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Heart Rate Correction of the J-to-Tpeak Interval.
Hnatkova, Katerina; Vicente, Jose; Johannesen, Lars; Garnett, Christine; Strauss, David G; Stockbridge, Norman; Malik, Marek.
Afiliação
  • Hnatkova K; National Heart and Lung Institute, Imperial College, London, England.
  • Vicente J; Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Johannesen L; Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Garnett C; Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Strauss DG; Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Stockbridge N; Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Malik M; National Heart and Lung Institute, Imperial College, London, England. marek.malik@imperial.ac.uk.
Sci Rep ; 9(1): 15060, 2019 10 21.
Article em En | MEDLINE | ID: mdl-31636317
Drug-induced changes of the J to T peak (JTp) and J to the median of area under the T wave (JT50) were reported to differentiate QT prolonging drugs that are predominant blockers of the delayed potassium rectifier current from those with multiple ion channel effects. Studies of drug-induced JTp/JT50 interval changes might therefore facilitate cardiac safety evaluation of new pharmaceuticals. It is not known whether formulas for QT heart rate correction are applicable to JTp and JT50 intervals. QT/RR, JTp/RR, and JT50/RR profiles were studied in 523 healthy subjects aged 33.5 ± 8.4 years (254 females). In individual subjects, 1,256 ± 220 electrocardiographic measurements of QT, JTp, and JT50 intervals were available including a 5-minute history of RR intervals preceding each measurement. Curvilinear, linear and log-linear regression models were used to characterize individual QT/RR, JTp/RR, and JT50/RR profiles both without and with correction for heart rate hysteresis. JTp/RR and JT50/RR hysteresis correction needs to be included but the generic universal correction for QT/RR hysteresis is also applicable to JTp/RR and JT50/RR profiles. Once this is incorporated, median regression coefficients of the investigated population suggest linear correction formulas JTpc = JTp + 0.150(1-RR) and JT50c = JT50 + 0.117(1-RR) where RR intervals of the underlying heart rate are hysteresis-corrected, and all measurements expressed in seconds. The established correction formulas can be proposed for future clinical pharmacology studies that show drug-induced heart rate changes of up to approximately 10 beats per minute.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article