Update on management of cardiac arrhythmias in acute coronary syndromes.

This review summarizes different types of arrhythmias in patients with acute coronary syndromes and provides an overview of the available therapeutic options for acute care and management of critical arrhythmias. The different therapeutic options are depending on the origin and type of arrhythmia. The main common dominant mechanisms are intramural re-entry in ischemia and triggered activity in reperfusion. The different forms of arrhythmia were explained in detail. Atrial arrhythmias are mainly atrial fibrillation; other forms are rare and usually self-limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias can be divided in premature ventricular complexes, accelerated idioventricular rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are available. The treatment with antiarrhythmic drug is rather cautious recommended, with the exception of beta-blockers. An additional drug therapy with ranolazine may be considered. The advantage of ICD therapy for long-term primary or secondary prophylactic therapy has been well documented. ICD therapy is associated with significant reduction in mortality compared with antiarrhythmic drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and stellate ganglion blockade are rather intended as therapeutically options for incessant VT/VF or electrical storm.

[Bradycardic arrhythmias]. / Bradykarde Rhythmusstörungen.

Clinically symptomatic bradycardia arrhythmias due to disorders of impulse formation and conduction usually lead to an indication for pacemaker implantation. On the other hand, there are also a number of prognostic indications for pacemaker implantation in asymptomatic patients, but often with a lower class of recommendation. After acute myocardial infarction or cardiac surgery the implantation of a pacemaker may be necessary for the occurrence of bradycardia. Prior to a definitive pacemaker implantation reversible or preventable causes must be investigated and treated. Only for acute treatment of symptomatic bradycardia as a bridging measure drug therapy can be considered. For pacemaker supply various systems are available. We distinguish temporary from permanent systems and one-, two-and three-chamber systems. In addition, leadless pacemaker systems are tested.

[Bradycardic arrhythmias--part 1: pathophysiology and symptoms]. / Bradykarde Rhythmusstörungen. Teil 1: Pathophysiologie und Klinik.

Bradycardic arrhythmias are classified into disorders of impulse formation and conduction. Impulse formation disorders are diseases of the sinus node. Conduction disturbances are the sinoatrial (SA), atrioventricular (AV) block and bundle branch block. The conduction disturbances are also subdivided in different grades (grade I to III). Clinical manifestations of bradycardic arrhythmias are usually syncope, Morgagni-Adam-Stokes seizures, dizziness, palpitations, or heart failure. The investigation of syncope as the most visible clinical manifestation of bradycardic arrhythmias, is performed in three steps with the goal of risk stratification for sudden cardiac death or major adverse cardiac events. If symptomatic bradycardia is present, there is usually an indication for pacemaker implantation. Prior to a definitive pacemaker implantation reversible or preventable causes must be investigated and treated.

[Therapy of atrial fibrillation in the critically ill]. / Therapie des Vorhofflimmern beim kritisch Kranken.

Atrial fibrillation (AF) is the most common form of arrhythmia in the intensive care unit (ICU) and is associated with increased mortality. A total of five types of AF can be distinguished: initially diagnosed, paroxysmal, persistent, long-standing persistent and permanent AF. In addition to the initial treatment, antithrombotic therapy, rate and rhythm management can be used. The treatment of comorbidities is part of the patient management and for patients with increased risk of thromboembolic events anticoagulation is recommended. The simplest risk assessment scheme is the CHADS score. In the acute setting rate control is important. Direct current cardioversion is urgently recommended for patients with AF when hemodynamic instability is present even in patients with AF and pre-excitation in Wolff-Parkinson-White syndrome. Pharmacological cardioversion may be considered in patients with AF when hemodynamic stability is present. When choosing the antiarrhythmic agent for critically ill patients only amiodarone can be considered with some exceptions due to the specific contraindications.

Clopidogrel-mediated reduction of circulating tissue factor in patients with stable coronary artery disease.

BACKGROUND: Tissue factor (TF), the initiator of coagulation, circulates in blood and contributes to thrombosis in patients with coronary artery disease (CAD). TF is present in the alpha-granules of platelets. Therapy with clopidogrel results in inhibition of platelet degranulation. Whether clopidogrel affects circulating TF is unknown. This study examined the effect of clopidogrel on TF level in the blood of patients with stable CAD and ST-elevation myocardial infarction (STEMI) as well as healthy controls. METHODS: Thirty-three patients with CAD and twenty with STEMI were studied pre and post clopidogrel therapy (loading dose 300 mg, then 75 mg daily). All were treated with aspirin 100 mg/d. The control groups consisted of thirty healthy male volunteers also treated with clopidogrel and ten patients with CAD treated with aspirin only. TF concentration in blood drawn pre and 96 h post clopidogrel administration was measured by enzyme-linked immunosorbent assay. RESULTS: Patients with CAD and STEMI had significantly more TF in blood than healthy controls. Clopidogrel reduced TF in stable CAD patients to levels seen in healthy controls. No alterations in TF were found in controls and patients with STEMI post clopidogrel therapy. Clopidogrel reduced sCD40L level in stable CAD patients, but not in STEMI patients. A correlation between TF and sCD40L was found for the combined CAD and control, but not STEMI group. CONCLUSION: Clopidogrel leads to a reduction of not only sCD40L but also TF in stable CAD. The reduction of TF may lead to a reduced thrombogenicity, contributing to the benefits of clopidogrel therapy.

Efficient transcription of the human angiotensin II type 2 receptor gene requires intronic sequence elements.

To investigate mechanisms of human angiotensin II type 2 receptor (hAT2) gene regulation we functionally characterized the promoter and downstream regions of the gene. 5'-Terminal deletion mutants from -1417/+100 to -46/+100 elicited significant but low functional activity in luciferase reporter gene assays with PC12W cells. Inclusion into the promoter constructs of intron 1 and the transcribed region of the hAT2 gene up to the translation start enhanced luciferase activity 6.7+/-1.6-fold and 11.6+/-1.7-fold (means+/-S.E.M.) respectively, whereas fusion of the promoter to the spliced 5' untranslated region of hAT2 cDNA did not, which indicated an enhancement caused by intronic sequence elements. Reverse transcriptase-mediated PCR confirmed that the chimaeric hAT2-luciferase mRNA was regularly spliced in PC12W cells. A Northern blot analysis of transfected cells showed levels of luciferase mRNA expression consistent with the respective enzyme activities. Mapping of intron 1 revealed that a 12 bp sequence in the centre of the intron was required for the increase in promoter activity, whereas the 5' adjacent intronic region mediated a decrease in luciferase activity. Mutation of the 12 bp region led to altered protein binding and markedly decreased luciferase activity. Cloned into a promoterless luciferase vector, a 123 bp intron 1 fragment was able to direct reporter gene expression to the same activity as occurred in conjunction with the 5' flanking region. These results indicate that sequence elements in intron 1 are necessary for efficient transcription of hAT2. In reporter gene assays, intron 1 might by itself function as a promoter and initiate transcription from an alternative start point.