QT间期延长专家共识-20200524

抗结核药物所致QT间期延长临床监测和管理专家共识贝达喹啉(bedaquiline,Bdq)、德拉马尼(delamanid,Dlm)、氯法齐明(clofazimine,Cfz)和以及氟喹诺酮类药物如莫西沙星(moxifloxacin，Mfx)、左氧氟沙星(Levofloxacin,Lfx)及氯法齐明(clofazimine,Cfz)对于提高耐多药和广泛耐药结核病的全球治愈率至关重要。然而，这些药物均有可能导致心电图（electrocardiograph，ECG）校正的QT间期延长，如果不及时处理，可导致危及生命的心律失常，需要临床医师予以关注。一、QT间期延长意义及危险因素本章主要介绍QT间期基本概念，QTc间期延长意义及风险，导致QTc间期延长的影响因素等。QT间期基本概念心电图（electrocardiogram，ECG）是利用心电图机从体表记录心脏每一心动周期所产生电活动变化的曲线图形。每一心动周期(图1)都遵循心脏电活动的基本模式，在下一次心动周期心之前，心脏需要通过心室去极化和复极化的循环为自己充电。图1显示了一个心电生理周期(心跳)，包括PR区间(包含P波和PR段)，QT间期（包含QRS波、ST段、T波）和U波ADDINEN.CITE<EndNote><CiteExcludeAuth="1"ExcludeYear="1"><RecNum>72</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>72</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574214814"guid="35894162-bc55-4bc8-aa5e-0f4280436b9e">72</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors></contributors><titles><title><2018Guidance_on_ECG_monitoring_in_NDR_v2.pdf></title></titles><dates></dates><urls></urls></record></Cite></EndNote>[1]。图1：心脏周期或一次心跳的电生理循环图QT间期是Q波的起点到T波终点之间的时间间隔，QT间期反映心室除极与复极过程的总时间，或是心肌在两次跳动之间重新充电所需的时间ADDINEN.CITE<EndNote><Cite><Author>Funck-Brentano</Author><Year>1993</Year><RecNum>74</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574858490"guid="8146ebbb-88ec-4508-8e66-88afed3d23b2">74</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Funck-Brentano,C.</author><author>Jaillon,P.</author></authors></contributors><auth-address>ClinicalPharmacologyUnit,Saint-AntoineUniversityHospital,Paris,France.</auth-address><titles><title>Rate-correctedQTinterval:techniquesandlimitations</title><secondary-title>AmJCardiol</secondary-title></titles><periodical><full-title>AmJCardiol</full-title></periodical><pages>17b-22b</pages><volume>72</volume><number>6</number><edition>1993/08/26</edition><keywords><keyword>*Electrocardiography/methods</keyword><keyword>HeartRate/*physiology</keyword><keyword>Humans</keyword><keyword>Mathematics</keyword></keywords><dates><year>1993</year><pub-dates><date>Aug26</date></pub-dates></dates><isbn>0002-9149(Print) 0002-9149</isbn><accession-num>8256750</accession-num><urls></urls><electronic-resource-num>10.1016/0002-9149(93)90035-b</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]，通常用秒（second，s）或者毫秒（millisecond，ms）来测量。从心脏电活动和机械活动角度讲，QT间期实际上相当于心室的收缩期，而心室收缩期会随心率的变化而变化，即心率越快，心室收缩期越短，这也就意味着心率越快，QT间期越短，心率越慢，QT间期越长ADDINEN.CITE<EndNote><Cite><Author>Funck-Brentano</Author><Year>1993</Year><RecNum>74</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574858490"guid="8146ebbb-88ec-4508-8e66-88afed3d23b2">74</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Funck-Brentano,C.</author><author>Jaillon,P.</author></authors></contributors><auth-address>ClinicalPharmacologyUnit,Saint-AntoineUniversityHospital,Paris,France.</auth-address><titles><title>Rate-correctedQTinterval:techniquesandlimitations</title><secondary-title>AmJCardiol</secondary-title></titles><periodical><full-title>AmJCardiol</full-title></periodical><pages>17b-22b</pages><volume>72</volume><number>6</number><edition>1993/08/26</edition><keywords><keyword>*Electrocardiography/methods</keyword><keyword>HeartRate/*physiology</keyword><keyword>Humans</keyword><keyword>Mathematics</keyword></keywords><dates><year>1993</year><pub-dates><date>Aug26</date></pub-dates></dates><isbn>0002-9149(Print) 0002-9149</isbn><accession-num>8256750</accession-num><urls></urls><electronic-resource-num>10.1016/0002-9149(93)90035-b</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]。