Advanced electrocardiographic parameters change with severity of mitral regurgitation in Cavalier King Charles Spaniels in sinus rhythm.

BACKGROUND: Multiple advanced resting ECG (A-ECG) techniques have improved the diagnostic or prognostic value of ECG in detecting human cardiac diseases even before onset of clinical signs or changes in conventional ECG. OBJECTIVE: To determine which A-ECG parameters, derived from 12-lead A-ECG recordings, change with severity of mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCSs) in sinus rhythm. ANIMALS: Seventy-six privately owned CKCSs. METHODS: Dogs were prospectively divided into 5 groups according to the degree of MR (estimated by color Doppler mapping as the percentage of the left atrial area affected by the MR jet) and presence of clinical signs. High fidelity approximately 5-minute 12-lead ECG recordings were evaluated using custom software to calculate multiple conventional and A-ECG parameters. RESULTS: Nineteen of 76 ECG parameters were significantly different (P < .05) across the 5 dog groups. A 4-parameter model that incorporated results from 1 parameter of heart rate variability, 2 parameters of QT variability, and 1 parameter of QRS amplitude was identified that explained 82.4% of the variance with a correlation coefficient (R) of 0.60 (P < .01). When age or murmur grade was included in the statistical model the prediction value further increased the R to 0.74 and 0.85 (P < .01), respectively. CONCLUSION: In CKCSs with sinus rhythm, 4 selected A-ECG parameters further improve prediction of MR jet severity beyond age and murmur grade, although the predictive increment in this study probably is not sufficient to warrant utilization in clinical veterinary practice.

Advanced electrocardiographic predictors of mortality in familial dysautonomia.

OBJECTIVE: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD). METHODS: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG. RESULTS: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease. CONCLUSION: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR > or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function.

Cardiac output measurements with electrical velocimetry in patients undergoing CABG surgery: a comparison with intermittent thermodilution.

BACKGROUND AND OBJECTIVE: The purpose was to study the agreement between cardiac output measurements with electrical velocimetry vs. intermittent thermodilution before and after coronary artery bypass graft surgery. METHODS: Cardiac output was measured simultaneously with electrical velocimetry and intermittent thermodilution before and immediately after coronary artery bypass graft surgery, and in the intensive care unit. Measurements were performed in three different body positions. The results were analysed according to Bland and Altman. RESULTS: The mean bias of all 150 paired measurements in 16 patients was 0.21 +/- 0.78 L min(-1), and the mean error was 40%. Before skin incision the mean bias was 0.04 +/- 0.41 L min(-1), and the mean error was 25%. After skin closure the mean bias was 0.57 +/- 0.92 L min(-1), and the mean error was 42%. In the intensive care unit the mean bias was 0.26 +/- 0.68 L min(-1), and the mean error was 32%. CONCLUSIONS: The agreement between cardiac output measurements with electrical velocimetry and intermittent thermodilution was clinically acceptable only before skin incision in coronary artery bypass graft surgery. The mean error was unacceptably high immediately after skin closure and was at a borderline level in the intensive care unit. Thus, the overall accuracy of cardiac output measurements with the electrical velocimetry technique during coronary artery bypass graft surgery is not clinically unacceptable.

The effect of estrogen replacement therapy on ventricular repolarization dynamics in healthy postmenopausal women.

Even though gender-specific differences in ventricular repolarization have gained wide recognition, the underlying mechanisms remain unknown. Because estrogen hormones may represent a causative factor for the changes in ventricular repolarization in women, this study evaluates a potential impact of estrogen replacement therapy on ventricular repolarization dynamics. Beat-to-beat QT and RR interval variability and QT/RR relationship during 5 minute resting high-resolution electrocardiogram recordings were measured in 30 healthy postmenopausal women (mean age 54.5 years) before and after 10 weeks of estrogen replacement therapy (ERT) with estradiol 2 mg/day. The 2 control groups included 12 healthy postmenopausal women of the similar age, who did not receive ERT, and 11 comparably healthy age-matched men. To evaluate ventricular repolarization dynamics, QT/RR linear regression slopes were calculated. After the 10-week period, the QT/RR regression slope increased by 93% in the ERT group (P <.001), but no alterations were noted in either the male or female controls. The overall variability of RR and QT intervals did not change in any of the groups studied. Our results suggest that ERT causes alterations in ventricular repolarization dynamics without significantly affecting the autonomic nervous tone.

Beat-to-beat QT interval variability in coronary patients.

Changes in ventricular repolarization have been described in patients after myocardial infarction, whereas data for coronary patients without prior myocardial infarction are lacking. This study was designed to evaluate ventricular repolarization in coronary patients with effort angina pectoris. Beat-to-beat QT interval variability (QTV) using 5-minute resting high-resolution ECG recordings was measured in 26 men (mean age 62.1 years) with effort angina pectoris and without prior myocardial infarction, and in 30 age-matched men without clinically evident coronary heart disease (controls). To evaluate the degree of coronary artery disease in coronary patients, coronary angiography was performed. Coronary patients displayed significantly higher values of QTV compared with the control patients (P < .001). Rate adaptation of QT interval correlated significantly with the degree of coronary artery disease in the study group patients (P < .05). The significant association between QTV and coronary heart disease suggests altered ventricular repolarization in coronary patients without prior myocardial infarction.

The reversible displacement of the passive diastolic p-V curve in the isolated guinea pig left ventricle.

We studied viscoelastic behaviour of the isolated diastolic guinea pig left ventricle (LV), manifested in changes of the hysteresis loop of the pressure-volume (p-V) diagram, produced by acute volume loading. Specifically, we investigated how the width of the hysteresis depends on the way LV volume loading, and whether changes in the hysteresis width are reversible. Each of 11 LV was instrumented with a catheter for injection and withdrawal of saline, and a micromanometer (Millar, 2F) to measure LV pressure. LV were loaded by the computer controlled injection of saline in 6-8 sequential injection steps of 100 microl each with a pause of 5 s, followed by a similar withdrawal pattern. In protocol A (N = 5), a 100 microl higher maximal LV volume (LVVmax) was reached during injection than in the control run, and in protocol B (N = 6), the time spent at LVVmax was longer (20 vs. 5 s pause). In both protocols a reproducible displacement of the passive p-V curve during volume unloading was observed, reflected in the increase of the hysteresis width by 23+/-8% in protocol A, and 12+/-3% in protocol B. Reversible displacement of the passive diastolic p-V curve after large aperiodic volume change suggests participation of reversible phenomena, like extracellular fluid filtration, and may in part provide an answer to the phenomenon of preconditioning.

Non-invasive beat-to-beat determination of changes in the small artery compliance after smoking.

We investigated the response of the small arterial compliance on smoking in 5 occasional smokers before, during and after inhaling the first cigarette in the day. For this purpose we used a non-invasive method based on interpretation of the oscillometric signal from the finger cuff coupled to the signal from photoplethysmograph. This system enables on-line determination of the finger artery compliance as function of transmural pressure (p(tm)) between 0 and 120 mm Hg, where each heart beat is presented by a set of compliance values in the range of the pulse pressure reduced by the cuff pressure. This procedure allowed construction of time course of the arterial compliance. When comparing the compliance value at ptm of 40 mm Hg, we found its fluctuations around the steady value during the rest and immediate lowering of the compliance after smoking, accompanied by the increase of blood pressure and heart rate.

Relaxation of epicardial strains after volume changes in the isolated guinea pig left ventricle.

Cardiac muscle is a porous viscoelastic material, exhibiting stress relaxation and hysteresis after being passively stretched. We investigated whether these material properties are also manifested in relaxation of epicardial segment lengths of the passive diastolic left ventricle (LV). For this purpose LV pressure and biaxial epicardial strains were measured simultaneously in isolated guinea pig hearts, arrested in diastole and instrumented to manipulate LV volume. Our study confirmed the existence of epicardial strain relaxation in both axial and circumferential directions, though it was much less expressed than LV pressure relaxation. Since the volume calculated from the segment lengths also revealed relaxation phenomena, our findings suggest that epicardial strain relaxation was connected with exchange of fluid from the LV cavity into the tightened epicardial vessels and back and not with the transformation of the LV shape.

Changes in blood pH, lactate concentration and pulmonary ventilation during incremental testing protocol on cycle ergometer.

We investigated mutual changes in the blood lactate concentration ([LA]), blood pH and pulmonary ventilation (VE) to obtain insight into the regulation of pH at different levels of the exercise intensity. For this purpose the ratio VE/[LA] (1/min/mmol/l) was determined at each particular pH corresponding to exercise intensity in seven healthy subjects on the cycle ergometer during incremental exercise test. Changes in VE/[LA] ratio were found to exhibit three phases. In the first phase, the ratio increased without significant changes in [LA] and pH until it reached certain individual peak value. In the second phase, VE/[LA] decreased because increases in [LA] were considerably bigger than those of VE. Decreases in blood pH followed those of VE/[LA], nevertheless differences existed among subjects depending on how successful individual subjects regulated their blood pH. In the third phase with the VE/[LA] values stabilized between 15 and 22 and pH values between 7.32 and 7.26, whereas differences between subjects became negligible. Similar trends to VE/[LA] were observed in case of the Onset of Blood Lactate Accumulation (OBLA) throughout the test at pH values below 7.32, as was manifested by the correlation coefficient. We conclude that blood pH regulation due to respiratory compensation of the lactate acidosis is more successful in subjects with better endurance (higher OBLA) but only when [LA] is slightly increased or at slight acidosis.

