Decrease In Deceleration Time Research Articles

Treatment of Sleep Apnea with Positive Airway Pressure and Its Association with Diastolic Dysfunction: A Systematic Review and Meta-Analysis

Background: This meta-analysis assessed the effect of long-term (>6 weeks) noninvasive positive airway pressure (PAP) on diastolic function in patients with obstructive sleep apnea (OSA). Methods: We searched the databases for randomized clinical trials including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 20, 2019. The search was not restricted to time, publication status, or language. Two independent investigators screened the studies and extracted the data, in duplicate. Risk of bias was assessed using Cochrane collaboration tools. Results: A total of 2,753 abstracts were resulted from literature search. A total of 9 randomized clinical trials assessing the effect of long-term (>6 weeks) PAP on diastolic function in patients with OSA including 833 participants were included. The following echo parameters were found in treated patients: a decrease in deceleration time (−39.49 ms CI [−57.24, −21.74]; p = 0.000), isovolumic relaxation time (−9.32 ms CI [−17.08, −1.57]; p = 0.02), and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (−1.38 CI [−2.6, −0.16]; p = 0.03). However, changes in left-atrial volume index and the ratio of early to late mitral inflow velocities were not statistically different. The risk of bias was mild to moderate among the studies. Conclusion: Our results suggest that chronic treatment of moderate to severe OSA with noninvasive PAP is associated with improvement in echocardiographic findings of diastolic dysfunction.

Abstract 16855: NOX4 NADPH Oxidase Mediates Diastolic Dysfunction in Stress Cardiomyopathy via Regulation of Inflammation and Fibrosis

Acute sympathetic stress in adults results in catecholamine overload and often leads to development of stress cardiomyopathy complicated by long-lasting diastolic dysfunction. We previously reported that activation of β-adrenergic signaling in the heart increases reactive oxygen species-mediated inflammasome activation and IL-18 release, inducing myocardial inflammation, fibrosis, and dysfunction. Here we tested the hypothesis that NOX4 NADPH oxidase is a primary mediator of myocardial inflammation and diastolic dysfunction in the setting of acute stress. Acute stress in wild-type and mice with cardiomyocyte (CM)-specific Nox4 deletion ( Nox4 CM-/- ) was induced with a single dose of β-adrenergic receptor agonist isoproterenol (ISO; 5 mg/kg) injection. After 3 days, ISO-treated wild-type mice had higher myocardial H 2 O 2 , inflammasome activation and IL-1β, IL-18, IL-6, CCL2, and TNF-α levels and enhanced myocardial interstitial macrophage infiltration compared with vehicle-treated or Nox4 CM-/- mice (p<0.001). Wild-type mice left ventricles had increased presence of activated fibroblasts (periostin + ) and myofibroblasts (α-actin-2 + ) and significantly higher interstitial collagen deposition compared with Nox4 CM-/- mice 7 days post-ISO. Assessment of left ventricular function showed significantly increased mitral valve E, decreased deceleration time, decreased tissue Doppler E’ and increased E/E’ without changes in ejection fraction and end systolic or diastolic volumes, suggesting restrictive pattern of diastolic dysfunction with increased filling pressure in wild-type compared with control or Nox4 CM-/- mice. ISO treatment of ventricular CMs isolated from wild-type mice significantly increased levels of H 2 O 2 and expression of NLRP3 and cleaved caspase-1 and IL-18 as compared with Nox4 -deficient or wild-type CMs pretreated with NOX4/NOX1 inhibitor GKT137831. These data suggest that NOX4 NADPH oxidase is a critical mediator of CM sympathetic overstimulation inducing inflammasome activation and cytokine release, myocardial inflammation, and fibrosis, resulting in impaired diastolic function. Inhibiting myocardial NOX4 during acute sympathetic stress may be beneficial to preserve cardiac function.

E-wave asymmetry elucidates diastolic ventricular stiffness-relaxation coupling: model-based prediction with in vivo validation.

