The role of invasive coronary physiology in Takotsubo Syndrome.

The pathophysiology of Takotsubo Syndrome has not yet been precisely defined. Different hypotheses have been proposed, including cardiotoxicity due to catecholaminergic hormone release, metabolic disorders, coronary microvascular dysfunction and epicardial coronary artery spasm. Invasive coronary physiology is considered the cornerstone to understand physiological assessment of coronary blood flow in this setting. We have reviewed most important studies in coronary invasive physiology in this field to update the state of the art in TakoTsubo Syndrome.

Usefulness of the Hybrid RFR-FFR Approach: Results of a Prospective and Multicenter Analysis of Diagnostic Agreement between RFR and FFR-The RECOPA (REsting Full-Cycle Ratio Comparation versus Fractional Flow Reserve (A Prospective Validation)) Study.

BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.

Magmaris very late in-scaffold restenosis: Has the "black boxes" nightmare come back?

Magnesium Bioresorbable Scaffold (Magmaris, Biotronik) is a device with promising outcomes at 24 months of follow up. Previous studies with first generation, everolimus-eluting Bioresorbable Vascular Scaffold (Absorb, Abbott) showed that very late restenosis seems to be attributed to pure intrascaffold tissue growth but very late. Magmaris very late restenosis has not been previously published, probably because of the 95% of resorption at 12 months. We present in-scaffold very late restenosis within Magmaris, with Optical Coherence Tomography, highlighting mechanism of degradation and in scaffold "neo-tissue" growth.

Bioresorbable vascular scaffolds in coronary chronic total occlusions revascularization: safety assessment related to struts coverage and apposition in 6-month OCT follow-up.

Beneficial properties of bioresorbable vascular scaffolds (BVS) regarding to vasomotility restoration and no caging of the vessel make them attractive devices in chronic total occlusions (CTO) revascularization. However, more evidence is needed attending to their use in this specific setting. We aim to determine feasibility and safety of BVS use in CTO revascularization attending to struts coverage and apposition, as well as re-stenosis and stent thrombosis (ST) rates. 29 BVS were deployed in 9 CTO lesions revascularization (mean J-CTO score ≥3) with an acute procedural success rate of 100%. Clinical and angiographic follow-up was performed 6 months later, including intracoronary analyses from optical coherence tomography (OCT) images. 44,723 struts were analyzed within the total 636 mm of scaffolded vessel. Mean length scaffolded per lesion was 70.66 ± 31.01 mm with a mean number of 3.22 BVS. 2051 struts (4.59%) were identified as uncovered, being most of them (98.4%) neither malapposed nor disrupted. Mean thickness of struts' coverage was 0.13 ± 0.05 mm. Incomplete strut apposition (ISA) percentage was 0% as no malapposed struts were detected and 134 struts were identified as disrupted, which represents a 0.29% from the total. Mean vessel, scaffold, and lumen diameters were 3.87 ± 0.51, 2.97 ± 0.49, and 2.68 ± 0.50 mm, respectively. Neither in-stent re-stenosis nor ST was detected. During follow-up, none of our patients died, suffered from stroke or needed target lesion revascularization. Clinical and angiographic 6-month follow-up (including OCT analyses) of BVS in CTO revascularization suggests their effectiveness and safety, even in very complex chronic occluded lesions. Nevertheless, more evidence is needed.

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

AIMS: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients. METHODS AND RESULTS: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status. CONCLUSION: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03772743.

The Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial has shown that physiology-guided complete revascularization reduces ischaemic adverse events in older patients with myocardial infarction (MI) and multivessel disease. Older patients who engage in light or vigorous physical activity before hospitalization for MI have a reduced risk of the primary composite outcome of death, MI, stroke, or ischaemia-driven revascularization. These benefits extend to all secondary cardiovascular outcomes as well. In the present subanalysis of the FIRE trial, we find that the positive prognosis associated with physiology-guided complete revascularization holds true even for patients with a sedentary lifestyle. This means that this type of revascularization can effectively reduce ischaemic adverse events in older patients with MI and multivessel disease, regardless of their physical activity levels.

Dosing of iodinated contrast volume: a new simple algorithm to stratify the risk of contrast-induced nephropathy in patients with acute coronary syndrome.

