QT/RR adaptation

When evaluating QT intervals, knowledge about the underlying heart rate (HR) is required. While one possibility for QT analysis would be to select ECG episodes preceded by stable HR, this does not seem an adequate option, since relevant information for arrhythmic risk stratification can be found in episodes with marked HR changes. The QT/RR adaptation method provides a characterization of the QT interval adaptation dynamics in response to HR changes. Taking those dynamics into consideration, QT analysis can be extended to more general scenarios.

Until very recently, QT interval adaptation after a change in HR was mainly investigated in invasive studies, where the QT interval was shown to take at least two minutes to completely reach a new steady state after an abrupt change in pacing rate. In (1) a technique was proposed to quantify QT interval adaptation to spontaneous HR changes in Holter ECGs of post-myocardial infarction patients. That technique considers weighted averages of RR intervals preceding each QT measurement so as to account for the QT dependence on HR history. On average, the QT interval was found to require two and a half minutes to follow HR changes, although the initial tens of seconds to one minute were the most clinically relevant in the majority of cases. Both the duration and profile of QT adaptation were found to be highly individual. In agreement with results from invasive studies, the QT adaptation profile showed two distinct phases: a very fast initial adaptation followed by a second slower accommodation.  A measure of the time for QT adaptation was able to discriminate between patients at high and low risk of arrhythmic death, with a more prolonged adaptation related to increased risk.

The technique developed in (1) was later extended to account for possibly different QT adaptation characteristics along the ECG recording of one and the same subject (2). With that extended methodology, the time taken by the QT interval to follow HR changes was shown to range from just a few seconds in episodes of the ECG recording with little HR changes up to several minutes in episodes with large HR changes.

Characterization of QT/RR adaptation, as described above, was used to assess prophylactic treatment with amiodarone in survivors of acute myocardial infarction (3).  The QT/RR adaptation was found to be altered after chronic treatment with amiodarone, with different effects found in patients who survived and patients who suffered from arrhythmic death while on therapy. The observations derived in (3) suggest a potential use of indices derived from QT adaptation dynamics as markers for identification of patients who are not protected by the treatment with amiodarone. 

The ionic basis underlying QT/RR adaptation and its link to proarrhythmic mechanisms were investigated in (4). Computer simulations and experiments in human ventricular tissue were conducted, from which it was concluded that the QT interval follows similar adaptation dynamics to the action potential duration, in both cases consisting of a fast and a slow adaptation phases. While the fast phase is mainly driven by the calcium current kinetics, the slow accommodation is related to the accumulation of sodium within the cell. Increased risk of cardiac arrhythmias in patients with delayed rate adaptation could be a reflection of adverse ionic changes involving calcium and sodium dynamics that, upon further deterioration, may facilitate arrhythmia initiation via an increased likelihood of afterdepolarizations.

References:

1. Pueyo E, Smetana P, Caminal P, de Luna AB, Malik M, Laguna P. Characterization of QT interval adaptation to RR interval changes and its use as a risk-stratifier of arrhythmic mortality in amiodarone-treated survivors of acute myocardial infarction. IEEE Trans Biomed Eng 51: 1511-1520, 2004.
2. Pueyo E, Malik M, Laguna P. A dynamic method to characterize beat-to-beat adaptation of repolarization to heart rate changes. Biomed Signal Process Control 3: 29-43, 2008.
3. Smetana P, Pueyo E, Hnatkova K, Batchvarov V, Laguna P, Malik M. Individual patterns of dynamic QT/RR relationship in survivors of acute myocardial infarction and their relationship to antiarrhythmic efficacy of amiodarone. J Cardiovasc Electrophysiol 15: 1147-1154, 2004.
4. Pueyo E, Husti Z, Hornyik T, Baczkó I, Laguna P, Varró A, Rodríguez B. Mechanisms of ventricular rate adaptation as a predictor of arrhythmic risk. Am J Physiol Heart Circ Physiol 298: 1577-1587, 2010.