为了比较不同时间点ECG的QT间期，必须使用不同的公式根据心率进行校正，获得的数字称为“校正QT”（QTc），应用于指导临床决策ADDINEN.CITE<EndNote><Cite><Author>Charbit</Author><Year>2006</Year><RecNum>73</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>73</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574858206"guid="c2cb9074-9215-4f70-8fe8-fb04145fca68">73</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Charbit,B.</author><author>Samain,E.</author><author>Merckx,P.</author><author>Funck-Brentano,C.</author></authors></contributors><auth-address>AssistancePublique-HopitauxdeParis,Saint-AntoineUniversityHospital,75571ParisCedex12,France.beny.charbit@sat.aphp.fr</auth-address><titles><title>QTintervalmeasurement:evaluationofautomaticQTcmeasurementandnewsimplemethodtocalculateandinterpretcorrectedQTinterval</title><secondary-title>Anesthesiology</secondary-title></titles><periodical><full-title>Anesthesiology</full-title></periodical><pages>255-60</pages><volume>104</volume><number>2</number><edition>2006/01/27</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Algorithms</keyword><keyword>Anesthesia,General</keyword><keyword>Electrocardiography/*statistics&numericaldata</keyword><keyword>Female</keyword><keyword>HeartRate/*physiology</keyword><keyword>Humans</keyword><keyword>LongQTSyndrome/*chemicallyinduced/*diagnosis/physiopathology</keyword><keyword>Male</keyword><keyword>MiddleAged</keyword><keyword>Monitoring,Intraoperative</keyword><keyword>ObserverVariation</keyword><keyword>PostoperativeComplications/*chemicallyinduced/*diagnosis/physiopathology</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0003-3022(Print) 0003-3022</isbn><accession-num>16436843</accession-num><urls></urls><electronic-resource-num>10.1097/00000542-200602000-00009</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。虽然Bazett的矫正公式是最常用的公式，但是，由于在增加心率时Bazett的QT校正不准确，因此世界卫生组织建议对耐药结核病患者使用Fridericia's（QTcF）校正公式ADDINEN.CITE<EndNote><CiteExcludeAuth="1"><Year>2014</Year><RecNum>8</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>8</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574152389"guid="b7efe622-ac90-4e9a-9d0b-30b240841760">8</key></foreign-keys><ref-typename="BookSection">5</ref-type><contributors></contributors><titles><title>WHOGuidelinesApprovedbytheGuidelinesReviewCommittee</title><secondary-title>CompanionHandbooktotheWHOGuidelinesfortheProgrammaticManagementofDrug-ResistantTuberculosis</secondary-title></titles><dates><year>2014</year></dates><pub-location>Geneva</pub-location><publisher>WorldHealthOrganization Copyright(c)WorldHealthOrganization2014.</publisher><accession-num>25320836</accession-num><urls></urls><language>eng</language></record></Cite></EndNote>[4]。目前大多数心电图机可使用校正公式自动生成QT值和QTc值，建议使用生成QTcF(由Fredericia公式生成QTc)的心电图机。自动生成QTc节省了工作人员的时间和精力，但自动生成的QTc值可能存在误差，因为在用于计算的算法中，心电图制造商之间存在不一致，此外，当T波和U波相互叠加时，在机械上很难识别它们，因此手动识别这些波并了解何时必须将其作为QT间期的一部分非常重要。QTcF矫校正公式为：（二）QTc间期正常值QTc间期正常值为男性<450ms，女性<470ms。QTc时间间隔具有昼夜变化的生理特征，在早晨QTc显著增加，并连续下降到基线水平，同一天不同时间的监测值差异最大可达75ms，建议每天选择大致相同的时间点进行ECG的QTc监测ADDINEN.CITE<EndNote><Cite><Author>Roden</Author><Year>2016</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574152996"guid="9bbf3e0e-c9a4-49ea-aa28-c72405deac86">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Roden,D.M.</author></authors></contributors><auth-address>VanderbiltUniversity,Nashville,TN,37232,USA.</auth-address><titles><title>Predictingdrug-inducedQTprolongationandtorsadesdepointes</title><secondary-title>JPhysiol</secondary-title></titles><periodical><full-title>JPhysiol</full-title></periodical><pages>2459-68</pages><volume>594</volume><number>9</number><edition>2015/12/15</edition><keywords><keyword>Animals</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions/genetics/physiopathology</keyword><keyword>Humans</keyword><keyword>*LongQTSyndrome/chemicallyinduced/genetics/physiopathology</keyword><keyword>Myocytes,Cardiac/physiology</keyword><keyword>*TorsadesdePointes/chemicallyinduced/genetics/physiopathology</keyword></keywords><dates><year>2016</year><pub-dates><date>May1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>26660066</accession-num><urls></urls><custom2>PMC4850203</custom2><electronic-resource-num>10.1113/jp270526</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[5]。考虑到QTc时间间隔的性质，与基线QTc相比，从基线增加60ms可能不是QTc延长的可靠依据。然而，增加60毫秒可能意味着需要更密切的随访监测，建议在不同日期的同一时间点复查。（三）QTc间期延长的意义当QTc间期延长时，意味着心肌需要比正常情况下更长的时间来除极与复极，长时间的QTc间期意味着一个人发生心律失常的风险增加。根据来自先天性长QT间期综合征大队列的数据研究显示，QTc间期延长超过500毫秒会增加尖端扭转型室性心动过速（torsadedepointes,TdP）的风险ADDINEN.CITE<EndNote><Cite><Author>Roden</Author><Year>2016</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574152996"guid="9bbf3e0e-c9a4-49ea-aa28-c72405deac86">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Roden,D.M.</author></authors></contributors><auth-address>VanderbiltUniversity,Nashville,TN,37232,USA.</auth-address><titles><title>Predictingdrug-inducedQTprolongationandtorsadesdepointes</title><secondary-title>JPhysiol</secondary-title></titles><periodical><full-title>JPhysiol</full-title></periodical><pages>2459-68</pages><volume>594</volume><number>9</number><edition>2015/12/15</edition><keywords><keyword>Animals</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions/genetics/physiopathology</keyword><keyword>Humans</keyword><keyword>*LongQTSyndrome/chemicallyinduced/genetics/physiopathology</keyword><keyword>Myocytes,Cardiac/physiology</keyword><keyword>*TorsadesdePointes/chemicallyinduced/genetics/physiopathology</keyword></keywords><dates><year>2016</year><pub-dates><date>May1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>26660066</accession-num><urls></urls><custom2>PMC4850203</custom2><electronic-resource-num>10.1113/jp270526</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[5]。TdP是一种短暂的心律失常，可自发终止，当出现快速连续复发时，可出现晕厥，胸痛，心悸，头晕以及意识丧失等临床症状，甚至可导致猝死ADDINEN.CITE<EndNote><Cite><Author>Passman</Author><Year>2001</Year><RecNum>13</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>13</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574153083"guid="c07b9ae7-dc0b-4e6f-b8ab-20acd45fbb9b">13</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Passman,R.</author><author>Kadish,A.</author></authors></contributors><auth-address>DepartmentsofMedicineandPreventiveMedicine,CardiacElectrophysiology,NorthwesternUniversityMedicalSchool,Chicago,Illinois,USA.r-passman@</auth-address><titles><title>Polymorphicventriculartachycardia,longQ-Tsyndrome,andtorsadesdepointes</title><secondary-title>MedClinNorthAm</secondary-title></titles><periodical><full-title>MedClinNorthAm</full-title></periodical><pages>321-41</pages><volume>85</volume><number>2</number><edition>2001/03/10</edition><keywords><keyword>Anti-ArrhythmiaAgents/therapeuticuse</keyword><keyword>CardiacPacing,Artificial</keyword><keyword>Defibrillators,Implantable</keyword><keyword>Diagnosis,Differential</keyword><keyword>DiseaseSusceptibility</keyword><keyword>Electrocardiography</keyword><keyword>Ganglionectomy</keyword><keyword>HeartRate</keyword><keyword>Humans</keyword><keyword>*LongQTSyndrome/diagnosis/etiology/physiopathology/therapy</keyword><keyword>Prognosis</keyword><keyword>StellateGanglion/surgery</keyword><keyword>*Tachycardia,Ventricular/diagnosis/etiology/physiopathology/therapy</keyword><keyword>*TorsadesdePointes/diagnosis/etiology/physiopathology/therapy</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0025-7125(Print) 0025-7125</isbn><accession-num>11233951</accession-num><urls></urls><electronic-resource-num>10.1016/s0025-7125(05)70318-7</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[6]ADDINEN.CITE<EndNote><Cite><Author>Shah</Author><Year>2002</Year><RecNum>75</RecNum><DisplayText><styleface="superscript">[7]</style></DisplayText><record><rec-number>75</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574859018"guid="442f23fd-6bdd-4673-b5b9-32b6a767c70e">75</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shah,R.R.</author></authors></contributors><auth-address>MedicinesControlAgency,MarketTowers,1NineElmsLane,Vauxhall,London,SW85NQ,UK.</auth-address><titles><title>ThesignificanceofQTintervalindrugdevelopment</title><secondary-title>BrJClinPharmacol</secondary-title></titles><periodical><full-title>BrJClinPharmacol</full-title></periodical><pages>188-202</pages><volume>54</volume><number>2</number><edition>2002/09/05</edition><keywords><keyword>ClinicalTrialsasTopic</keyword><keyword>DrugDesign</keyword><keyword>DrugEvaluation</keyword><keyword>DrugInteractions</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions</keyword><keyword>Electrocardiography/*drugeffects</keyword><keyword>Humans</keyword><keyword>Legislation,Drug</keyword><keyword>LongQTSyndrome/*chemicallyinduced</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0306-5251(Print) 0306-5251</isbn><accession-num>12207642</accession-num><urls></urls><custom2>PMC1874403</custom2><electronic-resource-num>10.1046/j.1365-2125.2002.01627.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[7]。QTc延长是药物开发过程中的安全监测指标ADDINEN.CITE<EndNote><Cite><Author>Shah</Author><Year>2002</Year><RecNum>75</RecNum><DisplayText><styleface="superscript">[7]</style></DisplayText><record><rec-number>75</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574859018"guid="442f23fd-6bdd-4673-b5b9-32b6a767c70e">75</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shah,R.R.</author></authors></contributors><auth-address>MedicinesControlAgency,MarketTowers,1NineElmsLane,Vauxhall,London,SW85NQ,UK.</auth-address><titles><title>ThesignificanceofQTintervalindrugdevelopment</title><secondary-title>BrJClinPharmacol</secondary-title></titles><periodical><full-title>BrJClinPharmacol</full-title></periodical><pages>188-202</pages><volume>54</volume><number>2</number><edition>2002/09/05</edition><keywords><keyword>ClinicalTrialsasTopic</keyword><keyword>DrugDesign</keyword><keyword>DrugEvaluation</keyword><keyword>DrugInteractions</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions</keyword><keyword>Electrocardiography/*drugeffects</keyword><keyword>Humans</keyword><keyword>Legislation,Drug</keyword><keyword>LongQTSyndrome/*chemicallyinduced</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0306-5251(Print) 0306-5251</isbn><accession-num>12207642</accession-num><urls></urls><custom2>PMC1874403</custom2><electronic-resource-num>10.1046/j.1365-2125.2002.01627.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[7]，药物引起的QTc延长的风险各异；超过170种药物与QTc延长有关。监管机构强调在新药研发期间进行QTc评估的重要性，然而这种监测在实效性使用过程中的临床意义尚未明确。TdP或心源性猝死的风险与药物治疗期间QT间期长度或QTc延长持续时间并不是线性相关的ADDINEN.CITE<EndNote><Cite><Author>Roden</Author><Year>2016</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574152996"guid="9bbf3e0e-c9a4-49ea-aa28-c72405deac86">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Roden,D.M.</author></authors></contributors><auth-address>VanderbiltUniversity,Nashville,TN,37232,USA.</auth-address><titles><title>Predictingdrug-inducedQTprolongationandtorsadesdepointes</title><secondary-title>JPhysiol</secondary-title></titles><periodical><full-title>JPhysiol</full-title></periodical><pages>2459-68</pages><volume>594</volume><number>9</number><edition>2015/12/15</edition><keywords><keyword>Animals</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions/genetics/physiopathology</keyword><keyword>Humans</keyword><keyword>*LongQTSyndrome/chemicallyinduced/genetics/physiopathology</keyword><keyword>Myocytes,Cardiac/physiology</keyword><keyword>*TorsadesdePointes/chemicallyinduced/genetics/physiopathology</keyword></keywords><dates><year>2016</year><pub-dates><date>May1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>26660066</accession-num><urls></urls><custom2>PMC4850203</custom2><electronic-resource-num>10.1113/jp270526</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[5]。对249例发生非心脏QTc延长药物相关TdP患者的文献回顾报道，除药物外，71%的患者至少同时存在其他两个危险因素ADDINEN.CITEADDINEN.CITE.DATA[8]。在荷兰的一项观察性研究中，在9年期间发现了775例心源性猝死病例，其中24例（3.1%）猝死前正在使用延长QTc的药物ADDINEN.CITE<EndNote><Cite><Author>Straus</Author><Year>2005</Year><RecNum>65</RecNum><DisplayText><styleface="superscript">[9]</style></DisplayText><record><rec-number>65</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574155815"guid="5e72b8a0-79be-4620-9d98-c903091e099d">65</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Straus,S.M.</author><author>Sturkenboom,M.C.</author><author>Bleumink,G.S.</author><author>Dieleman,J.P.</author><author>vanderLei,J.</author><author>deGraeff,P.A.</author><author>Kingma,J.H.</author><author>Stricker,B.H.</author></authors></contributors><auth-address>Pharmaco-EpidemiologyUnit,DepartmentofEpidemiologyandBiostatistics,ErasmusMedicalCenter,POBox1738,3000DRRotterdam,TheNetherlands.</auth-address><titles><title>Non-cardiacQTc-prolongingdrugsandtheriskofsuddencardiacdeath</title><secondary-title>EurHeartJ</secondary-title></titles><periodical><full-title>EurHeartJ</full-title></periodical><pages>2007-12</pages><volume>26</volume><number>19</number><edition>2005/05/13</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Anti-ArrhythmiaAgents/*therapeuticuse</keyword><keyword>Arrhythmias,Cardiac/*drugtherapy</keyword><keyword>Case-ControlStudies</keyword><keyword>Death,Sudden,Cardiac/*prevention&control</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>MiddleAged</keyword><keyword>RiskFactors</keyword></keywords><dates><year>2005</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0195-668X(Print) 0195-668x</isbn><accession-num>15888497</accession-num><urls></urls><electronic-resource-num>10.1093/eurheartj/ehi312</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[9]。在一项双盲研究中，使用一种、两种和三种延长QTc的药物后可导致QTcF分别延长27.0ms、30.1ms和40.3ms，有41名合并多种危险因素的患者无法耐受QTc间期的延长，甚至是QTcF的小幅增加，从而引发TdPADDINEN.CITEADDINEN.CITE.DATA[10]。（四）导致QTc间期延长的影响因素导致QTc间期延长的因素有先天性因素和获得性因素。1、先天性QTc间期延长因素遗传、性别、年龄、先天性心动过缓均是影响QTc间期延长的先天因素。先天性长QT综合征属于遗传性心律失常，患病率约为1/2000，是由于编码心肌细胞离子通道的基因异常或缺陷导致的，目前已发现20多种遗传或变异可导致该病ADDINEN.CITEADDINEN.CITE.DATA[11]ADDINEN.CITE<EndNote><Cite><Author>!!!INVALIDCITATION!!![12]</Author><RecNum>0</RecNum><DisplayText><styleface="superscript">[12]</style></DisplayText><record><dates><year>!!!INVALIDCITATION!!![12]</year></dates></record></Cite></EndNote>[12]。大多数患者无任何临床症状，部分患者可有猝死的家族史。先天性长QT间期综合征的患者服用导致QTc间期延长的药物后可极大的增加发生TdP的风险，故对于此类患者应慎用可导致QTc间期延长的药物。性别是导致QTc延长的风险之一，女性发生QTc间期延长风险是男性的2倍ADDINEN.CITE<EndNote><Cite><Author>Roden</Author><Year>2016</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574152996"guid="9bbf3e0e-c9a4-49ea-aa28-c72405deac86">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Roden,D.M.</author></authors></contributors><auth-address>VanderbiltUniversity,Nashville,TN,37232,USA.</auth-address><titles><title>Predictingdrug-inducedQTprolongationandtorsadesdepointes</title><secondary-title>JPhysiol</secondary-title></titles><periodical><full-title>JPhysiol</full-title></periodical><pages>2459-68</pages><volume>594</volume><number>9</number><edition>2015/12/15</edition><keywords><keyword>Animals</keyword><keyword>*Drug-RelatedSideEffectsandAdverseReactions/genetics/physiopathology</keyword><keyword>Humans</keyword><keyword>*LongQTSyndrome/chemicallyinduced/genetics/physiopathology</keyword><keyword>Myocytes,Cardiac/physiology</keyword><keyword>*TorsadesdePointes/chemicallyinduced/genetics/physiopathology</keyword></keywords><dates><year>2016</year><pub-dates><date>May1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>26660066</accession-num><urls></urls><custom2>PMC4850203</custom2><electronic-resource-num>10.1113/jp270526</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[5]ADDINEN.CITE<EndNote><Cite><Author>!!!INVALIDCITATION!!![13]</Author><RecNum>0</RecNum><DisplayText><styleface="superscript">[13]</style></DisplayText><record><dates><year>!!!INVALIDCITATION!!![13]</year></dates></record></Cite></EndNote>[13]。