臺灣博碩士論文加值系統

N端前腦力鈉激素（NT-proBNP）在心肌因容積或壓力過負荷而伸展、延長時釋出，其循環中濃度與心臟疾病的嚴重程度呈正相關。本研究的目的為在患有退行性二尖瓣疾病的犬隻，評估NT-proBNP與各臨床評估項目之間的相關性，以及針對有心衰竭的犬隻評估連續測量NT-proBNP的預後價值。共有80隻飼主飼養的犬隻符合條件進入研究，分別以美國獸醫美國獸醫內科協會提出的慢性瓣膜性疾病分級系統、心臟有無重塑、心臟有無衰竭等進行分組，比較組間初診數據的差異。其中，34隻犬診斷有心衰竭，因此進行3次的NT-proBNP連續測量並進行存活分析。結果顯示，由A階段至B2階段NT-proBNP濃度呈上升趨勢，且有心臟重塑組及有心衰竭組中其濃度顯著較高（p<.001）。此外，NT-proBNP濃度與臨床、影像分數以及所選的心臟超音波數值均呈顯著正相關（p值均<.001）。在心衰竭犬隻的存活分析當中，存活以及非存活犬隻之間NT-proBNP的初診濃度（p=.830）、第一次追蹤值（p=.650）、前後差值（p=.470）以及差值百分比（p=.376）均無統計學上的顯著差異；類別分組之間的死亡率也無統計學上的顯著差異。經性別分層分析後，發現性別可能干擾NT-proBNP的預測能力。本研究確認了NT-proBNP於評估心臟疾病嚴重程度，以及反映犬隻即時狀態的臨床應用性。未來需要針對NT-proBNP趨勢、性別以及絕育狀態進行更多研究。

The N-terminal pro-brain natriuretic peptide (NT-proBNP) is released from stretched cardiomyocytes and its circulating concentration is positively associated with heart disease severity. The purpose of this study was to evaluate the correlation between NT-proBNP and various clinical assessments, and to estimate the prognostic value of serial measurement of serum concentration of NT-proBNP in dogs with congestive heart failure (CHF) secondary to degenerative mitral valve disease (DMVD). Eighty client-owned dogs were enrolled and classified by American College of Veterinary Internal Medicine guideline, and they were also allocated into groups by cardiac remodeling and CHF. Thirty-four dogs with CHF further underwent serial measurements of NT-proBNP. The mortality rate between sub-categorical groups were compared. The results showed that NT-proBNP concentration had an increasing trend from stage A to stage B2, and was significantly higher in dogs with cardiac remodeling (p<.001) and dogs with CHF (p<.001). Moreover, NT-proBNP was significantly and positively correlated with clinical score (p<.001), radiographic score (p<.001) and several selected echocardiographic indices (all p<.001). In the survival analysis, the NT-proBNP of baseline (p=.830), first follow-up (p=.650), absolute (p=.470) and relative change (p=.376) had no significant difference between survivors and non-survivors. And the mortality rate between sub-categorical groups did not differ statistically. A possible sexual effect was observed by sex stratification. The study confirmed the clinical utility of NT-proBNP in assessing heart disease severity and in reflecting the instant clinical status in dogs with DMVD. Further study for evaluating the association among NT-proBNP trending, sex and neutered status was warrant.

摘要......................................................i
Abstract .........................................................ii
Contents .............................................. ..........iii
List of Tables.......................................................v
List of Figures..........................................vi
1. Introduction...........................................1
2. Literature review................................3
2.1 Degenerative mitral valve disease.................... 3
2.1.1 Introduction.............................. 3
2.1.2 Staging system ............................ 3
2.1.3 Pathophysiology ............................5
2.1.4 History and Clinical findings ..............6
2.1.5 Diagnostic imaging ......................8
2.1.6 Treatment .................................. 12
2.2 Heart failure ..................................... 13
2.2.1 Definition ................................... 13
2.2.2 Classification .................................. 13
2.2.3 History and Clinical findings in Left-side Congestive Heart Failure ............ 14
2.2.4 Diagnostic Imaging in Left-side Congestive Heart Failure ........................... 15
2.2.5 Treatment in Congestive Heart Failure..... 15
2.3 Natriuretic peptides ....................18
2.3.1 Definition and Classification of Biomarkers ....... 18
2.3.2 Background knowledge .............................. 19
2.3.3 Biologic Variabilities ..................... 21
2.3.4 Clinical Applications ............................. 23
2.3.5 Limitations ............................ 24
2.3.6 Prospects .................................... 25
3. Material and Method..........................27
3.1 Animals ..................27
3.2 Groupings................................................. ....27
3.2.1 Baseline comparison .......................27
3.2.2 Serial measurements in dogs with congestive heart failure........ 29
3.3 Clinical assessment............................. 32
3.3.1 History and Physical examination .......... 32
3.3.2 Blood pressure measurement .................32
3.3.3 Thoracic radiography ............................. 32
3.3.4 Echocardiogram ............................ 33
3.4 Blood sampling and NT-proBNP analyses ...........34
3.5 Follow-up .................................... 35
3.6 Statistical analysis ............................ 36
4. Results ......................................38
4.1 Animals ..................................... 38
4.2 Analysis of Variables at Baseline ................ 39
4.2.1 ACVIM Grouping.............................. 39
4.2.2 Cardiac Remodeling Grouping ...................... 43
4.2.3 Congestive Heart Failure Grouping ..................46
4.3 Correlation and Regression Analysis ..................48
4.4 Survival Analysis .........................51
4.4.1 Sex stratification ...................... 57
4.4.2 Impact of medications.................... 68
5. Discussion ....................................70
6. References ...................................83
Appendix: Table of abbreviation................101

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