RESUMEN Introducción y objetivos: La calcificación coronaria es uno de los principales factores que inciden negativamente en la seguridad y la eficacia del intervencionismo coronario percutáneo. Existen varias técnicas de modificación del calcio, pero falta evidencia de estudios aleatorizados sobre la terapia de elección en este escenario. Métodos: El ROLLERCOASTR es un estudio prospectivo, multicéntrico y aleatorizado, diseñado para comparar la seguridad y la eficacia de 3 técnicas de modificación de la placa en el contexto de calcificación coronaria moderada o grave: aterectomía rotacional (AR), aterectomía coronaria con láser láser excimer (ACLE) y litotricia intracoronaria (LIC). El objetivo primario es la expansión del stent evaluada mediante tomografía de coherencia óptica. Su análisis se hará por intención de tratar, con un α de 0,05 entre el grupo de referencia (AR) y cada uno de los otros grupos (ACLE y LIC). Se realizará también un análisis del objetivo primario por protocolo para mantener la coherencia. Si se confirma la hipótesis de no inferioridad, se realizará un análisis bilateral de superioridad. El comité de eventos clínicos y el laboratorio central independiente no conocerán la rama de tratamiento. Asumiendo un error α de 0,05, un error β de 0,2 (80% de potencia), un margen de irrelevancia (ε) del 7% y un 10% de pérdidas por dificultad de medición o imposibilidad de completar la intervención, se estima un tamaño de muestra de 56 casos en cada grupo. Los objetivos secundarios son el éxito del dispositivo, el éxito del procedimiento, la tasa de cruce entre técnicas y la presentación de eventos cardiovasculares adversos importantes al año de seguimiento. Conclusiones: El estudio ROLLERCOASTR evaluará y comparará la seguridad y la eficacia, en pacientes con estenosis coronaria calcificada, de 3 técnicas de modificación de placa: AR, ACLE y LIC. Este ensayo se ha registrado en Clinicaltrials.gov: NCT04181268.

ABSTRACT Introduction and objectives: Coronary calcification is one of the leading factors that affect negatively the safety and effectiveness of percutaneous coronary intervention. Several calcium modification techniques exist. However, there is a lack of randomized evidence on the therapy of choice in this scenario. Methods: The ROLLERCOASTR is a prospective, multicenter, randomized clinical trial designed to compare the safety and efficacy profile of 3 plaque modification techniques in the moderate-to-severe coronary calcification setting: rotational atherectomy (RA), excimer laser coronary angioplasty (ELCA), and intravascular lithotripsy (IVL). The study primary endpoint is stent expansion evaluated by optical coherence tomography. An intention-to-treat analysis will be conducted with an alpha coefficient of 0.05 between the reference group (RA) and the remaining 2 groups (ELCA and IVL). An analysis of the study primary endpoint per protocol will be conducted for consistency purposes. If the non-inferiority hypothesis is confirmed, a superiority 2-sided analysis will be conducted. Both the clinical events committee and the independent core laboratory will be blinded to the treatment arm. Assuming an α error of 0.05, an β error of 0.2 (80% power), a margin of irrelevance (ε) of 7, and losses of 10% due to measurement difficulty or impossibility to complete the intervention, we estimate a sample size of 56 cases per group. The study secondary endpoints are device success, procedural success, crossover rate among the different techniques used, and the occurrence of major adverse cardiovascular events at 1-year follow-up. Conclusions: The ROLLERCOASTR trial will evaluate and compare the safety and effectiveness of 3 plaque modification techniques: RA, ELCA, and IVL in patients with calcified coronary stenosis. This trial was registered at clinicaltrials.gov with identifier NCT04181268.

Resumo Fundamento Os limiares de corte para a “relação do ciclo completo de repouso” (RFR) oscilam em diferentes séries, sugerindo que as características da população podem influenciá-los. Da mesma forma, foram documentados preditores de discordância entre a RFR e a reserva de fluxo fracionado (FFR). O Estudo RECOPA, mostrou que a capacidade diagnóstica está reduzida na “zona cinzenta” da RFR, tornando necessária a realização de FFR para descartar ou confirmar isquemia. Objetivos Determinar os preditores de discordância, integrar as informações que eles fornecem em um índice clínico-fisiológico: a “RFR Ajustada”, e comparar sua concordância com o FFR. Métodos Usando dados do Estudo RECOPA, os preditores de discordância em relação à FFR foram determinados na “zona cinzenta” da RFR (0,86 a 0,92) para construir um índice (“RFR Ajustada”) que pesaria a RFR juntamente com os preditores de discordância e avaliar sua concordância com a FFR. Resultados Foram avaliadas 156 lesões em 141 pacientes. Os preditores de discordância foram: doença renal crônica, cardiopatia isquêmica prévia, lesões não envolvendo a artéria descendente anterior esquerda e síndrome coronariana aguda. Embora limitada, a “RFR Ajustada” melhorou a capacidade diagnóstica em comparação com a RFR na “zona cinzenta” (AUC-RFR = 0,651 versus AUC-“RFR Ajustada” = 0,749), mostrando também uma melhora em todos os índices diagnósticos quando foram estabelecidos limiares de corte otimizados (sensibilidade: 59% a 68%; especificidade: 62% a 75%; acurácia diagnóstica: 60% a 71%; razão de verossimilhança positiva: 1,51 a 2,34; razão de verossimilhança negativa: 0,64 a 0,37). Conclusões Ajustar a RFR integrando as informações fornecidas pelos preditores de discordância para obter a “RFR Ajustada” melhorou a capacidade diagnóstica em nossa população. Mais estudos são necessários para avaliar se os índices clínico-fisiológicos melhoram a capacidade diagnóstica da RFR ou de outros índices coronarianos.

Abstract Background Cutoff thresholds for the “resting full-cycle ratio” (RFR) oscillate in different series, suggesting that population characteristics may influence them. Likewise, predictors of discordance between the RFR and fractional flow reserve (FFR) have been documented. The RECOPA Study showed that diagnostic capacity is reduced in the RFR “grey zone”, requiring the performance of FFR to rule out or confirm ischemia. Objectives To determine predictors of discordance, integrate the information they provide in a clinical-physiological index, the “Adjusted RFR”, and compare its agreement with the FFR. Methods Using data from the RECOPA Study, predictors of discordance with respect to FFR were determined in the RFR “grey zone” (0.86 to 0.92) to construct an index (“Adjusted RFR”) that would weigh RFR together with predictors of discordance and evaluate its agreement with FFR. Results A total of 156 lesions were evaluated in 141 patients. Predictors of discordance were: chronic kidney disease, previous ischemic heart disease, lesions not involving the anterior descending artery, and acute coronary syndrome. Though limited, the “Adjusted RFR” improved the diagnostic capacity compared to the RFR in the “grey zone” (AUC-RFR = 0.651 versus AUC-“Adjusted RFR” = 0.749), also showing an improvement in all diagnostic indices when optimal cutoff thresholds were established (sensitivity: 59% to 68%; specificity: 62% to 75%; diagnostic accuracy: 60% to 71%; positive likelihood ratio: 1.51 to 2.34; negative likelihood ratio: 0.64 to 0.37). Conclusions Adjusting the RFR by integrating the information provided by predictors of discordance to obtain the “Adjusted RFR” improved the diagnostic capacity in our population. Further studies are required to evaluate whether clinical-physiological indices improve the diagnostic capacity of RFR or other coronary indices.

Abstract Objective: This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in coronary artery disease (CAD) patients. Methods: The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD, and 45 control volunteers) and we analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behavior in atherosclerosis. Results: Serum CypC levels were shown to be gradually increased in CAD patients (30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months [p = 0.25], and 47.27 pg/mL ± 5.65 at 12 months [p = 0.007]). In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c-statistic 0.76 at 6 months and 0.89 at 12 months; p < 0.001). Despite it, there was no significant association between CypC and cardiovascular events, but serum CypC levels tended to be higher in patients suffering cardiovascular events during the follow-up (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). In this regard, plasma levels of high-sensitivity C-reactive protein (hsCRP) > 2.3 mg/L plus NT-proBNP > 300 pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels >17.5 pg/mL (p = 0.048). Conclusions: Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP.

Resumen Objetivo: Este estudio tiene como objetivo investigar los cambios en los niveles séricos de CypC y su relación con eventos cardiovasculares a los 12 meses de seguimiento en pacientes con EAC. Método: El estudio incluyó un total de 125 sujetos (40 pacientes con EAC aguda, 40 pacientes con EAC crónica y 45 voluntarios de control) y se analizaron los niveles plasmáticos de CypC desde el inicio hasta los 6 y 12 meses para comprender mejor su comportamiento en la aterosclerosis. Resultados: Se demostró que los niveles séricos de CypC aumentaron gradualmente en pacientes con CAD [(30.63 pg/ml ± 3.77 al inicio del estudio, 38.70 pg/ml ± 6.41 a los 6 meses (p = 0.25) y 47.27 pg/ml ± 5.65 a los 12 meses (p = 0,007)]. Además, los niveles séricos de CypC durante el seguimiento fueron un predictor significativo de EAC (estadístico c 0.76 a los 6 meses y 0.89 a los 12 meses; p < 0.001). A pesar de ello, no hubo asociación significativa entre CypC y eventos cardiovasculares, pero los niveles séricos de CypC tendieron a ser más altos en los pacientes que sufrieron eventos cardiovasculares durante el seguimiento (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). En este sentido, los niveles plasmáticos de hsCRP > 2.3 mg/L más NT-proBNP> 300 pg/ml juntos fueron predictores significativos de eventos cardiovasculares durante el seguimiento en pacientes con EAC con niveles de CypC > 17.5 pg/ml (p = 0.048). Conclusiones: Tomados en conjunto, nuestros resultados sugieren que los niveles séricos de CypC aumentan durante el seguimiento en pacientes con EAC y podría ser un nuevo biomarcador con un posible valor pronóstico en combinación con hsCRP y NT-proBNP.

Abstract Introduction: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. Methods: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. Results: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. Conclusions: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

Resumen La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía Métodos: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. Resultados: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). Conclusiones: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.