Load, chamber stiffness, and relaxation are the three established determinants of global diastolic function (DF). Coupling of systolic stiffness and isovolumic relaxation has been hypothesized; however, diastolic stiffness-relaxation coupling (DSRC) remains unknown. The parametrized diastolic filling (PDF) formalism, a validated DF model incorporates DSRC. PDF model-predicted DSRC was validated by analysis of 159 Doppler E-waves from a published data set (22 healthy volunteers undergoing bicycle exercise). E-waves at varying (46-120 bpm) heart rates (HR) demonstrated variation in acceleration time (AT), deceleration time (DT), and E-wave peak velocity. AT, DT, and Epeak were converted into PDF parameters: stiffness ([Formula: see text]), relaxation ([Formula: see text]), and load (xo) using published numerical methods. Univariate linear regression showed that over a twofold increase in HR, AT, and DT decrease ([Formula: see text] = -0.44; P < 0.001 and r = -0.42; P < 0.001, respectively), while, DT/AT remains constant (r = -0.04; P = 0.67). Similarly, [Formula: see text] increases with HR (r = 0.55; P < 0.001), while [Formula: see text] has no significant correlation with HR (r = 0.08; P = 0.32). However, the dimensionless DSRC parameter ψ = c2/4k shows no significant correlation with HR (r = -0.03; P = 0.7). Furthermore, ψ is uniquely determined by DT/AT rather than AT or DT independently. Constancy of ψ in spite of a twofold increase in HR establishes that stiffness (k) and relaxation (c) are coupled and manifest via a HR-invariant parameter of E-wave asymmetry and should not be considered independent of each other. The manifestation of DSRC through E-wave asymmetry via ψ underscores the value of DT/AT as a physiological, mechanism-derived index of DF.NEW & NOTEWORTHY: Although diastolic stiffness and relaxation are considered independent chamber properties, the cardio-hemic inertial oscillation that generates E-waves obeys Newton's law. E-waves vary with heart rate requiring simultaneous change in stiffness and relaxation. By retrospective analysis of human heart-rate varying transmitral Doppler-data, we show that diastolic stiffness and relaxation are coupled and that the coupling manifests through E-wave asymmetry, quantified through a parametrized diastolic filling model-derived dimensionless parameter, which only depends on deceleration time and acceleration time, readily obtainable via standard echocardiography.

Left atrial pressure pattern without a-wave in sinus rhythm after cardioversion affects the outcomes after catheter ablation for atrial fibrillation.

The a-wave in left atrial pressure (LAP) is often not observed after cardioversion (CV). We hypothesized that repeated atrial fibrillation (AF) occurs in patients who do not show a-wave pattern after CV. We investigated the impact of "LAP pattern without a-wave" on the outcome after catheter ablation (CA) for AF. We studied 100 patients (64 males, age 66 ± 8years, 42 with non-paroxysmal AF) who underwent CA for AF. Sustained- or induced-AF were terminated with internal CV, and LAP was measured during sinus rhythm (SR) after CV. LAP pattern without a-wave was defined as absence of a-wave (the "a-wave" was defined as a protruding part by 0.2mmHg or more from the baseline) in LAP wave form. AF was terminated with CV in all patients. Recurrent AF was detected in 35/100 (35%) during the follow-up period (13.1 ± 7.8month). Univariate analysis revealed higher prevalence of LAP pattern without a-wave (71 vs. 17%, P < 0.0001), larger left atrial volume, elevated E wave, and decreased deceleration time as significant variables. On multivariate analysis, LAP pattern without a-wave was only independently associated with recurrent AF (P = 0.0014, OR 9.865, 95% CI 2.327-54.861). Moreover, patients with LAP pattern without a-wave had a higher risk of recurrent AF than patients with a-wave (25/36 patients, 69 vs. 10/64 patients, 16%, log-rank P < 0.0001). Left atrial pressure pattern without a-wave in sinus rhythm after cardioversion could predict recurrence after catheter ablation for AF.

Determinants of Normal Left Atrial Volume in Heart Failure with Moderate-to-Severely Reduced Ejection Fraction.

