Thesis (Ed.D.)--Teachers College, Columbia University, 1974. / Typescript. Sponsor: Marie Seedor. Dissertation Committee: Nathan Lefkowitz. Includes bibliographical references (leaves 160-168).

Thesis (Honors)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains 31 p.; also includes graphics. Includes bibliographical references (p. 22-23). Available online via Ohio State University's Knowledge Bank.

Thesis (M. Nursing)--Montana State University--Bozeman, 2007. / Typescript. Chairperson, Graduate Committee: Charlene Winters. Includes bibliographical references (leaves 54-58).

Heart failure (HF) is a pathological state indicating insufficient blood supply to the peripheral tissues from the heart. The pathophysiology of HF is multifactorial like cardiac remodeling including cardiac hypertrophy, perivascular fibrosis and apoptosis to compensate for the heart’s inability to pump enough blood. Cardiac hypertrophy is initially adaptive to hemodynamic overload; however, it chronically contributes to heart failure and sudden cardiac death. The extracellular regulatory factors and intracellular signaling pathways involved in the cardiac remodeling are not yet fully clear. PI3-kinase is an important intracellular kinase in organ size control. Cardiac overexpression of Class I PI3-kinase caused heart enlargement in transgenic mice. Autophagy as a dynamic process involving the degradation of damaged mitochondria prevents ROS overproduction which leads to the cardiac remodeling. Therefore, our aim was to study the relationship between PI3-kinases and Ang II-induced cardiac remodeling via an autophagy-dependent mechanism. Ang II significantly increased autophagy with two distinctive phases: an increasing phase at low doses and a decreasing phase at high doses in cardiomyocytes. The Ang II-induced autophagic depression was attenuated by a Class I PI3-kinase inhibitor and potentiated by Class III PI3-kinase inhibitor. Besides, Ang II-induced cardiac hypertrophy and mitochondria ROS generation were attenuated via blockade of Class I PI3-kinase or mTOR. To further validate our in vitro data, we studied the role of Class I PI3-kinase in Ang II-induced cardiac remodeling in vivo. We successfully transferred Lv-DNp85 (Class I PI3-kinase blockade) and Lv-GFP (control) into adult rat hearts and found that cardiac transfer of Lv-DNp85 did not alter Ang II-induced pressor effect, but attenuated Ang II-induced cardiac hypertrophy, perivascular fibrosis and cardiac dysfunction. Ang II-induced cardiac remodeling was associated with impaired autophagy and mitochondrial ROS overproduction, which were significantly attenuated by Lv-DNp85-induced blockade of Class I PI3-kinase. Taken together, these data suggest that Class I PI3-kinase is involved in Ang II-induced impairment of autophagy via Akt/mTOR pathway, leading to mitochondrial ROS overproduction and cardiac remodeling. These results are not only highly significant from a pathophysiological perspective, but also have important pharmacological implications in the control of cardiac hypertrophy to prevent decompensation and failure in cardiac function. / National Institute of Neurological Disorders and Stroke / National Institutes of Health (NIH, NS55008)

MSc (Med), School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Excess adiposity may increase the risk of heart failure through interactions with conventional risk factors. As cardiomyocyte apoptosis may be an important mechanism responsible for the development of heart failure the aim of the present study was to determine whether obesity enhances a) the increased cardiomyocyte apoptosis that accompanies pressure-overload hypertrophy and b) sympathetic-induced cardiomyocyte apoptosis. The impact of dietary-induced obesity on cardiomyocyte apoptosis was studied in elderly spontaneously hypertensive rats (SHR) and age-matched (8-9 months of age at the beginning of the study) Wistar Kyoto rats (WKY) after a 5 month feeding period and in young WKY rats (1 month of age at the beginning of the study) receiving either isoproterenol (ISO) or the vehicle (saline) for 5 days at the end of the feeding period. To induce obesity rats were fed a diet that promotes hyperphagia. At the end of the feeding period echocardiography was performed. Cardiac myocyte apoptosis was assessed using a TUNEL staining technique. Rats receiving the obesity-inducing diet had increases in body weight and visceral fat content. No further changes in systolic blood pressure were observed in rats during the feeding period. SHRs on the obesity-inducing diet had an increased left ventricular end-diastolic diameter and a decreased endocardial fractional shortening. As compared to lean rats, dietary-induced obesity resulted in an increase in the percentage of cardiomyocytes that were apoptotic in SHRs (3.4±0.5%, p<0.005 vs all other groups) and in WKYs receiving ISO (0.35±0.05%, p<0.05 vs Control-ISO and p<0.01 vs Control-saline and Diet-saline groups). In conclusion, obesity was associated with cardiomyocyte apoptosis through an interaction with pressure-overload hypertrophy v and excessive sympathetic activation. These findings provide insights into the potential mechanisms through which obesity may promote the development of heart failure.

Heart failure (HF) is a clinical syndrome associated with high morbidity and mortality with a large economic burden, and is the leading cause of hospitalizations among Medicare beneficiaries in the United States. Healthcare reform has focused on strategies to reduce HF readmissions, including outpatient HF clinics. Purpose: The purpose of this DNP Project was to answer the following question: In adult patients diagnosed with HF, how does enrollment in the HF clinic, compared to non-enrollment affect hospital admission and readmission rates? Methods: A retrospective analysis of 767 unique patients and their 1,014 respective admissions and readmissions was conducted. Continuous and categorical data was analyzed and presented as a mean (M), standard deviation (SD), absolute number (N) and percentage (%). A Pearson Chi Square test was used for categorical variables and Analysis of Variance was used for age and ejection fraction (EF). Results: Study sample demographics (N=767); age (M=79.72, SD=7.48); gender (57.6 % male) and EF (M=0.43, SD=0.16) were evaluated. The No HF clinic (No HFC) and HF clinic (HFC) enrollment groups (N=573) were compared for age (M=79.49, SD=7.65) (M=80.39, SD=6.94), male gender (54.6%, 66.5%) and EF (M= 0.44, SD=0.17) (M=0.42, SD=0.15), respectively. Each sample patient had at least one admission for HF during 2015; of which 573 (46.2%) were in the No HFC group and 194 (8.4%) were in the HFC group (p<0.001). There was no difference in all-cause readmissions between the No HFC group [n=95(14.5%)] and the HFC group [n=37(16.2%)] (p=0.534) and no difference in HF-related readmissions between the No HFC group [n=72(11.0%)] and the HFC group [n=23(10.0%)] (p=0.700). Conclusions: This DNP project demonstrated a significant difference in HF admission rates in favor of the HFC group. While no differences were found in all-cause or HF-related readmission rates in No HFC and HFC groups, the rates are less than the national average. Unintended findings were that datasets can be very poorly constructed and populated, resulting in large amounts of unusable data. Recommendations are for more rigor in the organization of datasets to assure accurate comparisons between admission and readmission rates based on enrollment in HF clinics.

Echocardiography has an prominent role in the era of CRT by virtue of its non-invasive nature with high feasibility and reproducibility. The clinical applications include not only quantification of the change in systolic function, hemodynamics, LV volume, or mitral regurgitation, but also assessment of systolic dyssynchrony. A number of new echocardiographic techniques were employed in this study, such as tissue Doppler imaging (TDI) and its post-processing modalities including strain, strain rate and displacement mappings, tissue synchronization imaging (TSI), as well as three-dimentional (3D) echocardiography. / For heart failure patients with wide QRS complexes who received CRT, LV volumes, cardiac function and synchronicity were shown to change acutely between CRT-on and CRT-off modes by both 2D and 3D echocardiography methods. Furthermore, the usefulness of 3D echocardiography and its accuracy in assessing volumetric changes / Systolic dyssynchrony, which illustrates discoordinated contraction of the heart, is relatively common in heart failure patients, in particular those with prolonged QRS complexes. It is caused by electromechanical delay in some regions of the failing heart and will result in further reduction of cardiac function. Cardiac resynchronization therapy (CRT) is a rapidly evolving pacing modality for advanced heart failure, characterized by implantation of the left ventricular (LV) lead through coronary sinus to the free wall region. It is recommended to patients who have refractory heart failure despite optimal medical treatment, LV dilatation with ejection fraction lower than 35%, and prolonged QRS duration on surface ECG. / The main findings were as followed: The Ts-SD was 17.0+/-7.8ms in normal control, 33.8+/-16.9ms in narrow QRS group and 42.0+/-16.5ms in wide QRS group, respectively. The prevalence of systolic dyssynchrony in heart failure population was 43% in the narrow QRS group, and 64% in the wide QRS group, when a Ts-SD of > 32.6 ms (+2 SD of normal controls) was used to define significant dyssynchrony. QRS duration does not have a linear relationship with systolic dyssynchrony. / TSI was useful to predict a reverse remodeling and gain in ejection fraction after CRT. Qualitative identification of the latest peak systolic contraction at the lateral wall was a quick and specific guide to predict a favorable reverse remodeling response while quantitative computation of "Asynchrony Index" from 12 LV segments in ejection phase was beneficial in the absence of lateral wall delay. In conclusion, the improvement of cardiac function and LV reverse remodeling after CRT is more obvious in heart failure patients with wide QRS complex and echocardiographic evidence of significant systolic dyssynchrony. Reverse remodeling is not only an objective measure of favorable responses, but also a prognosticator of disease outcomes. "Asynchrony Index" is a strong predictor of LV reverse remodeling response after CRT. Assessment of systolic dyssynchrony by various echocardiographic tools is promising, however, further studies are needed to compare the predictive values of different parameters objectively and prospectively. / We performed echocardiography with TDI in 200 subjects, including 67 patients with heart failure and narrow QRS complexes (&le; 120ms), 45 patients with heart failure and wide QRS complexes (>120ms), and 88 normal controls, which served as a polit study. Severity and prevalence of systolic dyssynchrony were assessed by the maximal difference in time to peak myocardial systolic velocity (Ts-dif-12) and the standard deviation (Ts-SD) of the 12 LV segments. / We recruited a group of seventy patients with chronic heart failure who fulfilled the established criteria and received CRT. Serial echocardiographic assessment with clinical evaluation was performed at baseline, predischarge, 1-month, 3-month, 6-month and long-term follow up. The objective was to demonstrate the improvement of cardiac function and dyssynchrony after CRT by echocardiographic parameters, in particular the reduction of LV end-systolic volume (LVESV) which is also known as reverse remodeling, and its relationship with the improvement in clinical status and prognosis. We also attempted to identify dyssynchrony parameters which are useful in predicting LV reverse remodeling after CRT. / Zhang Qing. / "October 2006." / Adviser: Yu Cheuk-Man. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5852. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Like any muscle, cardiac contraction is evoked by action potentials. In the healthy heart, atrial and ventricular activation occur through impulse conduction via the rapid conduction system. Normal cardiac function requires a highly synchronized series of mechanical events occurring in the atria and the ventricles. This synchronization is achieved by rapid conduction of action potentials through the electrical conduction system, which leads to coordinated mechanical activation and deactivation of the myocardium — a process known as electromechanical coupling. As a result of this coordinated electromechanical coupling, the left ventricle functions efficiently as a pump. On the contrary, asynchronous electrical activation leads to asynchronous contraction. The presence of a bundle branch block or other intraventricular conduction delay can worsen heart failure due to systolic dysfunction by causing ventricular dyssynchrony, thereby inducing regional loading disparities and reducing the efficiency of contraction. Consistent with the idea that ventricular dyssynchrony exacerbates left ventricular dysfunction is the observation that a variety of hemodynamic benefits follow the correction of dyssynchrony with cardiac resynchronization therapy (CRT) using biventricular pacing. With decades of research on electromechanical coupling in the heart, it is now recognized that (1) cardiac dyssynchrony worsens ventricular efficiency and contributes to the progression of systolic heart failure; (2) cardiac dyssynchrony can be accurately assessed by echocardiography; (3) cardiac dyssynchrony independently predicts worse prognosis in patients with systolic heart failure; and (4) CRT has established as an effective treatment for systolic heart failure, leading to improved symptomatic status and better survival. / Concerning the subject of cardiac dyssynchrony there are still a lot of unanswered questions which are important to complete understanding of disease mechanisms of heart failure and hence to develop better treatment strategies. First, patients with heart failure but with a preserved ejection fraction (HFPEF) constitutes about half of the heart failure occurrence. Yet, it is not completely understood whether cardiac dyssynchrony, as a potential pathogenic mechanism and therapeutic target, is present in these patients. Second, the heart and circulation is a dynamic system. Nevertheless, scarce data exists on how cardiac dyssynchrony alters in response to exercise and other hemodynamic stressors in patients with heart failure. The potential clinical significance of dynamic dyssynchrony is unknown. Furthermore, identification of precipitating factors of acute hemodynamic decompensation in heart failure is important to prevent recurrent acute exacerbation and hospitalization. Cardiac dyssynchrony has been suspected to be an insidious, potentially correctable trigger of acute decompensated heart failure (ADHF), but scientific evidence is limited. Last but not least, about 30% of the CRT recipients did not respond to the treatment. It was proposed that inadequate optimization of atrioventricular (AV) synchronization is the most common contributory factor, hence the routine practice of AV optimization after CRT implantation. But again, electromechanical coupling is a dynamic process. It is uncertain, however, whether AV optimization should be performed at rest or during exercise to achieve optimal hemodynamic and clinical benefit. / In Part I of this thesis, I will review the literature on heart failure, cardiac dyssynchrony, and exercise impact on the cardiovascular system. In Chapter 1, the definition, clinical classification, and epidemiology of heart failure, as well as the biomechanical model for heart failure progression will be discussed. In Chapter 2, the literature on the normal and pathological electromechanical coupling mechanism, the clinical implication of dyssynchrony in heart failure, and the effect of CRT will be reviewed. In Chapter 3, I will discuss the current understanding of the physiologic effect of exercise, heart rate and stress on cardiac function and synchronicity. In Part II, the hypotheses (Chapter 4) and general objectives (Chapter 5) of the studies included in this thesis will be specified. In Part III, I will describe in detail the general methodology used inthese studies including the study population involved (Chapter 6), the echocardiographic techniques (Chapter 7), and the exercise/pharmacological stress protocols (Chapter 8) used in these studies. / Part IV will be a thorough and logical reporting of the background, methods, findings, discussion, and conclusion of each of the clinical studies of this thesis. Chapter 9, 10 and 11 will focus on patients with preserved ejection fraction and Chapter 12 and 13 will attempt to fill the gap of knowledge of cardiac dyssynchrony in patients with systolic heart failure. / In the study discussed in Chapter 9, the prevalence of left ventricular mechanical dyssynchrony in coronary artery disease with preserved ejection fraction was evaluated. Ninety-four consecutive patients with chronic coronary artery disease and preserved ejection fraction (≥50%) were evaluated using echocardiography with tissue Doppler imaging and compared to 217 patients with depressed ejection fraction and (<50%) and 117 healthy subjects. Left ventricular systolic and diastolic dyssynchrony were determined by measuring the standard deviations of peak systolic (Ts-SD) and early diastolic myocardial (Te-SD) velocities, respectively, using a six-basal/six-mid-segmental model. In patients with coronary artery disease and preserved ejection fraction, both Ts-SD (32.2±17.3 compared with 17.7±8.6 ms; p<0.05) and Te-SD (26.2±13.6 compared with 20.3±8.1 ms; p<0.05) were significantly prolonged when compared with controls, although they were less prolonged than patients with coronary artery disease and depressed ejection fraction (Ts-SD, 37.8±16.5 ms; and Te-SD, 36.0±23.9 ms; both p<0.005). Patients with preserved ejection fraction who had no prior myocardial infarction had Ts-SD (32.9±17.5 ms) and Te-SD (28.6±14.8 ms) prolonged to a similar extent (p=NS) to those with prior myocardial infarction (Ts-SD, 28.4±16.8 ms; and Te-SD, 25.5±15.0 ms). Patients with class III/IV angina or multi-vessel disease were associated with more severe mechanical dyssynchrony (P<0.05). Furthermore, the majority of patients with mechanical dyssynchrony had narrow QRS complexes in those with preserved ejection fraction. This is in contrast with patients with depressed ejection fraction in whom systolic and diastolic dyssynchrony were more commonly associated with wide QRS complexes. / In Chapter 10, focus will be shifted to patients with acute coronary syndrome complicated by acute HFPEF. One hundred two patients presenting with acute coronary syndrome (ejection fraction ≥50%) and 104 healthy controls were studied using tissue Doppler imaging: group 1 (n=55) had HFPEF on presentation and group 2 (n=47) had no clinical HFPEF. Te-SD was found to be greater in group 1 (33±13 ms) than group 2 (21±9 ms) (p<0.001), and diastolic mechanical dyssynchrony was evident in 35% of patients in group 1 but in only 9% in group 2 (p<0.001). Worsening of the diastolic dysfunction grade was associated with a parallel increase in Te-SD (grades 0, 1, 2, and 3: 16±3 ms, 21±5 ms, 28±9 ms, and 41±17 ms, respectively; p<0.001). Te-SD correlated negatively with mean early diastolic basal myocardial velocity (Em) (r=-0.56, p<0.001) and positively with peak mitral inflow velocity of the early rapid-filling wave/Em (r=0.69, p<0.001). Multivariate analysis identified peak mitral inflow velocity of the early rapid-filling wave/Em as the only variable independently associated with HFPEF [odd sratio (OR)=1.48, p=0.001]. When peak mitral inflow velocity of the early rapid-filling wave/Em was excluded from the model, Te-SD (OR=1.13, p<0.001) and mean Em (odds ratio=0.37, p<0.001) became independently associated with HFPEF. / In Chapter 11, I will evaluate the impact of hemodynamic stress on left ventricular dyssynchrony and the relationship and predictive value of dynamic changes of left ventricular dyssynchrony on hypertensive HFPEF. In this study, a total of 131 subjects including 47 hypertensive HFPEF patients, 34 hypertensive patients with left ventricular hypertrophy without HFPEF, and 50 normal controls were studied by dobutamine stress echocardiography with tissue Doppler imaging. In normal controls, systolic and diastolic dyssynchrony did not develop during stress. The prevalence of resting systolic (36.2% vs. 38.2%, p=0.85) and diastolic (34.0% vs. 29.4%, p=0.66) dyssynchrony was similar in patients with HFPEF and left ventricular hypertrophy. During stress, the prevalence of systolic and diastolic dyssynchrony increased dramatically to 85.1% and 87.2%, respectively, in patients with HFPEF, but only 52.9% and 58.8% in patients with left ventricular hypertrophy (p<0.005). In HFPEF group, stress-induced increase in mean systolic basal myocardial velocity (Sm) was significantly blunted (2.8±2.0 vs. 4.2±2.4 cm/s, p=0.004), and the increase was abolished for mean Em (-0.3±2.5 vs. 2.4±3.4 cm/s, p<0.001). On multivariate analysis, stress-induced changes in mean Em (OR=0.69, p=0.004) and mean Sm (OR=0.56, p=0.004), and diastolic (OR=4.6, p=0.005) and systolic dyssynchrony during stress (OR=4.3, p=0.038) were independent determinants for occurrence of HFPEF. / In Chapter 12, the role of dyssynchrony in patients with systolic heart failure presentating with acute decompensation (ADHF) will be studied. In this study, it was hypothesized that acute left ventricular systolic dyssynchrony might be a hidden triggering mechanism for ADHF. Echocardiography with tissue Doppler imaging was performed in 145 subjects with systolic heart failure (ejection fraction <50%), including 84 consecutive patients presented with ADHF requiring hospitalization, comparing them to 61 chronic stable heart failure patients who had no heart failure exacerbation or hospitalization in the past 6 months. The ADHF group was observed to have higher heart rate on admission than patients with stable heart failure (82±15 vs 68±13 bpm, P<0.001), greater left ventricular wall thicknesses and mass (all P<0.05), and mitral regurgitation was more common (71% vs 46%, P<0.0001; ERO=0.12±0.11 vs 0.02±0.04 cm2, P<0.0001), but the overall severity of mitral regurgitation was mild or moderate. Despite no difference in ejection fraction, the ADHF group had significantly lower mean Sm (2.7±0.9 cm/s vs 3.0±0.9 cm/s, P=0.04). The Ts-SD was significantly prolonged in the ADHF group compared to patients with stable heart failure (44.7±16.6 vs 33.4±17.7 ms, P=0.0001). Significant left ventricular systolic dyssynchrony was evident in 75% (63 of 84) of patients of the ADHF group, compared to only 44% (27 of 61) of patients with chronic stable heart failure (P=0.0002). / In Chapter 13, I will focus on the role of dynamic AV dyssynchrony during exercise in patients with systolic heart failure who receive CRT. AV delay in CRT recipients are typically optimised at rest. However, there are limited data on the impact of exercise-induced changes in heart rate on the optimal AV delay and left ventricular function. In this study, AV delays were serially programmed in 41 CRT patients with intrinsic sinus rhythm at rest and during two stages of supine bicycle exercise with heart rates at 20 bpm (stage I) and 40 bpm (stage II) above baseline. The optimal AV delay during exercise was determined by the iterative method to maximise cardiac output using Doppler echocardiography. Results were compared to physiological change in PR intervals in 56 normal controls during treadmill exercise. The optimal AV delay was progressively shortened (p<0.05) with escalating exercise level (baseline: 123±26 ms vs. stage I: 102±24 ms vs stage II: 70±22 ms, p<0.05). AV delay optimisation led to a significantly higher cardiac output than without optimisation did during stage I (6.2±1.2 l/min vs. 5.2±1.2 l/min, p<0.001) and stage II (6.8±1.6 l/min vs. 5.9±1.3 l/min, p<0.001) exercise. A linear inverse relationship existed between optimal AV delays and heart rates in CRT patients (AV delay=241-1.61 x heart rate, R²=0.639, p<0.001) and healthy controls (R²=0.646, p<0.001), but the slope of regression was significantly steeper in CRT patients (p<0.001). / In conclusion, the works included in this thesis provide new evidence that left ventricular mechanical dyssynchrony is common in patients with coronary artery disease and preserved ejection fraction, even in patients without prior myocardial infarction or evidence of eletromechanical delay. In particular, left ventricular diastolic mechanical dyssynchrony may impair diastolic function and contribute to the pathophysiology of HFPEF during acute coronary syndrome. Moreover, dynamic dyssynchrony and impaired myocardial longitudinal function reserve during stress may contribute importantly to the pathophysiology of hypertensive HFPEF. In patients with heart failure and reduced ejection fraction, a high prevalence of left ventricular systolic dyssynchrony during acute decompensation suggests that acute or dynamic left ventricular systolic dyssynchrony may be an important precipitating factor and a potential therapeutic target. Progressive shortening of hemodynamically optimal AV delay with increasing heart rate during exercise suggests that dyssynchrony is dynamic and there may be a need for programming of rate-adaptive AV delay in CRT recipients to optimise clinical response. I believe this work will provide new understanding of the prevalence, mechanism, and clinical significance of cardiac dyssynchrony in heart failure. / Lee, Pui Wai. / Thesis (M.D.))--Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 138-174). / Title from PDF title page (viewed on 24, October, 2016).

Cardiac pacing has been the only effective treatment in the management of patients with symptomatic bradycardia caused by sinus node dysfunction or atrioventricular block for decades. Conventional dual-chamber pacing is performed by implanting two leads in right atrial (RA) appendage and right ventricular (RV) apex separately. RV apex is the most commonly applied pacing site because it can be easily reached and allows a chronically stable position and stimulation thresholds. However, large randomized clinical trials have suggested that right ventricular apical (RVA) pacing may cause abnormal ventricular contraction and reduce pump function and lead to myocardial hypertrophy, in particular in patients with impaired left ventricular (LV) function. Recent studies have also reported a reduced LV systolic function in patients with pacing indications and preserved ejection fraction. The deleterious effects of RVA pacing on LV function may be related to the abnormal electrical and mechanical activation pattern or ventricular dyssynchrony. During RVA pacing, conduction of the electrical wave front propagates slowly through ventricular myocardium rather than through the His-Purkinje conduction system, comparable to left bundle branch block (LBBB). In addition , RVA pacing alters ventricular synchrony and loading conditions which may result in diastolic heart failure with abnormal LV relaxation, high filling pressure and low cardiac output state. Furthermore, it is possible that left atrial (LA) remodeling and reduction of atrial function may occur during RVA pacing . However, it is not been carefully studied. / Echocardiography is a convenient, non-invasive and established tool to assess cardiac function in clinical practice. Conventional two-dimensional echocardiography is useful to assess cardiac chamber size, volume and function. With the development of real time three-dimensional echocardiography (RT3DE) and color tissue Doppler imaging (TDI), echocardiography provides further valuable information and more accurate measurements which include myocardial velocity and parameters of dyssynchrony. In the present study, the main echocardiographic parameters including the maximal left atrial volume (LAVmax), pre-atrial contraction volume (LAVpre) and the minimal left atria l volume (LAVmin) were assessed by two-dimensional echocardiography. Peak systolic (Sm-la), peak early diastolic (Em-la), peak late diastolic (Am-la) velocities of left atrium (LA) and atrial conduction time (from onset of P wave on electrocardiogram to onset of atrial velocity) were measured by TDI. / In a cross-sectional study, ninety-eight patients who had been implanted with RVA-based dual-chamber pacemakers were enrolled. Four patients with pacing dependent were excluded. Eventually 94 patients were included in the final analysis. Echocardiography was performed (iE33, Philips) during intrinsic ventricular conduction (V-sense) and RVA pacing (V-pace) modes with 15 minutes between switching modes. We aimed to investigate if RVA pacing has any acute effects on atrial remodeling and function in patients with preserved ejection fraction (LV ejection fraction> 45%). The result showed that during V-pace, LA volumes increased significantly when compared with V-sense (LAVmax: 52.0 +/- 18.8 vs. 55.2 +/- 21.1 ml, p = 0.005; LAVpre: 39.8 +/- 16.4 vs. 41.3 +/- 16.6 ml, p = 0.014; LAVmin: 27.4 +/- 14.0 vs. 29.1 +/- 15.1 ml, p = 0.001) . TDI parameters showed significant reduction in Sm-la (3.0 +/- 1.1 vs. 2.7 +/- 0.9 cm/s, p &lt; 0.01), Em-la (2.7 +/- 1.1 vs. 2.4 +/- 1.0 cm/s, p = 0.001). However, there was no change in Am-la. / In a prospective study, patients with symptomatic bradycardia, preserved ejection fraction, and received RVA pacing were recruited. Echocardiography was performed at both baseline and one year follow up through a standard protocol by experienced echocardiographers. LA volumes and velocities as well as intra- and interatrial dyssynchrony were measured offline with the use of dedicated software. The objectives of this study were to investigate: (1) if RVA pacing has any deleterious effects on LA remodeling and function during long-term follow up; (2) if RA appendage pacing has separate effects on atrial pump function, intra- and interatrial dyssynchrony; (3) if atrial dysfunction and dyssynchrony can predict atrial high rate episodes (AHREs) burden in the first year of RVA pacing. The main findings of this study were: (a) at one year follow up, LA volumes and indexes were increased with reduction in passive emptying fraction and total emptying fraction. Atrial velocities showed significant reduction when compared with baseline; (b) in multivariate regression analysis, the ratio of transmitral early diastolic filling velocity to mitral annular early diastolic velocity (E/e') > 15 at one year and reduction of LV ejection fraction &ge; 5% were independent predictors of reduction of Am-la > 30%; (c) high percent of RA appendage pacing prolonged atrial conduction and induced intra- and interatrial dyssynchrony. (d) Am-la &lt; 5.3 cm/s can predict AHREs burden which had a sensitivity of 71% and specificity of 75%. / In conclusion, our studies suggest even short-term RVA pacing induces LA dilatation and impaired passive atrial function, though it did not have direct effect on active atrial contractility. However, chronic RVA pacing results in LA remodeling and reduces atrial function with decreased contractility. This was more likely to occur in those with impaired LV ejection fraction and evidence of diastolic dysfunction. Atrial dysfunction and interatrial dyssynchrony can predict AHREs burden after chronic RVA pacing. Therefore, measures that may minimize such adverse effect of pacing on atrial function need to considered for patients receiving RVA pacing, such as the use of new pacing modalities. / Xie, Junmin. / "December 2010"--Abstract. / Adviser: Yu Cheuk Man. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 142-161). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

A learning effect has been shown to be present in the repeated performance of the six-minute walk test and contributes to the variability of walk distance up to the third walk test. The purpose of this study was to see if education about the performance of the walk test could minimize the learning effect. It was hypothesized that education about the learning effect would decrease the learning effect. There were a total of 18 subjects (5 female and 13 male) with a mean age of 63.7+12.1 years that completed three standardized six-minute walk tests. The subjects were randomly assigned to either a Learning Effect Education (LEE) group or a Usual Care (UC) group. The LEE group was provided with education material about the learning effect approximately two days prior to their first walk test, with additional instruction immediately prior to their first walk test. The mean walk distances for the LEE group over the three walk tests were 1,248±297.4, 1,361.9±275.7, and 1,355.1+291.7 feet, respectively. Mean walk distances for the UC group over the three walk tests were 1,149.6+392.3, 1,123.6+427.5, and 1,209.9±368.7 feet, respectively. The hypothesis was tested and the repeated measures ANOVA showed a significant (p=0.033) interaction between the groups with respect to six-minute walk distance. A Bonferroni's post hoc analysis showed that mean walk distance (113.9+42.3 feet) increased significantly (p=0.048) from test one to test two in the LEE group. There was no significant difference between mean walk distance from test two and test three (6.8+31.1 feet) in the LEE group. In the UC group, there was no significant increase in mean walk distance from test one to test two (-26+42.3 feet), while there was a significant (p=0.04) increase in mean walk distance from test two to test three (86.3+31.1 feet). There was a significant difference between walk tests (p=0.011) with no significant difference between groups (p=0.333). In conclusion, the results from this study suggest that education may reduce the number of familiarization trials needed prior obtaining an accurate baseline six-minute walk test distance. / School of Physical Education