Papers by Mads Peter Andersen
QT interval prolongation is one of the most common causes of delays and non-approvals in drug dev... more QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a
European Neuropsychopharmacology, 2008
Journal of Electrocardiology, 2008
Journal of Electrocardiology, 2008
Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; MP ... more Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; MP Andersen; JQ Xue; TB Hardahl; JK Kanters; E. Toft; M. Christiansen; HK Jensen; JJ Struijk.
Quantification of T-wave morphology may be useful in drug testing, but no robust method exists fo... more Quantification of T-wave morphology may be useful in drug testing, but no robust method exists for this purpose. We present a method for quantification of I Kr -related Twave morphology changes: T-wave asymmetry, flatness and the presence of notches on the T-wave combined to an overall morphology combination score (MCS). In a population of 30 LQT2-subjects (congenital I Kr inhibition) and 1096 healthy subjects, both QTcF and MCS yield clear separation between the groups (p<0.001), sensitivity 90%, specificity 95%.
Journal of Electrocardiology, 2010
Analysis of ST deviations from the 12-lead electrocardiogram allows for estimation of a spatial S... more Analysis of ST deviations from the 12-lead electrocardiogram allows for estimation of a spatial ST injury vector. The goal of the present study was to compare the location and extent of transmural myocardial ischemia evaluated by myocardial perfusion imaging with the direction and magnitude of the ST injury vector. Twelve-lead electrocardiograms were recorded from 75 acute myocardial infarction patients with single-vessel disease and thrombolysis in myocardial infarction (TIMI) flow 0/1 (30 left anterior descending [LAD], 28 right coronary artery [RCA], 17 left circumflex artery [LCX]). ST deviations were measured in the J point in all leads and used to estimate ST injury vectors for each patient. Myocardial perfusion imaging was performed to evaluate the extent and location of myocardial ischemia at the time of coronary intervention. Ninety-two percent of the patients showed ST injury vectors within the expected directional range for the identified anatomic segment of ischemia by myocardial perfusion imaging. ST injury vector direction separated LAD, RCA, and LCX occlusion patients; 90% of the LAD patients showed anterior vectors, 82% of the RCA patients showed posteroinferoseptal vectors, and 59% of the LCX patients showed posteroinferolateral vectors. Eight patients did not fulfill the ST elevation criteria for ST elevation myocardial infarction but showed anterior ST depression and prominent ST injury vectors in the posterior torso direction. There was a moderate correlation between the extent of ischemia and ST injury vector magnitude for the ischemic patients, r = 0.29. We found strong agreement between the direction of the ST injury vector and the location of myocardial ischemia. The ST injury vector may be the key to higher diagnostic accuracy for inferobasal transmural ischemia and may help distinguishing between RCA and LCX occlusions in the acute phase.
Journal of Electrocardiology, 2008
Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; J. ... more Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; J. Matz; MP Andersen; JK Kanters; E. Toft; S. Pehrson; JJ Struijk.
Journal of Electrocardiology, 2009
... T-wave morphology in long-QT syndrome. Esben Vedel-Larsen: Affiliations. Laboratory of Experi... more ... T-wave morphology in long-QT syndrome. Esben Vedel-Larsen: Affiliations. Laboratory of Experimental Cardiology, Dept. ... No abstract is available. To read the body of this article,please view the Full Text online. PII: S0022-0736(09)00399-9. ...
