Multiparametric electrocardiographic evaluation of left ventricular hypertrophy in idiopathic and hypertensive cardiomyopathy.

BACKGROUND: Electrophysiological abnormalities underlying the increased arrhythmogenicity of left ventricular hypertrophy (LVH) are still under investigation. The aim of this study was to assess non-invasively the electrophysiologic alterations in two different types of LVH, METHODS: Multiparametric non-invasive ECG analysis (R-R interval, QRS and QT intervals, QT dispersion, T-wave complexity, activation-recovery interval [ARI] dispersion, standard deviation of RR intervals [SDNN], filtered QRS duration [fQRS], root-mean-square voltage of the terminal 40 ms of the fQRS [RMS40] and low amplitude signal duration (< 40 microV) in the terminal portion of the fQRS [LAS]) was performed in 57 patients with hypertensive LVH and hypertrophic cardiomyopathy (HCM), and in 105 healthy subjects. RESULTS: The R-R interval and SDNN were similar in hypertrophic patients and controls. QRS and QT intervals were longer in hypertrophic patients without any differences between hypertensive LVH and HCM. QT dispersion, T-wave complexity and fQRS were greater in hypertrophic patients; QT dispersion was the greatest in HCM. ARI dispersion was lesser in hypertrophic patients without any differences between subgroups of LVH. fQRS showed a trend toward higher values in hypertensive patients. LAS at 25 Hz had a trend toward lower values in HCM patients, while LAS at 40 Hz and RMS40 showed no difference between controls and hypertrophic patients. Left ventricular mass index was not correlated with any of the above-mentioned parameters. CONCLUSIONS: The QT interval and dispersion did not identify the type of hypertrophy. Similarly, ARI dispersion which explores local variations of repolarization duration, and T-wave complexity could not distinguish patients with hypertensive LVH from those with HCM indicating that multiparametric ECG data are affected more by the presence of LVH, than by its type.

Beat-to-beat analysis of pressure wave morphology for pre-symptomatic detection of orthostatic intolerance during head-up tilt.

OBJECTIVES: The aim of this study was to noninvasively define the hemodynamic profile characterizing the early response to tilting. BACKGROUND: The mechanisms causing orthostatic intolerance have not been fully elucidated. Usually, patients undergoing tilt test are studied in a time-consuming way. Moreover, the test can cause discomfort to the patient and even be potentially hazardous. METHODS: Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects (HS), performed head-up tilt test while their arterial pressure waveform was noninvasively recorded. We elaborated data using the Pressure Recording Analytical Method to obtain hemodynamic parameters, then analyzing the variables by discriminant analysis. RESULTS: Compared with HS, OIP showed lower stroke volume index (SVI) values even in baseline conditions associated with higher values of systemic vascular resistance (SVR) and heart rate (HR). From the third minute of the tilted position and until symptoms appeared, patients exhibited lower values of blood pressure (BP) and SVI and higher HR values but no difference in SVR. At termination, patients showed a further significant reduction in BP and SVI and a persistent increase in HR. CONCLUSIONS: This investigation underlines: 1) the possibility of beat-to-beat monitoring of hemodynamic changes during tilting; 2) the cardiovascular profile of OIP at rest, characterized by lower SVI and higher SVR and HR; 3) the maladaptive response to postural challenge of OIP mainly identifiable in impaired vascular regulation; and 4) the possibility of detecting parameters that enable prompt identification of the positive response to tiltingin these patients, thus guiding the duration of the test.

Hypertrophic cardiomyopathy: electrical abnormalities detected by the extended-length ECG and their relation to syncope.

BACKGROUND: Ventricular repolarization abnormalities can represent a trigger for lethal arrhythmias in hypertrophic cardiomyopathy (HCM). We sought to assess whether multiparametric computerized surface ECG analysis identifies repolarization abnormalities in HCM patients, and whether this approach allows identification of patients with syncope. METHODS: In 28 HCM patients and 102 healthy subjects (14 and 51 males, mean age 44 +/- 15 and 41 +/- 14 years, respectively), 8-lead ECG (I, II, V1-V6) was recorded for 5 min, acquired in digital format and analyzed. Heart-rate corrected QT (QTc) and T wave complexity index (TWCc), QT dispersion, activation-recovery interval (ARI) and its dispersion, signal duration in the terminal portion of the filtered QRS at 25 Hz (LAS(25 Hz)) were analyzed among other parameters. RESULTS: Compared to healthy subjects, HCM patients exhibited longer QRS, filtered QRS, QTc and QTd, greater TWCc, minor ARId and LA(25 Hz). QRS duration and maximal septum thickness were linearly correlated (r=0.231 p<0.001). ARId shortening depended on ARI shortening in lead V1 (241 +/- 51 vs. 287 +/- 45, HCM vs. healthy subjects, p<0.0001) and lengthening in V6 (257 +/- 42 vs. 209 +/- 34, HCM vs. healthy subjects, p<0.0001). Significant factors for syncope at Wilks' stepwise discriminant analysis were TWCc, QRSd and LAS(25 Hz) (F=14.394, 10.098 and 9.226, respectively) with 92.3% positive predictive accuracy. CONCLUSIONS: In HCM, longer QRS and QT intervals are consequences of increased left ventricular mass, while ARI seems to reflect myocardial activation rather than inhomogeneity of recovery. The simultaneous evaluation of TWC, QRSd and LAS(25 Hz), unable by itself to hold a predictive value, yielded high accuracy in predicting cardiogenic syncope.