Background Indexed left atrial volume (LAVi) is a robust predictor of adverse cardiovascular events. A minority of patients with moderate-to-severe left ventricular (LV) systolic dysfunction maintain normal LAVi. We followed clinical and echocardiographic parameters for at least 6 months to understand how this population is different from patients with similar systolic dysfunction and dilated left atria. Methods and Results We searched our electronic medical records for “normal” (n=817) and “severely dilated” (n=1094) LA size and LV ejection fraction (EF) ≤ 35% on echocardiogram reports from 2009 to 2015. We analyzed 115 subjects for LAVi, biplane EF, and diastolic parameters over 2 echocardiograms at least 6 months apart. Younger age, white race, being on an angiotensin-converting enzyme inhibitor, smaller end-diastolic LV volume (LVEDV), and longer deceleration time (DT) were associated with having a normal LAVi. The receiver-operating characteristic curve has an area under the curve of 0.95 (p < 0.0001) for this model. An increase in LVESVi and early mitral flow velocity and a decrease in DT explain 32% of the variance seen in LAVi increase over time. Conclusion In patients with moderate-to-severely reduced EF, younger age, being on heart failure therapies, and better diastolic dysfunction were independently associated with a normal LAVi. Improvement in systolic and diastolic performances was associated with decreasing LAVi with 6-month to 1-year follow-up.

Abstract 11686: Pericellular Amyloid Infiltration in Biopsy-proven Cardiac Amyloidosis

Background: Cardiac amyloidosis is a rare disease characterized by the myocardial infiltration of amyloid. There are several histopathological patterns of amyloid accumulation, of which pericellular amyloid pattern is classified when amyloid is observed around each cardiomyocyte in endomyocardial biopsy. However, the relationship between pericellular amyloid deposition pattern and clinical characteristics has not yet been investigated. Objective: We retrospectively investigated endomyocardial biopsy-proven cardiac amyloidosis with pericellular amyloid deposition. Methods: Thirty cardiac amyloidosis patients in our institution were included. Results: Thirteen patients (43%) were pathologically classified into pericellular amyloid deposition. In the baseline characteristics, the patients with pericellular deposition had significantly lower age (69 ± 9 vs. 75 ± 6 years, p = 0.032) and higher brain natriuretic peptide levels (681 ± 516 vs. 267 ± 393 pg/ml, p = 0.003), compared with those without pericellular deposition. Electrocardiographic findings revealed that patients with pericellular amyloid deposition had significantly higher incidence of low voltage (46 vs. 12%, p = 0.045) and pseudoinfarction pattern (46 vs. 6%, p = 0.015), compared with patients without pericellular deposition. Echocardiography revealed that patients with pericellular deposition had significantly decreased deceleration time (152 ± 49 vs. 191 ± 50 ms, p = 0.049). Hemodynamic findings did not show significant difference between groups. High-sensitivity cardiac troponin-T levels were also analyzed in 14 cardiac amyloidosis patients without ischemic heart disease. Patients with pericellular amyloid deposition had significantly higher high-sensitivity cardiac troponin-T levels, compared with patients without pericellular deposition (0.128 ± 0.07 vs. 0.046 ± 0.03 pg/ml, p = 0.016). Conclusion: Pericellular amyloid deposition pattern was associated with electrocardiographic abnormalities, diastolic dysfunction, and ongoing myocardial damage. Our data suggest direct amyloid infiltration around the cardiomyocytes may cause myocardial damage, providing possible pathophysiological implication of the failing heart in cardiac amyloidosis.

Abstract 060: Adipose Derived Stem Cell (ADSC) Therapy Prevents The Progression Of Hypertension And Improves Cardiac Functions

