Lupus anticoagulant and mortality in patients hospitalized for COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by a procoagulant state that can lead to fatal thromboembolic events. Several studies have documented a high prevalence of lupus anticoagulant that may at least partially explain the procoagulant profile of COVID-19. However, the association between lupus anticoagulant and thrombotic complications in COVID-19 is controversial and no study has specifically evaluated the impact of lupus anticoagulant on mortality. The aim of our study was to investigate the association between lupus anticoagulant and mortality in a large group of 192 consecutive patients hospitalized for COVID-19. Lupus anticoagulant was found in 95 patients (49.5%). No difference in the percentage of patients with lupus anticoagulant was observed between 130 survivors and 62 non-survivors (47.7 versus 53,2%; p = 0.4745). When the combined outcome of death or need for mechanical ventilation in survivors was taken into account, the difference in the prevalence of patients with lupus anticoagulant between the patients with the combined outcome (n = 76) and survivors who did not require mechanical ventilation (n = 116) was not significant (52.6% versus 47.4%; p = 0.4806). In multivariate analysis predictors of mortality or need for mechanical ventilation in survivors were obesity, low oxygen saturation and elevated troponin levels measured on admission. In conclusion, our study did not show any association of lupus anticoagulant with mortality and with need for mechanical ventilation in survivors. The role of obesity, low SaO2 and elevated troponin levels as predictors of a worse prognosis in patients hospitalized for COVID-19 was confirmed.

Time course changes of cystatin C and inflammatory and biochemical markers in non-ST-elevation acute coronary syndromes.

BACKGROUND: Serum cystatin C (Cys-C), a good marker of renal function, predicts prognosis in non-ST-elevation acute coronary syndromes (NSTE-ACS). However, no data are available on the time course of Cys-C values after discharge. In this study, Cys-C was measured during admission (ACS sample) and 6 weeks after discharge, and was correlated with troponin (c-TNT), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and the N-terminal portion of the pro-brain natriuretic peptide (proBNP) peptide (NT-proBNP) in a highly selected homogeneous group of NSTE-ACS patients. METHODS: In this prospective, multicentre study, patients with a first NSTE-ACS, single-vessel disease and successful percutaneous coronary interventions (PCIs) had their sera collected, aliquoted and stored at the enrolling site and then shipped for analysis to the clinical chemistry core laboratory. RESULTS: Cys-C values slightly, but significantly, increased from the ACS samples to the 6-week samples. In contrast, hsCRP, NT-proBNP and IL-6 values significantly decreased from the ACS to the 6-week sample. Patients with elevated c-TNT levels had higher hsCRP, NT-proBNP and IL-6 values than patients with normal c-TNT levels in the ACS sample, whereas Cys-C levels were similar in patients with and without elevated c-TNT. Cys-C was highly correlated with estimated glomerular filtration rate in both the ACS and 6-week samples. CONCLUSIONS: In contrast to inflammatory and biochemical stress markers, Cys-C is not affected by the occurrence of myocardial necrosis or by acute left-ventricular impairment, being a reliable marker of renal function during NSTE-ACS.

The bivalirudin paradox: high evidence, low use.

A series of trials have shown that bivalirudin, a direct thrombin inhibitor that does not require the cofactor antithrombin III to be effective, is a reasonable alternative to unfractionated heparin (UFH) alone or associated with glycoprotein IIb/IIIa antagonists (GPI) in patients undergoing percutaneous coronary interventions (PCI). Particularly in patients with acute coronary syndromes (ACS), the effects of bivalirudin are striking. In the HORIZONS-AMI trial, patients with persistent ST-segment elevation (STEMI) had lower 30-day rates of net adverse clinical events and major bleeding, largely due to the significantly lower 30-day rate of non-coronary artery bypass grafting major bleeding. Bivalirudin also resulted in significantly lower rates of all-cause mortality and cardiac mortality, a benefit that extended up to 3-year follow-up. The beneficial effects of bivalirudin as compared to UFH associated with abciximab were also observed in 1721 non-ST elevation myocardial infarction (NSTEMI) patients undergoing PCI in the ISAR REACT 4 study. Although no difference was found between the two treatment strategies in the 30-day primary endpoint, bivalirudin use resulted in a lower rate of major bleeding. Despite the abundant evidence of benefit provided by bivalirudin in the treatment of ACS and the high level of recommendation received by the most recent Guidelines, its use is still low. The reasons for this underuse are multifactorial, the most likely being the preference of operators for the use of a low-cost agent, like UFH, that can be associated with a GPI. Countering platelet hyperreactivity is still the main goal of interventional cardiologists treating ACS patients invasively, apparently downplaying the pathogenetic role of thrombin in this clinical condition.

