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.

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.

Clinical Outcomes After Implantation of Polyurethane-Covered Cobalt-Chromium Stents: Insights from the Papyrus-Spain Registry.

BACKGROUND/PURPOSE: The main indication of covered stents (CS) is coronary artery perforation (CAP), but, they have been increasingly used in other scenarios. Data on the long-term follow-up of CS is limited, and no studies have been conducted specifically using new-generation polyurethane-covered cobalt-chromium Papyrus CS. PURPOSE: to evaluate the clinical outcomes after hospital discharge of Papyrus CS and to compare their outcome after implantation in CAP or coronary artery aneurysms (CAA). METHODS/MATERIALS: We evaluated the baseline clinical characteristics, lesion subsets, procedural features and the outcomes after initial discharge of Papyrus CS implanted in 17 high-PCI-volume centers. RESULTS: 127 Papyrus CS were implanted in 108 patients (68 ±â€¯1 years; 82.8% male) admitted for stable coronary disease (32.3%), NSTEMI (42.4%) or STEMI (25.3%). The number of CS per patient was 1.2 ±â€¯0.6 (diameter: 3.5 ±â€¯1.7 mm; length: 18.5 ±â€¯3.7 mm). Angiographic success rate was 96%. CS diameter was larger in CAA (CAP:3.04 ±â€¯0.5 mm vs CAA:4.1 ±â€¯2.7 mm; p = .022). Intracoronary imaging techniques were used more frequently in CAA (p < .0001). After a mean follow-up of 22 ±â€¯16 months, the major cardiovascular adverse events (MACE) rate was 7.1% [cardiac death: 2%, Myocardial infarction: 5%, Target Lesion Revascularization: 5% and Stent Thrombosis (ST): 3%]. MACE rate was similar in CAP (7.7%) and CAA (7.1%) (p = .9). However, CAA showed a higher ST rate (CAP: 0% vs CA: 7.1%; p = .04). CONCLUSION: After hospital discharge, clinical outcomes after Papyrus CS implantation are acceptable (considering the clinical scenario and compared with other treatment alternatives) with no significant differences in the MACE rate between those implanted in CAA or in CAP. However, CAA group showed a higher ST rate.

Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients.

BACKGROUND: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. METHODS: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured. RESULTS: CypA levels increased significantly in CAD patients compared with control subjects, but no differences were noted between acute CAD (7.80 ± 1.30 ng/mL) and chronic CAD (5.52 ± 0.76 ng/mL) patients (P = 0.13). No differences in CypB and CypD levels were showed between CAD patients and controls and between acute CAD and chronic CAD patients. In relation with CypC, the levels in CAD patients were significantly higher compared to controls (32.42 ± 3.71 pg/mL vs. 9.38 ± 1.51 pg/mL, P < 0.001), but no differences between acute and chronic CAD groups were obtained (P = 0.62). We analyzed the CypC > 17.5 pg/mL cut-off point, and it was significantly associated with older age, hypertension, dyslipidemia and more extensive CAD in acute and chronic CAD groups. CONCLUSIONS: CypA and CypC levels are increased in CAD patients. High CypC serum levels could be a novel biomarker in CAD patients correlating with a more severe disease.

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.

High Serum Cyclophilin C levels as a risk factor marker for Coronary Artery Disease.

Cyclophilins (Cyps) are ubiquitous proteins that belong to the immunophilins family consistently associated with inflammatory and cardiovascular diseases. While levels of CypA have been extensively studied, less data are available for other Cyps. The purpose of this case-control study was to determine the relationship of Cyps (A, B, C and D) with coronary artery disease (CAD) and eight inflammation markers. Serum levels of Cyps, interleukins and metalloproteinases were measured in serum collected from 84 subjects. Participants were divided into two sub-groups based on CAD diagnosis: 40 CAD patients and 44 control volunteers. Serum levels of CypA, CypB and CypC, IL-1ß and IL-6 were significantly higher in CAD patients. Bivariate correlation analysis revealed a significant positive correlation between Cyps and several blood and biochemical parameters. When the ability of Cyps levels for CAD diagnosis was evaluated, higher sensitivity and selectivity values were obtained with CypC (c-statistic 0.891, p < 0.001) indicating that it is a good marker of CAD disease, while less conclusive results were obtained with CypA (c-statistic 0.748, p < 0.001) and CypB (c-statistic 0.655, p < 0.014). In addition, significant correlations of traditional CAD risk factors and CypC were observed. In summary, high levels of CypC are a risk factor for CAD and therefore it can be proposed as a new biomarker for this disease.

Assessment with intracoronary pressure and flow guidewire, at baseline and after intracoronary adenosine infusion, in a patient with Takotsubo syndrome.

We present the case of a patient with Takotsubo syndrome assessed by intracoronary flow and pressure guidewire, showing elevation of intracoronary pressures at the level of the anterior descending artery, and thus demonstrating a new therapeutic target in a still little understood etiopathogenic entity. The results of this test have never been previously reported in Takotsubo patients.

Feasibility of use of magnesium reabsorbable scaffolds in complex coronary artery disease: True bifurcation, multiple overlapping scaffolds and chronic total occlusion treatment.

We present first-in-human treatment with bioabsorbable magnesium scaffolds for percutaneous coronary intervention in a patient with nickel allergy. We present images from angiography and optical coherence tomography at three months. We also review the current status of these novel devices.

Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

[Performance of glycated hemoglobin and a risk model for detection of unknown diabetes in coronary patients]. / Rendimiento de la glucohemoglobina y un modelo de riesgo para la detección de diabetes desconocida en pacientes coronarios.

INTRODUCTION AND OBJECTIVES: Traditionally, the oral glucose tolerance test has been useful to diagnose unknown diabetes. Recently, the American Diabetes Association committee has accepted glycated hemoglobin ≥ 6.5% as a criterion for unknown diabetes. The aim was to determine the benefit of glycated hemoglobin for diagnosing unknown diabetes and also create a predictive model that adjusts the indication for oral glucose tolerance test in coronary patients. METHODS: We examined the glycemic profile of 338 coronary patients without previous diagnosis of diabetes, applying 2010 American Diabetes Association criteria. A unknown diabetes risk predictive model was developed using logistic regression analysis, and then validated in another cohort. RESULTS: Using the glycated hemoglobin criteria and/or fasting plasma glucose, unknown diabetes was diagnosed in 26 patients. The remaining patients were classified according to oral glucose tolerance test as follows: unknown diabetes 53 (17%), prediabetes 144 (46.2%), and normoglycemic 115 (36.8%). The diagnostic method for unknown diabetes was fasting plasma glucose in 25.3%, glycated hemoglobin in 7.6%, and oral glucose tolerance test in 67.1%. A risk model including fasting plasma glucose, glycated hemoglobin, left ventricular ejection fraction, age, and noncoronary vascular disease was shown to effectively predict unknown diabetes after oral glucose tolerance test: area under the ROC curve 0.8 (95% confidence interval: 0.74-0.87). When the oral glucose tolerance test is restricted to patients with a risk score >6 (31% of our sample) we properly identify 83% of unknown diabetes cases (sensitivity: 75%, specificity: 73%, positive predictive value: 40%, negative predictive value: 93%). The model was adequately validated in another cohort of 115 patients (area under the ROC curve 0.84 [95% confidence interval: 0.74-0.95]). CONCLUSIONS: In coronary patients, glycated hemoglobin alone failed to detect many cases of unknown diabetes. However, its inclusion in a risk prediction model leads to optimizing the usefulness of oral glucose tolerance test.

"We have a tenant" a right atrial thrombus related to a central catheter.

Hemodialysis tunneled catheter are in constant motion due to the movement of the heart. For that reason catheter tip may cause damage to the wall of the vessel or the atrium, resulting in mural thrombus formation at the point of contact. We report the case of a 36 year old asymptomatic woman with a previous chronic vascular hemodialysis catheter who was referred for routine echocardiogram before kidney transplantation. An ovoid mass compatible with thrombus was present in the right atrium. We review literature about catheter-related thrombus.

[Haematoma of the floor of the mouth associated to acute myocardial infarction]. / Hematoma de suelo oral asociado al síndrome coronario agudo.

We report the case of an 80-year-old man who developed a haematoma in the floor of the mouth after receiving alteplase in the treatment of an acute myocardial infarction. Both the treatment received and appropriate preventive measures to avoid such haematomas are described.

Thrombi of different pathologies: implications for diagnosis and treatment.

OPINION STATEMENT: Stroke is the second leading cause of cardiovascular mortality in the modern world, accounting for 80% of strokes of ischemic origin. There are two main etiologies of ischemic stroke: 70% to 80% are caused by carotid atherosclerotic plaque rupture and superimposed thrombus formation, whereas 30% are caused by systemic embolism of a cardiac thrombus (mainly in atrial fibrillation [AF] patients). Therefore, antithrombotic therapy is the cornerstone of stroke treatment. In AF patients, thrombotic risk should be assessed by means of the CHADS2 score. Patients with a score of 0 should be treated with aspirin; for those with a score of 1, oral anticoagulation (target international normalized ratio, 2-3) or aspirin is recommended. For patients with a CHADS2 score ≥2, oral anticoagulation with warfarin should be initiated (unless contraindicated). If warfarin is contraindicated, antithrombotic treatment should be prescribed (the combination of aspirin and clopidogrel seems to be superior to aspirin alone). For primary prevention in atherosclerotic patients, low-dose aspirin is useful only in women older than 45 years who are not at risk for intracranial hemorrhage and do not have gastrointestinal intolerance (a very small but significant effect). For secondary prevention in atherosclerotic patients, antithrombotic therapy should be administered. It is recommended that patients who do not require anticoagulation receive clopidogrel or a combination of aspirin and dipyridamole. Alternatively, aspirin alone or triflusal may be used. Within 4.5 h of onset of acute stroke, thrombolytic therapy (recombinant tissue plasminogen activator) must be injected urgently (unless contraindicated). Dabigatran is a new oral anticoagulant (competitive thrombin inhibitor) with a promising role in stroke prevention; at low doses, it is noninferior to warfarin for stroke prevention and is safer, whereas at high doses, it is superior to warfarin in stroke prevention with the same incidence of bleeding. Percutaneous left atrial appendage occluders recently were approved for systemic embolism prevention. The use of warfarin after implantation is still under discussion. Dronedarone, a new antiarrhythmic agent, has been shown to decrease cardiovascular mortality and stroke in patients with AF. Carotid endarterectomy surgery is indicated in symptomatic patients with stenosis greater than 70% and in selected patients with 50% to 70% stenosis. Currently, carotid endarterectomy surgery is superior to carotid angioplasty and stenting.