Franco Semprini

Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.

BackgroundPatients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris. Methods and ResultsAccording to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P=.035) and an improvement in both the time to 1-mm ST segment depression (P=.008) and the peak ST segment depression (P=.015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P=.016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P=.0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding. Conclsions. Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.

Comparison of efficacy of low molecular weight heparin (parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects

Arterial thrombosis is typically platelet-rich. In this study, it is shown that heparin levels resulting in the usual activated partial thromboplastin time therapeutic range provide only a small anticoagulant effect in the presence of activated platelets. Thrombin inhibition is also negligible when heparin is added to platelet-rich plasma. Aspirin improves the anticoagulant effect of heparin in these circumstances, but the degree of anticoagulation is still considerably lower than that observed in platelet-poor plasma. A low molecular weight heparin (parnaparin) is more active in the presence of activated platelets (such as may occur in acute coronary syndromes) regardless of whether aspirin is used concomitantly.

Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction.

TNKase is a genetically engineered variant of the alteplase molecule. Three different mutations result in an increase of the plasma half-life, of the resistance to plasminogen-activator inhibitor 1 and of the thrombolytic potency against platelet-rich thrombi. Among available agents in clinical practice, TNKase is the most fibrin-specific molecule and can be delivered as a single bolus intravenous injection. Several large-scale clinical trials have enrolled more than 27,000 patients with acute myocardial infarction, making the use of this drug truly evidence-based. TNKase is equivalent to front-loaded alteplase in terms of mortality and is the only bolus thrombolytic drug for which this equivalence has been formally demonstrated. TNKase appears more potent than alteplase when symptoms duration lasts more than 4 hours. Also, TNKase significantly reduces the rate of major bleeds and the need for blood transfusions. The efficacy of TNKase may be further improved by enoxaparin substitution for unfractionated heparin, provided that enoxaparin dose adjustment is made for patients more than 75 years old. Hitherto, the small available randomized studies and international clinical registries suggest that pre-hospital TNKase is as effective as primary angioplasty, thus laying the foundations for a new fibrinolytic, TNKase-based strategy as the backbone of reperfusion in acute myocardial infarction.

On the value of the activated clotting time for monitoring heparin therapy in acute coronary syndromes.

Abstract Heparin therapy may be monitored at the bedside with new portable machines measuring the activated clotting time (ACT) of the whole blood and the activated partial thromboplastin time (aPTT). Although the ACT is usually believed to be a convenient substitute for the aPTT, the value of its measurement in patients with acute coronary syndromes has never been evaluated. This study prospectively compares the ACT and the aPTT for monitoring heparin therapy in the coronary care unit.

Cardiac neurosis and psychopathology.

Psychiatric illness according to DSM-III-R criteria was investigated in 54 consecutive patients suffering from cardiac neurosis (neurocirculatory asthenia or Da Costas syndrome). Thirty-seven of the 54 patients (68.5%) were found to suffer from a psychiatric disorder. Generalized anxiety disorder, social phobia and panic disorder accounted for most of the diagnoses. Panic disorder was frequently preceded by (and associated with) generalized anxiety, phobic avoidance and hypochondriasis. The results should alert the physician to inquire for symptoms of an anxiety disorder when a patient presents with cardiac neurosis.

Neurocirculatory asthenia: a reassessment using modern psychosomatic criteria

The purpose of this study was to assess the prevalence of mental illness and to evaluate the quality of life of patients with neurocirculatory asthenia. A consecutive series of 80 patients who satisfied the diagnostic criteria developed by Kannel et al. for neurocirculatory asthenia was included in this study. Patients underwent a psychiatric diagnostic research interview and extensive psychometric evaluation, with both observer and self‐rated scales for depression, anxiety, phobic symptoms, quality of life and abnormal illness behavior. In 47 patients (59%), a psychiatric diagnosis (mainly an anxiety disorder) antedated the onset of neurocirculatory asthenia, which was thus defined as secondary, also because cardiorespiratory symptoms were part of the mental symptoms. In the remaining 33 patients (41%) neurocirculatory asthenia was the primary disorder. Patients with secondary neurocirculatory asthenia reported significantly higher levels of anxiety, depression, social phobia, abnormal illness behavior and an impaired quality of life compared with patients with primary neurocirculatory asthenia. This latter did not significantly differ in these variables (except for depression) from healthy control subjects matched for sociodemographic variables. At a 1‐year follow‐up, patients with primary neurocirculatory asthenia had a much better prognosis than those with secondary neurocirculatory asthenia. The results indicate the feasibility of the primary/secondary distinction based on the time of onset of mental and cardiorespiratory symptoms in neurocirculatory asthenia. Since only about one quarter of the patients were found to suffer from decreased energy and fatigue according to specified criteria, the terms neurocirculatory asthenia and effort syndrome should probably be discarded.

Pharmacodynamic characteristics of low-molecular-weight dermatan sulphate after subcutaneous administration in acute myocardial infarction.

Sixteen patients (5 female and 11 male, mean age 59.1 years) who had had an acute myocardial infarction within the previous 7 days, were enrolled in an open pharmacodynamic study. Patients were randomly allocated to two treatment groups and given a single subcutaneous dose of 100 or 200 mg of a new low-molecular-weight dermatan sulphate. The drug pharmacodynamic profile was determined 1, 2, 4, 6, 8, 12 and 24 h after administration. The following coagulation and fibrinolysis tests were performed: activated partial thromboplastin time, thrombin time, activated factor X inhibition, Heptest (global clotting time), heparin cofactor II affinity, functional and antigenic plasminogen activator inhibitor and fibrin plate assay. Both Heptest and heparin cofactor II affinity were significantly increased (P < 0.001) in a dose-dependent manner. The Xal was enhanced, though to a lesser extent. None of the other coagulation or fibrinolysis tests showed significant changes at either dose. Systemic and local tolerance were always very good.

Effects of two dosages of subcutaneous low molecular weight heparin (Parnaparin) and of unfractionated heparin on fibrin formation and lipolysis in acute myocardial infarction

Although low molecular weight heparins (LMWH) have been extensively investigated for the prophylaxis and treatment of venous thromboembolism in surgical environments, few data in acute myocardial infarction are available in the literature. In this study two dosages of a new LMWH, Parnaparin, and unfractionated heparin (UF) were investigated in 50 pts with acute myocardial infarction. 20 pts received UF (15.000 units, three subcutaneous injections, Group 1), 20 pts received Parnaparin (6.400 units, single injection, Group 2) and 10 pts received a higher dose of Parnaparin (12.800 units, single injection, Group 3). Similar fibrinopeptide A (FpA) levels were observed in Group 1 and Group 2. In Group 3 the dosage of Parnaparin resulted in a significant prolongation of the APTT and in lower FpA levels. Fibrin formation was decreased by Parnaparin in a concentration-dependent way, according to both the anti-Xa activity and the APTT ratio. Parnaparin did not result in a significant increase in free fatty acid concentration, in comparison with UF. Thus, Parnaparin may offer the advantage of a single subcutaneous injection in patients with acute myocardial infarction.

Troponin T elevation in acute aortic syndromes: Frequency and impact on diagnostic delay and misdiagnosis

Aims: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS. Methods and results: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05–3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12–5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86–3.10, p = 0.131). Conclusions: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Impact of high-sensitivity Troponin T on hospital admission, resources utilization, and outcomes:

Aims: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs-cTnT in the everyday clinical practice of an Emergency Department. Methods and Results: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 ± 37.2 vs. 136.7 ± 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change ≥ 50% or ≥ 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216). Conclusions: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality.