Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed. METHODS Eighty-five patients with end-stage HF, QRS duration >120 ins, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up. RESULTS Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs. 35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony :65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ins (p < 0.001). CONCLUSIONS Patients with LV dyssynchrony greater than or equal to65 ms respond to CRT and have an excellent prognosis after CRT. (C) 2004 by the American College of Cardiology Foundation.

Prognostic value of intraventricular dyssynchrony according to clinical stage of left ventricular impairment

Intraventricular dyssynchrony has prognostic implications in patients who have severe functional limitation and decreased ejection fraction. Patients with less advanced cardiac disease often exhibit intraventricular dyssynchrony, but there is little available information about its prognostic relevance in such patients. We investigated the prognostic effect of intraventricular dyssynchrony on outcome in 318 patients with known or suspected coronary artery disease who were classified according to the presence or absence of left ventricular dysfunction and heart failure symptoms. Mortality was considered the primary end point over a median follow-up of 56 months, and a Cox proportional hazards model was used for survival analysis. Despite a low prevalence (8%) of left bundle branch block, there was a high prevalence of intraventricular dyssynchrony even in patients without symptomatic heart failure. The magnitude of intraventricular dyssynchrony correlated poorly with QRS duration (r = 0.25),end-systolic volume index (r = 0.27), and number of scar segments (r = 0.25). There,were 58 deaths during follow-up. Ventricular volume, ischemic burden, and magnitude of intraventricular dyssynchrony predicted outcome, but magnitude of intraventricular dyssynchrony was an independent predictor of survival only in patients with asymptomatic left ventricular dysfunction. In conclusion, patients with known or suspected coronary artery disease have a high prevalence of intraventricular dyssynchrony. Although ventricular volume, ischemic burden, and intraventricular dyssynchrony are potentially important prognostic markers, the relative importance of intraventricular dyssynchrony changes with the clinical setting and, may be greatest-in patients with preclinical disease. (c) 2006 Elsevier Inc. All rights reserved.

Evaluation of resynchronization of contractile function following biventricular pacing using colour tissue Doppler imaging

Biventdcular (BV) pacing is evaluated as an alternative treatment for patients with dilated cardiomyppathy (both ischemic and non-ischemic) and end-stage heart failure. Colour tissue Doppler imaging using echocardiography allows noninvasive, quantitative assessment of radial motion in the long-axis with measurement of peak systolic velocity timing. The aim of the present study was to evaluate quantitatively, the systolic performance of the left ventricle and the resynchrenization of contraction (before vs after implantation). Patients and methods: 25 patients with dilated cardiomyopathy (11 ischemic), NYHA class III or IV, QRS duration >120 ms received a biventricular pacemaker. Routine 2D echo and colour tissue Doppler imaging were performed before and within 1 week following implantation. LVEF was assessed using the biplane Sampson's method.Peak systolic velocity (PSV) and time to PSV (TPV) were assessed in 4 regions (basal anterior, inferior, lateral and septal). By averaging the TPV from all 4 regions, a synchronization index was dedved from these measurements. Reaults: LVEF improved by 9±9% following pacing; 17 patients improved LVEF 5% or more. The change in PSV in the septal and lateral regions related significantly to the change in LVEF (r=0.74, r=0.62).The change in synchronization index before vs after pacing (as a measurement of REsynchronization) was related to the change in LVEF (y=120x+5.6, r=0.79, P

The relationship between diurnal type and time duration estimation at morning and evening times of day

This study investigates whether different diurnal types (morning versus evening) differ in their estimation of time duration at different times of the day. Given that the performance of morning and evening types is typically best at their preferred times of day, and assuming different diurnal trends in subjective alertness (arousal?) for morning and evening types, and adopting the attentional gate model of time duration estimation, it was predicted that morning types would tend to underestimate and be more accurate in the morning compared to evening types where the opposite pattern was expected. Nineteen morning types, 18 evening types and 18 intermediate types were drawn from a large sample (N=1175) of undergraduates administered the Early/Late Preference Scale. Groups performed a time duration estimation task using the production method for estimating 20-s unfilled intervals at two times of day: 0800/1830. The median absolute error, median directional error and frequency of under- and overestimation were analysed using repeated-measures ANOVA. While all differences were statistically non-significant, the following trends were observed: morning types performed better than evening types; participants overestimated in the morning and underestimated in the evening; and participants were more accurate later in the day. It was concluded that the trends are inconsistent with a relationship between subjective alertness and time duration estimation but consistent with a possible relationship between time duration estimation and diurnal body temperature fluctuations. (C) 2002 Elsevier Ltd. All rights reserved.

Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation

Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery. (C) 2003 Elsevier Science (USA). All rights reserved.

Dynamic force balances for short-duration hypersonic testing facilities

Two force balance techniques for use in hypersonic impulse facilities are compared by measuring the drag force on a 30&DEG; semi-apex-angle blunt cone model in a hypersonic shock tunnel at a free stream Mach number of 5.75. An accelerometer-based balance and a stress-wave force balance were tested simultaneously on the same model to measure the drag force. It was found that drag force measurements could be made using both techniques in a flow with a 450-μ s test period. The measured drag forces compared well with the theoretical values estimated using Newtonian theory.

The effect of an algorithm-based sedation guideline on the duration of mechanical ventilation in an Australian intensive care unit

To examine the effect of an algorithm-based sedation guideline developed in a North American intensive care unit (ICU) on the duration of mechanical ventilation of patients in an Australian ICU. The intervention was tested in a pre-intervention, post-intervention comparative investigation in a 14-bed adult intensive care unit. Adult mechanically ventilated patients were selected consecutively (n =322) The pre-intervention and post-intervention groups were similar except for a higher number of patients with a neurological diagnosis in the pre-intervention group. An algorithm-based sedation guideline including a sedation scale was introduced using a multifaceted implementation strategy. The median duration of ventilation was 5.6 days in the post-intervention group, compared with 4.8 days for the pre-intervention group (P = 0.99). The length of stay was 8.2 days in the post-intervention group versus 7.1 days in the pre-intervention group (P = 0.04). There were no statistically significant differences for the other secondary outcomes, including the score on the Experience of Treatment in ICU 7 item questionnaire, number of tracheostomies and number of self-extubations. Records of compliance to recording the sedation score during both phases revealed that patients were slightly more deeply sedated when the guideline was used. The use of the algorithm-based sedation guideline did not reduce duration of mechanical ventilation in the setting of this study.

Duration of cannabis use - a novel phenotype?

Although cannabis is the most commonly used illicit drug, duration of cannabis use is typically short, with many of those who initiate cannabis use ceasing use by their late twenties. In this paper we analyze data from a volunteer Australian cohort of 6265 male and female twins to examine whether the duration of cannabis use is an informative phenotype for future genetic analyses. Genetic modeling indicated: (a) moderate genetic influences on duration of cannabis use in both males (41%; 95% CI = 31–51) and females (55%; 95% CI = 46–63); (b) strong genetic influences on cannabis dependence in both males (72%, 95% CI = 61–81) and females (62%, 95% CI = 48–74); (c) no evidence of shared environmental influences on duration of cannabis use or on cannabis dependence in either males or females. Importantly, this model fitting indicated that a substantial component of genetic influences (rg = .90, 95% CI = .77–.99 (males); .70, 95% CI = .57–.83 (females)) on duration of cannabis use was shared with those influencing liability to cannabis dependence. While there were high genetic correlations in both women and men, lifetime duration of cannabis may be uniquely informative in assessing components of liability to cannabis use.

Clinical signs and duration of cyanide toxicosis delivered by the M-44 ejector in wild dogs

Sodium cyanide poison is potentially a more humane method to control wild dogs than sodium fluoroacetate (1080) poison. This study quantified the clinical signs and duration of cyanide toxicosis delivered by the M-44 ejector. The device delivered a nominal 0.88 g of sodium cyanide, which caused the animal to loose the menace reflex in a mean of 43 s, and the animal was assumed to have undergone cerebral hypoxia after the last visible breath. The mean time to cerebral hypoxia was 156 s for a vertical pull and 434 s for a side pull. The difference was possibly because some cyanide may be lost in a side Pull. There were three distinct phases of cyanide toxicosis: the initial phase was characterised by head shaking, panting and salivation; the immobilisation phase by incontinence, ataxia and loss of the righting reflex; and the cerebral hypoxia phase by a tetanic seizure. Clinical signs that were exhibited in more than one phase of cyanide toxicosis included retching, agonal breathing, vocalisation, vomiting, altered levels of ocular reflex, leg paddling, tonic muscular spasms, respiratory distress and muscle fasciculations of the muzzle.

