Aberrant salience relationship with first rank symptoms.

BACKGROUND: Aberrant salience is the incorrect assignment of salience, significance, or value to different innocuous stimuli that might precede the onset of psychotic symptoms. The present study aimed to perform a preliminary evaluation of potentially different correlations between the Aberrant Salience Inventory (ASI) score and dimensional or categorical diagnostic approaches. METHODS: 168 adult outpatients with a current psychiatric diagnosis were consecutively enrolled. Patients were evaluated using different psychometric scales. ASI was used to evaluate aberrant salience, and to evaluate the association between ASI scores and first rank symptoms (FRS), and/or with a psychiatric diagnosis. Principal dichotomic clusters of ASI were identified using the Chi-square automatic interaction detection (CHAID) method. RESULTS: Current (16.76 ± 6.02 vs 13.37 ± 5.76; p = 0.001), lifetime (15.74 ± 6.08 vs 13.16 ± 5.74; p = 0.005) and past (15.75 ± 6.01 vs 13.33 ± 5.80; p = 0.009) FRS were the main clusters dichotomizing ASI. The average ASI score did not significantly differ among patients with different diagnoses. CONCLUSIONS: ASI could be used as a tool to identify psychopathological dimensions, rather than the categorical diagnoses, in the schizophrenic spectrum.

Myocardial phenotypes and dysfunction in HFpEF and HFrEF assessed by echocardiography and cardiac magnetic resonance.

Heart failure (HF) with either reduced or preserved ejection fraction is an increasingly prevalent condition. Cardiac imaging plays a central role in trying to identify the underlying cause of the underlying systolic and diastolic dysfunction, as the imaging findings have implications for patient's management and individualised treatment. The imaging modalities used more frequently in patients with heart failure in clinical routine are echocardiography and cardiac magnetic resonance. Both techniques keep some strengths and weakness due to their spatial and temporal resolution. Notably, several features in the diagnostic algorithm of heart failure with preserved systolic function (HFpEF) may be improved by an integrated approach. This review focuses on the role of each modality in characterising cardiac anatomy, systolic and diastolic function as well as myocardial tissue characterisation in the most common phenotypes of dilated and hypertrophied hearts.

A systematic review on mediators between adversity and psychosis: potential targets for treatment.

Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as 'fair'. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure).

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

Acute Modifications of Left Ventricular Torsional Mechanics Induced by Cardiac Resynchronization Therapy Affect Short-Term Reverse Remodeling.

BACKGROUND: Left ventricular (LV) torsion is an important aspect of cardiac mechanics and is altered in heart failure patients. Cardiac resynchronization therapy (CRT) has a positive effect on LV function, but the exact mechanisms through which it works are not completely depicted. Our aim was to investigate (1) the acute CRT effect on LV torsional mechanics in heart failure patients using 3D speckle tracking echocardiography (3DSTE) and (2) its effect on short-term LV remodeling. Methods and Results: We considered 48 patients (age 72±11 years, 35 men) who received CRT. They underwent 3DSTE during CRT-on (biventricular stimulation) vs. CRT-off (intrinsic conduction/right atrial/ventricular stimulation alone), in a random fashion. Patients were classified as CRT responders based on LV systolic volume reduction ≥15% at 6 months (final population: 31 responders, 17 non-responders). Acute CRT positively affected responders in terms of LV torsion (from 0.32±0.06°/cm CRT-off to 0.41±0.06°/cm CRT-on), but adversely affected non-responders (from 0.54±0.08°/cm CRT-off to 0.28±0.08°/cm CRT-on, interaction P=0.02). A similar trend was confirmed for apical (interaction P<0.04), but not for basal torsion (interaction P=0.351). CONCLUSIONS: CRT has a positive role in acute recovery of LV torsion (particularly in its apical component) in responders, likely modulating the improvement in LV remodeling at early follow-up.

Impact of adenosine A2a receptor polymorphism rs5751876 on platelet reactivity in ticagrelor treated patients.

Dual antiplatelet therapy constitutes a key point in the management of patients with acute coronary syndromes. In particular, ticagrelor, an ADP-antagonist, can provide a more potent and predictable platelet inhibition as compared to clopidogrel, and adenosine-mediated pathways have been involved in its beneficial effects on mortality and myocardial perfusion. However, a quote of patients still displays a suboptimal platelet inhibition on ticagrelor, and, while the role of genetics in conditioning clopidogrel resistance is well established, few data have been reported for ticagrelor. We investigated the impact of rs5751876 C > T polymorphism of adenosine A2a receptor (ADORA2a) on platelet reactivity in patients during chronic treatment with ticagrelor. We included patients treated with ASA and ticagrelor for a recent ACS or elective coronary revascularization. Platelet reactivity was assessed at 30-90 days post-discharge by multiple-electrode aggregometry. HRPR for ticagrelor was defined as ADP-test results >417 AU*min. Genetic analysis was performed to assess the presence of rs5751876 C > T polymorphism of ADORA2a receptor. We included 244 patients in our study, 174 (71.3%) patients carried the polymorphism (T allele), 51 (20.9%) of them in homozygosis (T/T). C-allele carriers (homozygotes C/C and heterozygotes C/T) showed no difference in baseline characteristics but for lower HDL-cholesterol (p = 0.01). An absolute lower rate of HRPR on ticagrelor was observed in homozygotes T/T (p = 0.03). At multivariate analysis, C allele carriage was independently associated with the rate of HRPR on ticagrelor (adjusted OR[95%CI] = 4.63[1.02-21.01], p = 0.048). Our study results showed a significant independent association between rs5751876 allele C carriage and a higher rate of high residual platelet reactivity in patients on ticagrelor after a recent ACS or PCI.

Feasibility of cathodic-anodal left ventricular stimulation for alternative multisite pacing.

BACKGROUND: Simultaneous cathodic-anodal capture by a bipole of a cardiac resynchronization therapy (CRT) left-ventricular (LV) catheter may depolarize a larger LV area than conventional multipoint pacing. We evaluated the feasibility of cathodic-anodal LV stimulation. METHODS: In 30 patients undergoing CRT with a quadripolar LV lead, we evaluated the cathodic and anodal capture threshold for each LV pole and compared QRS on electrocardiogram (ECG) during single-point cathodic biventricular stimulation (S-BS), multipoint BS (M-BS), and cathodic-anodal BS (CA-BS). RESULTS: Anodal capture was obtained by three poles in 23/30 patients, by two poles in five, and was not feasible in two. The mean single-point anodal threshold was 3.93 V versus single-point cathodic threshold of 1.95 V. On comparing ECGs, M-BS and CA-BS produced similar QRS wavefront activation in 90% of patients. CONCLUSIONS: CA-BS is feasible and may be used in LV pacing to achieve a different wavefront of electrical activation. Further prospective studies are needed in order to verify the clinical impact of this kind of stimulation.

Occurrence of simultaneous cathodal-anodal capture with left ventricular quadripolar leads for cardiac resynchronization therapy: an electrocardiogram evaluation.

AIMS: The occurrence of left ventricular (LV) anodal activation during pacing with modern multipolar cardiac resynchronization therapy (CRT) systems has never been reported. The aim of our study was to demonstrate, by means of electrocardiogram (ECG) analysis, the occurrence of simultaneous cathodal-anodal LV capture with quadripolar LV leads. METHODS AND RESULTS: We studied 10 first-time recipients of a CRT device equipped with a quadripolar LV lead. During follow-up, standard supine 12-lead ECGs were obtained in available cathode-to-anode LV pacing configurations with a pulse amplitude equal to twice the pacing threshold. The occurrence of simultaneous cathodal-anodal LV capture was defined as the presence of variations in electrocardiographic ventricular activation (EVA) when the distal tip (cathode)-to-device can (anode) pacing configuration was compared with the distal tip (cathode)-to-proximal ring (anode) configuration. In eight patients, we found differences in EVA when different LV sites were paced through the unipolar LV tip and unipolar LV ring configurations. In these patients, a difference in EVA was detected in 61.5% (59 of 96) of the ECG leads (marked difference in 31.3%, slight difference in 30.2%). Changes in EVA between unipolar tip-to-can and bipolar tip-to-ring pacing that were suggestive of cathodal-anodal LV capture were found in six patients. In these patients, a total of 30 (41.7%) ECG leads showed a difference in EVA (marked difference in 20.8%, slight difference in 20.8%). CONCLUSION: In our experience, additional anodal capture by the proximal LV ring during LV pacing is provable in most recipients of a resynchronization device equipped with a multipolar LV lead.

Persistence of ICD indication at the time of replacement in patients with initial implant for primary prevention indication: Effect on subsequent ICD therapies.

BACKGROUND: Indication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR. METHODS: We identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR. RESULTS: At the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01-1.96; p = 0.041). CONCLUSION: In heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null.

Indications and immediate and long-term results of a novel pericardium covered stent graft: Consecutive 5 year single center experience.

BACKGROUND: The use of covered stent grafts during percutaneous coronary intervention (PCI) is a life saving solution to seal acute iatrogenic vessel rupture. However, the presence of an impenetrable mechanical barrier is also appealing during treatment of friable coronary plaques but the synthetic PTFE-membrane that might trigger excessive neointimal proliferation has limited its elective-use. Pericardium tissue may offer an appealing "natural" alternative. Aim of our study is to report the consecutive 5-year single center experience with the use of pericardium-covered stents (PCS) (ITGI-Medical, Israel) in a variety of emergency and elective applications. METHODS: Nineteen consecutive patients undergoing implantation of PCS at the Royal Brompton in the last 5-years. Reasons for PCS implantation included treatment of degenerated vein grafts, large coronary aneurysms, and acute iatrogenic vessel rupture. RESULTS: Angiographic success, defined as the ability of the device to be deployed in the indexed lesion with no contrast extravasation with residual angiographic stenosis <30% and a final thrombolysis in myocardial infarction (TIMI)-3 flow was achieved in all cases. Procedural success, defined as the achievement of angiographic success without any major adverse cardiovascular event (MACE) was achieved in 94.7% of patients. In-stent restenosis (ISR) was observed in 26.3% and all patients underwent successful target vessel revascularization with DES (mean time to restenosis 9.0 ± 4.0 months). At a mean follow-up of 32.5 ± 23.3 months no acute or late stent thrombosis was observed. CONCLUSION: PCSs were effective in the treatment of friable embolization-prone coronary plaques, sealing of acute iatrogenic vessel rupture and exclusion of large aneurysms with no thrombosis but high target lesion revascularization.

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy.

BACKGROUND: Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists). RESULTS: We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17-4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20-11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52-1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59-1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62-2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63-2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99-5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28-2.29], p = 0.68). CONCLUSION: In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.

Immature platelet fraction and high-on treatment platelet reactivity with ticagrelor in patients with acute coronary syndromes.

Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; ≥4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.

Impact of diabetes on immature platelets fraction and its relationship with platelet reactivity in patients receiving dual antiplatelet therapy.

Contrasting data have been reported so far on the role of reticulated platelets in suboptimal response to antiplatelet therapies. In particular, still unexplored is whether they may contribute to explain the higher risk of thrombotic complications observed in diabetic patients. Aim of the present study was to evaluate the impact of diabetes on the levels of reticulated platelets and its relationship with high residual on-treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy. In patients treated with ASA (100-160 mg) and clopidogrel (75 mg daily) or ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days post-discharge for an acute coronary syndrome or elective PCI. Aggregation was assessed by multiple-electrode aggregometry. We included 386 patients, 158 (40.9 %) diabetics. The percentage of IPF was similar in diabetic and non diabetic patients, both at baseline (3.5 ± 2.5 vs 3.6 ± 2.7 %, p = 0.91) and at 30-90 days re-assessment (3.3 ± 2.1 vs 3.5 ± 2.5 %, p = 0.30), with diabetes not emerging as an independent predictor of IPF above III tertile (adjusted OR [95 %CI] = 0.58 [0.30-1.09], p = 0.10). Diabetic patients displayed an enhanced platelet reactivity and a higher rate of HRPR with ADP antagonists (32.8 vs 22.5 %, p = 0.009). However, no association was found between the percentage of IPF and platelet function (r = -0.004; p = 0.95 for ASPI test, r = -0.04; p = 0.59 for ADP-mediated aggregation), or the rate of HRPR for ADP antagonsist across IPF tertiles. Results were similar for diabetics both receiving clopidogrel and ticagrelor. Diabetic patients display a higher platelet reactivity and suboptimal response to ADP-antagonists. However, the rate of reticulated platelets is neither influenced by diabetic status nor associated with an increased platelet reactivity among diabetic patients receiving dual antiplatelet therapy for a recent acute coronary syndrome or PCI.

