Circulation
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Randomized Controlled Trial Clinical Trial
Early and 1-year clinical outcome of patients' evolving non-Q-wave versus Q-wave myocardial infarction after thrombolysis. Results from The TIMI II Study.
There are few data comparing clinical outcome and potential indications for routine post-myocardial infarction cardiac catheterization and revascularization of patients who sustain a non-Q-wave versus Q-wave infarct after thrombolytic therapy. ⋯ Angiographic and clinical differences were observed between patients who present with initial ST-segment elevation and evolve early non-Q-wave versus Q-wave myocardial infarcts after treatment with rTPA, heparin, and aspirin. Early mortality and adverse clinical cardiac events in these patients are not significantly different after a conservative compared with an invasive treatment strategy, regardless of whether the infarct type is non-Q wave or Q wave.
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Two missense mutations in the gene for alpha-tropomyosin have been described that segregate with hypertrophic cardiomyopathy in single families. To confirm that these mutations are the cause of the disease, we have investigated the origins of one of these mutations, Asp175Asn, in a third and unrelated family. ⋯ De novo mutations in the alpha-tropomyosin gene can result in hypertrophic cardiomyopathy that may appear to be sporadic but in subsequent generations gives rise to familial disease. Individuals with sporadic hypertrophic cardiomyopathy should be advised of the risk of transmission to offspring. In addition, these findings provide the strongest genetic evidence that mutations in the alpha-tropomyosin gene are directly responsible for hypertrophic cardiomyopathy.
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Although programmed electrical stimulation is widely used for provoking sustained ventricular tachycardia (VT), the mechanism by which repetitive extrastimulation evokes VT is still little understood. Specifically, it is not clear why several closely coupled extrastimuli are frequently required to induce VT. Although regularly paced human ventricular myocardium exhibits a near constant relation between myocardial repolarization and refractoriness, the effect of repetitive extrastimulation on the relation between repolarization and excitability in the human heart and its relevance for arrhythmia induction by programmed stimulation are unknown. We hypothesized that the induction of VT by repetitive extrastimulation is facilitated by an altered relation between repolarization and refractoriness, and this leads to disturbances in ventricular impulse propagation, which trigger the onset of VT. ⋯ Repetitive extrastimulation not only shortens APD and subsequently ERP but also alters the ERP/APD relation by allowing capture to occur at progressively less complete repolarization levels. This progressive encroachment onto the preceding repolarization phase is associated with impaired impulse propagation and a high incidence of VT induction. This may help explain how repetitive, closely coupled extrastimulation induces ventricular tachycardia in the human heart.
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Clinical Trial Controlled Clinical Trial
Reversal of heparin anticoagulation by recombinant platelet factor 4 in humans.
Protamine is used to reverse the anticoagulant effects of heparin, but it can have important side effects. Platelet factor 4 (PF4) is a protein found in platelet alpha granules that binds to and thereby neutralizes heparin. We evaluated the safety and effectiveness of intravenous recombinant PF4 to neutralize heparin anticoagulation after cardiac catheterization in a phase 1, open-label trial. ⋯ rPF4, in doses ranging from 0.5 to 5.0 mg/kg over 3 minutes, had no serious side effects. Given in sufficient amounts, rPF4 can completely and rapidly reverse the anticoagulant effects of heparin.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Randomized study of implantable defibrillator as first-choice therapy versus conventional strategy in postinfarct sudden death survivors.
In retrospective studies of sudden cardiac death survivors, the implantable cardioverter-defibrillator (ICD) compares favorably with medical and surgical therapy. Thus, use of the conventional strategy of starting treatment with antiarrhythmic drugs (AD), at least in certain patient categories, may be questionable. The goal of this study was to analyze the effectiveness of ICD implantation as first-choice therapy versus the conventional therapeutic strategy of starting with AD. ⋯ These data suggest that ICD implantation as first choice is preferable to the conventional approach in survivors of cardiac arrest caused by old myocardial infarction. Conventionally treated patients are likely to end up with an ICD, and those who remain on AD as sole therapy have a high risk of death regardless of efficacy assessment, including PES.