Onset of sheath extension and duration of lamina extension are major determinants of the response of maize lamina length to plant density

Background and Aims Plants regulate their architecture strongly in response to density, and there is evidence that this involves changes in the duration of leaf extension. This questions the approximation, central in crop models, that development follows a fixed thermal time schedule. The aim of this research is to investigate, using maize as a model, how the kinetics of extension of grass leaves change with density, and to propose directions for inclusion of this regulation in plant models. • Methods Periodic dissection of plants allowed the establishment of the kinetics of lamina and sheath extension for two contrasting sowing densities. The temperature of the growing zone was measured with thermocouples. Two-phase (exponential plus linear) models were fitted to the data, allowing analysis of the timing of the phase changes of extension, and the extension rate of sheaths and blades during both phases. • Key Results The duration of lamina extension dictated the variation in lamina length between treatments. The lower phytomers were longer at high density, with delayed onset of sheath extension allowing more time for the lamina to extend. In the upper phytomers—which were shorter at high density—the laminae had a lower relative extension rate (RER) in the exponential phase and delayed onset of linear extension, and less time available for extension since early sheath extension was not delayed. • Conclusions The relative timing of the onset of fast extension of the lamina with that of sheath development is the main determinant of the response of lamina length to density. Evidence is presented that the contrasting behaviour of lower and upper phytomers is related to differing regulation of sheath ontogeny before and after panicle initiation. A conceptual model is proposed to explain how the observed asynchrony between lamina and sheath development is regulated.

Systematic changes in the duration and precision of interception in response to variation of amplitude and effector size

The results of two experiments are reported that examined how performance in a simple interceptive action (hitting a moving target) was influenced by the speed of the target, the size of the intercepting effector and the distance moved to make the interception. In Experiment 1, target speed and the width of the intercepting manipulandum (bat) were varied. The hypothesis that people make briefer movements, when the temporal accuracy and precision demands of the task are high, predicts that bat width and target speed will divisively interact in their effect on movement time (MT) and that shorter MTs will be associated with a smaller temporal variable error (VE). An alternative hypothesis that people initiate movement when the rate of expansion (ROE) of the target's image reaches a specific, fixed criterion value predicts that bat width will have no effect on MT. The results supported the first hypothesis: a statistically reliable interaction of the predicted form was obtained and the temporal VE was smaller for briefer movements. In Experiment 2, distance to move and target speed were varied. MT increased in direct proportion to distance and there was a divisive interaction between distance and speed; as in Experiment 1, temporal VE was smaller for briefer movements. The pattern of results could not be explained by the strategy of initiating movement at a fixed value of the ROE or at a fixed value of any other perceptual variable potentially available for initiating movement. It is argued that the results support pre-programming of MT with movement initiated when the target's time to arrival at the interception location reaches a criterion value that is matched to the pre-programmed MT. The data supported completely open-loop control when MT was less than between 200 and 240 ms with corrective sub-movements increasingly frequent for movements of longer duration.

Can myocardial contrast echo provide incremental benefit to exercise echo? Implications of the intensity and duration of hyperaemia

Background. Stress myocardial contrast echo (MCE) is technically challenging with exercise (Ex) because of cardiacmovementandshort duration ofhyperemia.Vasodilators solve these limitations, but are less potent for inducing abnormal wall motion (WM). We sought whether a combined dipyridamole (DI; 0.56 mg/kg i.v. 4 min) and Ex stress protocol would enable MCE to provide incremental benefit toWManalysis for detection of CAD. Methods. Standard echo images were followed by real time MCE at rest and following stress in 85 pts, 70 undergoing quantitative coronary angiography and 15 low risk pts.WMAfrom standard and LVopacification images, and then myocardial perfusion were assessed sequentially in a blinded fashion. A subgroup of 13 pts also underwent Ex alone, to assess the contribution of DI to quantitative myocardial flow reserve (MFR). Results. Significant (>50%) stenoses were present in 43 pts, involving 69 territories. Addition of MCE improved SE sensitivity for detection of CAD (91% versus 74%, P = 0.02) and better appreciation of disease extent (87% versus 65%territories, P=0.003), with a non-significant reduction in specificity. In 55 territories subtended by a significant stenosis, but with no resting WM abnormality, ability to identify ischemia was also significantly increased by MCE (82% versus 60%, P = 0.002). MFR was less with Ex alone than with DIEx stress (2.4 ± 1.6 versus 4.0 ± 1.9, P = 0.05), suggesting prolongation of hyperaemia with DI may be essential to the results. Conclusions. Dipyridamole-exercise MCE adds significant incremental benefit to standard SE, with improved diagnostic sensitivity and more accurate estimation of extent of CAD.