Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens.

We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration.

Cardio4Health Study, a Cardiac Telerehabilitation Pilot Program Aimed at Patients After an Ischemic Event: Cross-sectional Study.

BACKGROUND: Center-based cardiac rehabilitation programs (CRPs) reduce morbidity and mortality after an ischemic cardiac event; however, they are widely underused. Home-based CRP has emerged as an alternative to improve patient adherence; however, its safety and efficacy remain unclear, especially for older patients and female patients. OBJECTIVE: This study aimed to develop a holistic home-based CRP for patients with ischemic heart disease and evaluate its safety and impact on functional capacity, adherence to a healthy lifestyle, and quality of life. METHODS: The 8-week home-based CRP included patients of both sexes, with no age limit, who had overcome an acute myocardial infarction in the previous 3 months, had a left ventricular ejection fraction of ≥40%, and had access to a tablet or mobile device. The CRP was developed using a dedicated platform designed explicitly for this purpose and included 3 weekly exercise sessions combining tailored aerobic and strength training and 2 weekly educational session focused on lifestyle habits, therapeutic adherence, and patient empowerment. RESULTS: We initially included 62 patients, of whom 1 was excluded for presenting with ventricular arrhythmias during the initial stress test, 5 were excluded because of incompatibility, and 6 dropped out because of a technological barrier. Ultimately, 50 patients completed the program: 85% (42/50) were male, with a mean age of 58.9 (SD 10.3) years, a mean left ventricular ejection fraction of 52.1% (SD 6.72%), and 25 (50%) New York Heart Association functional class I and 25 (50%) New York Heart Association II-III. The CRP significantly improved functional capacity (+1.6 metabolic equivalent tasks), muscle strength (arm curl test +15.5% and sit-to-stand test +19.7%), weekly training volume (+803 metabolic equivalent tasks), adherence to the Mediterranean diet, emotional state (anxiety), and quality of life. No major complications occurred, and adherence was excellent (>80%) in both the exercise and educational sessions. In the subgroup analysis, CRP showed equivalent beneficial effects irrespective of sex and age. In addition, patient preferences for CRP approaches were equally distributed, with one-third (14/50, 29%) of the patients preferring a face-to-face CRP, one-third (17/50, 34%) preferring a telematic CRP, and one-third (18/50, 37%) preferring a hybrid approach. Regarding CRP duration, 63% (31/50) of the patients considered it adequate, whereas the remaining 37% (19/50) preferred a longer program. CONCLUSIONS: A holistic telematic CRP dedicated to patients after an ischemic cardiac event, irrespective of sex and age, is safe and, in our population, has achieved positive results in improving maximal aerobic capacity, weekly training volume, muscle strength, quality of life, compliance with diet, and anxiety symptoms. The preference for a center- or home-based CRP approach is diverse among the study population, emphasizing the need for a tailored CRP to improve adherence and completion rates.

Clinical profile and prognosis of young patients with ST-elevation myocardial infarction managed by the emergency-intervention Codi IAM network.

INTRODUCTION AND OBJECTIVES: Data on the clinical profile and outcomes of younger patients with ST-elevation myocardial infarction (STEMI) is scarce. This study compared clinical characteristics and outcomes between patients aged<45 years and those aged ≥ 45 years with STEMI managed by the acute myocardial infarction code (AMI Code) network. Sex-based differences in the younger cohort were also analyzed. METHODS: This multicenter study collected individual data from the Catalonian AMI Code network. Between 2015 and 2020, we enrolled patients with an admission diagnosis of STEMI. Primary endpoints were all-cause mortality within 30 days, 1 year, and 2 years. RESULTS: Overall, 18 933 patients (23% female) were enrolled. Of them, 1403 participants (7.4%) were aged<45 years. Younger patients with STEMI were more frequently smokers (P<.001) and presented with cardiac arrest and TIMI flow 0 before pPCI (P<.05), but the time from first medical contact to wire crossing was shorter than in the older group (P<.05). All-cause mortality rates were lower in patients aged<45 years (P<.001). Among younger patients, cardiogenic shock was most prevalent in women than in their male counterparts (P=.002), with the time from symptom onset to reperfusion being longer (P<.05). Compared with men aged<45 years, younger women were less likely to undergo pPCI (P=.004). CONCLUSIONS: Despite showing high-risk features on admission, young patients exhibit better outcomes than older patients. Differences in ischemia times and treatment were observed between men and women.

Long-term outcomes of extended DAPT in a real-life cohort of consecutive STEMI patients.

