A Review on Electrical Inhomogeneity and Cardiac Dysfunctions

Electrical Inhomogeneity

The mechanical functioning of the human heart depends on the normal electrical function of the cardiac muscles (Bordachar et.al, 2012). This electrical activity is a sequence of ionic events from specific pacemaker regions of the heart and subsequent propagation of this activity through the ventricles. A normal unidirectional homogenous propagation of excitation through the myocardium generates normal cardiac rhythms and subsequent normal cardiac functions. Thus, changes in the characteristics or the functions of these myocardial ionic or electric events lead to various life threatening cardiac dysfunctions. Electrical inhomogeneity in the heart as a cause to cardiac dysfunctions has, thus, caught the attention of the researchers in the recent years. Various factors have been shown to cause electrical inhomogeneity in the heart as evidenced by research publications and numerous concepts have been elucidated with reference to electrical inhomogeneity of the heart.

Repolarization Variations in the Myocardium

Recent research in the past decade have shown that the heart ventricles are not just composed of two basic cell types, namely the conducting cells comprising the His-Purkinje system and the ventricular myocytes; instead, exhibit considerable diversity among the cells of the ventricular myocardium. These variations point to regional differences in the electrical properties of these cells and also variations in the response of these cells to various drugs and pathophysiological states (Karim et.al, 2012). Recent studies have also elucidated major differences between the endocardium and the epicardium. A specific group of cells lodged in the middle part of the myocardial layers have been identified and shown to have distinct electrophysiological profiles as compared to the epicardium and endocardium. These cells have been named ‘M cells’ and have been detected in human and other mammalian ventricles (Letsas et.al, 2012). It is interesting to note that the M cells, epicardial cells and endocardial cells show marked differences in various aspects. The variation in the repolarization characteristics of these cells is the most important distinction that has caught the attention of the researchers. Further, the M cells and epicardial cells of the ventricles show action potentials with a conspicuous transient outward current (Ito)-mediated phase

This is responsible for the notched appearance of the action potential.

The normal J wave or J point elevation in the ECG clearly shows this transmural gradient in the amplitude of the Ito-mediated action potential notch (Keller et.al, 2012). Recent research has shown that the development of life-threatening arrhythmias in patients with the Brugada syndrome and various forms of idiopathic ventricular fibrillation is due to amplifications of this J wave particularly in the right ventricle (Antzelevitch et.al, 2013). It is also imperative to mention that the T wave of the electrocardiogram is primarily due to the transmural electric gradients generated by variations in the time of repolarization of these three ventricular myocardial cell types and any amplification of these final repolarization transmural heterogeneities can cause the development of abnormalities like the long-QT syndrome (Antzelevitch et.al, 2013).

Studies have shown that known antiarrhythmic IKr blockers (D-sotalol), calcium channel agonists like BayK 8644 or agents that augment late INa (anthopleurin-A) prolong the QT interval, increase transmural and interventricular dispersion of repolarization and induce extrasystoles that can precipitate torsade de pointes (Gussak et.al, 2012). Drugs that can prolong action potential duration (APD), are also capable of amplifying the transmural dispersion by prolonging APD of the M cell more than that of epicardial or endocardial cells and also by triggering early afterdepolarizations in M cells.

Repolarization Heterogeneity

Repolarization heterogeneity can be defined as the differences in repolarization instants in the heart. Normally, repolarization in the human heart is a rhythmic continuous process where adjacent areas repolarize almost simultaneously. Several drugs and cardiac diseases disturb this repolarization process and increase the repolarization heterogeneity, giving significant scope for arrhythmias. Repolarization heterogeneity is the maximum in hypertensive stress and recovery from physical exercise. An assessment of this repolarization heterogeneity has a sound diagnostic clinical value and the standard 12-lead electrocardiogram is a valuable tool to detect repolarization heterogeneity. Repolarization heterogeneity can be further categorized into Transmural Heterogeneity and Apico-Basal Heterogeneity (Letsas et.al, 2012).

