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研究生:陳科維
研究生(外文):CHEN, KE-WEI
論文名稱:以非侵入性心肌作功指標作為尿毒性心肌症之量化診斷及預後評估:從臨床到基礎科學研究
論文名稱(外文):Using Non-Invasive Myocardial Work Index as a Quantitative Diagnostic and Prognostic Assessment Tool for Uremic Cardiomyopathy: From Clinical to Basic Science Research
指導教授:張坤正
指導教授(外文):CHANG, KUAN-CHENG
口試委員:汪貴珍張志宗林晏年劉哲育
口試委員(外文):WANG, GUEI-JANECHANG, CHIZ-TZUNGLIN, YEN-NIENLIU, JER-YUH
口試日期:2024-01-13
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:臨床醫學研究所博士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2024
畢業學年度:112
語文別:英文
論文頁數:57
中文關鍵詞:尿毒性心肌症心臟作功
外文關鍵詞:uremic cardiomyopathycardiac work
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末期腎病患者的主要死因通常是心因性猝死和復發性心臟衰竭。由於缺乏早期檢測慢性腎臟病患者心臟功能障礙的良好方法,制定預防和治療策略具有挑戰性。本項目的動物研究部分在實驗大鼠身上建立了慢性腎病早期和晚期的動物模型。研究人員測量了不同的非侵入性心臟功能參數,包括左心室射血分率、左心室圓周應變率和心臟作功指數,並將其與侵入性心臟作功的壓力-容積環形圖生理值進行了比較。心臟作功指數的結果顯示出與侵入性壓力-容積環形圖生理值相似的趨勢,在早期和晚期腎病模型中,慢性腎病組與對照組之間均有顯著差異(中位值分別為1313.4 vs. 1924.7,P=0.0122;929.8 vs. 1783.2,P=0.02)。左心室圓周應變率僅在晚期階段在慢性腎病組和對照組之間有顯著差異(中位值分別為-9 vs. -16,P=0.02)。左心室射血分數的差異則在各階段皆不明顯。這些結果表明,通過非侵入性方法評估心臟作功,特別是心臟作功指數,有可能發現與尿毒性心肌症有關的早期心肌功能變化,並可方便地應用於臨床,作為未來藥物開發和早期預防策略的參考。此外,心臟功能評估對於定期接受血液透析的末期腎病患者也非常重要。有些研究顯示心臟作功指數在評估心臟功能和預測患者預後方面也很有效。本項目的臨床研究部分旨在驗證這一新方法,並建立一個獨立、準確地預測定期血液透析的末期腎病患者預後的指數。我們回顧性地招募了接受持續性血液透析的末期腎病患者,這些患者接受了至少三個月的持續性血液透析,(每週三次,每次四小時)。這些患者於2009年至2014年間在台中市中國醫藥大學附設醫院接受了心臟超音波檢查。我們對傳統心臟超音波參數如左心室射血分率和左心室應變參數:包括整體縱向應變和新提出的心臟作功指數進行了全面分析。心臟作功指數由估計的左心室壓力-心肌應變環形圖面積得出。我們的研究結果表明,死亡和存活患者的左心室射血分率(0.57 ± 0.12 vs. 0.59 ± 0.09,P = 0.27)和整體縱向應變(-16.12 ± 6.57% vs. -18.44 ± 5.54%,P = 0.07)之差異無統計學意義。然而,在心臟作功指數(1339 ± 683.05 mmHg% vs. 1883.38 ± 640.99 mmHg%,P = 0.0002)方面觀察到了明顯的差異。與存活患者相比,死亡患者的心臟作功指數明顯較低。我們使用曲線下面積評估了這些參數的預測性能,其中左心室射血分率的曲線下面積為0.499,整體縱向應變的曲線下面積為0.619,而心臟作功指數則超過了這兩個參數,曲線下面積為0.724。 總之,本研究證實心臟作功指數是預測定期接受血液透析的末期腎病患者全因死亡率的可靠且獨立的指標。重要的是,與左心室射血分率和整體縱向應變等常用預測指標相比,心臟作功指數顯示出潛在的優越性。這些發現強調了非侵入性左心室壓力應變分析在評估心臟功能和預測這類患者預後方面的價值。
The leading cause of death in patients with end-stage renal disease (ESRD) is often due to sudden cardiac death and recurrent heart failure. Due to the lack of methods for early detection of heart dysfunction in patients with chronic kidney disease (CKD), it was challenging to develop prevention and treatment strategies. The animal study part of this project created a model of early and late-stage chronic kidney disease in SD rats. Different non-invasive cardiac functional parameters, including left ventricular ejection fraction, left ventricular circumferential strain, and cardiac work index, were measured and compared to invasive physiological values of cardiac stroke work. The results of the cardiac work index showed a similar tendency as cardiac stroke work, had a significant difference in both the early and late stages between CKD and sham groups (median values of 1313.4 vs. 1924.7, p=0.0122, and 929.8 vs. 1783.2, p=0.02, respectively). Left ventricular circumferential strain showed a significant difference only in the late stage between CKD and sham groups (median values of -9 