David Vivas

Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy

OBJECTIVES We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. BACKGROUND Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. METHODS This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. RESULTS A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. CONCLUSIONS In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR.

Impact of Insulin Receptor Substrate-1 Genotypes on Platelet Reactivity and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

OBJECTIVES The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. BACKGROUND The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. METHODS The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. RESULTS Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). CONCLUSIONS Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE.

Contemporary epidemiology and prognosis of septic shock in infective endocarditis

AIMS The prognosis of patients with infective endocarditis (IE) remains poor despite the great advances in the last decades. One of the factors closely related to mortality is the development of septic shock (SS). The aim of our study was to describe the profile of patients with IE complicated with SS, and to identify prognostic factors of new-onset SS during hospitalization. METHODS AND RESULTS We conducted a prospective study including 894 episodes of IE diagnosed at three tertiary centres. A backward logistic regression analysis was undertaken to determine prognostic factors associated with SS development. Multivariable analysis identified the following as predictive of SS development: diabetes mellitus [odds ratio (OR) 2.06; confidence interval (CI) 1.16-3.68], Staphylococcus aureus infection (OR: 2.97; CI: 1.72-5.15), acute renal insufficiency (OR: 3.22; CI: 1.28-8.07), supraventricular tachycardia (OR: 3.29; CI: 1.14-9.44), vegetation size ≥15 mm (OR: 1.21; CI: 0.65-2.25), and signs of persistent infection (OR: 9.8; CI: 5.48-17.52). Risk of SS development could be stratified when combining the first five variables: one variable present: 3.8% (CI: 2-7%); two variables present: 6.3% (CI: 3.2-12.1%); three variables present: 14.6% (CI: 6.8-27.6%); four variables present: 29.1% (CI: 11.7-56.1%); and five variables present: 45.4% (95% CI: 17.5-76.6%). When adding signs of persistent infection, the risk dramatically increased, reaching 85.7% (95% CI: 61.2-95.9%) of risk. CONCLUSIONS In patients with IE, the presence of diabetes, acute renal insufficiency, Staphylococcus aureus infection, supraventricular tachycardia, vegetation size ≥15 mm, and signs of persistent infection are associated with the development of SS.

Assessment of the diagnostic accuracy of 18 F-FDG PET/CT in prosthetic infective endocarditis and cardiac implantable electronic device infection: comparison of different interpretation criteria

PurposeThe diagnosis of prosthetic valve (PV) infective endocarditis (IE) and infection of cardiac implantable electronic devices (CIEDs) remains challenging. The aim of this study was to assess the usefulness of 18F-FDG PET/CT in these patients and analyse the interpretation criteria.MethodsWe included 41 patients suspected of having IE by the Duke criteria who underwent 18F-FDG PET/CT. The criteria applied for classifying the findings as positive/negative for IE were: (a) visual analysis of only PET images with attenuation-correction (AC PET images); (b) visual analysis of both AC PET images and PET images without AC (NAC PET images); (c) qualitative analysis of NAC PET images; and (d) semiquantitative analysis of AC PET images. 18F-FDG PET/CT was considered positive for IE independently of the intensity and distribution of FDG uptake. The gold standard was the Duke pathological criteria (if tissue was available) or the decision of an endocarditis expert team after a minimum 4 months follow-up.ResultsWe studied 62 areas with suspicion of IE, 28 areas (45 %) showing definite IE and 34 (55 %) showing possible IE. Visual analysis of only AC PET images showed poor diagnostic accuracy (sensitivity 20 %, specificity 57 %). Visual analysis of both AC PET and NAC PET images showed excellent sensitivity (100 %) and intermediate specificity (73 %), focal uptake being more frequently associated with IE. The accuracy of qualitative analysis of NAC PET images depended on the threshold: the maximum sensitivity, specificity and accuracy achieved were 88 %, 80 %, 84 %, respectively. In the semiquantitative analysis of AC PET images, SUVmax was higher in areas of confirmed IE than in those without IE (∆SUVmax 2.2, p < 0.001). When FDG uptake was twice that in the liver, IE was always confirmed, and SUVmax 5.5 was the optimal threshold for IE diagnosis using ROC curve analysis (area under the curve 0.71).ConclusionThe value of 18F-FDG PET/CT in the diagnosis of suspected IE of PVs and CIEDs is highly dependent on patient preparation and the method used for image interpretation. Based on our results, the best method is to consider a study positive for IE when FDG uptake is present in both AC PET and NAC PET images.

