Tamás Fenyvesi

Angiotensin II type 1 receptor gene polymorphism and mitral valve prolapse syndrome

BACKGROUND Mitral valve prolapse syndrome (MVPS), a term applied to patients who have a variety of symptoms, has been associated with autonomic or neuroendocrine dysfunction. Recent evidence suggests that effects of angiotensin II mediated by the angiotensin II type 1 (AT(1)) receptor are involved in modulation of cardiovascular autonomic control in human beings. Association of a genetic polymorphism (A-C(1166)) of the AT(1) gene with abnormal vasomotion and low blood pressure related to autonomic control has been reported recently. Because the role of this genetic variant in MVPS has not been studied, we performed a case-control study of the A-C(1166) variant in a group of 76 white subjects with MVPS. METHODS AND RESULTS All patients were genotyped by use of a mismatch polymerase chain reaction/Afl II restriction fragment length polymorphism analysis. Frequency of the C(1166) allele was 0.4 in patients with MVPS and 0.26 in control patients. The difference in genotype (chi square = 6.5; P <.05) and allele (chi square = 5.9; P =.02) frequencies between the groups was significant. The odds ratio in favor of carrying the C allele was 4 times greater for patients with MVP than for control patients (95% confidence interval 1.4 to 12.1). CONCLUSIONS The current results indicate that the A-C(1166) polymorphism of the angiotensin II type 1 receptor gene is associated with MVPS in the white population.

A study of modulated ventricular parasystole by programmed stimulation

To analyze the phase-dependent sensitivity of the parasystolic pacemaker to nonparasystolic beats, 11 patients with modulated ventricular parasystole were studied using the ventricular extrastimulus method. The intrinsic parasystolic cycle lengths ranged from 1,100 to 1,800 ms. Premature stimuli altered the duration of the parasystolic cycle lengths by amounts that depended on timing of the test impulses within the parasystolic cycles. Premature impulses delivered during the first part of the parasystolic cycles prolonged the parasystolic cycle lengths to 107 to 151% of the intrinsic parasystolic cycle lengths and impulses applied during the second part abbreviated them to 70 to 81% of the intrinsic parasystolic cycle lengths. In 10 patients the accelerating effects were of greater magnitude than the decelerating effects. Transition from the accelerating to slowing phases was progressive or unstable in 9 patients and abrupt in 2. Changes induced by individual stimuli were short-lived and the parasystolic pacemakers returned immediately to their original rates. In 1 patient the biphasic sensitivity of parasystole to premature stimuli was shown to sustain for 21 days.

Endothelins: a possible mechanism of cytostatics-induced cardiomyopathy

Endothelium responds to physical and chemical stimuli by synthesis and release of a variety of vasoactive and signal molecules. Cardiac performance is regulated by cardiac endothelial cells in a paracrine manner, analogous to vascular endothelial control of vascular tone. Endothelin-1 (ET-1), one of the most potent vasoconstrictor peptides, which is synthetized and released by endothelial cells. The role of ET-1 in some special pathological state is still unclear. Authors have investigated the effect of anthracyclines (maximal dose: 450 mg/bodysurface m2) on left ventricular systolic and diastolic function and on the level of plasma ET-1, in 31 (13 male, aged 19 – 70 years, mean: 38.9) patients suffered from Hodgkin (24) and Non-Hodgkin (7) lymphomas. They have also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA method. Left ventricular function analyzed by echocardiography: ejection fraction (EF), time velocity integral (VTI), E and A waves, E/A ratio, deceleration time (DT), Doppler index were assessed. Statistical analysis was made by the Wilcoxon rank test. ET-1 plasma level decreased significantly after therapy (5.6 ± 3.5 vs. 3.1 ± 0.9 pg/ml, P < 0.0006). EF (56.4 ± 5.0% vs. 48.7 ± 5.1%, P < 0.0001) decreased, and DT (168.1 ± 36.8 ms vs. 206.5 ± 58.8 ms, P < 0.0073) increased significantly after administration of anthracycline, showing that both systolic and diastolic left ventricular performance was deteriorated. There was no difference in other echocardiographic parameters before and after therapy. In conclusion, decrease of serum ET-1 concentration might be a result of anthracyclins direct cytotoxic effect and the decreasing level of ET-1 may play a role in the reduction of the EF. More studies are needed to evaluate the presence and severity of endothelial damage, and long-term follow-up may reveal the importance of low ET-1 level and may show the time is needed for the restoration of the ET-1 concentration to the basic level after cessation of cytostatic therapy.

Electrophysiologic Study of Tachycardia-Dependent Paroxysmal His Bundle Block in Man

Electrophysiologic sludy was performed in a potienl with tachycardia‐dependent paroxysmal atrioventricular block. The site of block was within the His bundle. The effective refractory period of the His bundle was markedly prolonged and it was comparable to the critical atrial cycle length producing type II His bundle block. The most likely mechanism of paroxysmal atrioventricular block was repetitive concealed penetration of the blocking zone by nonconducted impulses that reached the proximal His bundle. Enhancing the blocking ratio at the atrioventricular nodal level resulted in improvement of overall atrioventricular conduction.

The effects of probucol on QT QS2 relation and systolic time intervals

The QT, QTc, QS2 intervals, pre-ejection period-left ventricular ejection time ratios and serum lipoprotein levels were measured in 8 patients with primary hypercholesterolemia before and after a 3-month therapy with probucol, 1 g/day. Both QT and QTc intervals increased significantly, whereas no significant changes were observed between the pre- and post-treatment QT/QS2 and pre-ejection period-left ventricular ejection time ratios. These results help to explain why treatment with probucol, while effecting a prolongation of the QTc interval, does not result in serious arrhythmias in man.

Role of endothelin-1 in the development of a special type of cardiomyopathy

The role of endothelin-1 (ET-1) in certain pathological states is still unclear. We have investigated the effect of anthracyclines (maximum dose, 450 mg/m(2) of body surface) on left ventricular systolic and diastolic function and how it influences the level of plasma ET-1 in 21 patients (12 female and nine male) with Hodgkin and non-Hodgkin lymphoma. We also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA. Left ventricular function was analysed by echocardiography: ejection fraction (EF), velocity-time integral, E- and A-waves, E:A ratio, deceleration time (DT) and Doppler index were all measured. Statistical analysis was made by the Wilcoxon rank test. EF and serum ET-1 level decreased significantly (EF, 56.29+/-5.0% to 48.57+/-5.9%, P<0.0001; ET-1, 6.45+/-4.0 pg/ml to 2.9+/-1.0 pg/ml, P<0.0001). DT increased significantly (179.8+/-47.8 ms to 215.5+/-66.7 ms, P<0.01) after anthracycline therapy. There was no difference in other echocardiographic parameters before and after therapy. The decrease in serum ET-1 concentration might be a result of anthracyclines direct cytotoxic effect and the decreasing level of ET-1 can play a role in the reduction of EF. However, more studies are needed to evaluate the presence and severity of endothelial damage.

Simple Approach to an Apparently Chaotic Arrhythmia

Deciphering complex arrhythmias requires a strict, systematic approach. In a step-by-step analysis of an electrocardiogram recorded from a patient with severe metabolic disturbances, we present a few simple suggestions that may often be helpful in electrocardiographic interpretation.

Wenckebach periodicity with apparent 1:2 conduction over the atrioventricular node: the problem of interpretation.

Abstract A rare finding during atrial pacing-induced atrioventricular (AV) nodal Wenckebach periodicity is the demonstration of double ventricular responses to a single P wave. 1–4 This peculiar conduction pattern is generally believed to represent dual AV nodal pathways with simultaneous conduction of a single atrial impulse over the fast and slow pathways. 1–4 We report 2 additional cases of apparent 1:2 conduction during AV nodal Wenckebach periodicity and offer a different interpretation.