D-dimer for risk stratification and antithrombotic treatment management in acute coronary syndrome patients: asystematic review and metanalysis

Background: Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-dimer and no-reflow phenomenon.Methods: Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality.Results: Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-dimer levels with CVEs. D-dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134-1.409). Five out of 7 studies (4195 STEMI patients) investigating the association between D-dimer levels and no-reflow showed a positive correlation of D-dimer levels with no-reflow.Conclusions: In patients with ACS, D-dimer was associated with higher in-hospital and short/long-term complications. D-dimer was also higher in patients with no-reflow phenomenon. The use of D-dimer may help to identify patients with residual thrombotic risk after ACS

Acute atrial ischemia associates with early but not late new-onset atrial fibrillation in STEMI patients treated with primary PCI: relationship with in-hospital outcomes

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf N/A Background. New-onset atrial fibrillation (NOAF) is known to be a common complication in STEMI patients undergoing primary percutaneous coronary intervention (PCI), which is associated with a negative short- and long-term prognosis. Recently, two distinct phenotypes of NOAF have been described, namely early (EAF) and late NOAF (LAF). However, whether EAF and LAF recognize different pathogenetic mechanisms is unknown. Purpose. To investigate atrial branches occlusion and EAF or LAF onset in STEMI patients undergoing primary PCI. Methods. Retrospective cohort study including 155 STEMI patients. Patients were divided into 3 groups: sinus rhythm (SR), EAF or LAF. Clinical characteristics, angiographic features including occlusion of atrial branches, namely ramus ostia cavae superioris (ROCS), atrio-ventricular node artery (AVNA), right intermediate atrial artery (RIAA) and left intermediate atrial artery (LIAA), were assessed. We also investigated in-hospital complications, death, and a composite of major post-NOAF adverse events (AEs) including cardiogenic shock, acute pulmonary edema, sustained ventricular tachycardia and ventricular fibrillation. Results. Mean age was 63.8 ± 11.9 years; 78.7% of men. NOAF was detected in 22 (14.2%) patients: 10 (6.4%) EAF and 12 LAF (7.7%). Compared to EAF, LAF patients were older (p = 0.013), with higher GRACE risk score (p = 0.014) and Killip class (p = 0.015), depressed ejection fraction (p = 0.007), elevated filling pressures (p = 0.029), higher c-reactive protein (p = 0.014) and more TIMI flow <3 (p = 0.015). As shown in Figure 1, EAF was associated with higher prevalence of occluded ROCS (p = 0.010), AVNA (p = 0.005) and RIAA (p < 0.001), compared to SR. Moreover, EAF patients had more frequently ≥2 diseased atrial branches than SR (19.5%, p < 0.001) and LAF (25%, p < 0.030) patients. In LAF patients, a higher incidence of pre-PCI cardiogenic shock, post-PCI AEs (p = 0.019 vs SR; p = 0.029 vs EAF) and death (p = 0.004 vs SR) was found. Conclusions. The occlusion of atrial branches is associated with early but not late NOAF following STEMI. LAF patients had worse in-hospital AEs and mortality. Abstract Figure

A pilot study on the H-1-NMR serum metabolic profile of Takotsubo patients reveals systemic response to oxidative stress

Takotsubo syndrome (TTS) presents as an acute coronary syndrome characterized by severe left ventricular (LV) dysfunction and non-obstructive coronary artery disease that typically shows spontaneous recovery within days or weeks. The mechanisms behind TTS are mainly related to beta-adrenergic overstimulation and acute endogenous catecholamine surge, both of which could increase oxidative status that may induce further deterioration of cardiac function. Although several studies reported evidence of inflammation and oxidative stress overload in myocardial tissue of TTS models, systemic biochemical evidence of augmented oxidant activity in patients with TTS is lacking. In this study, serum samples of ten TTS patients and ten controls have been analyzed using H-1-NMR spectroscopy. The results of this pilot study show a marked alteration in the systemic metabolic profile of TTS patients, mainly characterized by significant elevation of ketone bodies, 2-hydroxybutyrate, acetyl-L-carnitine, and glutamate levels, in contrast with a decrease of several amino acid levels. The overall metabolic fingerprint reflects a systemic response to oxidative stress caused by the stressor that triggered the syndrome's onset

Relationship between non-invasively detected liver fibrosis and in-hospital outcomes in patients with acute coronary syndrome undergoing PCI