年龄大于60岁患者易出现QTc间期延长，且年龄与长QTc呈线性关系，故此类患者应加强QTc间期监测ADDINEN.CITE<EndNote><Cite><Author>!!!INVALIDCITATION!!![13]</Author><RecNum>0</RecNum><DisplayText><styleface="superscript">[13]</style></DisplayText><record><dates><year>!!!INVALIDCITATION!!![13]</year></dates></record></Cite></EndNote>[13]。先天性心动过缓患者心肌收缩时间长，故QTc间期也相应延长ADDINEN.CITE<EndNote><Cite><Author>!!!INVALIDCITATION!!![14]</Author><RecNum>0</RecNum><DisplayText><styleface="superscript">[14]</style></DisplayText><record><dates><year>!!!INVALIDCITATION!!![14]</year></dates></record></Cite></EndNote>[14]。2、获得性QTc间期延长因素药物、心脏疾病或代谢异常等因素可引起离子通道功能异常而导致QTc间期延长，我们称为获得性QTc间期延长因素。获得性QTc间期延长在医疗实践中比先天性原因更常见，经常存在多个危险因素引起QTc延长或心脏事件。危险因素越多，QTc间期延长导致心律失常的风险越高ADDINEN.CITE<EndNote><Cite><Author>Schwartz</Author><Year>1993</Year><RecNum>18</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574153417"guid="72340b21-126b-4909-963b-a80a38e2ba40">18</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Schwartz,P.J.</author><author>Moss,A.J.</author><author>Vincent,G.M.</author><author>Crampton,R.S.</author></authors></contributors><auth-address>IstitutodiClinicaMedicaII,UniversityofMilan,Italy.</auth-address><titles><title>DiagnosticcriteriaforthelongQTsyndrome.Anupdate</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>782-4</pages><volume>88</volume><number>2</number><edition>1993/08/01</edition><keywords><keyword>Electrocardiography</keyword><keyword>Humans</keyword><keyword>LongQTSyndrome/*diagnosis</keyword></keywords><dates><year>1993</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0009-7322(Print) 0009-7322</isbn><accession-num>8339437</accession-num><urls></urls><electronic-resource-num>10.1161/01.cir.88.2.782</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[15]。以下是Schwartz在1993年最初描述的QTc延长的危险因素，随后得到证实并有所增加（表1）。1：QTc间期延长和室性心动过速的危险因素电解质失衡钾、镁和钙是参与心肌收缩力的重要离子。低钾血症、低镁血症和低钙血症可能是获得性QTc延长的最常见原因之一。由于不同的和潜在的伴随原因，耐药结核病患者的血钾水平可能较低：1）钾丢失增多：由于严重呕吐和腹泻可导致钾离子的丢失的钾丢失；2）钾摄入量减少：因药物所致胃肠道反应导致，患者食欲减退，摄入减少；3）药物因素：使用常用药物如袢利尿剂（呋塞米，氢氯噻嗪），卷曲霉素或替诺福韦可增加尿液中钾和其他电解质的丢失；4）使用氨基糖甙类药物，引起电解质紊乱，可导致低钾血症、低镁血症和低钙血症。故建议耐药患者治疗随访期间常规监测血钾、镁、钙水平。结构性和功能性心脏问题继发性心肌病和潜在的传导异常是心脏病学中QTc间期延长的常见病因，特别是近期复律后的心房颤动、缺血性心肌病、扩张或肥厚性充血性心脏病、充血性心力衰竭等都会增加QTc间期延长的风险。合并肺部毁损的结核患者，肺功能下降，导致肺心病，可增加QTc间期延长风险。获得性心动过缓药物因素或甲状腺功能减退症可导致心率减慢，从而导致QTc间期延长。合并HIV感染者HIV感染已被描述为导致QTc间期延长的一种危险因素，合并HIV感染患者常并发营养不良，出现消瘦综合征，易出现QTc间期延长，同时抗HIV病毒药物也可增加QTc间期延长风险。肾功能损害在患有合并耐药结核病的糖尿病患者中经常观察到，肾功能不全可增加电解质紊乱发生率，减少影响药物代谢，增加药物蓄积甚至导致药物中毒风险，增加延长QTc药物的血药浓度。另外，部分抗结核药物如氨基糖苷类具有肾毒性，可加重使肾功能的恶化。肝功能损害肝功能异常患者细胞色素P450系统的作用减弱，可能会增加一些延长QTc药物的血药浓度。药物因素影响心脏离子通道的药物可导致QTc间期延长。药物诱导的QT延长通常限于约50毫秒，相当于发生TdP心脏死亡风险增加约30％ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2011</Year><RecNum>83</RecNum><DisplayText><styleface="superscript">[16]</style></DisplayText><record><rec-number>83</rec-number><foreign-keys><keyapp="EN"db-id="erzv2pwztxzvzde5p9jv2fxwpewzw92pd5av"timestamp="1574867819"guid="f154e246-1653-45ed-9a1c-5a207e025484">83</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,Y.</author><author>Post,W.S.</author><author>Blasco-Colmenares,E.</author><author>Dalal,D.</author><author>Tomaselli,G.F.</author><author>Guallar,E.</author></authors></contributors><auth-address>DepartmentofEpidemiology,JohnsHopkinsUniversityBloombergSchoolofPublicHealth,Baltimore,MD21205,USA.<