INTRODUCTION AND OBJECTIVES: Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate. METHODS: We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients. RESULTS: A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P <.01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P=.049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P <.001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses. CONCLUSIONS: Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis.

An open secret in porcine acute myocardial infarction models: The relevance of anaesthetic regime and breed in ischaemic outcomes.

Large animal models of acute myocardial infarction (AMI) play a crucial role in translating novel therapeutic approaches to patients as denoted by their use in the right-before-human testing platform. At present, the porcine model of AMI is used most frequently as it mimics the human condition and its anatomopathological features accurately. We want to describe to, and share with, the translational research community our experience of how different anaesthetic protocols (sevoflurane, midazolam, ketamine+xylazine+midazolam, and propofol) and pig breeds [Large White and Landrace x Large White (LLW)] can dramatically modify the outcomes of a well-established porcine model of closed-chest AMI. Our group has extensive experience with the porcine model of reperfused AMI and, over time, we reduced the time of ischaemia used to induce the disease from 90 to 50 min to increase the salvageable myocardium for cardioprotection studies. For logistical reasons, we changed both the anaesthetic protocol and the pig breed used, but these resulted in a dramatic reduction in the size of the myocardial infarct, to almost zero in some cases (sevoflurane, 50-min ischaemia, LLW, 2.4 ± 3.9% infarct size), and the cardiac function was preserved. Therefore, we had to re-validate the model by returning to 90 min of ischaemia. Here, we report the differences in infarct size and cardiac function, measured by different modalities, for each combination of anaesthetic protocol and pig breed we have used. Furthermore, we discuss these combinations and the limited literature pertaining to how these two factors influence cardiac function and infarct size in the porcine model of AMI.

Blood glucose monitoring during hospitalisation: Advanced practice nurse and semi-automated insulin prescription tools.

INTRODUCTION: Hyperglycemia is very common in hospitalized patients and is associated with worse clinical outcomes. AIMS: We implemented a clinical and educational program to improve the overall glycemic control during hospital admission, and, in patients with HbA1c > 8%, to improve their metabolic control after hospital admission. METHODS: Non-critical patients admitted to cardiovascular areas between October-2017 and February-2019. The program was led by an advanced nurse practitioner (ANP) and included a semiautomated insulin prescription tool. Program in 3 phases: 1) observation of routine practice, 2) implementation, and 3) follow-up after discharge. RESULTS: During the implementation phase the availability of HbA1c increased from 42 to 81%, and the ANP directly intervened in 73/685 patients (11%), facilitating treatment progression at discharge in 48% (de novo insulin in 36%). One-year after discharge, HbA1c in patients who were admitted during the observation phase with HbA1c > 8% (n = 101) was higher than similar patients admitted during implementation phase (8,6 ±â€¯1,5 vs. 7,3 ±â€¯1,2%, respectively, p < 0,001). We evaluated 47710 point of care capillary blood glucose (POC-glucose) in two 9 months periods (one before, one during the program) in cardiology and cardiovascular surgery wards. POC-glucose ≥250 mg/dl (pre vs. during: cardiology 10,7 vs. 8,4%, and surgery 7,4 vs. 4,5%, both p < 0,05) and <70 mg/dl (2,3 vs. 0,8% y 1,5 vs 1%, p < 0,05), respectively, improved during the program. CONCLUSIONS: The program allowed improving inpatient glycemic control, detect patients with poor glycemic control, and optimize metabolic control 1-year after discharge.

Impact of Chronic Kidney Disease in Chronic Total Occlusion Management and Clinical Outcomes.

BACKGROUND: Data on the impact of chronic kidney disease (CKD) on clinical outcomes in chronic total occlusion (CTO) patients is scarce, and the optimal treatment strategy for this population is not well established. This study aims to compare differences in CTO management and long-term clinical outcomes, including all-cause and cardiac mortalities, according to baseline glomerular filtration rate (GFR). METHODS: All patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortalities were assessed during a median follow-up of 4.03 years (IQR 2.6-4.8). Clinical outcomes were compared between patients with CKD (GFR < 60 mL/min/1.73 m2) and without CKD (GFR ≥ 60 mL/min/1.73 m2). RESULTS: A total of 1248 patients (67.3 ± 10.9 years; 32% CKD) were identified. CKD patients were older and had a higher prevalence of hypertension, type 2 diabetes, peripheral arterial disease, and severe left ventricular dysfunction compared to patients with normal renal function (p < 0.05). Subjects with renal dysfunction were more often treated with MT alone, compared to patients without CKD (63% vs 45%; p < 0.001), who were more likely to undergo PCI or surgery. During follow-up, 386 patients [31%] died. CKD patients had a higher rate of all-cause and cardiac mortalities compared to patients without CKD (p < 0.001). The independent predictors for all-cause mortality were age, GFR < 60 mL/min/1.73 m2, Syntax Score I, and successful revascularization of the CTO (CABG or PCI-CTO). Among patients with CKD, advanced age, eGFR <30 mL/min/1.73 m2, and CTO successful revascularization were predictors of all-cause mortality. CONCLUSIONS: Patients with CKD were more often treated with MT alone. At long-term follow-up, revascularization of the CTO is associated with lower all-cause and cardiac mortalities in this population.