How to reduce mortality in ST-elevation myocardial infarction patients treated with primary percutaneous coronary interventions: cut the bleeding.

BACKGROUND: In-hospital mortality for ST-elevation myocardial infarction (STEMI) has declined thanks to a greater use of primary percutaneous coronary interventions (PCI) associated with more effective antiplatelet and anticoagulant drugs. In this regard, bivalirudin has been shown to decrease total and cardiac mortality as compared to unfractionated heparin (UFH). OBJECTIVE: The primary purpose of this analysis is to evaluate the hypothesis that the reduction of in-hospital bleeding is the most plausible explanation for the improved survival of STEMI patients treated with bivalirudin during primary PCI. The secondary objective is to reconsider the prognostic significance of the radial access alone or in association with bivalirudin on the basis of the published data. METHODS: We have done a comprehensive evaluation of the main and related publications of the HORIZONS-AMI trial in addition to an extensive research by Medline of randomized trials evaluating the prognostic impact of radial access as compared with the femoral one in primary PCI. RESULTS: In the HORIZONS-AMI trial bivalirudin resulted in significantly lower rates of the 30 day primary endpoint (defined as major adverse ischemic outcomes plus major bleeding) over UFH plus GPI, largely due to the significantly lower rate of the protocol-defined major bleeding. All-cause and cardiac mortality were also reduced in the bivalirudin arm at 3 year follow-up. Recent studies have also shown that the use of the radial instead of the femoral approach for primary PCI is associated with reduced bleeding as well as reduced mortality. CONCLUSIONS: Our research suggests that decreasing bleeding by either a pharmacologic strategy (use of bivalirudin) or a technical approach (the transradial access) improves survival in STEMI patients undergoing primary PCI. The validity of this hypothesis should be confirmed by specific randomized trials.

Efficacy and safety of prasugrel compared with clopidogrel in patients with acute coronary syndromes: results of TRITON-TIMI 38 trials.

Current guidelines recommend dual antiplatelet therapy using aspirin and clopidogrel for non-ST elevation acute coronary syndromes (ACS). Despite the established benefits of this approach, many patients continue to have recurrent atherothrombotic events. Moreover, it is often difficult to achieve an adequate inhibition of platelet aggregation with clopidogrel in clinical practice. Prasugrel is an orally administered P2Y12 receptor antagonist that is more potent, more rapid in onset and more consistent in its inhibition of platelet aggregation than currently approved doses of clopidogrel. The trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel - Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) randomized 13,608 moderate-to-high-risk patients with ACS (with or without ST-segment elevation) undergoing percutaneus coronary intervention to compare prasugrel with clopidogrel for a median of follow-up time of 14.5 months. The TRITON-TIMI 38 trial demonstrated a significant reduction in ischemic events in patients randomized to prasugrel compared with those treated with clopidogrel. This beneficial effect, however, was associated with a significant increase in major bleeding.

Management of splenic abscess: report on 16 cases from a single center.

OBJECTIVES: Splenic abscess is an uncommon disease, with a reported incidence of 0.14-0.7% in autoptic series. The best treatment option remains unclear. We report our experience of percutaneous drainage of splenic abscess under ultrasound (US) guidance. METHODS: From 1979 to 2005, 16 consecutive patients (12 male and four female; mean age 39.9 years, range 16-72 years) were diagnosed with splenic abscess by means of US, and were treated with medical therapy alone or combined with US-guided percutaneous aspiration or catheter drainage. RESULTS: Ten of 16 patients had bacterial abscesses (including one case of tubercular abscess), two had an amebic abscess, and four had fungal abscesses. Seven of ten patients with bacterial abscesses were successfully treated with fine needle aspiration alone, one patient was successfully treated with fine needle aspiration for one abscess and catheter drainage for another, and one patient, who subsequently required a splenectomy for an abdominal trauma, successfully underwent percutaneous catheter drainage alone. Four patients with fungal lesions were treated with medical therapy alone, and two patients later required a splenectomy. One patient with a bacterial abscess due to endocarditis was treated with medical therapy alone, and his recovery was uneventful. CONCLUSIONS: US-guided percutaneous aspiration of splenic abscesses is a safe and effective procedure. It can be used as a bridge to surgery in patients who are critically ill or have several comorbidities. Percutaneous aspiration may allow complete non-operative healing of splenic abscesses or temporize patients at risk for surgery.

