QT interval duration

The determinant that mostly influences the QT interval duration is cycle length (RR interval) the longer the RR interval, the longer the QT interval and vice versa. Therefore, a number of formulas (see [94] for a list) are used to normalize the QT interval for heart rate and obtain a corrected QT interval (QTc), a key issue especially... 

Schematic illustration of an integrated risk assessment aimed at assessing the liability for an NCE to prolong the QT interval in man. APD = Action Potential Duration NCE = New Chemical Entity QTCV = Van de Water corrected QT interval duration.

Chezalvielguilbert, F., Davy, J.M., Poirier, J.M. and Weissenburger, J. (1995) Mexiletine antagonizes effects of sotalol on qt interval duration and its proarrhythmic effects in a canine model of torsade-de-pointes. Journal of the American Collie of Cardiology, 26, 787—792. 

QT interval Duration of the ventricular systole or contraction of the heart. 

The QT interval duration is heart rate dependent. The use of correction formulae derived from clinical data are not appropriate for use with dog ECGs. Algo-rhythms designed specifically for the dog are required and historical data from the dogs actually used in a given study is the preferred way to derive any QT correction (Meyners and Markert, 2004). Still better, if no drag-induced effect on heart rate is observed, no correction of the QT interval should be undertaken. 

The guinea pig has been shown to demonstrate drag-induced effects on the QT interval duration (Hamlin et al. 2003) and is suitable for use with telemetry-based systems. However, their intolerance of arterial catheters limits their use for simultaneously measuring arterial blood pressure. 

The electrocardiogram can be obtaining using standard limb leads and/or precordial leads. A lead should be selected that is stable over time and that has a sharp demarcation at the end of the T wave to facilitate the measurement of the QT interval duration. One can also position a monophasic action potential electrode catheter through the femoral or carotid artery to obtain endocardial monophasic action potentials (see below Modification of the Method). 

Demolis JL, Funck-Brentano C, Ropers J, Ghadanfar M, Nichols DJ, JaUlon P. Influence of dofetilide on QT-interval duration and dispersion at various heart rates during exercise in humans. Circulation 1996 94(7) 1592-9. 

Chezalveil-Guilbert F, Davy J-M, Poirier J-M, Weissenburger J. Mexiletine anla mizes effects of sotalol on QT interval duration and its proarrh3dhmic effects in a canine model of torsade de pointes. J Am Coll Cardiol (1995) 26,787-92. 

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

Glass IB Antiarrhythmic Agents. Class IB antiarrhythmic agents produce less inhibition of the inward sodium current than Class lA agents. In normal myocardial tissue, phase 0 may be unaffected or minimally depressed. However, in ischemic or infarcted tissue, phase 0 is depressed. Myocardial tissue exposed to Class IB agents exhibits decreased automaticity, shortened action potential duration, ie, shortened repolarization, and shortened refractory period. Excitability of the myocardium is not affected and conduction velocity is increased or not modified. The refractory period is shortened less than its action potential duration, thus the ratio of refractory period to action potential duration is increased by these agents. The net effect is increased refractoriness. The PR and QT intervals of the ECG are shortened and the QRS interval is unchanged (1,2). 

The Class III antiarrhythmic agents markedly prolong action potential duration and effective refractory period of cardiac tissue. The QT interval of the ECG is markedly prolonged. 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

Several intervals and durations are routinely measured on the ECG. The PR interval represents the time of conduction of impulses from the atria to the ventricles through the AV node the normal PR interval in adults is 0.12 to 0.2 seconds. The QRS duration represents the time required for ventricular depolarization, which is normally 0.08 to 0.12 seconds in adults. The QT interval represents the time required for ventricular repolarization. The QT interval varies with heart rate—the faster the heart rate, the shorter the QT interval, and vice versa. Therefore, the QT interval is corrected for heart rate using Bazett s equation3, which is ... 

Alternatively, a continuous magnesium infusion may be initiated after the first bolus, at a rate of 0.5 to 1 g/hour. Alternative treatments include transvenous insertion of a temporary pacemaker for overdrive pacing, which shortens the QT interval and may terminate torsades de pointes intravenous isoproterenol 2 to 10 mcg/minute, to increase the heart rate and shorten the QT interval intravenous lidocaine, which may shorten the duration of ventricular repolarization or intravenous phenytoin, which may also shorten the duration of ventricular repolarization, administered at a dose of 10 to 15 mg/kg infused at a rate of 25 to 50 mg/minute. 