Myocardial Injury in COVID-19 Patients: Association with Inflammation, Coagulopathy and In-Hospital Prognosis.

The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4-7) vs. 2 (1-4), p = 0.001), higher CRP values (18.3 (9.6-25.9) mg/dL vs. 12.0 (5.4-19.4) mg/dL, p ˂ 0.001) and CAC score (1 (0-2) vs. 0 (0-1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.

Pulmonary ridge coverage and device-related thrombosis after left atrial appendage occlusion.

AIMS: The aim of this study was to evaluate the impact of pulmonary ridge (PR) coverage on both clinical and imaging follow-up outcomes in patients undergoing left atrial appendage occlusion (LAAO). METHODS AND RESULTS: The study included consecutive patients with non-valvular atrial fibrillation who underwent LAAO with disc and lobe devices. Patients were classified into two groups according to the PR coverage. A total of 147 patients were included. Among these, the PR was covered in 109 (74%) and uncovered in 38 (26%). Successful implantation was achieved in 98.6%. No differences in procedural outcomes were observed between the groups. The rate of procedural major adverse events was 3% (only major bleedings and/or vascular access complications). No device embolisation, cardiac tamponade or in-hospital mortality was observed. After a mean follow-up of 1.77±2.2 years, the annualised ischaemic stroke and major bleeding rate was 1.3%/year and 6.5%/year, respectively, without differences between groups. At follow-up, patients with a covered PR presented a lower incidence of device-related thrombosis (DRT) (1%) than those with an uncovered PR (27%); p<0.001. In multivariable analysis, the presence of PR coverage emerged as an independent predictor of DRT. CONCLUSIONS: Pulmonary ridge coverage was associated with a lower incidence of DRT after LAAO. Procedural and follow-up clinical outcomes did not differ between covered PR and uncovered PR patients.

Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. OBJECTIVES: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. METHODS: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. RESULTS: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. -0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. -145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. -35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). CONCLUSIONS: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).

Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction.

OBJECTIVE: Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. METHODS: We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. RESULTS: Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). CONCLUSIONS: Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older.

Sex-based differences in chronic total occlusion management and long-term clinical outcomes.

BACKGROUND: Sex differences in coronary artery disease presentation and outcomes have been described. The aim of this study was to compare sex disparities in chronic total occlusion (CTO) management and long-term outcomes. METHODS: All consecutive patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortality were assessed during a median follow-up of 4.03 years (IQR 2.6-4.8). RESULTS: A total of 1248 patients (67.3 ± 10.9 years; 16% female) were identified. Women were older, had a higher prevalence of type 2 DM and a lower ventricle ejection fraction compared to men (p < .05). Although women had major proportion of positive result for severe ischemia-viability test (86% vs. 74%; p = .01), they were more often treated with MT alone compared to male (57% vs 51%; p = .02). During follow-up, 386 patients (31%) died. Women presented a higher rate of all-cause and cardiac mortality, and hospitalizations for heart failure independently of treatment strategy, compared to men (p < .001). In multivariable analysis female sex was associated with higher cardiac mortality [HR 1.67, 95% CI 1.10-2.57; p < .001]. Among women, the independent predictors for all-cause and cardiac mortalities were age, MT of the CTO and ACEF (age, creatinin and ejection fraction) score. CONCLUSIONS: A significant sex gap regarding CTO treatment was observed. Female sex was an independent predictor for cardiac mortality at long-term follow-up. More data are needed to support these findings.

Kv1.3 blockade inhibits proliferation of vascular smooth muscle cells in vitro and intimal hyperplasia in vivo.