Transmural Repolarization Heterogeneity

The human QRS complexes and T waves obtain the same polarity in most ECG leads in spite of opposite polarities of de- and repolarization currents. This relation between QRS complexes and T waves is better explained by an inverse transmural repolarization order that is in existence from the epicardium to the endocardium rather than by an order of excitation from the endocardium to the epicardium. The presence of a ventricular gradient, caused by such non-homogeneous action potential durations throughout the heart was first postulated by Wilson in 1931 (Patel et.al, 2009).

Apico-Basal Repolarization Heterogeneity

Apart from a feeble transmural gradient, an apico-basal gradient seem to be also present under normal conditions. The apico-basal gradient is also important for the interpretation and understanding of the normal T wave. The normal T wave thus, forms the basis for further studies on irregular T waves and electrocardiographic indices of repolarization heterogeneity (Chinushi et al, 2012).

Ventricular Gradient

There are strong experimental evidences that show that the QRST deflection area of the electrocardiogram is dependent on disparity of repolarization. Ventricular Gradient can be thus, defined as the sum of the areas within the QRS complex and the T wave on the electrocardiogram. Ventricular Gradient can be also understood as the algebraic sum of the net electrical difference between the area enclosed within the QRS complex and that within the T wave in the electrocardiogram (Marek, 2011). Recently, the ventricular gradient G has been shown to have close relationship with an area marked as ¿ of the cellular action potential (Keller et.al, 2012). In fact, an expression has been developed to relate the secondary T wave to the QRS complex and the shape of the action potential.

Conclusion

Electrical inhomogeneity in the heart can cause serious cardiac dysfunctions like arrhythmias. It is important to note that the cardiac risk factors, especially of arrhythmias can be easily obtained from the standard electrocardiogram. Hence, clinical electrocardiographic measurement of QRST area to predict arrhythmias and the angle of the ventricular gradient (VG) has gained wide recognition.

Reference

•Antzelevitch C, Gussak I. Author’s response to Letter to the Editor from Perez and Froelicher. J Electrocardiol. 2013; 46:116.

•Bordachar P, Ploux S, and Lumens Endocardial pacing: the wave of the future? J.Curr Cardiol Rep. 2012 Oct; 14(5):547-51.

•Chinushi M, Sato A, Izumi D, Furushima H.Nifekalant enlarged the transmural activation-recovery interval difference as well as the peak-to-end interval on surface ECG in a patient with short-QT syndrome. J Cardiovasc Electrophysiol. 2012 Aug; 23(8):877-80.

•Gussak I, Antzelevitch C. Early repolarization syndrome: A decade of progress. J Electrocardiol. 2013; 46:110-113.

•Karim Talib A, Sato N, Sakamoto N, Tanabe Y, Takeuchi T, Saijo Y, Kawamura Y, Hasebe N.Enhanced transmural dispersion of repolarization in patients with J wave syndromes. J Cardiovasc Electrophysiol. 2012 Oct; 23(10):1109-14.

•Keller DU, Weiss DL, Dossel O, Seemann G.Influence of I(Ks) heterogeneities on the genesis of the T-wave: a computational evaluation.IEEE Trans Biomed Eng. 2012 Feb;59(2):311-22.

•Letsas KP, Charalampous C, Korantzopoulos P, Tsikrikas S, Bramos D, Kollias G, Efremidis M, Sideris A.Novel indexes of heterogeneity of ventricular repolarization in subjects with early repolarization pattern. Europace. 2012 Jun; 14(6):877-81.

•Marek Malik. Ventricular gradient and cardiac risk. Europace (2011) 13 (5): 605-607.

•Patel C, Burke JF, Patel H, Gupta P, Kowey PR, Antzelevitch C, Yan GX. Is there a significant transmural gradient in repolarization time in the intact heart? Cellular basis of the T wave: a century of controversy.Circ Arrhythm Electrophysiol. 2009; 2:80-88.

•Perez GJ, Desai M, Anderson S, Scornik FS. Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons. Am J Physiol Cell Physiol. 2013; 304:C280-C286.

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