The QT interval (measured from the beginning of the Q wave to the end of the T wave of the surface electrocardiogram) reflects the duration of individual action potentials in cardiac myocytes (Figure 3.1) indeed, a prolongation of the action potential duration (APD) of myocytes will result in a prolonged QT interval. 

Data analysis and interpretation (i.e. extrapolation to the target patient population) Different formulas are used to correct duration of the QT interval for heart rate some formulas may overcorrect at high heart rates and undercorrect at low heart rates (e.g. Bazett s formula) consider that with some formulas (e.g. Bazetf s) a QTc increase of 4-5 ms may result from measurement bias Need for an individualized correction formula... 

Figure 4.2 Cartoon representation of an ECC trace and ventricular cardiac action potential, (a) A representation of an ECC trace with its five typical deflections (PQRST) arising from the spread of electrical activitythrough the heart. The QRS wave denotes the ventricular depolarization, while the T wave represents ventricular repolarization. The QT interval therefore estimates the duration of a ventricular action potential, (b) Schematic of the five phases of a ventricular action potential. Phase 0 is the rapid depolarization phase due to a large influx of Na+ ions (Ina). Phase 1 occurs with the inactivation of Na+ channels and the onset of transient outward (repolarizing) currents (/to)...

QTc Duration of the QT interval corrected for changes in the heart rate... 

Because phenytoin improves A-V conduction and shortens the action potential duration of ventricular myocardium, it may decrease the PR and QT intervals of the surface electrocardiogram. 

Flecainide increases the PR, QRS, and to a lesser extent, QTc intervals. The rate of ventricular repolarization is not affected, and the QT interval prolongation is caused by the increase in the QRS duration. 

Administration of sotalol is associated with dose- and concentration-dependent slowing of the heart rate and prolongation of the PR interval. The QRS duration is not affected with plasma concentrations within the therapeutic range. The corrected QT interval is prolonged as a result of the increase in the ERP of ventricular myocardium. 

The most profound effect of adenosine is the induction of an A-V block within 10 to 20 seconds of administration. Mild sinus slowing may be observed initially followed by sinus tachycardia. There is no effect on the QRS duration or QT interval. Rarely, an adenosine bolus injection is accompanied by atrial fibrillation or ventricular tachyarrhythmias. 

Overdose may increase QRS duration, prolong QT interval, cause conduction disturbances, reduce myocardial contractility, and cause hypotension. 

Mechanism of Action An antiarrhythmicthat prolongs both atrial and ventricular action potential duration and increases the atrial and ventricular refractory period. Activates slow, inward current (mostly of sodium), produces mild slowing of sinus node rate and AV conduction, and causes dose-related prolongation of QT interval. Therapeutic Effect Converts arrhythmias to sinus rhythm. 

Mechanism of Action An anticonvulsant agent that stabilizes neuronal membranes in motor cortex, and decreases abnormal ventricular automaticity. Therapeutic Effect Limits spread of seizure activity Stabilizes threshold against hyperexcitability. Decreases post-tetanic potentiation and repetitive discharge. Shortens refractory period, QT interval, and action potential duration. 

It is a anticonvulsant drug and depresses the ventricular automaticity and accelerates the AV conduction. It also reduces the duration of action potential like quinidine. It also shortens the QT interval. It mainly blocks inactivated Na+ channels. It is used for the suppression of ectopic beats and for prophylaxis of recurrent paroxysmal tachycardia and also for the treatment of rapid supraventricular or ventricular tachycardia. 

Ranolazine Inhibits late sodium current in heart also may modify fatty acid oxidation Reduces cardiac oxygen demand fatty acid oxidation modification may improve efficiency of cardiac oxygen utilization Prophylaxis of angina Oral, duration 6-8 h Toxicity QT interval prolongation, nausea, constipation, dizziness Interactions Inhibitors of CYP3A increase ranolazine concentration and duration of action... 

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