Despite major advances in pharmacological and interventional therapies, 30% of hypertensive patients do not achieve their blood pressure (BP) target and have apparent treatment resistant hypertension (TRH). Thus, innovative strategies are urgently needed for the control of TRH considering its prevalence and deleterious complications. The objective of the current study was to evaluate effects of ADSC on BP in spontaneously hypertensive rats (SHR). The rational for using ADSC is that they have multipotent differentiation capacities and potent anti-inflammatory effects. Moreover, autologous ADSC are an attractive therapeutic option for clinical trials based on availability, less invasive isolation procedure, and safety in several hundred patient studies. ADSC were isolated from inguinal adipose tissue of a normotensive WKY rat, characterized using flow cytometry (CD44 + ,CD90 + ,CD34 - and CD45 - ), and their differentiation ability to adipocyte was confirmed by Oil Red “O” staining. Basal systolic BP for SHR at 13 week age was 191.6 ± 5.6 mmHg measured by a tail-cuff method. SHR animals were then randomly assigned to control and ADSC-treated groups. ADSC (5х10 6 cells/animal) was intravenously administered through jugular vein into treated SHR. Three weeks after treatment, left ventricular function was assessed using echocardiography and direct BP was measured using a Millar catheter. The SHR control exhibited 82% increase in systolic BP (198.4 ± 25.9 vs WKY: 109.0 ± 1.6, mmHg) and 14% elevation in ventricular mass (3.3 ± 0.2 vs WKY: 2.9 ± 0.1, g/kg). Furthermore, the SHR control demonstrated 42% increase in deceleration time of mitral valve (58.1 ± 6.0 vs WKY: 40.8 ± 2.3; ms) and 21% decrease in ejection fraction (69.9 ± 4.2 vs WKY: 88.2 ± 1.3, %). Single injection of ADSC resulted in a 28% decrease in systolic BP (142.5 ± 25.8mmHg), 18% reduction in ventricular mass (2.7 ± 0.3g/kg), 36% decrease in deceleration time of mitral valve (36.9 ± 16.3ms), and 17% increase in ejection fraction (80.0 ± 3.4%). Collectively, our data demonstrate that ADSC arrested the progression of hypertension and associated left ventricular dysfunction in the hypertensive animals. It warrants additional study on ADSC intervention as a potential alternative treatment for hypertension.

Echocardiographic evaluation and comparison of the effects of sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction scheduled for coronary artery bypass grafting surgery

Background Effect of inhalational anesthetics on diastolic function in humans is still controversial, although inhalational anesthetics have been shown to have negative lusitropic action in experimental studies, which were explained by interference of inhalational anesthetics with calcium homeostasis. Aim This prospective randomized study aims to evaluate and compare the effects of sevoflurane and desflurane on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. Patients and methods After approval from the local ethics committee and informed consent, 24 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative transthoracic echocardiographic diagnosis of impaired relaxation or grade 1 diastolic dysfunction. Anesthetic induction was standardized in both groups. Patients randomly received 1 MAC of sevoflurane ( n = 12) or desflurane ( n = 12) for maintenance of anesthesia. Hemodynamic parameters and transesophageal echocardiography (TEE) derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept within normal range throughout the study period to exclude the effect of the loading conditions on diastolic function. Results The two study drugs significantly reduced the systemic vascular resistance index with a significant increase in the cardiac index. Hemodynamic changes measured by invasive arterial line and pulmonary artery catheter were comparable between the two groups. In terms of LV relaxation indices, the two agents led to a significant improvement in diastolic function. Transmitral and tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of the two agents on diastolic relaxation parameters was comparable. Conclusion Sevoflurane and desflurane appear to improve LV relaxation. This can be explained by a significant reduction in afterload produced by these vapors. The positive effect of these inhalational agents on LV relaxation can have a beneficial effect on the anesthetic management of patients with diastolic dysfunction.

Exercise Training Improves Diastolic Function in Heart Failure Patients

The study's purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved, mild, and moderate to severe reduction of left ventricular ejection fraction (LVEF). Ninety-eight patients with moderate to severe (n = 34), mild (n = 33), and preserved (n = 31) LVEF were randomly assigned to exercise training plus usual care (n = 65) or usual care alone (n = 33) in a randomization ratio of 2:1. Left ventricular function, left ventricular dimensions, and exercise tolerance were assessed before and after each intervention. Exercise tolerance and LVEF increased with exercise training in all patient groups, whereas they remained unchanged after usual care alone. Exercise training increased the mean ratio of early to late mitral inflow velocities (E/A ratio) and decreased deceleration time (DT) of early filling in patients with mild and preserved LVEF. In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction (DT < 160 ms), exercise training decreased E/A ratio and increased DT, both of which were unchanged after usual care alone. In the remaining patients (DT > 160 ms), exercise training also improved mitral inflow patterns. Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF. These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction.

Effect of simulated dives on diastolic function in healthy men

Scuba diving may elicit acute changes to human cardiovascular function. Environmental stresses such as immersion, cold, and venous gas microbubbles all have been shown to contribute to right ventricular overload and impaired left ventricular filling after single dives. We investigated cardiac function after simulated dry chamber dives. Twenty male divers [mean age 31 years, standard deviation (SD) 8 years, mean body mass index 26 kgm(-2) (SD 3 kgm(-2))] participated in the study. All subjects had normal ECG, stress-ECG, and transthoracic echocardiography at rest. Echocardiographic assessment of diastolic function [E/A-ratio, deceleration time (DT), isovolumic relaxation time (IVRT), E/e'-ratio] was performed directly prior to and 20 and 80 min after two simulated dry hyperbaric chamber dives (maximal pressure 600 kPa, duration 60 min) that were conducted within 1 week. DT statistically significantly decreased from 163 ms (SD 14 ms) to 125 ms (SD 15 ms) 20 min after the dive (p < 0.0001), whereas 80 min after decompression these changes tended to return to baseline [146 ms (SD 14 ms); p = 0.06]. There was no statistically significant change in heart rate, E/A-ratio or E/e'-ratio after 20 or 80 min compared to baseline. These changes could be reproduced after the second dry chamber dive. No gas microbubbles were detectable during or after decompression from either dive. Simulated hyperbaric dry chamber dives were associated with a transient decrease in deceleration time in healthy men. Factors other than immersion, cold, or nitrogen microbubbles may contribute to acute changes in cardiac function after single scuba dives.

A Murine Model of Isolated Cardiac Steatosis Leads to Cardiomyopathy

Lipid accumulation in the heart is associated with obesity and diabetes mellitus and may play an important role in the pathogenesis of heart failure seen in this patient population. Stored triglycerides are synthesized by the enzyme diacylglycerol acyl transferase (DGAT). We hypothesized that forced expression of DGAT1 in the cardiac myocyte would result in increased lipid accumulation and heart dysfunction. A cardiac myocyte-selective DGAT1 transgenic mouse was created and demonstrated increased lipid accumulation in the absence of hyperglycemia, plasma dyslipidemia or differences in body weight. Over time, expression of DGAT1 in the heart resulted in the development of a significant cardiomyopathy. Echocardiography revealed diastolic dysfunction with increased early mitral inflow velocity to late mitral inflow velocity ratio and decreased deceleration time, suggesting a restrictive pattern in the transgenic mice. Moderate systolic dysfunction was also seen at 52 weeks. Histological analysis showed increased cardiac fibrosis and increased expression of procollagen type 1A, matrix metalloproteinase 2, and tissue inhibitor of matrix metalloproteinase 2 in the transgenic mice. Mitochondrial biogenesis was reduced in the transgenic hearts, as was expression of cytochrome c oxidase 1 and cytochrome c. Expression of key transcription factors important in the regulation of mitochondrial biogenesis were reduced. These findings suggest that triglyceride accumulation, in the absence of systemic metabolic derangement, results in cardiac dysfunction and decreased mitochondrial biogenesis.

Homocysteine Thiolactone Induces Cardiac Dysfunction: Role of Oxidative Stress

This study investigates the cardiac functioning in male Wistar rats after treatments with methionine and homocysteine thiolactone (HcyT). The rats were distributed into 3 groups and treated for 8 weeks. Group I was the control (CO) group, given water, group II was treated with methionine, and group III with HcyT (100 mg/kg). Morphometric and functional cardiac parameters were evaluated by echocardiography. Superoxide dismutase (SOD), catalase, and glutathione S-transferase activities, chemiluminescence, thiobarbituric acid reactive substances, and immunocontent were measured in the myocardium. Hyperhomocysteinemiawas observed in rats submitted to the both treatments. The results showed diastolic function was compromised in HcyT group, seen by the increase of E/A (peak velocity of early (E) and late (A) diastolic filling) ratio, decrease in deceleration time of E wave and left ventricular isovolumic relaxation time. Myocardial performance index was increased in HcyT group and was found associated with increased SOD immunocontent. HcyT group demonstrated an increase in SOD, catalase, and glutatione S-transferase activity, and chemiluminescence and thiobarbituric acid reactive substances. Overall, these results indicated that HcyT induces a cardiac dysfunction and could be associated with oxidative stress increase in the myocardium.

Echocardiographic evaluation and comparison of the effects of isoflurane, sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction

This prospective randomized study aims to evaluate and compare the effects of isoflurane, sevoflurane and desflurane (study drugs) on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. After approval of the local ethics committee and informed consent, 45 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative Transthoracic Echocardiographic diagnosis of impaired relaxation or Grade 1 Diastolic Dysfunction. They randomly received fentanyl and midazolam anesthesia with 1 MAC of isoflurane (n=16), sevoflurane (n=14) or desflurane (n=15). Hemodynamic parameters and TEE derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept constant throughout the study period to exclude the effect of the loading conditions on diastolic function. Four patients in the sevoflurane group and three in the desflurane group were excluded from the study, after baseline TEE examination revealed normal diastolic filling pattern. All the three study drugs significantly reduced the systemic vascular resistance index with a significant increase in cardiac index. Mean arterial pressure was reduced by all the drugs, although the decrease was not statistically significant. Hemodynamic changes were comparable between all the three groups. In terms of LV relaxation indices, all three agents led to a significant improvement in diastolic function. Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of all three agents on diastolic relaxation parameters was comparable. In conclusion , Isoflurane, sevoflurane and desflurane, do not appear to have a detrimental effect in patients with early diastolic dysfunction. On the contrary, these inhalational agents actually improve the LV relaxation. A significant reduction in afterload produced by these vapors can be a possible reason for these findings. The positive effect of these inhalational agents on LV relaxation can have a profound effect on the perioperative anesthetic management of patients with diastolic dysfunction.

Physiologic Determinants of Mitral Inflow Pattern Using a Computer Simulation: Insights into Doppler Echocardiography in Diverse Phenotypes

Although echo Doppler recordings of mitral inflow patterns are often employed clinically to identify "diastolic dysfunction," abnormal flow profiles may be seen in a diverse set of disorders in which the specific physiologic determinants are not well defined. We used a validated cardiovascular simulation model to assess the effects of four hemodynamic parameters on Doppler measures of LV filling: (1) total blood volume, (2) diastolic stiffness (LV Beta), (3) systemic vascular resistance (SVR), and (4) pulmonary vascular resistance (PVR). In each simulation, we calculated instantaneous flow through the mitral valve as a function of time. Increases in blood volume led to an increase in the E:A ratio and a decrease in deceleration time (DT), such that for every 100 mL of volume, DT decreased by approximately 3 ms. Increases in LV Beta increased the E:A ratio and decreased DT such that for every 0.005 mmHg/mL increase in LV Beta, DT decreased by approximately 8 ms. While changes in SVR did not significantly alter the Doppler pattern, increases in PVR effected a prolongation of DT and an impaired relaxation E:A pattern. Increasing blood volume and LV Beta simultaneously was additive, while increasing PVR attenuated the effect of increasing volume on the E:A ratio. Computer simulations demonstrate that both blood volume and LV stiffness significantly impact the mitral inflow profile indicating that both filling pressure and intrinsic properties of the ventricle are contributors. These data confirm that there are multiple determinants of the Doppler mitral inflow pattern and suggest a new approach toward understanding complex physiologic interactions.

Rehabilitation of Reaching After Stroke: Comparing 2 Training Protocols Utilizing Trunk Restraint

Background and Purpose . Task-related training (TRT) but not resistive exercise (RE) was found to improve the path of the hand of a hemiparetic upper extremity when reaching to targets. Forward movement of the trunk, however, compensated for the poststroke motor impairment. Prior studies also demonstrated that short-term practice of reaching to grasp objects with truncal motion restrained (compared to unrestrained practice) increased elbow extension, lessened compensatory trunk movement, and improved interjoint coordination during performance with the trunk unrestrained. Objective. To determine the effects of TRT and RE on unrestrained reaching following extended practice in which compensatory truncal motion was limited. Methods. Using a restraining device to reduce movement of the trunk, hemiparetic patients with moderately severe motor impairment were given 12 sessions over 4 weeks of TRT (n = 5) or RE (n = 6). Reaching when the trunk was not restrained to targets located ipsilateral, midline, and contralateral to the impaired arm was tested before and 2 days after training by 3D kinematic analyses. Results. After both training protocols, kinematic analysis showed that trunk flexion decreased (P < .01, η2 = .53) scapular motion shifted toward protraction (P < .01, η2 = .57) and elbow extension increased (P < .04, η2 = .39). Only after TRT did the path of the hand straighten (P < .02, η2 = .46), deceleration time decrease (P < .03, η2 = .44), and, at the difficult ipsilateral target, shoulder flexion increase (P < .03, η 2 = .31). Conclusions. Training that restricted compensatory truncal motion during TRT improved the precision of reaching more than during RE. Truncal restraint during rehabilitation of reaching may be an effective therapeutic strategy in patients with moderately severe hemiparetic stroke, especially when combined with TRT.

Abstract 843: Restrictive Cardiomyopathy Linked cTnI Mutation (K178E) Causes Severe Heart Failure and Early Mortality

Multiple mutations in cardiac troponin I (cTnI) have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. Among them, K178E mutation has the worst clinical phenotype. K178E mutation may influence the inhibitory function through actin binding since previous studies have shown that amino acids number 173–181 bind to actin and increase the inhibitory effect of TnI. We modeled the mutation of lysine 178→glutamate (K178E) in human cTnI by cardiac specific expression of the mutated protein (cTnI 179Glu in mouse sequence) in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship. Increased resting tension in isolated cardiac myocytes and decreased myofibrillar compliance were the main manifestations in cellular function measurements. In vivo cardiac function measured by high-resolution ultrasonic imaging and Doppler echocardiography revealed a significant diastolic dysfunction characterized with decrease of left ventricular end diastolic dimension (LVEDD), decreased cardiac ejection fraction (EF) and left ventricular faction of shortening (FS) as well as a decreased cardiac output (CO). Doppler measurements showed a restrictive left ventricular filling pattern, i.e. reversed E/A ratio; decreased deceleration time (DT); decreased isovolumic relaxation time (IVRT). Enlarged left and right atria was a dramatic sign, which was observed in most of the transgenic mice, and was developed early and fast (at age of 2–3 weeks). Severely affected lines developed a pathology similar to that observed in human restrictive cardiomyopathy patients who carry the same mutation and with a high early mortality. Our data indicate the causality of this mutation for diastolic dysfunction and heart failure and provide a useful animal model for further understanding the thin filament structure-function relationships and the physiological function of triponin in cardiac contraction and relaxation. (Supported by NIH GM073621 and AHA0715116B) This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico &amp; Tennessee).

Differential effects of nebivolol and atenolol on transmitral diastolic filling parameters in patients with essential hypertension

Impaired left ventricular (LV) diastolic relaxation, detected by pulsed Doppler echocardiography, is predictive of a higher incidence of major cardiovascular events in hypertensive patients. An improvement in LV diastolic function is an important goal of treatment. However, treatment of LV diastolic dysfunction remains empirical. The objective of our study was to compare the short-term effects of nebivolol and atenolol on Doppler diastolic filling parameters in hypertensive patients. A total of 32 patients with mild-to-moderate hypertension were enrolled in the study. The patients were randomly assigned to receive treatment with either nebivolol (5 mg/day) or atenolol (50 mg/day) for 1 month. Diastolic filling parameters, with pulsed-wave Doppler transmitral flow velocities, were measured 1 day before and 1 month after treatment. Compared with baseline, both agents significantly decreased heart rate and blood pressure. However, there was no significant difference in pre-and post-treatment values between the nebivolol and atenolol groups. Both drugs significantly improved LV transmitral flow measured by early diastolic flow/atrial contraction signal (E/A) ratio, decreased deceleration time (DT) and isovolumetric contraction time (IVRT), but post-treatment improvement in E/A, DT and IVRT values was more significant with nebivolol compared with atenolol (P=0.05, P=0.05 and P=0.003, respectively). Although treatment with nebivolol or atenolol results in improved LV transmitral diastolic function filling parameters (E/A ratio, IVRT and DT), nebivolol has a greater effect compared with atenolol in patients with mild-to-moderate hypertension.

