seguimiento a largo plazo, los pacientes diabéticos presentaron alto riesgo de eventos cardiovasculares mayores. Este riesgo se observó particularmente incrementado en pacientes DM-IR. Sin embargo, no se evidenciaron diferencias significativas en el riesgo de eventos entre los pacientes DM-NIR y los No-DM.

ABSTRACT Background: Diabetes mellitus (DM) has been associated with an increase in adverse outcomes in patients treated with coronary angioplasty, compared to non-diabetic patients. Objective: To evaluate the risk of major adverse cardiovascular events in diabetic patients, stratified according to the treatment (non-insulin dependent or insulin-dependent), in a population of unselected patients treated with coronary angioplasty. Methods: Registry-based analysis of patients with coronary artery disease undergoing percutaneous coronary intervention from March 2009 to June 2018, according presence of DM stratified according to the established treatment for the metabolic disorder: insulin-dependent DM (ID -DM) and non-insulin dependent DM (NID -DM). An adjusted Cox regression model was applied to evaluate the relationship between the diabetic status and the risk of major adverse cardiovascular events. Results: A total of 6313 patients were included (mean follow-up 4.1 ± 1.8 years), with a global prevalence of DM of 22,8% (non-insulin dependent DM 19,1%, insulin-dependent DM 3,8%). Diabetic patients showed a higher risk profile, particularly those with ID-DM. At the average follow-up, the adjusted risk of MACE was similar between Non-DM patients and the NIR-DM patients (HR 1,02 [0,81-1,27], p 0.85). In relation to DM-IR patients, it was observed a higher risk of MACE in comparison to Non-DM (HR 1,73 [1,20-2,49], p 0.003) and NIR-DM (HR 1,65 [1,10-2,48], p 0.015). A significant interaction was observed between the diabetic status and the risk of MACE according to the indication of the percutaneous coronary artery intervention (pint 0.045). Conclusions: In our registry of patients undergoing PCI, with long-term follow-up, DM patients had a higher risk of MACE. The risk of MACE was particularly increased in ID-DM patients. However, there were no significant differences in the risk of MACE between DM-NIR and non-DM patients.

StentBoost Visualization for the Evaluation of Coronary Stent Expansion During Percutaneous Coronary Interventions.

INTRODUCTION: Inadequate stent implantation is associated with stent thrombosis and restenosis. StentBoost can enhance stent visualization and evaluate stent expansion. Currently, there are limited comparison studies between StentBoost and intravascular ultrasound (IVUS). We aimed to test the correlation and agreement between IVUS and StentBoost measurements. METHODS: From December 2010 to December 2011, 38 patients (54 stents) were analyzed using IVUS and StentBoost. Minimal stent diameter and proximal and distal edge stent diameter were compared between imaging techniques using Pearson correlation and Bland-Altman scatter plot. RESULTS: There was good correlation between StentBoost and IVUS measurements regarding minimal stent diameter (p < 0.001 in all stent portions) and an optimal agreement between IVUS and StentBoost, while lesser agreement was found between IVUS and quantitative coronary angiography. CONCLUSION: The assessment of stent implantation using StentBoost showed an adequate correlation and agreement with IVUS. This easily applicable angiographic technique can be used to guide stent implantation.

Implementación de un programa de angioplastia coronaria ambulatoria en pacientes con riesgo incrementado / Implementation of an Ambulatory Percutaneous Coronary Intervention Program in Higher Risk Patients

RESUMEN: Introducción: La hipercolesterolemia familiar es una hiperlipidemia primaria. Se trata de un trastorno genético autosómico dominante del metabolismo de las lipoproteínas, caracterizado por concentraciones plasmáticas elevadas de colesterol unido a lipoproteínas de baja densidad y presencia de xantomas tendinosos, y está asociado con el desarrollo prematuro de enfermedad cardiovascular. Objetivos: Investigar la presencia de mutaciones en el principal gen asociado al desarrollo de hipercolesterolemia familiar (LDLR) en un grupo de pacientes identificados como "casos índices", de entre aquellos que concurren al Servicio de Lípidos del Hospital Universitario Fundación Favaloro con diagnóstico clínico de hipercolesterolemia familiar. Determinar la composición ancestral de la población estudiada. Material y métodos: Se estudió una población de 38 pacientes con diagnóstico clínico de hipercolesterolemia familiar. La región codificante y las zonas intrónicas adyacentes del gen LDLR se secuenciaron automáticamente por el método de Sanger. Se investigó el componente ancestral de la población estudiada a partir del análisis de 46 marcadores informativos de ancestralidad (AIM-Indel). Resultados: Se identificaron 50 variantes diferentes, de las cuales el 48% se consideraron patogénicas. Se logró establecer una correlación genotipo-gravedad del fenotipo en el 60,5% de los pacientes estudiados. El componente ancestral de la población estudiada fue predominantemente europeo, seguido de un componente nativo-americano y, en menor proporción, africano. Conclusiones: El análisis genético por secuenciación del gen LDLR en pacientes identificados como "casos índices" con diagnóstico clínico de hipercolesterolemia familiar permite correlacionar el dato genético con la gravedad del fenotipo observado clínicamente y efectuar un diagnóstico en cascada en los miembros de la familia que presentan los criterios de inclusión considerados.

ABSTRACT: Background: Familial hypercholesterolemia is a primary hyperlipidemia. It is an autosomal dominant genetic disorder of lipoprotein metabolism, characterized by elevated plasma low-density lipoprotein cholesterol and presence of tendon xanthomas, and is associated with early cardiovascular disease. Objectives: The aim of this study was to investigate the presence of mutations in the main gene associated with the development of familial hypercholesterolemia (LDLR) in a group of patients identified as "index cases" attending the Lipid Clinic of the Hospital Universitario Fundación Favaloro with clinical diagnosis of familial hypercholesterolemia. The ancestral composition of the study population was determined. Methods: We evaluated 38 patients with clinical diagnosis of familial hypercholesterolemia. Mutation screening of the LDLR gene coding regions and adjacent intronic areas was performed using Sanger sequencing. The ancestral component of the study population was investigated using 46 ancestry inference markers (AIM-Indel). Results: Fifty different variants were identified, 48% of which were considered pathogenic. A genotype-phenotype severity correlation was established in 60.5% of the patients evaluated. The ancestral component of the study population was predominantly European, followed by native-American and African in lower proportion. Conclusions: Genetic testing by LDLR gene sequencing in patients identified as "index cases" with clinical diagnosis of familial hypercholesterolemia allows the correlation between the genetic information and the severity of the clinical phenotype to a cascade testing of the family members presenting the inclusion criteria considered.