QT interval prolongation is one of the most common causes of delays and non-approvals in drug dev... more QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a
Journal of Electrocardiology, 2011
Background: The myocardial area at risk (MaR) has been estimated in patients with acute myocardia... more Background: The myocardial area at risk (MaR) has been estimated in patients with acute myocardial infarction (AMI) by using ST segment based ECG methods. However, as the process from ischemia to infarction progresses, the ST segment deviation is typically replaced by QRS abnormalities, causing a falsely low estimation of the total MaR if determined by using ST segment based methods. A previous study showed the value of the consideration of the abnormalities in the QRS complex, in addition to those in the ST segment estimating the total MaR for patients with anterior AMI. The purpose of this study was to investigate the same method for patients with inferior AMI. Methods: Thirty-two patients with acute inferior ST elevation myocardial infarction received 99m Tc-Sestamibi before percutaneous coronary intervention. SPECT was performed within 2 hours after treatment and was used as a gold standard for the estimation of the total MaR. The ECG recorded at admission in the hospital was used for the ECG estimates of the total MaR. This included a ST segment estimation of the ischemic component of the total MaR (Aldrich score) and an estimation of the infarcted component of the total MaR in the acute phase of AMI by QRS abnormalities (Selvester score). These scores were added for the combined ECG score. Results: The ischemic component of the total MaR estimated by the Aldrich score alone no statistically significant correlation with SPECT (r = 0.17, p = 0.36). The infarcted component of the total MaR estimated by the Selvester score showed a significant correlation with SPECT (r = 0.55, p = 0.001). When the Aldrich and Selvester scores were combined, the correlation with SPECT improved (r = 0.58, p b 0.001). Both the Aldrich and Selvester score alone underestimated the mean MaR measured by SPECT (respectively p = 0.007 and p b 0.0001). There was no statistically significant difference between the mean MaR estimated by the sum of Aldrich and Selvester and the MaR measured by SPECT (p = 0.636). Conclusion: The estimation of the total MaR was more accurate by taking both ST deviation and QRS abnormalities in account than by using either method alone. A new ECG method to determine the total MaR during acute coronary occlusion should consider both its ischemic and infarcted components.
European Neuropsychopharmacology, 2008
Journal of Electrocardiology, 2008
Journal of Electrocardiology, 2008
Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; MP ... more Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; MP Andersen; JQ Xue; TB Hardahl; JK Kanters; E. Toft; M. Christiansen; HK Jensen; JJ Struijk.
Journal of Electrocardiology, 2009
Quantification of T-wave morphology may be useful in drug testing, but no robust method exists fo... more Quantification of T-wave morphology may be useful in drug testing, but no robust method exists for this purpose. We present a method for quantification of I Kr -related Twave morphology changes: T-wave asymmetry, flatness and the presence of notches on the T-wave combined to an overall morphology combination score (MCS). In a population of 30 LQT2-subjects (congenital I Kr inhibition) and 1096 healthy subjects, both QTcF and MCS yield clear separation between the groups (p<0.001), sensitivity 90%, specificity 95%.
Journal of Electrocardiology, 2010
Analysis of ST deviations from the 12-lead electrocardiogram allows for estimation of a spatial S... more Analysis of ST deviations from the 12-lead electrocardiogram allows for estimation of a spatial ST injury vector. The goal of the present study was to compare the location and extent of transmural myocardial ischemia evaluated by myocardial perfusion imaging with the direction and magnitude of the ST injury vector. Twelve-lead electrocardiograms were recorded from 75 acute myocardial infarction patients with single-vessel disease and thrombolysis in myocardial infarction (TIMI) flow 0/1 (30 left anterior descending [LAD], 28 right coronary artery [RCA], 17 left circumflex artery [LCX]). ST deviations were measured in the J point in all leads and used to estimate ST injury vectors for each patient. Myocardial perfusion imaging was performed to evaluate the extent and location of myocardial ischemia at the time of coronary intervention. Ninety-two percent of the patients showed ST injury vectors within the expected directional range for the identified anatomic segment of ischemia by myocardial perfusion imaging. ST injury vector direction separated LAD, RCA, and LCX occlusion patients; 90% of the LAD patients showed anterior vectors, 82% of the RCA patients showed posteroinferoseptal vectors, and 59% of the LCX patients showed posteroinferolateral vectors. Eight patients did not fulfill the ST elevation criteria for ST elevation myocardial infarction but showed anterior ST depression and prominent ST injury vectors in the posterior torso direction. There was a moderate correlation between the extent of ischemia and ST injury vector magnitude for the ischemic patients, r = 0.29. We found strong agreement between the direction of the ST injury vector and the location of myocardial ischemia. The ST injury vector may be the key to higher diagnostic accuracy for inferobasal transmural ischemia and may help distinguishing between RCA and LCX occlusions in the acute phase.