Baroreflex function in vasodepressive syncope: detection of early impairment.

BACKGROUND: Defective baroreflex function has been suggested as a potential mechanism accounting for the development of syncopal episodes. The present study was therefore aimed at assessing the non-invasive, indirect hemodynamic profile and baroreflex function by means of tilting, which is a natural stimulation crucial to physiological baroreflex activity, in syncopal patients and healthy controls. MATERIAL/METHODS: Seventeen consecutive patients with a positive response to head-up tilting and fourteen healthy subjects as controls underwent continuous and non-invasive beat-to-beat heart rate and arterial pressure measurements in order to evaluate systolic, diastolic, and dicrotic pressures, as well as heart rate. Baroreflex function was calculated as the slope of the linear regression line relating systolic arterial pressure to RR interval changes during upward and downward phases of tilting, respectively. RESULTS: When compared to healthy subjects, vasodepressive patients showed a significantly weaker correlation between systolic pressure and RR interval changes both in upward tilting, (r = 0.68 vs r = 0.91, p<0.05) and downward tilting (r = 0.48 vs r = 0.93, p<0.01). CONCLUSIONS: Our results show that an impairment in baroreflex-mediated adjustment to postural challenge can be detected in syncopal patients also during upward tilting, that is, in the early phase of the test. Moreover, our investigation emphases the utility of a noninvasive, complete hemodynamic evaluation of the early phase of tilting in order to detect peculiar behaviours of pulse wave contour and related parameters.

Simultaneous assessment of electrocardiographic parameters for risk stratification: validation in healthy subjects.

BACKGROUND: Sudden cardiac death represents a major public health problem, but in the general population the identification of those subjects at very high risk remains poor. Simultaneous multiparametric ECG analysis can improve the identification of high-risk patients. METHODS: Five-min ECG recordings at a 5 MHz sampling rate (extended length-XL-ECG, Mortara Instruments, Milwaukee, WI, USA) were acquired in 105 healthy subjects (age range 21 to 80 years), equally distributed for age decades and sex, and three additional recordings, 30 min apart, were repeated in 30 subjects on the second day. The following parameters were recorded and analyzed: the RR interval, QRS duration, QT interval corrected according to the Bazett and Fridericia formulae, QT dispersion, T wave complexity, activation-recovery interval dispersion, standard deviation of the RR intervals, filtered QRS duration, the square root of the mean voltage of the last 40 ms of the filtered QRS, and the length of time that the terminal vector magnitude complex remains < 40 microV. RESULTS: QRS duration, activation-recovery interval dispersion, and filtered QRS differed in the two sexes. The standard deviation of the RR intervals, T wave complexity and QT dispersion were significantly correlated with age. The reproducibility was good for each parameter. CONCLUSIONS: The XL-ECG allows the simultaneous calculation of eight adequately reproducible different parameters the values of which are in agreement with those of the literature. Thus, XL-ECG is a reliable time- and cost-saving tool.

Continuous recording of dicrotic and pulse pressures during head-up tilting test: the vasodepressive profile. Preliminary data.

BACKGROUND: The aim of this study was to assess whether a non-invasive automatic evaluation of the pulse wave characteristics could provide clinical clues when monitoring the hemodynamic adjustments to head-up tilting. METHODS: A continuous assessment of the peripheral pulse wave characteristics (systolic, diastolic, dicrotic and pulse pressures) in 8 control subjects with a negative response to head-up tilting (60 degrees for 45 min) compared to 13 syncopal patients with a vasodepressive one was performed. RESULTS: Controls exhibited, when up-tilted, an increase in blood pressure as well as in the dicrotic and pulse pressures and no changes in heart rate. On the contrary, syncopal patients showed a progressive increase in heart rate associated with a progressive decrease in dicrotic pressure and a trend towards lower values of pulse pressure, but no changes in systolic pressure. Thereafter and until the pre-syncopal symptoms supervened, the systolic, diastolic and dicrotic pressures progressively declined. A decrease in dicrotic pressure mainly characterized the early vasodepressive response while its increase identified the negative one. CONCLUSIONS: Our data, even though preliminary, strongly suggest that automatic hemodynamic evaluation is to be used in the clinical setting as a monitor of the sudden changes in blood pressure induced by head-up tilting. Furthermore, the dicrotic and pulse pressures, even those measured during the early phases of the test, should be considered as non-invasive parameters characterizing the vasodepressive response to head-up tilting.

PreproEndothelin-1 expression in human mesangial cells: evidence for a p38 mitogen-activated protein kinase/protein kinases-C-dependent mechanism.

Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor alpha (TNFalpha). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFalpha resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFalpha-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca(2+) release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5'-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5' portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFalpha, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.