vs. -16, p=0.02, respectively). The difference of left ventricular ejection fraction was insignificant. These results suggest that the assessment of cardiac work through non-invasive methods, specifically cardiac work index, may have the potential to detect early cardiac muscle changes related to chronic kidney disease-associated cardiomyopathy or uremic cardiomyopathy and can be easily applied in clinical settings as a reference for future drug development and early prevention strategies. Besides, cardiac evaluation is crucial for patients with end-stage kidney disease undergoing regular hemodialysis. The cardiac work index is promising for assessing cardiac function and predicting patient outcomes. The clinical study part of this project aims to validate this new approach and create an index for independently and accurately predicting the prognosis of ESRD patients on regular hemodialysis. We retrospectively enrolled ESRD patients who received maintenance hemodialysis sessions lasting four hours, three times weekly, for at least three months. These patients underwent echocardiography between 2009 and 2014 at China Medical University Hospital, Taichung, Taiwan. We conducted a comprehensive analysis of conventional echocardiography parameters, such as left ventricular ejection fraction (LVEF), and strain echocardiography parameters, including global longitudinal strain (GLS) and the newly proposed cardiac work index (CWI). The CWI was derived from the estimated left ventricular pressure-myocardial strain loop area. Our findings indicated no statistically significant differences in LVEF (0.57 ± 0.12 vs. 0.59 ± 0.09, P = 0.27) and GLS (-16.12 ± 6.57% vs. -18.44 ± 5.54%, P = 0.07) between deceased and surviving patients. However, a significant distinction was observed in CWI (1339 ± 683.05 mmHg% vs. 1883.38 ± 640.99 mmHg%, P = 0.0002). Specifically, deceased patients had notably lower CWI values compared to surviving patients. The predictive performance of these parameters was assessed using the area under the curve (AUC), with LVEF yielding an AUC of 0.499, GLS demonstrating an AUC of 0.619, and CWI surpassing both with an AUC of 0.724. In conclusion, this study establishes CWI as a robust and independent predictor of all-cause mortality in ESRD patients undergoing regular hemodialysis. Importantly, CWI shows potential superiority over commonly used predictors like LVEF and GLS. These findings emphasize the value of non-invasive left ventricular pressure-strain analysis for assessing cardiac function and predicting outcomes in this patient population.
致謝辭……………………………………………….……………….I
中文摘要…………………………………………………….………….II
英文摘要…………………………………………………….……….IV
目次……………………………………………….…………………VII
圖表目次………………………………………………………VIII
第一章 前言……………………………………………………………1
第二章 臨床研究……………………………………..........................6
第三章 動物實驗……………………………………………………..13
第四章 討論…………………………………………………………..21
第五章 總結…………………………………………………………..30
參考文獻……………………………………………………………....53


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