The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in 2 porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. The therapeutic potential of PAP-1 was then evaluated in vivo in swine models of ISR and AV. At 15-days follow-up, morphometric analysis demonstrated a substantial reduction of luminal stenosis in the allografts treated with PAP-1 (autograft 2.72 ± 1.79 vs allograft 10.32 ± 1.92 vs allograft + polymer 13.54 ± 8.59 vs allograft + polymer + PAP-1 3.06 ± 1.08 % of luminal stenosis; P = 0.006) in the swine model of femoral artery transplant. In the pig model of coronary ISR, using a prototype of PAP-1-eluting stent, no differences were observed regarding % of stenosis compared to control stents (31 ± 13 % vs 37 ± 18%, respectively; P = 0.372) at 28-days follow-up. PAP-1 treatment was safe and did not impair vascular healing in terms of delayed endothelialization, inflammation or thrombosis. However, an incomplete release of PAP-1 from stents was documented. We conclude that the use of selective Kv1.3 blockers represents a promising therapeutic approach for the prevention of intimal hyperplasia in AV, although further studies to improve their delivery method are needed to elucidate its potential in ISR.

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.

Falsos positivos en la activación por IAMCEST en una red regional: análisis integral e impacto clínico. Resultados del registro Codi Infart de Cataluña / False positive STEMI activations in a regional network: comprehensive analysis and clinical impact. Results from the Catalonian Codi Infart Network

Introducción y objetivos. Una red para la atención del infarto agudo de miocardio con elevación del segmento ST (IAMCEST) activada por no cardiólogos reduce los retrasos en la atención, pero pueden aumentar los falsos positivos. El objetivo es evaluar la prevalencia, los predictores y el impacto de los diagnósticos falsos positivos dentro de la red catalana para la atención del IAMCEST (Codi Infart). Métodos. Se incluyó a los pacientes atendidos por el Codi Infart entre enero de 2010 y diciembre de 2011. Se consideró activación apropiada si se cumplían los criterios clínicos y electrocardiográficos de IAMCEST. Las activaciones apropiadas se clasificaron como falso positivo según 2 definiciones no excluyentes: a) «angiográfica» si no se identificó una arteria causal, y b) «clínica» si el diagnóstico al alta no era IAMCEST. Resultados. Se incluyó un total de 5.701 activaciones. La activación resultó apropiada en el 87,8% de las veces. Los falsos positivos angiográficos fueron el 14,6% y los clínicos, el 11,6%. El sexo femenino, el bloqueo de rama izquierda y el antecedente de infarto de miocardio se asociaron con el falso positivo. Utilizando la definición clínica, se observó una tasa de falsos positivos mayor en los hospitales sin sala de hemodinámica y los pacientes con complicaciones durante el primer contacto. La mortalidad hospitalaria y a los 30 días fue similar entre los falsos y los verdaderos positivos. Conclusiones. La evolución clínica es similar entre los pacientes con falsos positivos y aquellos con verdaderos positivos. La identificación de predictores de falsos positivos justifica una evaluación cuidadosa para optimizar el uso de las redes de IAMCEST (AU)

Introduction and objectives. ST-segment elevation myocardial infarction (STEMI) network activation by a noncardiologist reduces delay times but may increase the rate of false-positive STEMI diagnoses. We aimed to determine the prevalence, predictors, and clinical impact of false-positive activations within the Catalonian STEMI network (Codi Infart). Methods. From January 2010 through December 2011, all consecutive patients treated within the Codi Infart network were included. Code activations were classified as appropriate if they satisfied both electrocardiogram and clinical STEMI criteria. Appropriate activations were classified as false positives using 2 nonexclusive definitions: a) "angiographic" if a culprit coronary artery was not identified, and b) "clinical" if the discharge diagnosis was other than STEMI. Results. In total, 5701 activations were included. Appropriate activation was performed in 87.8% of the episodes. The rate of angiographic false positives was 14.6%, while the rate of clinical false positives was 11.6%. Irrespective of the definition, female sex, left bundle branch block, and previous myocardial infarction were independent predictors of false-positive STEMI diagnoses. Using the clinical definition, hospitals without percutaneous coronary intervention and patients with complications during the first medical contact also had a false-positive STEMI diagnoses rate higher than the mean. In-hospital and 30-day mortality rates were similar for false-positive and true-positive STEMI patients after adjustment for possible confounders. Conclusions. False-positive STEMI diagnoses were frequent. Outcomes were similar for patients with a true-positive or false-positive STEMI diagnosis treated within a STEMI network. The presence of any modifiable predictors of a false-positive STEMI diagnosis warrants careful assessment to optimize the use of STEMI networks (AU)

False Positive STEMI Activations in a Regional Network: Comprehensive Analysis and Clinical Impact. Results From the Catalonian Codi Infart Network.