Background Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) still experience a high rate of in-hospital complications. Liver fibrosis (LF) is a risk factor for mortality in the general population. We investigated whether the presence of LF detected by the validated fibrosis 4 (FIB-4) score may indicate ACS patients at higher risk of poor outcome.Methods In the prospective ongoing REAl-world observationaL rEgistry of Acute Coronary Syndrome (REALE-ACS), LF was defined by a FIB-4 score> 3.25. We repeated the analysis using an APRI score> 0.7. The primary endpoint was in-hospital adverse events (AEs) including a composite of in-hospital cardiogenic shock, PEA/asystole, acute pulmonary edema and death.Results A total of 469 consecutive ACS consecutive patients were enrolled. Overall, 21.1% of patients had a FIB-4 score> 3.25. Patients with LF were older, less frequently on P2Y12 inhibitors (p = 0.021) and admitted with higher serum levels of white blood cells (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001), C-reactive protein (p = 0.013), hs-TnT (p < 0.001), creatine-kinase MB (p < 0.001), D-Dimer levels (p < 0.001). STEMI presentation and higher Killip class/GRACE score were more common in the LF group (p < 0.001). 71 patients experienced 110 AEs. At the multivariate analysis including clinical and laboratory risk factors, FIB-4> 3.25 (OR 3.1, 95%CI 1.4-6.9), admission left ventricular ejection fraction% below median (OR 9.2, 95%CI 3.9-21.7) and Killip class >= II (OR 6.3, 95%CI 2.2-18.4) were the strongest independent predictors of in-hospital AEs. Similar results were obtained using the APRI score.Conclusion LF detected by FIB-4 score> 3.25 was associated with more severe ACS presentation and worse in-hospital AEs irrespective of clinical and laboratory variables.[GRAPHICS]

Relation of atrial fibrillation to angiographic characteristics and coronary artery disease severity in patients undergoing percutaneous coronary intervention

Patients with atrial fibrillation (AF) have an increased risk of coronary artery disease (CAD) compared to patients without. Angiographic characteristics, clinical presentation and severity of CAD according to the presence of AF have been poorly described. We performed a retrospective study of 303 consecutive patients (mean age 69.6 ± 10.8 years; 23.1% women) with and without AF undergoing percutaneous coronary intervention. Data on (1) type of CAD presentation, (2) coronary involvement, and (3) number of diseased coronary vessels (≥70%/luminal narrowing) were collected. CHA2DS2-VASc and 2 major adverse cardiac event (MACE) scores were calculated. Presentation of CAD was ST-segment elevation myocardial infarction (STEMI) in 37.6% of patients, non–STEMI- unstable angina in 55.1%, and other in 7.3%. Non–STEMI-unstable angina was more common in AF (69.6% vs 46.6%, p <0.001), while STEMI was more in the non-AF (22.3% vs 46.6%, p <0.001) group. Left anterior descending artery (LAD) was the most common diseased vessel (70.6%) followed by right coronary artery (RCA, 56.4%) and obtuse marginal artery (36.6%). Patients with AF had a significantly lower RCA involvement (47.3% vs 61.8%, p = 0.016), with a trend for LAD (64.3% vs 74.3%, p = 0.069). At multivariable logistic regression analysis, AF remained inversely associated with RCA involvement (odds ratio [OR] 0.541, 95% confidence interval [CI] 0.335 to 0.874, p = 0.012) and with ≥3 vessel CAD (OR 0.470, 95% CI 0.272 to 0.810, p = 0.007). The 2MACE score was associated with diseased LAD (OR 1.301, 95% CI 1.103 to 1.535, p = 0.002) and with ≥3 vessel CAD (OR 1.330, 95% CI 1.330 to 1.140, p <0.001). In conclusion, patients with AF show lower RCA involvement and generally less severe CAD compared to non-AF ones. The 2MACE score was higher in LAD obstruction and identified patients with severe CAD

Mediterranean diet: a tool to break the relationship of atrial fibrillation with the metabolic syndrome and non-alcoholic fatty liver disease

Atrial fibrillation (AF) is the most common supraventricular arrhythmia associated with increased cardiovascular and non-cardiovascular morbidity and mortality. As multiple factors may predispose the onset of AF, the prevention of the occurrence, recurrence and complications of this arrhythmia is still challenging. In particular, a high prevalence of cardio-metabolic comorbidities such as the metabolic syndrome (MetS) and in its hepatic manifestation, the non-alcoholic fatty liver disease (NAFLD), have been described in the AF population. A common pathogenetic mechanism linking AF, MetS and NAFLD is represented by oxidative stress. For this reason, in the past decades, numerous studies have investigated the effect of different foods/nutrients with antioxidant properties for the prevention of, and their therapeutic role is still unclear. In this narrative comprehensive review, we will summarize current evidence on (1) the association between AF, MetS and NAFLD (2) the antioxidant role of Mediterranean Diet and its components for the prevention of AF and (3) the effects of Mediterranean Diet on MetS components and NAFLD