Vitamin D levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

BACKGROUND: Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCIs). However, very few are known so far on the predictors of high-residual platelet reactivity (HRPR) despite antiplatelet strategies. Increasing attention has been paid in the last years to the role of vitamin D in atherothrombosis. Therefore, the aim of our study was to evaluate the impact of vitamin D levels on platelet function in patients treated with dual antiplatelet therapy (DAPT). Patients treated with DAPT (ASA and clopidogrel or ticagrelor) after a recent acute coronary syndrome (ACS) or elective PCI were scheduled for platelet function assessment at 30-90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®-Roche Diagnostics AG), HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values ≥417 AU*min (for ADP-antagonists). Fasting samples were obtained for main chemistry parameters and vitamin D level assessment. Our population is represented by 503 patients, who were divided according to vitamin D quartiles (≤9.1; 9.2-14.4; 14.5-21.7; >21.7 ng/ml). Lower vitamin D levels related with age (p = 0.04), diabetic status (p = 0.05), and previous coronary surgery (p = 0.007), therapy with beta-blockers and statins (p = 0.01 and p = 0.02). Vitamin D inversely related to the levels of total cholesterol (p = 0.01), triglycerides (p < 0.001), hemoglobin (p = 0.05), and HbA1c (p < 0.001). Significantly higher platelet reactivity was observed after platelet stimulation with ADP (p = 0.01), but not with other platelet activators. The prevalence of HRPR for ASA was low (1.2%) and not conditioned by Vitamin D levels (adjusted OR[95%CI] = 1.56[0.71-3.5], p = 0.27). HRPR with ADP-antagonists was observed in 26% of patients, and the rate increased with lower vitamin D quartiles (37.3% vs 22.2% vs 24.4% vs 20.2%, p = 0.005, adjusted OR[95%CI] = 1.23[1.02-1.49], p = 0.04). An absolute increase in HRPR with lower vitamin D levels was similarly observed among patients receiving ticagrelor (adjusted OR[95% CI] = 1.40[0.95-2.06], p = 0.08), and those on clopidogrel (adjusted OR[95%CI] = 1.31[0.99-1.75], p = 0.06). Thus, lower vitamin D levels are associated with higher platelet reactivity and impaired effectiveness of ADP-antagonists, while not influencing the effectiveness of ASA. Future studies will tell whether vitamin D supplementation can reduce platelet reactivity, overcoming the phenomenon of resistance to antiplatelet agents.

Echocardiographically Derived Pulse Wave Velocity and Diastolic Dysfunction Are Associated with an Increased Incidence of Atrial Fibrillation in Patients with Systolic Heart Failure.

BACKGROUND: Chronic heart failure (CHF) is an established risk factor of atrial fibrillation (AF), but the prognostic value of cardiac and hemodynamic parameters in assessing the risk of developing AF among patients with CHF is less defined. METHODS AND RESULTS: We followed an outpatients cohort of CHF patients secondary to left ventricular (LV) systolic dysfunction, who were free of AF at baseline. All patients underwent clinical evaluation, comprehensive echocardiography, and blood drawing in the same morning. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was determined by Doppler echocardiography. A total of 77 patients (age 63 ± 9 years; 79% male) with mean LVEF (34 ± 8%) formed the study population. Fifteen patients developed incidental AF. At baseline, CHF patients who developed AF during follow-up had higher E-wave velocity (75 ± 2 cm/sec vs. 60 ± 2 cm/sec; P = 0.02), higher difference duration between mitral and pulmonary vein A velocity (A'-A), (10 ± 35 msec vs. 43 ± 44 msec P = 0.02), aPWV (7.1 ± 2.6 vs. 5.3 ± 1.9 m/sec P = 0.004), and furosemide dosage (110 ± 145 mg vs. 49 ± 48 mg P = 0.01) than those remaining free from AF. The two groups of patients did not significantly differ in terms of NYHA, LV volumes, ejection fraction, left atrial volume, creatinine, hemoglobin, renin, epinephrine, amino-terminal propeptide of type III and I procollagens, ACE inhibitor, and ß-blocker dose (P > 0.1 for all). Notably, higher aPWV (P = 0.01) and longer A-A' duration (P = 0.04) were associated with an increased incidence of AF, independently of potential confounders. CONCLUSIONS: Increased aortic stiffness and LV diastolic dysfunction are strong predictors of new onset of AF among patients with systolic CHF.

Effect of diabetes mellitus on periprocedural myocardial infarction in patients undergoing coronary stent implantation.

BACKGROUND: Diabetic patients undergoing percutaneous coronary interventions are still regarded as a very high risk category because of an increased platelet reactivity and risk of complications, especially in patients with inadequate glycaemic control. However, although its prognostic effect on long-term outcome is well-defined, still unclear is the effect of diabetes on the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions, which was therefore the aim of our study. METHODS: Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous coronary interventions. Periprocedural myocardial infarction was defined as creatine kinase-MB increase by three times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as troponin I increase by three times the upper limit normal or 50% of baseline. RESULTS: Of 1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated with age (p = 0.03), hypertension (p < 0.001), renal failure (p = 0.01), previous MI (p = 0.03), previous coronary revascularization (p < 0.001), higher fasting glycaemia and lower haemoglobin (p < 0.001), more severe coronary disease (p < 0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary calcification (p = 0.003) and in-stent restenosis (p < 0.001) but lower presence of thrombus (p = 0.03). Diabetic patients were receiving significantly more frequent specific pharmacological treatment at admission. Diabetic status did not influence the risk of periprocedural myocardial infarction or periprocedural myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not observe any effect of chronic glycaemic control on periprocedural myocardial infarction. CONCLUSIONS: Diabetic status, independent of chronic glycaemic control, is not associated with increased risk of periprocedural myocardial infarction and myonecrosis in patients undergoing percutaneous coronary interventions.

Body Mass Index and Platelet Reactivity During Dual Antiplatelet Therapy With Clopidogrel or Ticagrelor.

INTRODUCTION: Dual antiplatelet therapy (DAPT) is considered essential in clinical management of patients undergoing percutaneous coronary revascularization or acute coronary syndromes. However, the optimal platelet inhibition is not always obtained, with high residual platelet reactivity (HRPR) increasing stent thrombosis and recurrent ischemic events. Aim of this study was to investigate the impact of body mass index (BMI) on platelet reactivity in patients on DAPT. METHODS: We included patients treated with acetylsalycilic acid (ASA) (100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day) for acute coronary syndromes or drug-eluting stent implantation. Platelet reactivity was assessed at 30-90 days postdischarge by multiple-electrode aggregometry. HRPR for adenosine diphosphate (ADP) antagonists was defined as ADP test results >417 AU*min. HRPR for ASA was considered for ASPI test >862 AU*min. RESULTS: Our population is represented by 498 patients, 308 (61.8%) were treated with clopidogrel and 190 (38.2%) with ticagrelor. Overall, higher BMI was related with younger age (P = 0.003), higher prevalence of diabetes mellitus (P < 0.001), hypercholesterolemia (P = 0.017), hypertension (P < 0.001), chronic therapy with angiotensin-receptor blockers (P = 0.019), calcium channel blockers (P = 0.003). Higher values of BMI directly related with hemoglobin (P = 0.02), triglycerides (P < 0.001), glycemia (P = 0.035), HbA1c (P < 0.001), and inversely related with high-density lipoprotein cholesterol (P = 0.01). BMI did not influence the effectiveness of ASA, whereas it was associated to a nonsignificant trend for higher platelet reactivity (r = 0.08, P = 0.08) for ADP antagonists. In fact, 111 patients (22.3%) displayed HRPR at ADP test (>417 AU*min) with no statistically significant difference according to BMI {20.3% vs. 27.1% vs. 25.7%, P = 0.28; adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.19 [0.86-1.64], P = 0.30}. However, results were different when considering separately patients receiving clopidogrel or ticagrelor. In the clopidogrel-treated subgroup, significantly higher ADP-mediated aggregation values were found in patients with higher BMI (r = 0.14, P = 0.023) that emerged as an independent predictor of HRPR with clopidogrel [OR (95% CI), 1.45 (1.01-2.12), P = 0.049]. On the contrary, no impact of BMI was observed in the ticagrelor-treated subgroup for platelet reactivity (r = -0.036, P = 0.62) or the prevalence of HRPR [adjusted OR (95% CI), 0.73 (0.39-1.36), P = 0.32]. CONCLUSIONS: This study shows that among patients treated with DAPT for coronary artery disease, higher BMI is related to increased platelet reactivity and a higher prevalence of HRPR in clopidogrel-treated patients while not significantly influencing the effectiveness of ticagrelor or ASA.

Homocysteine Levels Influence Platelet Reactivity in Coronary Artery Disease Patients Treated With Acetylsalicylic Acid.

BACKGROUND: Suboptimal platelet inhibition with antiplatelet treatments is associated with a severe prognosis in patients with coronary artery disease (CAD), and the identification of its determinants is still challenging. Homocysteine elevation has emerged as a prothrombotic factor, influencing coagulative status and endothelial function and potentially modulating platelet aggregation. We therefore aimed to evaluate the effects of homocysteine (Hcy) levels on platelet reactivity in patients receiving acetylsalicylic acid (ASA) with or without ADP antagonists. METHODS: Patients undergoing coronary angiography and receiving ASA (100-160 mg daily) for >7 days, with or without ADP antagonists, were included. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition was defined as on-treatment aggregation above the lower limit of normality. RESULTS: Our population is represented by 508 ASA-treated patients, 406 (80.1%) of whom on dual antiplatelet therapy (ASA and ADP antagonists). Hcy levels above the median (15.1 nmol/mL) were associated with male gender (P = 0.04), hypertension (P = 0.004), hypercholesterolemia (P = 0.03), aging, renal failure (P < 0.001, respectively), previous coronary bypass grafting (P = 0.04), therapy with calcium antagonists (P = 0.04) and diuretics (P = 0.001), and multivessel CAD (P = 0.03). Higher Hcy is directly related with serum creatinine and uric acid (P < 0.001). Suboptimal platelet inhibition was found in 16 patients (3.2%) for ASA and for ADP antagonists in 80 patients (19.7%). Hcy levels significantly affected suboptimal response to ASA, but not to ADP-mediated aggregation. In fact, a linear relationship was found between homocysteine and platelet reactivity after stimulation with arachidonic acid (r = 0.14, P = 0.004) and collagen (r = 0.12, P = 0.02), but not with ADP (r = 0.02, P = 0.77). Moreover, after correction for baseline differences, Hcy above the median was confirmed as an independent predictor of impaired ASA response [adjusted odds ratio (95% confidence interval) = 3.7 (1.08-12.4), P = 0.04]. CONCLUSIONS: Among patients with CAD, elevated homocysteine is an independent predictor of suboptimal response to ASA, but not to ADP antagonists.

Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual Antiplatelet Therapy.

