2010-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657507摘要：猝死症的發生，最多見於各種原因的心臟衰竭病患。無論是缺血性或非缺血性病因，整流去顫器(簡稱去顫器)已經臨床實驗證明都是最確定能挽救病人於一瞬的重要利器。不過，預防性的去顫器使用卻也衍生了不少的問題，譬如：價格效益性不高、有效壽命延長不多、不適當或適當電擊反致心衰竭增多以及生心理的調適不良、乃至去顫器本身的功能異常。因此，對於心衰竭病人，尤其功能分類第2，3 級者，如何辨別最需要使用去顫器的對象，或者最不需要者，成了相當重要的研究方向。另一方面，心衰竭的研究與治療上，也有兩大主題的發展。其一是左心室收縮不協調的認知，瞭解到收縮不協調性可導致心室結構與功能的不斷惡化，且由雙心室同步節律器的植入獲得臨床的改善上獲得印證。其二是心電圖T 波變異的交替變化測量，雖有爭議，已被初步證明與重度心室快速不整脈(易致猝死)有相當的關聯性，尤其是在心臟衰竭的病人更是明顯可見其臨床指示價值。兩者之間，更有興趣的是，動物實驗上也能證明心室收縮不協調所造成的局部壓力差，確可藉由各種離子通道的調控導致局部或區域性的再極化異常，形成心室的再極化不均勻，而很可能與心電圖T 波之變異或甚至危險性心室不整脈有所關聯。不過，在病人方面的實際觀察與評估，目前均相當欠缺。本三年研究計劃乃是針對長期使用心室節律器病患(第一年)、缺血性低射出分率心衰竭病患(第二年)及非缺血性，或稱擴張性，低射出分率心衰竭病患(第三年)，進行包括三度空間心臟超音波、心臟組織超音波、心臟磁振(第二、三年)、運動T 波變異量等非侵襲性檢查，以及三度空間磁場定位之侵襲性心臟電生理檢查，以研究區域性心室收縮不協調性與心室去極化、再極化均勻性的影響，還有局部單極動作電位導管之定位測量，俾探討心臟機械力不協調所造成之心室壁受力不均與區域性心室肌再極化不均勻。此種再極化之不均勻，也可用以與同步之心電圖T 波變異做數位化比較與關連性分析。所有心衰竭病患均須追蹤為期三年，記錄所有臨床不良事件或危險事件，以分析藉由心室收縮不協調與心室局部再極化不均勻的交互影響所得的指標，是否能夠更有用於低射出分率心衰竭病患的臨床治療選擇，譬如：去顫器之植入時機。<br> Abstract: Risk stratification in heart failure patients with low left ventricle ejection fraction ( LVEF,< 35% ) is a red hot topic in the contemporary practice of implantablecardioverter-defibrillator ( ICD ) service for prevention of life-threatening ventriculartachyarrhythmias. Following current AHA/ACC/ESC guidelines to practice primary ICDprevention for all low EF postinfarction or nonischemic heart failure patients has resulted inthe serious critiques of low cost-effectiveness and risk of high inappropriate shocks or devicemalfunction. The dilemma of “To Be Or Not To Be “surely warrants more research devotion.On the horizon of new concepts are two: ventricular mechanical dyssynchrony andsurface ECG T-wave alternans. The former is believed to be highly responsible for theprogression of left ventricular structural and functional remodeling in heart failure owing toenergy inefficiency, worsened mitral regurgitation, and asynchrony-related diastolic fillingfailure. The latter results from discordant repolarization wavefronts in the ventricle andcontributes to the multiple reentry-driven ventricular tachyarrhythmias, particularly undercalcium-overloaded sympathetic outburst. Interestingly, the two concepts are not mutuallyexclusive, instead they are tightly connected by the concept of mechanic-electrical feedbackmechanism, as recently demonstrated in canine model of artificial ventricular pacing. Thelocation of the most delayed mechanical dyssynchrony is subjected to repolarizationprolongation and subsequent global repolarization heterogeneity. Apparently, the complexinteraction between the systolic mechanical dyssynchrony and stretch-related repolarizationabnormality poses an intriguing platform for the potential emergence of novel risk indicatorsfor low EF heart failure patients, particularly in regards of effective choice of ICD therapy. Ofcourse, whether the relationship between LV mechanical dyssynchrony and relevantrepolarization heterogeneity can be translated into the clinical appearance of surface ECGT-wave alternans would deserve in-depth investigations in humans, which is very rare up tonow.The present 3-year project is to investigate the interaction of intra-LV mechanicaldyssynchrony, local and global repolarization, surface ECG T wave alternans, ventriculartachyarrhythmias inducibility, and long-term outcome (up to three years). The target studypopulations will include patients receiving obligatory ventricular pacig from right ventricle( the first year, a definite model of ventricular dyssynchrony, “prove-of-concept “), low EFischemic cardiomyopathy patients ( the second year, mostly late post-myocardial infarction, dichotomized into that with and without intra-LV mechanical dyssynchrony ), and low EFnon-ischemic cardiomyopathy patients ( the third year, dichotomized into that with or withoutintra-LV mechanical dysysnchrony ). The mechanical dyssynchrony will be documented bytissue Doppler imaging with speckle tracking strain/strain rate analysis and 3-Dechocardiography. The global and local repolarization abnormality in LV will be studied by3-D electro-anatomical mapping and combined local extrastimulus and monophasic actionpotential ( MAP ) evaluation. Surface ECG T wave fluctuation during exercise and atrialpacing will be studied by time domain method. Up to 3-year follow up of any adverse eventsin the low EF ischemic and non-ischemic heart failure patients will help document the role ofthese novel determinants derived from thus-correlated parameters in clinical service.In conclusion, interaction between mechanical and electrical components of low EF heartfailure, with or without ischemic background, deserves detailed investigation in regards ofcurrent drawback in the application of life-saving ICD for high-risk heart failure patients. Theconcept of mechanic-electrical feedback is an intriguing access to the complexpathophysiology of sudden cardiac death in heart failure.