Clinical and prognostic comparison between left ventricular transient dyskinesia and a first non-ST-segment elevation acute coronary syndrome.

ObjectivesApical ballooning shares features with acute coronary syndromes. Recently, atypical forms have been reported without apical involvement. Usually, the prognostic reports have compared them with ST-segment elevation infarction. Left ventricular transient dyskinesias (LVTD), however, frequently occur without ST-segment elevation and when present, these patients always have open arteries. Our aim was to assess the baseline features, clinical presentation, natural history and compare long-term prognosis in an LVTD-cohort with a first non-ST-segment elevation acute coronary syndrome (NSTEMI) group. MethodsWe performed a prospective observational study including consecutive patients in two groups: (i) LVTD group: 62 patients with this syndrome between 2003 and 2007. Inclusion criteria were LV segmental transient motion abnormalities; ECG new alterations and elevated troponin; absence of recent significant head trauma or obstructive coronary artery lesions. (ii) Control group: 169 patients admitted for a first NSTEMI in 2004. ResultsMedian follow-up was 35 months. Mean age was 65 years. LVTD group included 83.9% females. NSTEMI group was predominantly males. Eleven in-hospital deaths happened in NSTEMI cohort and none in LVTD. Four patients in the LVTD group required readmission and two patients died. In the NSTEMI group, heart failure, unstable angina, myocardial infarction (P<0.001) and death (P=0.11) were more frequent. Cox regression showed that diabetes mellitus, significant onset mitral regurgitation and NSTEMI versus LVTD were found as event-independent predictors. ConclusionLVTD diagnosis represents a decreased risk of events when compared with classic non-ST-segment acute coronary syndrome, pointing out a different pathophysiologic mechanism.

Prognostic implications of bundle branch block in patients undergoing primary coronary angioplasty in the stent era.

The presence of bundle branch block (BBB) in patients with ST-segment elevation myocardial infarction has been associated with a poor outcome. However, the implications of BBB in patients undergoing primary angioplasty in the stent era are poorly established. Furthermore, the prognostic implications of BBB type (right vs left and previous vs transient or persistent) remain unknown. We analyzed the data from 913 consecutive patients with ST-segment elevation myocardial infarction treated with primary angioplasty. All clinical, electrocardiographic, and angiographic data were prospectively collected. The median follow-up period was 19 months. The primary end point was the combined outcome of death and reinfarction. BBB was documented in 140 patients (15%). Right BBB (RBBB) was present in 119 patients (13%) and was previous in 27 (23%), persistent in 45 (38%), and transient in 47 (39%). Left BBB (LBBB) was present in 21 patients (2%) and was previous in 8 (38%), persistent in 9 (43%), and transient in 4 (19%). Patients with BBB were older, and more frequently had diabetes, anterior infarctions, a greater Killip class, a lower left ventricular ejection fraction, and greater mortality (all p <0.005) than patients without BBB. The short- and long-term primary outcome occurred more frequently in patients with persistent RBBB/LBBB than in those with previous or transient RBBB/LBBB. On multivariate analysis, persistent RBBB/LBBB emerged as an independent predictor of death and reinfarction. In conclusion, in patients undergoing primary angioplasty in the stent era, BBB is associated with poor short- and long-term prognosis. This risk appears to be particularly high among patients with persistent BBB.

Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo").

Objectives Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. Methods This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80–120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y12 reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Results Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9±13.2% vs 59.1±17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. Conclusions In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

Revaluación de la endocarditis con hemocultivos negativos: su perfil es similar al de la endocarditis con hemocultivos positivos