[Obesity paradox in patients with coronary artery disease or heart failure]. / Il fenomeno "obesity paradox" nei pazienti con coronaropatia o scompenso cardiaco.

Several studies have shown an inverse relationship between obesity and mortality of patients who survived an acute myocardial infarction or a revascularization procedure, the so-called "obesity paradox". These findings should be considered very cautiously due to several confounding factors, not adequately taken into account by the adjustment models. Similar evidences and considerations have been drawn by studies conducted in patients with acute or chronic heart failure. In these clinical conditions, prospective studies to assess the role of intentional weight loss should be specifically designed.

Significance of total and differential leucocyte count in patients with acute myocardial infarction treated with primary coronary angioplasty.

AIMS: The aim of this study was to correlate total and differential leucocyte (WBC) count with myocardial blush, peak CK levels, and left ventricular (LV) functional recovery at 6 months in 238 consecutive acute myocardial infarction (MI) patients treated with successful primary coronary angioplasty (PCI). METHODS AND RESULTS: Total and differential WBC counts were measured on admission and every 24 h for at least 4 days after PCI. ST-segment resolution and myocardial blush were evaluated immediately after successful primary PCI. LV functional recovery (defined as improvement involving at least two segments, or at least one segment, when only two were asynergic on the basal examination) was obtained through echocardiographic evaluation of LV wall motion at the baseline and at 6 months. Basal CK (P<0.001) and increased neutrophil levels (P<0.001) were the only independent factors related to peak CK, whereas neutrophils and monocytes peaks were related to ST-segment resolution as well as to myocardial blush grade (MBG) 2-3. MBG 2-3 and monocytes number (both as continuous values as well as percentile values) were the only variables independently associated with 6-month LV functional recovery. CONCLUSION: The present study shows that neutrophils and monocytes counts on the first days after acute MI treated with primary PCI are related to markers of effective myocardial reperfusion such as MBG 2-3 and ST-segment resolution. However, only monocytes and MBG are significantly and independently associated with contractile recovery of the infarcted area at 6 months.

C-reactive protein increase in unstable coronary disease cause or effect?

A crucial point in understanding the clinical and pathophysiologic meaning of C-reactive protein (CRP) elevation in acute coronary syndromes (ACS) is whether CRP release is predominantly a response to even small amounts of myocardial necrosis, for which troponin is a sensitive and specific marker, or is an independent indicator of the inflammatory process occurring in that clinical condition. Whereas troponin is a good predictor of both mortality and myocardial infarction (MI), although the highest values are associated with a decreased probability of MI, CRP predicts mortality but has no relation with the early or late occurrence of MI. The large variability of CRP values in ACS may depend on the different response of this inflammation marker to various stimuli, some patients being particularly hyperresponsive, especially those with elevated CRP values at baseline. We hypothesize that myonecrosis, as detected by troponin increases, would represent the strongest stimulus for CRP increase in ACS, causing in some patients, especially those with already-elevated CRP values at baseline, a disproportionate increase of this marker. Accordingly, the highest CRP values during ACS are likely to be observed in patients with already-elevated CRP values at baseline (which would increase the probability of having death and MI in the follow-up) and the highest troponin values (which would increase the probability of death in the follow-up, but not of subsequent MI). This hypothesis would explain why high CRP levels in unstable coronary disease are good predictors of death, but not of MI.

Acute severe coronary spasm associated with initial first dose of 5-fluorouracil chemotherapy.