Journal of Electrocardiology, 2008
Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; J. ... more Journal of Electrocardiology, Volume 41, Issue 6, Pages 644, November 2008, Authors:C. Graff; J. Matz; MP Andersen; JK Kanters; E. Toft; S. Pehrson; JJ Struijk.
Journal of Clinical Pharmacology, 2009
This study investigates repolarization changes induced by a new candidate drug to determine wheth... more This study investigates repolarization changes induced by a new candidate drug to determine whether a composite electrocardiographic (ECG) measure of T-wave morphology could be used as a reliable marker to support the evidence of abnormal repolarization, which is indicated by QT interval prolongation. Seventy-nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an I(Kr)-blocking antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35-138 increased the QTc interval with corresponding changes in T-wave morphology as determined by MCS. For subjects taking Lu 35-138, T-wave morphology was a more reliable indicator of I(Kr) inhibition than QTcF (chi(2) = 20.3, P = .001). At 80% study power for identifying a 5-millisecond placebo-adjusted change from baseline for QTcF, the corresponding study power for MCS was 93%. As a covariate to the assessment of QT interval liability, MCS offered important additive information to the effect of Lu 35-138 on cardiac repolarization.
Journal of Electrocardiology, 2009
... T-wave morphology in long-QT syndrome. Esben Vedel-Larsen: Affiliations. Laboratory of Experi... more ... T-wave morphology in long-QT syndrome. Esben Vedel-Larsen: Affiliations. Laboratory of Experimental Cardiology, Dept. ... No abstract is available. To read the body of this article,please view the Full Text online. PII: S0022-0736(09)00399-9. ...
Journal of Electrocardiology, 2011
Background: The myocardial area at risk (MaR) has been estimated in patients with acute myocardia... more Background: The myocardial area at risk (MaR) has been estimated in patients with acute myocardial infarction (AMI) by using ST segment based ECG methods. However, as the process from ischemia to infarction progresses, the ST segment deviation is typically replaced by QRS abnormalities, causing a falsely low estimation of the total MaR if determined by using ST segment based methods. A previous study showed the value of the consideration of the abnormalities in the QRS complex, in addition to those in the ST segment estimating the total MaR for patients with anterior AMI. The purpose of this study was to investigate the same method for patients with inferior AMI. Methods: Thirty-two patients with acute inferior ST elevation myocardial infarction received 99m Tc-Sestamibi before percutaneous coronary intervention. SPECT was performed within 2 hours after treatment and was used as a gold standard for the estimation of the total MaR. The ECG recorded at admission in the hospital was used for the ECG estimates of the total MaR. This included a ST segment estimation of the ischemic component of the total MaR (Aldrich score) and an estimation of the infarcted component of the total MaR in the acute phase of AMI by QRS abnormalities (Selvester score). These scores were added for the combined ECG score. Results: The ischemic component of the total MaR estimated by the Aldrich score alone no statistically significant correlation with SPECT (r = 0.17, p = 0.36). The infarcted component of the total MaR estimated by the Selvester score showed a significant correlation with SPECT (r = 0.55, p = 0.001). When the Aldrich and Selvester scores were combined, the correlation with SPECT improved (r = 0.58, p b 0.001). Both the Aldrich and Selvester score alone underestimated the mean MaR measured by SPECT (respectively p = 0.007 and p b 0.0001). There was no statistically significant difference between the mean MaR estimated by the sum of Aldrich and Selvester and the MaR measured by SPECT (p = 0.636). Conclusion: The estimation of the total MaR was more accurate by taking both ST deviation and QRS abnormalities in account than by using either method alone. A new ECG method to determine the total MaR during acute coronary occlusion should consider both its ischemic and infarcted components.
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Papers by Mads Peter Andersen