A Novel Finding to Assess Ischemia in Pacing Stress Echocardiography (PASE)

Normalization of heart rate post-pacing stress echocardiography (PASE) could enable evaluation of effect of ischemia on diastolic function. We examined the effect of pacing on left ventricular (LV) filling in 55 patients who underwent a transesophageal PASE. Pulse wave Doppler of mitral inflow was obtained at baseline and during transition from peak pacing to up to three beats immediate post pacing. Thirty-four patients (62%; 62 +/- 12 years) had normal (NL) PASE, wall motion score index (WMSI) 1 +/- 0 at baseline and during PASE. Sixteen patients (29%; 64 +/- 12 years) had ischemic (ISCH) PASE, WMSI 1.07 +/- 0.08 at baseline and 1.40 +/- 0.21 during PASE. Five patients (9%; 81 +/- 5 years) had abnormal (ABN) PASE, WMSI 1.55 +/- 0.34 at baseline and 1.55 +/- 0.34 during PASE. The ABN group had the most pronounced decrease in deceleration time (DT) seen in all three post-PASE beats (221 +/- 29 ms at baseline vs. 145 +/- 46, 144 +/- 26 and 144 +/- 18 ms at beats 1, 2, and 3, P < 0.005 from baseline for all). The DT reduced significantly at post-PASE beat 1 from baseline (234 +/- 45 ms vs. 158 +/- 36 ms, P = 0.02) in the ISCH group, whereas no significant change in DT occurred in the NL group (239 +/- 74 ms vs. 222 +/- 58 ms, P = 0.14) at beat 1. In ISCH and ABN ventricles the duration of early diastolic filling decreased post-pacing. This new finding of a shortened deceleration time (DT) may be a marker of an ischemic response in PASE reflecting abnormal LV compliance.

Regression of left ventricular hypertrophy and improvement of diastolic function in hypertensive patients treated with telmisartan

Objectives: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. Methods: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mm Hg, diastolic blood pressure [DBP] >90 mm Hg) and mild-to-moderate LV hypertrophy (LV mass index related to body surface area [LVMI] 117–150 g/m 2 for men and 105–150 g/m 2 for women) treated with telmisartan monotherapy 40–80 mg once daily for 1 year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood pressure was also monitored at all visits. Diastolic function was assessed by examination of transmitral inflow and pulmonary vein flow patterns. Results: Telmisartan reduced blood pressure; after 12 months, the mean±S.D. SBP and DBP were reduced from 144±10 to 126±8 mm Hg ( p<0.001) and from 98±8 to 86±7 mm Hg ( p<0.001), respectively. The LVMI was decreased from 119±7 to 109±3 g/m 2 ( p<0.001) after 12 months' telmisartan treatment. All patients had diastolic dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern of transmitral inflow was present in 21% of patients. The regression of LV hypertrophy observed after 12 months was associated with increased peak early diastolic velocity/peak late diastolic velocity ratio from 0.60±0.18 to 0.83±0.20 ( p<0.001), shortened isovolumic relaxation time (IVRT) from 110±13 to 105±13 ms ( p<0.001), and decreased deceleration time from 229±30 to 215±28 ms ( p=0.002). Univariate analysis showed that shortened IVRT was related to a reduction in the LVMI and LA maximal and minimal volumes. In the multivariate analysis, the reduction in LVMI and the reduction in LA maximal and minimal volumes were independently associated with IVRT reduction. Conclusions: Telmisartan 40–80 mg is effective in LV hypertrophy regression in hypertensive patients. The reduction in LVMI due to telmisartan monotherapy was associated with a significant improvement of diastolic filling parameters and with a significant reduction of LA volumes.

Plasma levels of natriuretic peptide and echocardiographic parameters in patients with Duchenne's progressive muscular dystrophy.

We investigated the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and systolic and diastolic cardiac function, determined by echocardiography, in 63 patients with Duchenne's progressive muscular dystrophy (DMD) (age range 8-21 years). The relationship between shortening fraction of the left ventricle and ANP and BNP levels was curvilinear rather than linear: When the shortening fraction was >15%, increases in ANP and BNP levels were minimal. However, if the shortening fraction was <15%, both natriuretic peptide levels increased dramatically. Stepwise regression analysis revealed that only the deceleration time of the early diastolic filling wave predicted plasma BNP concentration among various diastolic echocardiographic parameters determined by mitral flow. Three patients died of cardiac dysfunction during a 2-year follow-up period. These patients had a severely decreased deceleration time (<65% of normal) in association with increases in both natriuretic peptide levels. In conclusion, plasma ANP and BNP levels are not sensitive markers for the early detection of cardiac systolic dysfunction in patients with DMD. However, in patients with systolic dysfunction, an increase in the concentrations of these peptides, associated with a decrease in the deceleration time of early diastolic filling, suggests poor prognosis.