2017-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645654摘要：精準化的個人醫療目前由於基因測定、臨床判斷以及遠距科技大幅的進步，已在癌症治療產生了 鉅大的影響。不過，心律不整疾病方面的運用則正在萌芽階段，特別是性命交關的心室快速不整脈與 猝死症。猝死症及其主因心室快速不整脈的發生，雖然常見到的是缺血性或非缺血性的擴張心肌症與其合 併之心衰竭，但如同常見的心房顫動，其實大多暗藏著各種程度的心肌基因變異特質。此外，缺血性 或非缺血性心肌症之病源，也因為損害不一而有很高的個人差異。相伴而生的心臟自主神經失衡，尤 其是交感神經分佈不均，更導致心衰竭之下的大量致命心室不整脈。本研究計劃將以三年的時間，針 對最常見的結構性心臟病，尤其是缺血性或非缺血性心肌症患者，運用新一代的高速檢定判斷各種常 見的基因變異(如：NOS1AP, PLN, SCN5A, KCNQ1, KCNN2, BAZ2B等)及可能新變異，比較發生心室 快速不整病人與正常對照的不同，尋找可預先篩揀出高危險病人疾群的基因指標(第一年）。其次，針 對個別發生心室不整脈之結構性心臟病病人，我們將運用已具經驗之高解析心臟磁振「切片」影像技 術，精準解析不整脈病源之三度空間結構以及可能的不整脈迴旋路徑，結合新型超高密度三度空間電 腦定位，導引個人化之精準電氣燒灼手術以達成最有效而少傷害的心室不整脈袪除效果(第二年）。其 三，針對不易評估之個人自主神經失衡程度，我們將針對缺血或非缺血性心肌症併心衰竭與去顫器連 續電擊之重症病患，運用碘123的MIBG造影以呈現心臟之交感神經失衡嚴重度。藉著H/M比值、 MIBG缺痕指數及CWR值判定為重度交感神經失衡，並與神經外科合作以精準微創手術切除心臟左 侧交感神經供應，俾重建自主神經平衡，治療此群重症心室快速不整脈病人(第三年）。心室快速不整脈乃至猝死症病人之治療，固然已能藉遠距科技的進步達到精確調控去顫器植入者 處置效率，但本研究計劃期望能再增進為預防性的基因變異分析以精確判定結構性心臟病人的心室快 速不整脈發生可能，併以精準個人化心臟磁振影像規劃介入性電氣燒灼手術策略，以及量化評估心臟 交感神經失衡嚴重度，運用精準微創手術調控心臟交感/副交感神經再平衡，如此之下，精準個人化 的醫療模式將可對致命性心室不整脈之預防或再復發控制產生最佳效益，改善病人生活品質乃至綜合 存活率。<br> Abstract: Despite the success in cancer therapy, precision or personalized medicine remains like a dream in the management of arrhythmic diseases especially regarding life-threatening ventricular tachyarrhythmia (VT/VF) and sudden cardiac death in those with structural heart diseases.Based on genotyping, substrate targeting and neuraxial modulation, the present three-year study project is designed to reestablish the concept of precision medicine in VT/VF and sudden cardiac death therapy. For precision risk identification, in the 1st year, we attempt to perform genotyping for patients with clinical VT/VF and structural heart diseases by genome-wide association study via next-generation sequencing technology. Simultaneous clinical phenotype registration will suffice the requirement of both genotype and phenotype manifestation according to “Two-Hit” hypothesis of sudden cardiac death. For precision characterization of VT/VF substrate, in the 2nd year, we attempt to combine magnetic resonance imaging with ultra-high density 3-D electroanatomical mapping to precision roadmapping of vulnerable ventricular substrate responsible for emergence of clinical VT/VF in ischemic or nonischemic cardiomyopathy with low LVEF. Thus targeted transcatheter intervention will serve to confirm the precision accuracy. For precision tailoring of cardiac autonomic dysregulation, in the 3rd year, we attempt to incorporate 123-I MIBG imaging to quantitate precisely the cardiac sympathetic denervation status in patients with disastrous electrical storm in ischemic or nonischemic cardiomyopathy with low LVEF and implanted with implantable cardioverter defibrillation (ICD). Those who with significant cardiac sympathetic denervation according to quantitative 123-I MIBG imaging will be managed by left cardiac sympathetic denervation surgery to modulate the neuraxial imbalance to the heart, so as to prevent individual cardiac events and ICD therapies.Precision or personalized medicine for life-threatening VT/VF in structural heart disease might well be easy to reach someday, when we start to identify in advance the susceptible population by genotyping, to target in precision the most vulnerable of arrhythmogenic substrate and to correct early the disastrous cardiac autonomic dysregulation by precision neuraxial modulation.個人化醫療心室不整脈缺血性心肌症非缺血性心肌症基因變異磁振影像交感 神經失衡Precision medicineVentricular tachyarrhythmiaIschemic cardiomyopathyNonischemic cardiomyopathyGenomic variantsMagnetic resonance imagingCardiac sympathetic denervation