INTRODUCTION AND OBJECTIVES: ST-segment elevation myocardial infarction (STEMI) network activation by a noncardiologist reduces delay times but may increase the rate of false-positive STEMI diagnoses. We aimed to determine the prevalence, predictors, and clinical impact of false-positive activations within the Catalonian STEMI network (Codi Infart). METHODS: From January 2010 through December 2011, all consecutive patients treated within the Codi Infart network were included. Code activations were classified as appropriate if they satisfied both electrocardiogram and clinical STEMI criteria. Appropriate activations were classified as false positives using 2 nonexclusive definitions: a) "angiographic" if a culprit coronary artery was not identified, and b) "clinical" if the discharge diagnosis was other than STEMI. RESULTS: In total, 5701 activations were included. Appropriate activation was performed in 87.8% of the episodes. The rate of angiographic false positives was 14.6%, while the rate of clinical false positives was 11.6%. Irrespective of the definition, female sex, left bundle branch block, and previous myocardial infarction were independent predictors of false-positive STEMI diagnoses. Using the clinical definition, hospitals without percutaneous coronary intervention and patients with complications during the first medical contact also had a false-positive STEMI diagnoses rate higher than the mean. In-hospital and 30-day mortality rates were similar for false-positive and true-positive STEMI patients after adjustment for possible confounders. CONCLUSIONS: False-positive STEMI diagnoses were frequent. Outcomes were similar for patients with a true-positive or false-positive STEMI diagnosis treated within a STEMI network. The presence of any modifiable predictors of a false-positive STEMI diagnosis warrants careful assessment to optimize the use of STEMI networks.

Estrategias diuréticas en insuficiencia cardiaca aguda con disfunción renal: terapia convencional frente a guiada por el antígeno carbohidrato 125. Diseño de ensayo clínico / Diuretic strategies in acute heart failure and renal dysfunction: conventional vs carbohydrate antigen 125-guided strategy. Clinical trial design

Introducción y objetivos: El tratamiento óptimo de pacientes con insuficiencia cardiaca aguda (ICA) y síndrome cardiorrenal tipo 1 (SCR-1) no está bien definido. La hipoperfusión arterial y la congestión venosa tienen un papel fundamental en la fisiopatología del SCR-1. El antígeno carbohidrato 125 (CA125) ha emergido como marcador indirecto de sobrecarga de volumen en la ICA. El objetivo de este estudio es evaluar la utilidad del CA125 para el ajuste del tratamiento diurético de pacientes con SCR-1. Métodos: Ensayo clínico multicéntrico, abierto y paralelo, que incluye a pacientes con ICA y creatinina ≥ 1,4 mg/dl al ingreso, aleatorizados a: a) estrategia convencional: titulación basada en la evaluación clínica y bioquímica habitual, o b) estrategia basada en CA125: dosis altas de diuréticos si CA125 > 35 U/ml y bajas en caso contrario. El objetivo principal es el cambio en la función renal a las 24 y las 72 h tras el comienzo del tratamiento. Como objetivos secundarios: a) cambios clínicos y bioquímicos a las 24 y las 72 h, y b) cambios en la función renal y eventos clínicos mayores a 30 días. Resultados: Los resultados de este estudio aportarán datos relevantes sobre la utilidad del CA125 para guiar el tratamiento diurético en el SCR-1. Además, permitirá ampliar el conocimiento de la fisiopatología de esta compleja entidad clínica. Conclusiones: La hipótesis del presente estudio es que las concentraciones de CA125 aumentadas pueden identificar a una población de pacientes con SCR-1 para quienes una estrategia diurética más intensa puede ser beneficiosa. Por el contrario, las concentraciones bajas de esta glucoproteína seleccionarían a los pacientes para los que serían perjudiciales las dosis altas de diuréticos (AU)

Introduction and objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72 hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72 hours, and b) renal function changes and major clinical events at 30 days. Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses (AU)

Complicaciones cardiacas graves por shabu: una droga emergente en Europa / Severe cardiac complications of shabu use: an emerging drug in Europe

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Intracoronary Administration of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction.

BACKGROUND: Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. METHODS AND RESULTS: Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; P=0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P=0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P=0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P=0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm2 in vehicle; P=0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. CONCLUSIONS: In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed.