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Community detection of non-ischemic stage B heart failure
thesisposted on 2023-05-27, 10:57 authored by Yang, H
\\(Background.\\) Stage B Heart Failure (SBHF) is an early stage with no symptoms but evidence of cardiac impairment. It is difficult to diagnose and manage without echocardiography (Echo, ultrasound of the heart), and the availability of this test in primary care and in rural areas is very limited. To date, there is no effective screening strategy for the identification of non-ischemic SBHF. There is also no evidence available on the efficacy of treatment of this condition to reduce outcome events. Aims. This research aimed to study the following: 1) how to assess heart failure (HF) risks clinically (before echocardiogram); 2) what screening tools to use; 3) how to develop a community screening program combining cardio-protective therapy in at-risk elderly individuals; 4) to define the best strategies in community screening, including the role of electrocardiogram (ECG) versus Echo; 5) to identify the best echo predictors (advanced versus conventional echo markers) for outcome at 1 year follow up; 6) to investigate the benefits of an intervention response based on imaging guided care versus usual care - randomized controlled trial; 7) to investigate the benefit of community screening in a young population and association with childhood adiposity. \\(Methods.\\) A systematic review and meta-analysis was performed to identify possible clinical markers to be used to select subjects at high risk of HF for echo in the community. A method validation study was performed on comparing strain measurement variabilities between and among vendors as well as software versions. Data from CDAH3 pilot trial (Childhood Determinants of Adult Health) was used to assess the association of childhood adiposity and evidence of SBHF in a young population. An important study platform for this research was the Tasmanian Study of Echocardiographic Detection of Left Ventricular Dysfunction (TasELF). Between 9/2013 and 11/2015, a total of 1026 community individuals responded to our study advertisement. Of these, 618 stage A HF individuals met inclusion criteria and were eligible (mostly hypertension, diabetes and obesity). At baseline, participants underwent standard clinical evaluation, anthropometry, blood pressure, functional capacity using 6-minute walk test, 12-lead ECG and comprehensive echo assessment. Four ECG markers were assessed including Cornell Product (Cornell-P), P wave terminal force in lead V1 (PTFV1), ST depression in lead V5 V6 (minSTmV5V6) and increased heart rate. Four echo markers were used to define the presence of SBHF, including left ventricular hypertrophy (LVH), left atrial enlargement (LAE), impaired E/e' or impaired global longitudinal strain (GLS). Participants were then randomized into two arms: imaging guided care using advanced echocardiography (AE arm, including myocardial deformation and detailed diastolic function examination) or usual care (UC arm). The presence of abnormal findings was used to justify subsequent cardio-protective treatment. A process evaluation was conducted at 3 months, and adherence to therapy was assessed. Patients were followed for 1 year for outcome. The primary composite end point was new HF and death from cardiovascular causes. \\(Results.\\) First, prediction of incident HF can be calculated from 7 common clinical variables (age, gender, BMI, smoking, hypertension, diabetes and coronary artery disease). Second, the strain measurement variability has improved after the joint standardization task force, is analogous to that of ejection fraction and can be used widely. Third, cardiac impairment was present in otherwise healthy but overweight and obese young adults. Cardiac impairment was associated with adult body adiposity but not with childhood adiposity. Fourth, comparing with patients with hypertension, patients with diabetes had more impaired global longitudinal strain (GLS) and reduced 6-minute walk test distance. Hypertensive patients had more impaired diastolic function. Fifth, abnormal ECG markers showed low sensitivity for SBHF but were associated with poor outcome in those with early cardiac impairment. Sixth, the overall annualized incident rate for new HF was 10% in these elderly individuals at risk of HF. The initial clinical risk assessment combing functional assessment facilitated effective HF screening by identifying the high and intermediate risk groups for echocardiographic screening. Seventh, the prevalence of SBHF was 62% defined by the presence of ‚Äöv¢‚Ä¢ 1 of the four echo markers (LVH, LAE, impaired GLS and abnormal E/e'). These markers were associated with outcome. The presence of ‚Äöv¢‚Ä¢ 1 of any of four SBHF markers was associated with more than 3-fold higher risk. Impaired GLS was a more sensitive marker and provided incremental value over clinical information for prediction. Eighth, imaging guided cardio-protective therapy was ineffective with only 43% having treatment up-titration and 9% reaching target dose. At 1 year follow-up, the incidence of HF was no different between two arms. Among subjects needing therapy on the basis of imaging and adherence to therapy, imaging guided care showed a 77% lower hazard for outcome. Participant non-adherence to treatment was a potential obstacle in HF prevention in patients with SBHF. Attitude to additional therapy seemed the main barrier to success of cardio-protection of SBHF. At 1 year follow-up, the trial was stopped for futility. \\(Conclusions:\\) Screening for SBHF in the community using echocardiography was feasible. Given the high annualized incident rate of new HF and the recognized adverse outcome of SBHF, the identification of those at higher risk was important. However, the adherence to preventive therapy was low. In order to reduce the burden of heart failure, effort needs to be made not only to identify but also to initiate effective preventive treatment.
Rights statementCopyright 2016 the author Chapter 2 appears to be the equivalent of a post-print version of an article published as: Yang, H., Negishi, K., Otahal, P., Marwick, T. H., 2015. Clinical prediction of incident heart failure risk: a systematic review and meta-analysis, Open heart, 2(1), 1-8, e000222. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ Chapter 4 appears to be the equivalent of a post-print version of an article published as: Yang, H., Marwick, T. H., Fukuda, N., Oe, H., Saito, M., Thomas, J. D., Negishi, K., 2015. Improvement in strain concordance between two major vendors after the strain standardization initiative, Journal of the American Society of Echocardiography, (JASE), 28(6), 642-648 Chapter 5 appears to be the equivalent of a post-print version of an article published as: Yang, H., Huynh, Q. L., Venn, A. J., Dwyer, T., Marwick, T. H., 2017. Associations of childhood and adult obesity with left ventricular structure and function, International journal of obesity, 41(4), 560-568 Chapter 6 appears to be the equivalent of a post-print version of an article published as: Yang, H., Wang, Y., Negishi, K., Nolan, M., Marwick, T. H., 2016. Pathophysiological effects of different risk factors for heart failure, Open heart, 3(1), 1-11, e000339. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ Chapter 7 appears to be the equivalent of a post-print version of an article published as: Yang, H., Marwick, T. H., Wang, Y., Nolan, M., Negishi, K., Khan, F., Okin, P. M., 2017. Association between electrocardiographic and echocardiographic markers of stage B heart failure and cardiovascular outcome. ESC heart failure, 4(4), 417‚Äö-431. doi: 10.1002/ehf2.12151. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ Chapter 8 appears to be the equivalent of a post-print version of an article published as: Yang, H., Wang, Y., Nolan, M., Negishi, K., Okin, P. M., Marwick, T. H., 2016. Community screening for nonischemic cardiomyopathy in asymptomatic subjects ‚Äöv¢‚Ä¢65 years with stage B heart failure, American journal of cardiology, 117(12), 1959-1965 Chapter 9 appears to be the equivalent of the peer reviewed version of the following article: Yang, H., Negishi, K., Wang, Y., Nolan, M., Saito, M., Marwick, T. H. 2016. Echocardiographic screening for non‚ÄövÑv™ischaemic stage B heart failure in the community. European journal of heart failure, 18(11), 1331-1339, which has been published in final form at http://doi.org/10.1002/ejhf.643. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Chapter 10 appears to be the equivalent of a post-print version of an article published as: Yang, H., Negishi, K., Wang, Y., Nolan, M., Marwick, T. H., 2017. Imaging guided cardio-protective treatment in a community elderly population of stage B heart failure, JACC cardiovascular imaging, 10(3), 217-226