[Pharmacogenetic aspects of antiarrhythmic drug therapy].

It is known for a long time that individuals vary widely in their responses to therapy with different drugs. Variability in drug response may be due to variability in the relationship between drug dose and concentrations of the drug at target sites (pharmacokinetic variability). Another mechanism is that individuals vary in their response to identical exposures to a drug due to variability in the target molecule with which a drug interacts or in biological microenvironment in which the "drug-target" interaction occurs (pharmacodynamic variability). Variants (polymorphisms and mutations) of genes that encode proteins important for pharmacokinetics or for pharmacodynamics are described as important contributors to variable drug actions. In this article pharmacogenetic and pharmacogenomic aspects of antiarrhythmic drug therapy and genetic factors contributing to proarrhythmia are reviewed.

[Cardiac resynchronization therapy in patients with permanent atrial fibrillation].

UNLABELLED: In our study we compared effect of cardiac resynchronization therapy (CRT) in chronic heart failure (CHF) patients with permanent atrial fibrillation (AF) and patients with sinus rhythm. Special feature of our work was that patients with permanent atrial fibrillation didnt have obligatory ablation of atrio-ventricular node but underwent aggressive rate control to achieve more than 90% of biventricular (BV) complexes. We used 24 hours Holter monitoring because there are data that this method is more accurate than CRT counters. METHODS: We included 30 patients: 21 patients with sinus rhythm and 9 patients with permanent AF with ejection fraction <35%, II-IV NYHA class and wide QRS (>120 ms). We examined patients before implantation of CRT and after 6 months. RESULTS: mean NYHA class decreased from III to II. Distance at 6-min walk test increased by 107 m in AF group and by 105 in sinus rhythm group. EF increased by 7% in AF group and by 6% in sinus rhythm group. Mean time of further observation was 2 years (from 10 months to 5 years). There was 1 death (11.1%) in AF group and 3 deaths (15%) in sinus rhythm group (p>0,05). CONCLUSION: CRT is effective in CHF patients with permanent AF and pharmacological rate control if percent of BV pacing is more than 90% on Holter monitoring.

[Prediction of results of antiarrhythmic drug therapy in patients with malignant ventricular tachyarrhythmias, based on the prognostic value of left ventricular contractility parameters].

In 44 patients (3 women and 41 men, mean age 54 +/- 11 years) with malignant ventricular tachyarrhythmias (MVT) we assessed dependence of results of testing of antiarrhythmic drugs and efficacy of their long term use for prevention of recurrences of MVT on topography of derangement of local left ventricular (LV) contractility. Regional LV contractility was assessed with transthoracic echocardiography and radionuclide ventriculography (RNV). Testing of antiarrhythmic drugs was performed under control of repetitive intracardiac electrophysiological studies. Duration of follow-up was 28 (13 - 61) months. According to ROC-analysis most precise markers of positive results of drug testing were values of local ejection fraction (EF) in apical LV segment (10th segment on RNV) above 55%. Signs predisposing to absence of MVT recurrences during long term use of antiarrhythmic drugs were lack of mitral regurgitation (above I degree) according to echocardiography data, values of local EF in segment of lateral LV wall (4th segment on RNV) exceeding 42%, or value of LV end diastolic volume less than 365 ml according to RNV data. Parameters of local LV contractility are most precise markers of results of the use of antiarrhythmic drugs in patients with MVT, their diagnostic value is hair than that of global LVEF. Efficacy of antiarrhythmic drugs at electrophysiologic testing and long term follow-up are associated with different parameters of local LV contractility.

[New approaches to treatment of bradyarrhythmia in patients with obstructive sleep apnea syndrome].

AIM: To confirm or reject effects of CPAP on sleep asystole and to elucidate possible dependence on correction of respiratory disorders. MATERIAL AND METHODS: Thirteen patients (11 males and 2 females aged 19 to 66 years) with bradyarrhythmia (BA) arising in sleep participated in the study. BA was caused by transient atrioventricular block of the degree II-III in 9 cases (69%), episodes of sinus node arrest and/or synoatrial block in 6 (46%) cases. Two (15%) patients had combination of BA forms. To diagnose sleep respiratory disorders, polysomnography (PSG) was made. Diagnostic criteria of sleep obstructive apnea syndrome (SOAS) were apnea/hypopnea index (AHI) more than 5 episodes for 1 hour sleep. The patients were divided into two groups. Individual selection of therapeutic pressure under PSG control was performed in SOAS patients (the study group). CPAP-therapy was effective in AHI < 5. In the control group (AHI < 5) such selection was made too. CPAP-therapy was effective in the controls if episodes of apnea/hypopnea were not registered through the night of monitoring. RESULTS: In the study group CPAP-therapy was effective. The AHI decreased from 73.2 to 4.4, oxygen saturation of arterial blood increased from 74 to 85%, mean duration of asystoles fell from 5.2 to 1.3 s, pauses with duration more than 2 s disappeared. In the control group sleep apnea/hypopnea episodes disappeared but in asystole CPAP was uneffective. CONCLUSION: CPAP-therapy is effective and pathogenetically sound method of treating patients with nocturnal bradyarrhythmia associated with sleep respiratory disorders.

[Efficiency of antiarrhythmic therapy and resistance to it in patients with malignant ventricular tachyarrhythmias: formulation of prognosis]. / Effektivnost' antiaritmicheskoi terapii i refrakternost' k nei u bol'nykh so zlokachestvennymi zheludochkovymi takhiaritmiiami: postroenie prognoza.

AIM: To study feasibility of predicting results of drug antiarrhythmic therapy in patients with malignant ventricular arrhythmias (MVA) basing on the results of clinical and device examinations. MATERIALS AND METHODS: 136 patients with documented MVA entered the study. 100 patients were in the retrospective analysis group, 36 patients comprised the study group. All the patients underwent physical examination, resting ECG, chest x-ray, radionuclide ventriculography. Intracardiac electrophysiological examination, Holter 24-h ECG monitoring and bicycle exercise provided data for diagnosis of MVA and control over effects of antiarrhythmic drugs. The mathematical model was derived using discriminant analysis. RESULTS: Significant differences were obtained in patients with positive and negative results of drug testing by the number and recurrence time of ventricular tachycardia (VT) for 3 years, survival, cardiac and sudden death, some other parameters. A mathematic model has been designed which allows prognosis of the results of antiarrhythmic therapy (AAT) in patients with MVA. 7 independent predictors of AAT efficiency are shown: left ventricular ejection fraction, duration of P-Q interval, cardiac failure, left ventricular aneurysm, age, number of VT morphologies, insufficiency of aortic valve. Verification of the model on the study group patients showed that prognostic accuracy of the model was 82%. CONCLUSION: The results of the drug tests predict life span of MVA patients. The developed mathematical model allows prediction of AAT results in such patients before the pharmacological test with accuracy 82-87%. The model can help objectivize indications to use of non-pharmacological methods for each patient basing on prognosis of resistance to drug AAT.