Bořivoj Semrád

Circadian variations in the occurrence of ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators.

KOZÁK, M., et al.: Circadian Variations in the Occurrence of Ventricular Tachyarrhythmias in Patients with Implantable Cardioverter Defibrillators. A circadian distribution has been demonstrated in episodes of sudden cardiac death, acute myocardial infarction, ventricular premature complexes, heart rate variability, and ventricular tachyarrhythmias. The aim of this study was to evaluate the circadian distribution of ventricular tachyarrhythmia episodes in a population of ICD patients. Data were gathered from 72 patients (55 men, 17 women; mean age 62.7 ± 12.2 years, mean LVEF 0.0037 ± 0.0011 ) with ICDs implanted for standard indications. Patients were followed every 3 months over a mean period of 21 ± 12.8 months. At each examination, symptoms at arrhythmia onset and perception of ICD therapy were recorded, and the ICD memory was interrogated. During follow‐up, 1,023 episodes of malignant ventricular arrhythmias were detected and effectively terminated, 506 of which were fully analyzed. A morning peak in ventricular tachyarrhythmias was demonstrated between 7:00 and 11:00 am, and an afternoon peak between 6:00 and 7:00 pm. A significantly lower occurrence of VT was observed at 1:00 am and between 4:00 and 6:00 am. A circadian distribution in the occurrence of ventricular tachycardias was found. The three striking features of the data are: the early morning peak (about three hours after waking up), relatively stable incidence throughout waking hours, and decline in incidence in the previous period. (PACE 2003; 26:731–735)

Influence of age, body mass index, and blood pressure on the carotid intima-media thickness in normotensive and hypertensive patients

Abstract We investigated whether body mass index and blood pressure have an additive influence on the carotid intima-media thickness (IMT). In 27 patients treated for hypertension (47.2±8.7 years) and 23 normotensive subjects (44.1±8.1 years), 24-h recording of blood pressure was performed. The carotid IMT was determined by ultrasonography and baroreflex sensitivity by a spectral method from 5-min recordings of blood pressure. Significant differences between hypertensive and normotensive subjects were observed for carotid IMT (0.60±0.08 vs. 0.51±0.07 mm; p<0.001) and baroreflex sensitivity (3.5±1.8 vs. 5.6±2.1 ms/mm Hg; p<0.001). Hierarchical multiple regression analysis (p<0.01) showed that carotid IMT was positively correlated with age (p<0.001) and body mass index (p<0.05) in normotensive subjects. The increased carotid IMT in hypertensive patients was not additively influenced by either age or body mass index. Baroreflex sensitivity decreased with age (p<0.01) and with carotid IMT (p<0.05) in normotensive subjects only. Multiregression analysis showed that an additive influence of age and body mass index on the development of carotid IMT is essential only in normotensive subjects. In hypertensive subjects the influence of blood pressure predominates, as documented by a comparison of the carotid IMT between hypertensive and normotensive subjects.

Ageing and Cardiac Autonomic Status

Recent studies have shown the significance of autonomic changes for the diagnosis and prognosis of many cardiovascular diseases. A consensus exists that, in the setting of acute myocardial ischaemia, sympathetic hyperactivity facilitates the onset of malignant arrhythmias, whereas vagal activation can exert an antifibrillatory effect. Thus, evaluation of the activity of the autonomic nervous system can contribute to more refined post-myocardial infarction risk stratification. Decreased heart rate variability (HRV) which is a marker of lower parasympathetic and/or higher sympathetic activity and depressed baroreflex sensitivity (BRS) indicate an increased risk of sudden cardiac death (SCD) in these patients.1–3 BRS is also decreased in patients with essential hypertension and therapeutic normalisation of blood pressure is not accompanied by BRS increase.4,5 On the other hand, both BRS and HRV physiologically decline with age6 which complicates the evaluation of cardiac autonomic status in the elderly.

Endothelin-1 gene polymorphism in patients with malignant arrhythmias.

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive patients with malignant ventricular arrhythmias and implantable cardioverterdefibrillators with a mean age of 62.7 ± 12.2 years and a mean left ventricular ejection fraction of 0.37 ± 11.0. Taq polymorphism of ET-1 was detected using our original polymerase chain reaction method. The polymerase chain reaction product with a length of 358 basepairs (bp) (primers 5′-CAA ACC GAT GTC CTC TGT A-3′ and 5′-ACC AAA CAC ATT TCC CTA TT-3′) in its non-mutated form contains a target sequence for TaqI restrictive enzyme, while a mutated product loses this cleavage site. Of 26 patients, nine (34%) had recurrent palpitations and eight (30.8%) had syncopes during their malignant arrhythmias. Nineteen patients were given amiodarone after implantable cardioverter-defibrillator insertion and seven were not treated with amiodarone. Fifteen patients had (++), 11 (+-) and 0 (- -) ET-1 genotype. The risk for syncopes was associated with the (++) genotype of the ET-1 gene (P = 0.01). Patients receiving amiodarone had significantly higher frequency of the (++) genotype (P = 0.011). All our results indicate that the presence of the ET-1 genotype (++) in patients with structural heart disease, severe left ventricular dysfunction and malignant ventricular arrhythmias increases the risk for these patients of hemodynamic collapse during these arrhythmias.

Baroreflex Sensitivity: Do We Have Any Progress?

The barore_ex is a homeostatic mechanism decreasing the variation of blood pressure. Its physiological function is well described, although its signi~cance for animals and human bodies is unknown. It was suggested that it is important for blood pressure regulation during changes of the position of the body from lying to standing, but patients with orthostatic hypotension have normal barore_ex sensitivity. People with low barore_ex sensitivity (BRS) do not have problems with changes of position of the body. A barore_ex gain similar to that seen in humans was observed in small animals such as cats and rabbits, where the difference in blood pressure in brain arteries between a horizontal and vertical position is only a few mmHg. The barore_ex probably protects the brain arteries from hypertrophy of the vascular wall. The autoregulatory reaction, which normally returns _ow in brain arteries to its original value after a decrease of blood pressure [1], is not seen in subjects with untreated hypertension [2]. During exercise, the barore_ex gain is rapidly diminished [3] or the set point is shifted to higher blood pressures [4]. In this way, the perfusion of the brain is maintained during vasodilatation in working muscles. Surgical elimination of the barore_ex causes an increase of blood pressure, which disappears after several days in experimental animals but elicits hypertension in man. Because of several other control mechanisms, barore_ex elimination is not a threat to life. Several years ago, a low BRS was found to be a risk factor for cardiac death in patients after myocardial infarction. This is why the barore_ex in humans is extensively studied in many laboratories. Research is concentrated into three areas: the search for a convenient method for determination of BRS, the study of barore_ex in patients after myocardial infarction at risk of cardiac death and the study of the barore_ex in other diseases. The large number of methods for determination of BRS indicates that an ideal method has not been found. The methods can be classi~ed according to several criteria. Classi~cation according to invasiveness of the approach is not up-to-date because the classical intraarterial recording of blood pressure has mostly been replaced by the Penaz volume clamp method of non-invasive recording of blood pressure in digital arteries using the Physiocal criteria of Wesseling. Monitors using this technique include Finapres, Ohmeda or Portapres, TNO-BMI Amsterdam [5]. An analysis of spontaneous barore_ex sensitivity shows the changes of pulse interval (PI) elicited by spontaneous changes of between systolic blood pressure (SBP). Laboratory methods evaluate the changes of PI elicited by arti~cially produced changes of SBP. Two methods estimate spontaneous BRS, the sequence technique method and the spectral method. Sequences of three or more beats with a high correlation between SBP and PI are used to calculate the average slope of the relation (in ms/mmHg) over several minutes of beat-to-beat blood pressure recording. The disadvantage of this approach is that the slope of the line expressing the relationship between PI and SBP re_ects respiratory arrhythmia as well as BRS, the former being mediated by several mechanisms. Apart from BRS, the direct connection of respiratory and cardio-inhibiting centres play a role in central nervous system and respiration-induced changes in diastolic ~lling of the right atrium with its re_ex and direct mechanical effect on pacemaker cells in the sinoatrial node. This disturbance by respiration is common for many methods for BRS determination. If the respiratory rate is suf~ciently high, a method based on the spectral analysis of several minutes’ blood pressure recording is free of this respiratory in_uence. The method uses a calculation of the BRS spectral peak on SBP and PI power spectra at 0.1 Hz (0.05–0.15 Hz). We use metronome-controlled breathing at 0.33 Hz in our laboratory. Two modi~cations of the calculation are used (Robe technique and Pagani alpha coef~cient); the difference is low if the association between SBP and PI oscillation at 0.1 Hz is high. This association is re_ected by the coherence; a high coherence between 0.5 and 1 is a requirement for a reliable BRS estimate. A high coherence also occurs at the respiratory frequency, but the gain in this frequency band re_ects not only BRS,

Preliminary report: Endothelin-1 gene polymorphism in malignant ventricular arrhythmias

The aim of this study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation to states leading to hemodynamical colaps during malignant ventricular arrhythmias (MVA) in patients with structural heart disease (SHD) and left ventricular dysfunction.