BACKGROUND: Low response to antiplatelet agents has been associated to an increased risk of thrombotic complications and recurrent ischemic events. Platelet size has been proposed as a potential marker of platelet reactivity. Therefore, the aim of the present study was to evaluate the impact of platelet Larger Cell Ratio (p-LCR) on platelet aggregation and the prevalence of residual high-on treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy (DAPT) after a recent acute coronary syndrome or coronary revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. HRPR was considered for ASPI test >862 AU*min (for ASA) or ADP test values ≥417 AU*min (for ADP-antagonists) using impedance aggregometry. RESULTS: Our population consisted of 530 patients receiving DAPT, who were divided in tertiles according to values of p-LCR (< 27.6; 27.6-34.7; ≥34.7 l). p-LCR was related with use of beta-blockers (p = 0.02) and statins (p = 0.002), and inversely with acute presentation (p = 0.05). Higher platelet count (p < 0.001) and haemoglobin levels (p = 0.001) were observed in higher p-LCR tertiles. The prevalence of HRPR for ASA was low and not significantly different across tertiles of p-LCR (1.1 vs 1.1 vs 1.7%, p = 0.66; adjusted OR[95%CI] = 1.68[0.66-4.29], p = 0.27). Moreover, p-LCR did not influence the occurrence of HRPR for ADP-antagonists (24.4% vs 20.9% vs 25.6 %%, p = 0.80, adjusted OR[95%CI] = 0.88[0.67-1.17], p = 0.38) and similar results were obtained when considering separately patients receiving clopidogrel (adjusted OR[95%CI] = 1.21[0.86-1.69], p = 0.29) or ticagrelor (adjusted OR[95%CI] = 1.17[0.69-2], p = 0.56). CONCLUSION: In patients receiving DAPT for coronary artery disease, p-LCR does not impact platelet reactivity. Larger platelets did not influence the prevalence of high-on treatment platelet reactivity with the antiplatelet agents ASA, clopidogrel or ticagrelor.

Absolute eosinophils count and the extent of coronary artery disease: a single centre cohort study.

Leukocytes have been involved in the pathogenesis of atherosclerosis, and recent attention has been raised on eosinophils, that have been claimed for a wide number of cardiovascular pathologies, affecting endocardium, myocardium and vascular walls. However, few data have been reported so far on the relationship between absolute eosinophils count (AEC) and the prevalence and extent of coronary artery disease (CAD), that was the aim of present study. Consecutive patients undergoing non-urgent coronary angiography were included. Haematological parameters were measured at admission. Significant CAD was defined as at least 1 vessel stenosis >50 %, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Our population is represented by 3,742 patients, divided according to tertiles values of AEC (≤0.1; 0.1-0.2; >0.2 × 10(3)/µl). Higher eosinophils values were significantly associated to male gender, main established cardiovascular risk factors, previous percutaneous or surgical coronary revascularization, antihypertensive and antiplatelet therapy at admission but inversely with acute presentation. Higher AEC was directly related with platelets count (p < 0.001), haemoglobin levels (p = 0.02), white blood cells count (p = 0.02), higher serum creatinine (p < 0.001), triglycerides (p < 0.001) and glycosylated haemoglobin (p < 0.001), while inversely with HDL cholesterol (p < 0.001). AEC was associated with multivessel disease (p = 0.03), chronic occlusions (p = 0.01), in-stent restenosis (p = 0.002), while inversely with the presence of intracoronary thrombus (p < 0.001). A significant relationship was found between AEC and the prevalence of coronary artery disease (p = 0.049), but not for the extent of more severe LM/trivessel CAD (p = 0.31). At multivariate analysis no independent role of eosinophils was found for CAD (adjusted OR [95 % CI] = 1.02 [0.91-1.15], p = 0.70), or severe CAD (adjusted OR [95 % CI] = 0.99 [0.89-1.1], p = 0.9), even when considering separately acute and elective patients. In conclusion, among patients undergoing coronary angiography, higher eosinophils levels are not independently associated with the prevalence and extent of coronary artery disease, but appear confounded by their link with major cardiovascular risk factors.