Clinical frailty and triggers in Takotsubo syndrome: The notable role of a new classification

AimsTakotsubo syndrome (TTS) is a mainly transient and acute heart failure mimicking an acute coronary syndrome. Originally described in postmenopausal women, over time TTS has been associated with an increasingly advanced age. Emotional and physical triggers precipitating TTS have been correlated in most cases. The aim of our work was to detect differences between patients with or without recognizable triggers preceding the onset of symptoms.MethodsWe enrolled 22 consecutive patients. They were all women with an average age of 71 ± 12 (range 40-90) years. Twelve patients correlated the onset of TTS symptoms with a trigger (group 1) and 10 patients (group 2) denied any correlation with stressful events.ResultsPatients in group 1 showed a higher average age than group 2 (76 ± 10 vs. 64 ± 12 years; P = 0.023), a longer hospitalization period (22 ± 12 vs. 11 ± 10 days; P = 0.01) and greater value of frailty score (P = 0.004). Despite a decrease and subsequent recovery of systolic function, there was no significant difference between groups. Group 1 showed a longer corrected QT (QTc) (505 ± 53 vs. 453 ± 42 ms, P = 0.03), a greater decrease in QTc at discharge (-57 ± 44 vs. 0.3 ± 39 ms; P = 0.004), with the result that at discharge both groups showed a comparable QTc.ConclusionOur results emphasized that typical TTS female patients with precipitating triggers have advanced age, clinical frailty and QTc abnormalities

Acute atrial ischemia associates with early but not late new-onset atrial fibrillation in STEMI patients treated with primary PCI: relationship with in-hospital outcomes

Background: New-onset atrial fibrillation (NOAF), both early (EAF) or late (LAF), may complicate ST-segment elevation myocardial infarction (STEMI). The mechanisms underlying EAF or LAF are poorly described. We investigated atrial branch occlusion and EAF or LAF onset in STEMI patients undergoing primary percutaneous coronary intervention. Methods: This was a retrospective cohort study including 155 STEMI patients. Patients were divided into 3 groups: sinus rhythm (SR), EAF, or LAF. Clinical characteristics, angiographic features including occlusion of atrial branches, namely ramus ostia cavae superioris (ROCS), atrio-ventricular node artery (AVNA), right intermediate atrial artery (RIAA), and left intermediate atrial artery, were assessed. We also investigated in-hospital adverse events (AEs) and death. Results: Mean age was 63.8±11.9 years; 78.7% were men. NOAF was detected in 22 (14.2%) patients: 10 (6.4%) EAF and 12 LAF (7.7%). Compared to EAF, LAF patients were older (p=0.013), with higher GRACE risk score (p=0.014) and Killip class (p=0.015), depressed ejection fraction (p=0.007), elevated filling pressures (p=0.029), higher C-reactive protein (p=0.014) and more with thrombolysis in myocardial infarction flow <3 (p=0.015). Compared to SR, EAF was associated with higher prevalence of occluded ROCS (p=0.010), AVNA (p=0.005), and RIAA (p<0.001). Moreover, EAF patients had more frequently ≥2 diseased atrial branches than SR (19.5%, p<0.001) and LAF (25%, p<0.030) patients. LAF patients had a higher in-hospital AEs (p=0.019 vs SR; p=0.029 vs EAF) and death (p=0.004 vs SR). Conclusions: The occlusion of atrial branches is associated with EAF but not LAF following STEMI. LAF patients had worse in-hospital AEs and mortality

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes. insights from the CLIMA study

Purpose: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. Methods: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. Results: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p <0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p =0.019), lower macrophage infiltration (p <0.001) and intra-plaque layered tissue (p =0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (>67 degrees) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p =0.018) and a small minimum lumen area (HR 4.97, p =0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180 degrees) was associated with AEs in men (HR 2.56, p =0.003) but not in women. Conclusion: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events — Results from the CLIMA Registry

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2–4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5–5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events. Graphical abstract: [Figure not available: see fulltext.