?????QT?????

1
?????QT?????
Fabio Badilini, PhD AMPS LLC New York, NY
??? ?
2
?????ECG????

• FDA?2001??????????ECG??????????,???ECG???????QT???
  ?,??QT???????ECG??????????????????
• ???????? (ICH E14)???????????????????????????(1)
  ?
• ??,???ECG?????????????????ECG,????????QT??????????
  ??ECG???QT?????????(2,3)?

3
??????????????
??
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?????
SAS ???
?????
??????????????
????
?????
?????????????????
???????
By courtesy of Mortara Instruments
4
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???????????? ??????????????
??
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??????
SAS ???
??????
?? ???
??????
????
?????
????
?????????????
By courtesy of Mortara Instruments
5
???????????ECG????

• ???????,????????????????????????1997?????????(CPMP
  )???,???????????????,?????II??(4)?
• ??,??????????????????????????,???????????????(5)?
  

6
???????????ECG????

• ?????ECG???????????????????????????,??????????????
  ?????
• ??,??????????????????????????,????????????????????
  ?????????????????????????????????

7
??????? ????

• ????????.
• ???????
• ?????????10?????,
• ???????? (??????)?
• ????????,??????(???,???.)?
• ???????????????????????????????

8
???? ????????

• ????(????)
• ???????????
• ???????X????
• ????10?
• ???????
• ???????????????????????(????)
• ????????????????????(P-QRS-T)
• ????1.2?

9
???? ????????

• ?????
• ??????????? (? II??)
• ??????????????
• ?????
• ????????
• ??????????

10
??
???? ??? (?????)
???? ??II????3?QT?? ? ?10????????3?QT??
??????? (????) ? ????????II?????QT?? ? ???????????????QT??
??
??
11
????????
Lead I
???????????!!!
????????
Lead II
12
????????
????!!!
13
????????????
Lead I
II?????????????QT??
Lead II
14
????????????
?????T???????????? ???????????QT??
??????????????
15
????????????
??????????????????T??????
16
????????????

• ??????????
• ????T??????????
• ???12?????????? (???????)?
• ???12?????????? (???????)?
• ???12???????????????
• ????12???????????????????????T???(???????)?

?????????????? ??????????,???????????????
17
??????? ?????(6)

• ??CalECG2 (AMPS-LLC)?????
• ?????????3???4??4????????QT
• ????????
• 26??????,???4????
• ??160mg?????????1?2?3??

Badilini et al. J Electrocardiol 2006
39S152-156.
18
??????? ?????

• ????II????3?QT/RR (M1)
• ???????????? QT/RR(M2)
• II??????????????QT/RR (M3)
• ??????????QT/RR (M4)
• ???QT???12???QT??????

Badilini et al. (6)
19
??????? ?????
Sotalol 160 mg
Badilini et al. (6)
20
??????? ?????
?QTcF (msec)
???????? NS
??? 160 mg
Badilini et al. (6)
21
??????? ??????

• ??????????????
• ??,??????????????????????

22
??????? ????? (7)

• ??????Cardionics ????????
• ?????????????????
• ?? QTc?II?V2?V3??? QTc?? (????????)?
• ???????,50??
• ?? QT??????????????

Kligfield et al. A.N.E. 2007 12(2)145-152 .
23
??????? ?????
Mean and SE of Bazett-corrected QTc
?? QTc????? ????????????QTc
Kligfield et al. (7)
24
???? ?????

• ???
• ????
• ????

25
???IDM?????????
?????
?????
By courtesy of Dr. M. Malik (8)
26
???? ????????????????????????????????(??)????

• ????
• ??14??21?????????
• ?????
• ??800x600, 1024x768 ? 1400x1050?????????
• ????
• ??????/?? (?????) ?
• ?????
• ??????????????????(?????????)????????????(????
  ???????)?
• ??????
• ????????????????????

??????????..
27
???????

• ????????????????????????????????????
• ??????????????????(?????????????)??????????????
  (??500????????????2????)?
• ????????????????(?????????????),??????????????????
  (??1024x768 ???????1024????768??????)?
• ???????????????????????????????,??????????????????
  ??
• ????????..

28
???????
?????? (1400x1050 ??),?????????? 1255 ??
250 Hz ECG, (4 ms ECG ???)
??????1?????????250???
????/???? 1255/250 5.02,???????????????? ????-??
???? 0.8 ms
?????????!! ????????????????!!
29
???????
??????? (1400x1050), ?????1255??
?? 250 Hz ECG, (?? 4 ms ECG ???)
??????????10?????????2500???
????/???? 1255/2500 0.502, ???????????????? ????
??-????? 8 ms
???????!! ?2????????????!!
30
???????
???????????,???????????????? ????????????????????
?!!!!
?????????4 ms,???????8 ms!!
31
?????????????
250 Hz Example
QT 376 (multiple of 4 msec)
QT 374 (NON multiple of 4 msec)
??2 ms????????
32
???? ??????
??????????????????
33
??

• ????????????????ECG????????
• ??,?????????????????????????
• ????????????????????,???????????
• ?????QT (????????)?
• ????QT (???,????????)?
• ????????????
• ????????,????????????,?????????????,??????????????
  ????????????????

34
????

• 1. International Conference on Harmonization of
  Technical Requirements for Registration of
  Pharmaceuticals for Human Use (ICH). E14 Guidance
  on clinical evaluation of QT/QTc interval
  prolongation and proarrhythic potential for
  non-antiarrythmic drugs. 2005
• Available from URL http//www.fda.gov/cder/guida
  nce/6922fnl.pdf
• 2. Stockbridge N, Throckmorton DC. Regulatory
  advice on evaluation of the proarrhythmic
  potential of drugs. J Electrocardiol 2004 37
  (Suppl.)40-41.
• 3. Stockbridge N, Brown, BD. Annotated ECG
  waveform data at FDA. J Electrocardiol 2004 37
  (Suppl.)83-84.
• 4. Points to Consider the assessment of the
  potential for QT interval prolongation by
  non-cardiovascular medicinal products. Committee
  for Proprietary Medicinal Products (CPMP),
  London, 17 December 1997.
• 5. Murray A, McLaughlin NB, Bourke JP, Doig JC,
  Furniss SS,Campbell RWP. Errors in manual
  measurement of QT intervals. Br Heart J
  199471386-390
• 6. Badilini F, Sarapa N. Implications of
  Methodological Differences in Digital
  Electrocardiogram Interval Measurement. J
  Electrocardiol 2006 39S152-156.
• 7. Kligfield P, Tyl B, Maarek M, Maison-Blanche
  P. Magnitude, Mechanism, and Reproducibility of
  QT Interval Differences Between Superimposed
  Global and Individual Lead ECG Complexes. A.N.E.
  2007 12(2)145-152.
• 8. Malik M. Errors and Misconceptions in ECG
  Measurements Used for the Detection of Drug
  Induced QT Interval Prolongation. J
  Electrocardiol 2004 37S25-33.