History and current use of mild therapeutic hypothermia after cardiac arrest.

In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.

Alterations in serum selenium levels and their relation to troponin I in acute myocardial infarction.

Selenium (Se) is an essential trace element with antioxidant function. The aim of the present study was to estimate the alterations of Se serum level during the acute phase of myocardial infarction and its relation to biomarkers of myocardial necrosis. Serum Se levels were measured at admission and after 24 h in 60 consecutive patients with acute coronary syndrome (both with and without ST elevation). Troponin I (TnI) was assessed at admission and then twice daily for 3 days; patients with normal levels were excluded. Fifty-five patients with acute MI (positive TnI) were included into the analysis. During the first day of hospitalization, patients received standard therapy, including acetylsalicylic acid, clopidogrel, and heparin or enoxaparin; all underwent urgent coronary angiography and percutaneous intervention, when appropriate. Mean Se levels at baseline and 24 h later were comparable (67.1 ± 2.1 vs. 67.2 ± 1.8 µg/L, ns). Linear regression has shown significant correlation between baseline Se levels and peak TnI (y = 3.4x - 116, r (2) = 0.13, P = 0.008). Positive correlation was found also between the peak TnI and the difference from baseline to 24 h (y = 2.2x + 115, r (2) = 0.08, P = 0.04). Moreover, close negative correlation was observed between baseline Se levels and the difference from baseline to 24 h (y = -0.9x + 62.7, r (2) = 0.55, P<0.001). Our results have shown marked individual changes in Se levels during the acute phase of MI as well as correlation between Se levels and peak TnI. These results suggest that alterations in serum Se may be related to the extent of myocardial infarction.

Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).

BACKGROUND: Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. METHODS: The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy. RESULTS: We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037). CONCLUSIONS: This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS. TRIAL REGISTRATION: NCT00171275.

Treatment of a large left main coronary artery thrombus by aspiration thrombectomy.

A left main coronary artery thrombosis is a life-threatening condition demanding immediate therapeutic management. Traditional treatment options include thrombolysis, percutaneous coronary intervention (PCI) with stenting or cardiac bypass surgery. The number of reported cases in which aspiration thrombectomy has been used is limited. Indications for this therapeutic approach are determined by coronary anatomy, clinical stability, and hemodynamic condition of the patient. We present the case of an acute left main coronary artery thrombosis leading to progressive deterioration of left ventricle function that was successfully treated with aspiration thrombectomy.

Anti-Xa activity of enoxaparin and nadroparin in patients with acute coronary syndrome.

BACKGROUND: Clinical studies have clearly revealed that low-molecular-weight heparins (LMWHs) are an effective alternative to unfractionated heparin in the therapy of acute coronary syndrome (ACS); however, data on the comparison of different LMWHs are sparse. AIM: To compare the inhibition of coagulation factor Xa by enoxaparin and nadroparin in the therapy of ACS. METHODS: Thirty-eight consecutive patients with ACS were randomly assigned to enoxaparin (group E, n=18) or nadroparin (group N, n=20) in the recommended dose. Anti-Xa activity was measured 3 h after administering the first dose of LMWH. RESULTS: Baseline demographics (age, sex) and clinical (type of ACS, pain-to-door time, elevation of troponin, percutaneous coronary intervention performed, smoking status, and history of diabetes, hypertension and hyperlipoproteinemia) characteristics were similar in both groups. Anti-Xa activity was significantly higher in group E than in group N (0.65+/-0.05 U/mL versus 0.30+/-0.03 U/mL; P<0.001). Moreover, the therapeutic target (0.5 U/mL to 0.8 U/mL) was achieved in 66.7% of patients in group E; on the other hand, effective therapy was observed in 10.0% of patients in group N (P<0.001). CONCLUSIONS: The results of the present study demonstrate a highly significant difference in anti-Xa activity of enoxaparin and nadroparin in their recommended dosing regimens, in the therapy of ACS 3 h after subcutaneous administration; the anticoagulant effect of enoxaparin was markedly stronger than that of nadroparin.

Multiple mobile aortic thrombosis treated by thrombolysis. A case report.

Mobile aortic thrombosis is a relatively rare condition with a high morbidity particularly due to peripheral embolisation. The most frequent management is anticoagulant or surgical therapy but the number of cases reported is limited and therapeutic approaches are still not well established. We present a case of large multiple mobile pedunculated thrombosis in descending aorta treated by thrombolysis.

Immediate effect of fluvastatin on lipid levels in acute coronary syndrome.

It is widely assumed that acute benefit of statin therapy is mediated especially by non-lipid effects. The immediate influence of statins on lipid levels in patients with acute coronary syndrome (ACS) is, however, not clear. A total of 64 consecutive patients with ACS were randomized at admission to fluvastatin 80 mg (Group 1, N = 32) or standard therapy without statin (Group 2, N = 32). The levels of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG) were examined at admission and after 24 h. Baseline characteristics were comparable in both groups. In Group 1, fluvastatin significantly decreased the levels of TC by 14.5%, LDL-C by 17.2%, and HDL-C by 10.0% (P < 0.001); TG were not influenced. In Group 2 only marginal reductions in TC (by 4.1%, P = 0.03) and HDL-C (by 7.5%, P < 0.01) were detected; the levels of LDL-C and TG were not changed. As compared with Group 2, in Group 1 the final levels of TC (P = 0.02) and LDL-C (P = 0.01) were significantly lower. Fluvastatin therapy, when started at admission in patients with ACS, significantly reduces TC and LDL-C already after 24 h. We suggest that the lipid-lowering effect of statins in the therapy of ACS is probably as prompt as non-lipid effects.

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696].

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.

Statins in the first-line therapy of acute coronary syndrome - similar to aspirin?

Statins are cholesterol-lowering drugs, highly effective in the primary and secondary prevention of coronary artery disease. It has been found, however, that statins also have nonlipid effects; they can influence different pathways, which have been described to participate in the pathogenesis of acute coronary syndrome (ACS). Inflammation or decreased production of nitric oxide are obvious targets for statin therapy. Recently, several large clinical trials have been published, showing safety and, in some areas, efficacy of administration of statins early after ACS. Furthermore, there is growing evidence from both experimental and small clinical studies that statin therapy may have favourable effects when started as soon as possible after the development of ACS. Confirmation of this approach by large randomized trials is needed; however, based on currently available data, statins have high chance of achieving a similar place in the first-line therapy of ACS as the pillar of contemporary therapeutic strategy, aspirin.

The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in the patients with unstable angina and non-Q-wave myocardial infarction.

The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris (UAP) or non-Q-wave myocardial infarction (NQMI) can influence the serum level of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) 24 h later. Forty-four patients with rest chest pain and subendocardial ischemia on ECG were randomized to receive cerivastatin 0.3 mg at the time of admission (group C+) to standard therapy or to remain just on standard therapy (group C-). Blood samples for determination of troponin I (TI), CRP, IL-6 and IL-8 were collected at admission (entry level) and 24 h later (final level). Patients with non-physiological baseline levels of TI, as well as patients with progression to Q wave MI were excluded. All baseline, clinical and demographic data and final values of TI were comparable in the two groups. In patients treated with cerivastatin (group C+, n = 13) we observed decrease in the CRP level (-6.73 +/- 3.93 mg/L); on the other hand, in group C- (n = 17) the CRP level increased (+7.92 +/- 2.77 mg/L, p = 0.004). Similar differences were observed also in IL-6: in group C+ the level was significantly reduced as compared with the increase in group C- (-0.76 +/- 0.52 vs. 4.58 +/- 1.49 ng/L, p = 0.005). The level of IL-8 was not affected. Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI; this might positively influence their prognosis. Nevertheless, further studies are needed to support this hypothesis.