INTRODUCTION AND OBJECTIVES Left-sided infective endocarditis with blood culture-negative has been associated with delayed diagnosis, a greater number of in-hospital complications and need for surgery, and consequently worse prognosis. The aim of our study was to review the current situation of culture-negative infective endocarditis. METHODS We analyzed 749 consecutive cases of left-sided infective endocarditis, in 3 tertiary hospitals from June 1996 to 2011 and divided them into 2 groups: group I (n=106), blood culture-negative episodes, and group II (n=643) blood culture-positive episodes. We used Duke criteria for diagnosis until 2002, and its modified version by Li et al. thereafter. RESULTS Age, sex, and comorbidity were similar in both groups. No differences were found in the proportion of patients who received antibiotic treatment before blood culture extraction between the 2 groups. The interval from symptom onset to diagnosis was similar in the 2 groups. The clinical course of both groups during hospitalization was similar. There were no differences in the development of heart failure, renal failure, or septic shock. The need for surgery (57.5% vs 55.5%; P=.697) and mortality (25.5% vs 30.6%; P=.282) were similar in the 2 groups. CONCLUSIONS Currently, previous antibiotic therapy is no longer more prevalent in patients with blood culture-negative endocarditis. This entity does not imply a delayed diagnosis and worse prognosis compared with blood culture-positive endocarditis. In-hospital clinical course, the need for surgery and mortality are similar to those in patients with blood culture-positive endocarditis. Full English text available from:www.revespcardiol.org.

Risk score for cardiac surgery in active left-sided infective endocarditis

Objective To develop and validate a calculator to predict the risk of in-hospital mortality in patients with active infective endocarditis (IE) undergoing cardiac surgery. Methods Thousand two hundred and ninety-nine consecutive patients with IE were prospectively recruited (1996–2014) and retrospectively analysed. Left-sided patients who underwent cardiac surgery (n=671) form our study population and were randomised into development (n=424) and validation (n=247) samples. Variables statistically significant to predict in-mortality were integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK-E). The predictive performance of the score and four existing surgical scores (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II), Prosthesis, Age ≥70, Large Intracardiac Destruction, Staphylococcus, Urgent Surgery, Sex (Female) (PALSUSE), EuroSCORE ≥10) and Society of Thoracic Surgeons’s Infective endocarditis score (STS-IE)) were assessed and compared in our cohort. Finally, an external validation of the RISK-E in a separate population was done. Results Variables included in the final model were age, prosthetic infection, periannular complications, Staphylococcus aureus or fungi infection, acute renal failure, septic shock, cardiogenic shock and thrombocytopaenia. Area under the receiver operating characteristic curve in the validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other surgical scores when compared with the RISK-E was inferior (p=0.010). Our score also obtained a good predictive performance, area under the curve 0.76 (95% CI 0.64 to 0.88), in the external validation. Conclusions IE-specific factors (microorganisms, periannular complications and sepsis) beside classical variables in heart surgery (age, haemodynamic condition and renal failure) independently predicted perioperative mortality in IE. The RISK-E had better ability to predict surgical mortality in patients with IE when compared with other surgical scores.

Prognostic Value of First Fasting Glucose Measurement Compared With Admission Glucose Level in Patients With Acute Coronary Syndrome

INTRODUCTION AND OBJECTIVES The admission plasma glucose (APG) level is a recognized prognostic factor in patients with acute coronary syndrome (ACS). However, little is known about the prognostic value of the first fasting plasma glucose (FPG) measurement. The aim of this study was to determine the prognostic value of the first FPG measurement relative to that of the APG level in patients with ACS. METHODS The study involved 547 consecutive patients who were admitted to our center with a diagnosis of ACS in 2006. Patients were divided into three groups according to their first FPG or APG level (i.e., <126 mg/dL, 126-200 mg/dL, or >200 mg/dL). The primary endpoint was the combined outcome of death or reinfarction during hospitalization. RESULTS The primary endpoint was observed in 46 patients, 25 of whom died. Patients in this group were older, were more often diabetics or smokers, more often had had a prior myocardial infarction, were in a higher admission Killip class, showed more than one vessel disease on catheterization, had a lower left ventricular ejection fraction, and had higher admission creatinine, APG, and first FPG levels. Multivariate analysis, adjusted for previously identified factors, revealed that the first FPG level was an independent risk factor for death or reinfarction (126-200 mg/dL, odds ratio [OR]=5.26; 95% confidence interval [CI], 1.09-25.45; >200 mg/dL, OR=6.66; 95% CI, 2.05-21.63), but that the APG level was not (126-200 mg/dL, OR=0.84; 95% CI, 0.63-1.05; >200 mg/dL, OR=1.14; 95% CI, 0.29-4.51). CONCLUSIONS The first FPG level was found to be a better predictor of an adverse outcome (i.e., death or reinfarction) during hospitalization in ACS patients than the APG level.