2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648895摘要：研究目的：研究在高血壓併左心室肥厚病人，使用血管收縮劑受體抑制劑(ARB)加上If 通道阻斷劑控制心跳速率，是否更能改善左心室肥厚？背景：目前針對正常心室射出分率心臟衰竭病人，由於仍無相關顯示良好療效的臨床試驗，因此仍無確切的治療方式。故預防其發生顯得更為關鍵，而此必須要針對可逆轉的危險因子來加以治療。高血壓是發生正常心室射出分率心臟衰竭最重要的因子，當中與預後最相關的結構變化是左心室肥厚，降低血壓是改善左心室肥厚最重要的治療，然而過快的心跳速率也會促進左心室肥厚。可惜β-blockers雖然可以改善左心室肥厚，但對高血壓病人的預後卻存在爭議，主要是這類藥對會引起代謝相關的不良作用。目前臨床上有If 通道阻斷劑(ivabradine)，可降低心率卻無代謝相關的不良作用且不影響血壓。另外，根據Framingham Heart Study，brain natriuretic peptide (BNP)和high-sensitivity troponin I (hs TNI)是在調整臨床因子後和左心室肥厚最相關的生物指標。研究方法：此臨床研究為單一中心隨機性對照研究，收納100位高血壓併左心室肥厚且心跳速率大於每分鐘70下的病人，按1:2的比例隨機分配到對照組(irbesartan 150 mg once daily, 33位病人)或If 通道阻斷劑組((irbesartan 150 mg once daily+ivabradine 5 mg twice daily, 67位病人)。而在隨機分配一年之後，我們將追蹤其心電圖、較具敏感性的組織都普勒超音波追蹤其各心臟功能指標和血清生物指標proBNP和hsTNI的變化情形。比較沒有調控心率和有調控心率的高血壓病人其左心室肥厚改善的情形，並評估各自心臟功能和生物指標的反應情形。預期結果：此研究可解答在高血壓併左心室肥厚病人除使用血管收縮劑受體抑制劑(ARB)為主的降血壓藥物並控制好血壓之外，再單純降低心跳速率，是否更能改善左心室肥厚。這可能對高血壓的治療帶來新的思考方向。而當這些結構或功能指標有改善時，更可追蹤這群病人更久的時間，來評估這群病人預後是否也隨之改善。<br> Abstract: Aim of study: To investigate the impact of heart rate (HR) reduction by If channel blocker (ivabradine) with angiotensin receptor blocker (ARB)-based antihypertensive treatment on regression of left ventricular hypertrophy (LVH).Background: The high lifetime risk of heart failure (HF) combined with the aging population has led to a dramatic rise in HF prevalence worldwide. Up to half of HF patients have a preserved LV ejection fraction (HFpEF). Thus, preventing HF is critical, and should be based upon modifying reversible HF risks. Hypertension, as the most important causes of HFpEF, there is widespread agreement that LV hypertrophy (LVH) is an important intermediate phenotype in the progression of hypertensive heart disease1 and is associated with adverse outcomes.Antihypertensive therapy aimed at reducing blood pressure (BP) can produce regression of LVH and reduces the increased risk of major cardiovascular (CV) events. The LIFE study demonstrated a greater reduction in CV events in patients taking losartan than in those taking atenolol. However, the pathway from hypertension to concentric LVH is not unidirectional. It is generally accepted that increased HR is involved in cardiovascular pathology, promotes LVH in different ways, and was an independent predictor of CV mortality. However, β-blocker has been proved to reverse LVH in earlier studies, but is controversial to improve prognosis, partially due to its adverse metabolic effects.Currently, If-channel blocker (ivabradine) without any direct actions on blood pressures and adverse metabolic effects, (46) might serve as a potential agent accompanied with AT1-receptor blockers for studying the impacts of HR reduction on LVH in hypertension management. Meanwhile, in the large community-based Framingham Heart Study sample, brain natriuretic peptide (BNP) and high-sensitivity troponin I (hs TNI) were associated with LVH after adjusting for clinical risk factors.Study protocol: We will conducted a single-center randomized controlled trial to investigate the impacts of HR reduction by ivabradine with ARB-based antihypertensive agents on the 1-year response of LVH and its related biomarkers. A total of 100 hypertensive patients with ECG-defined LVH and HR > 70 bpm will be randomized in a 1:2 ratio to the control (irbesartan 150 mg once daily, 33 patients) or the If-blocker (irbesartan 150 mg once daily+ivabradine 5 mg twice daily, 67 patients) group. At baseline and 1 year, ECG, echocardiography coupled with tissue-Doppler imaging, and biomarkers will be measured and compared between groups, and between baseline and follow-up.Expected results: The current study using ivabradine as HR reduction agent in hypertension management would provide an answer that whether simply decreasing HR would cause further benefit to AT-1 receptor blockers for lowering the degree of LVH. If the hypothesis is true, it could be a possible future direction in the treatment of hypertensive patients with relatively increased HR. The hypothesis provides another thought regarding therapeutic potential for preventing stage B HF (asymptomatic structural heart) into stage C/D HF. If the study results are encouraging, these patients will continue the pharmacological therapy and to be followed for a longer time to monitor the incidence of future clinical events.高血壓心跳速率If 通道阻斷劑左心室肥厚心臟超音波hypertensionheart rateIf-channel blockerleft ventricular hypertrophyechocardiography