Viscoelastic behavior of the isolated guinea pig left ventricle in diastole.

To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles arrested in diastole. The left ventricle was loaded and unloaded by manual injection and withdrawal of saline in 10 x 0.1-ml steps, controlling the steadiness of LV volume by measuring LV major and minor diameters (ultrasonic crystals). Cyclic stepwise volume loading and unloading resulted in a hysteresis loop, the complexity of which was caused by stress relaxation at each steady volume. With the use of linear regression analysis, the gross elastic effect of the pressure signal was separated from the viscoelastic part, decomposed into the fast and the slow component with time constants of relaxation equal to 1 and 20 s, respectively. The amplitudes of the fast and the slow component showed that 1) stress relaxation is more expressed at higher LV volume and 2) it is asymmetric, i.e., it is well expressed during volume loading and almost absent during volume unloading. Both suggest that viscoelasticity of passive myocardium is not quasilinear, when the left ventricle is subjected to aperiodic volume loading to a high LV volume. The asymmetric viscoelastic behavior is consistent with the hypothesis of extracellular fluid filtration.

Blood pH and lactate kinetics in the assessment of running endurance.

To study how two types of testing protocols for the determination of the [LA] and blood pH kinetics during running match each other, a group of nine runners participated in two testing protocols. The first protocol consisted of a sequences of 8 x 2000 m runs at constant speed, which was increased on different testing days. The first protocol was used for the determination of running speed (v), [LA], pH and heart rate (HR) corresponding to the Lactate Threshold (LT) and the Threshold of Acidosis (TA), both occurring at similar running speeds (4.21 +/- 0.44 and 4.22 +/- 0.40 m/s) (mean +/- SD) and HR (159 +/- 7 and 160 +/- 9 1/min), [LA] = 2.0 +/- 0.6 mmol/l and pH = 7.411 +/- 0.018. Maximal steady values for [LA] (maxLAss) and minimal steady values for pH (minpHss) obtained by the second protocol were higher (p < 0.01) according to running speed (4.62 +/- 0.38 and 4.66 +/- 0.38 m/s), HR (172 +/- 7 and 174 +/- 8 1/min) and [LA] (5.7 +/- 1.3 mmol/l) and lower according to pH (7.364 +/- 0.021), respectively. Unlike similar running speeds determined by LT and TA, the minimal steady pH level occurred at a slightly higher speed than the speed at maxLAss. Additionally, we found a drift of pH towards a resting level, when [LA] fluctuated around a steady level. Furthermore, the parameters of pH kinetics correlated better with the running speed of the 4000 m run that was taken as the parameter of short endurance performance, than those of [LA] kinetics. We conclude that these differences in [LA] and pH kinetics could serve to predict the capabilities of runners with respect to the two endurance performance types: long and short.

Shifts in contractile regulatory protein subunits troponin T and troponin I in cardiac hypertrophy.

To examine the molecular basis of hypertrophied heart failure, we investigated the changes in cardiac contractile regulatory proteins. The guinea pigs were subjected to chronic pressure overload with aortic banding to induce ventricular hypertrophy, and in-situ pressure-volume relations were recorded together with biochemical characterizations to ascertain the contractile modifications. Immunoblots of left and right ventricular samples revealed four distinct troponin T isoforms, which underwent alterations during hypertrophy. The higher molecular weight bands TnT1 and TnT2 shifted towards the lower molecular weight isoforms TnT3 and TnT4. For TnI, a single prominent band was detected, whose intensity also increased with pump failure. The findings provide the first direct evidence of TnT and TnI shifts in an experimentally induced hypertrophied heart failure and has novel mechanistic implications for the future studies.

Influence of diastolic fibre orientation on the left ventricular power generation.

A mathematical model is described which in a simplified way, without directly taking into account the elastic properties of the heart wall, describes the EDV which corresponds to the experimental data. The model further describes the power generation of the left ventricle at high EDV. The volume density of power is expressed with a product of three factors (1) average density of the CE, (2) a factor which contains the inotropic properties of a single CE and (3) a form factor, which involves structural changes in the heart wall at various EDV.