Among the various pathophysiologic mechanisms proposed to explain the 5-fluorouracil cardiotoxicity, coronary vasospasm, occurring most frequently after the completion of the second or third dose of the cycle, has gained wide acceptance. We describe what to our knowledge is the first observation of typical Prinzmetal variant angina occurring very early after having started a 5-fluorouracil infusion administered as a chemotherapy regimen to a 66-year-old man with an adenocarcinoma of the right colon.

Different patterns of interleukin-6 and von Willebrand factor antigen changes after coronary stenting in unstable versus stable angina.

BACKGROUND: Inflammation plays an important role in the pathogenesis of acute coronary syndromes. The purpose of our study was to evaluate the time course and the clinical relevance of inflammatory markers in patients with unstable angina undergoing successful coronary stent implantation. METHODS: Fifty-six patients (33 with unstable and 23 with stable angina) scheduled for single vessel coronary angioplasty followed by successful stent implantation were studied. Blood samples for measurements of interleukin-6 (IL-6) and von Willebrand factor antigen (vWf) were taken immediately before coronary angioplasty and 24 hours and 1 month after the procedure. Patients were clinically examined 1 month after the procedure. RESULTS: The mean levels of IL-6 before stenting were significaNtly higher in unstable than in stable angina patients (p = 0.002), whereas baseline values of vWf showed no difference between the two groups. In unstable angina, serum levels of IL-6 and of vWf did not change 24 hours after stent implantation, but significantly decreased 1 month after the procedure (p = 0.005 and p = 0.0015 respectively). In stable patients, serum levels of IL-6, but not of vWf, increased 24 hours after the procedure and returned to baseline levels 1 month after stent implantation (p = 0.046). CONCLUSIONS: In unstable angina, successful treatment of the culprit lesion by coronary stenting results in a significant decrease in the serum levels of IL-6 and of vWf 1 month after the procedure, suggesting that, in this clinical condition, elevated levels of these parameters correlate with the instability of the atheromatous plaque and that their decrease after successful stent implantation is the result of plaque stabilization.

Comparative short-term prognostic value of hemostatic and inflammatory markers in patients with non-ST elevation acute coronary syndromes.

BACKGROUND: Recent data show that markers of inflammation, endothelial perturbation as well as activation of the coagulation and fibrinolytic systems are altered in unstable angina. The purpose of this study was to compare the 30-day prognostic value of the indexes of inflammation [interleukin-6 (IL-6)], endothelial activation [von Willebrand factor antigen (vWf)], fibrinolysis [plasminogen activator inhibitor-1 (PAI-1)] and coagulation (F1 + 2), in a consecutive series of patients with non-ST elevation acute coronary syndromes. METHODS: Eighty-eight patients consecutively admitted to the coronary care unit because of chest pain occurring within the previous 24 hours were included in the study. Blood was drawn on admission to the coronary care unit and 72 hours thereafter for the assessment of plasma levels of IL-6, vWf, F1 + 2 and PAI-1. Troponin I serum levels were measured 6 to 12 hours after admission. All patients underwent coronary arteriography. RESULTS: Patients were divided into two groups according to their 30-day outcome: 57 patients (group 1) had an uneventful outcome, whereas 31 patients had an adverse clinical event (4 died, 1 had a Q wave myocardial infarction and 26 had refractory angina). The baseline biochemical variables were similar between group 1 and group 2 patients. Seventy-two hours following admission, an increase in the serum levels of IL-6 was observed in 71% of group 2 patients and in 28% of group 1 patients (p = 0.0001). The other measured variables showed significant changes at 72 hours versus entry only in group 1 patients, and no significant difference between the two groups. The areas under the ROC curves were higher for IL-6 (0.72) than for the other variables (0.58 for F1 + 2, 0.52 for vWf and 0.54 for PAI-1). In a multivariate model, including clinical, angiographic, and biochemical variables, only the change in IL-6 over 72 hours was significantly associated with a worse 30-day outcome (odds ratio 8.472, 95% confidence interval 1.030-69.671). CONCLUSIONS: This study shows that a mounting inflammatory process, as indicated by increasing levels of IL-6 over the first 72 hours after admission, is the most powerful predictor of the 30-day prognosis in patients with non-ST elevation acute coronary syndromes.