OBJECTIVES AND BACKGROUND: Previous studies on contrast-induced nephropathy (CIN) have identified contrast volume (CV) as a risk factor. The aim of our research was to define the safe dose of contrast media based on absolute CV, maximum allowable contrast dose (MACD) and estimated glomerular filtrate rate (eGFR). METHODS AND RESULTS: A total of 940 consecutive patients with acute coronary syndrome (ACS) were enrolled. Fifty-four patients developed CIN. MACD was defined as 5*body weight/serum creatinine. When using a CV higher than MACD, CIN-risk was increased 19-fold (OR 9.810-39.307, P < 0.001). For the CV/eGFR ratio, we found that for every increase of one-tenth, CIN-risk increased by 4.9% (OR 1.037-1.061, P < 0.001). The discriminative ability of CV (C statistic = 0.626 ± 0.038) was significantly lower than for the CV/MACD (C statistic = 0.782 ± 0.036, P = 0.003) and CV/eGFR (C statistics: 0.796 ± 0.033 for MDRD-4, 0.796 ± 0.034 for Cockcroft-Gault, and 0.803 ± 0.033 for CKD-EPI; P < 0.001). There were no differences in the discriminative ability to predict CIN between the three eGFR equations. The combination of CV/MACD and CV/eGFR in a single protocol increases the positive predictive value of the Mehran risk score (40.7% vs. 8.8%) with the same sensitivity (90.7% vs. 83.3%). High doses of relative CV (CV/MACD and CV/eGFR) were also significantly associated with higher in-hospital mortality, reinfarction, and heart failure. CONCLUSIONS: A sequential protocol based on CV/MACD and CV/eGFR appropriately identified those ACS patients who developed CIN, with predictive values similar to a Mehran score, reducing the false positive rate. It is also useful to predict risk of in-hospital cardiac events regardless of GRACE score.

High-sensitivity C-reactive protein predicts adverse outcomes after non-ST-segment elevation acute coronary syndrome regardless of GRACE risk score, but not after ST-segment elevation myocardial infarction.

INTRODUCTION: Atherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). C-reactive protein (CRP) is an acute phase protein that appears in the circulation in response to inflammatory cytokines. The present study investigated the association between high-sensitivity C-reactive protein (hsCRP) on admission and follow-up prognosis after an ACS. METHODS: We included 151 consecutive patients admitted to the coronary care unit with a diagnosis of ACS (47% ST-segment elevation myocardial infarction [STEMI]). The primary endpoint was the combination of cardiac death and myocardial reinfarction during the follow-up period (median 19.8 months, interquartile range 16.3-23.7 months). RESULTS: The occurrence of follow-up events was significantly related to admission hsCRP level, which was an excellent predictor of cardiac death and reinfarction during follow-up (HR 1.091, 95% CI 1.014-1.174; p=0.019). Stratifying the population based on type of ACS, adjusted by variables associated with cardiac events in univariate analysis (hsCRP, diabetes, depressed ejection fraction and GRACE risk score), hsCRP proved to be an independent predictor of follow-up outcomes only in non-STEMI patients (HR 1.217, 95% CI: 1.093-1.356, p<0.001), not in STEMI patients. The best cutoff level of hsCRP to predict follow-up outcomes was 1.1mg/dl, with sensitivity of 77.8% and specificity of 63.2%. CONCLUSION: Although the GRACE risk score is routinely used for stratification of patients with ACS, assessment of hsCRP may provide additional prognostic value in the follow-up of non-STEMI patients.

Association of cyclophilins and cardiovascular risk factors in coronary artery disease.

Cyclophilins are chaperone proteins that play important roles in signal transduction. Among them, cyclophilins A, B, C, and D were widely associated with inflammation and cardiovascular diseases. Cyclophilins A and C have been proposed as coronary artery disease biomarkers. However, less is known about their relationship with cardiovascular risk factors. Therefore, this study aimed to determine the association between cyclophilin A, B, C, and D and cardiovascular risk factors in coronary artery disease. Serum levels of cyclophilins were measured in 167 subjects (subdivided according to cardiovascular risk factors presence). This study reveals that cyclophilin A and C are elevated in patients regardless of the risk factors presence. Moreover, cyclophilin B is elevated in male patients with hypertension, type 2 diabetes, or high glucose levels. In addition, cyclophilins A, B, and C were significantly correlated with cardiovascular risk factors, but only cyclophilin B was associated with type 2 diabetes. The multivariate analysis strengthens the predictive value for coronary artery disease presence of cyclophilin A (>8.2 ng/mL) and cyclophilin C (>17.5 pg/mL) along with the cardiovascular risk factors tobacco, hypertension, dyslipidemia, and high glucose and cholesterol levels. Moreover, the risk of coronary artery disease is increased in presence of cyclophilin B levels above 63.26 pg/mL and with hypertension or dyslipidemia in male patients. Consequently, cyclophilins A and C serum levels are reinforced as useful coronary artery disease biomarkers, meanwhile, cyclophilin B is a valuable biomarker in the male population when patients are also suffering from hypertension or dyslipidemia.

Increase of serum cyclophilin C levels in the follow-up of coronary artery disease: A biomarker and possible clinical predictor. / Aumento de niveles séricos de Ciclofilina C en el seguimiento de la enfermedad arterial coronaria: un biomarcador y posible predictor clínico

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.

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.

Adjusting RFR by Predictors of Disagreement, "The Adjusted RFR": An Alternative Methodology to Improve the Diagnostic Capacity of Coronary Indices. / Ajustando a RFR por Preditores de Discordância, "A RFR Ajustada": Uma Metodologia Alternativa para Melhorar a Capacidade Diagnóstica dos Índices Coronarianos.

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.

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.