Ballester-Rodés and Others-A New Look at the T Wave

Over a century ago a Dutch physician, Willem Einthoven, developed a galvanometer that could record the voltages produced during the cardiac cycle using electrodes placed on the body surface [1,2]. Einthoven assigned the letters P, Q, R, S and T to the various deflections, a terminology that is still in use today. His seminal discovery eventually led to the clinically useful field of electrocardiography, and Einthoven received the Nobel Prize in Medicine in 1924.


Introduction
Over a century ago a Dutch physician, Willem Einthoven, developed a galvanometer that could record the voltages produced during the cardiac cycle using electrodes placed on the body surface [1,2]. Einthoven assigned the letters P, Q, R, S and T to the various deflections, a terminology that is still in use today. His seminal discovery eventually led to the clinically useful field of electrocardiography, and Einthoven received the Nobel Prize in Medicine in 1924.
Physicians rely on the electrocardiogram (ECG) for the diagnosis of a variety of cardiac diseases, which reveal themselves characteristically in the electrocardiogram. However, few physicians and few cardiologists realize that our understanding of how the electrocardiographic signals are produced and propagated to the skin surface is incomplete. The T wave is especially important clinically because it is dramatically altered when there are cardiac abnormalities, but its relationship to electrical activity at the cellular level is poorly understood [3].
An early question in cardiology was precisely how the electrical fields produced during the beating of the heart travel to the surface of the body. In 1913, Einthoven and colleagues made the simplifying assumption that the human body is a homogeneous "volume conductor" with the heart's electricity conducted through tissues, with dissolved electrolytes serving as the charge carriers [4]. This overly simplistic model was useful in the early stages of research on the electrocardiogram.
The volume conductor assumption continues to dominate electrophysiology. For example, a recent treatise on electromagnetic field effects summarizes ''electrical transport within tissues'' as follows: ''The fundamental bioengineering perspective is that the human body is considered to be a compartmentalized (or lumped element) conducting dielectric'' . It consists of about 60% of water by weight, in which 33% is intracellular and 27% is extracellular. Body fluid in both the intracellular and the extracellular compartments is highly electrolytic, and these two compartments are separated by a relatively impermeable, highly resistive plasma membrane. Current within the body is carried by mobile ions in the body fluid [5].
With this approximation, the various organs and layers of tissue are ''lumped'' together, essentially disregarding anatomy, histology, and the dielectric properties of connective tissues. This is a classic example of ''meaning invariance'' [6][7][8][9]. It is a problem that occurs again and again in science when tentative assumptions, useful in the early stages of an investigation, gradually come to be taken as facts. Reliance on the volume conductor assumption has encouraged the use of approximations that affect virtually every aspect of physiology and medicine. The problem is that the diffusing hydrated ion and molecular charge transfer complex are simply too large to move fast enough through tissues to explain the speed and subtlety of living processes, including the electrocardiogram.
Controversy about the electrocardiogram began during the 1930's, when physiologists looked more carefully at the mechanisms of conduction of cardiac electricity. It was realized that the electrical pathways through the body to the sensing electrodes are anatomically intricate, and that each tissue has a different conductivity [10][11][12]. These factors are neglected in the volume conductor model. Confusion about the precise nature of the electrocardiogram persists to this day, and extends to many other biological phenomena involving charge transfer.
A further complication arises because the myocardium has traditionally been viewed as having a more or less homogenous morphology. This assumption dates to the 17 th century, when physician William Harvey described the circulatory system [13]. His simplistic anatomical perspective, which is widely accepted to this day, was that the heart is a single homogenous muscle. The ventricles, however, had posed profound mysteries for almost five centuries, and were referred to in 1864 by the well-known British professor of Anatomy, James Bell Pettigrew as a 'Gordian Knot' , a term that is often used as a metaphor for an intractable problem (as disentangling a "hopelessly impossible" knot in a rope) [14]. After some 50 years of research, Spanish Professor Torrent Guasp untangled the ventricular knot for the first time, discovering that the 3D configuration of the ventricles is a double helix, known as the helical ventricular myocardial band (HVMB) [15]. Guasp's discovery has been confirmed, and has led us to reconsider the significance of the T wave.
The Purkinje system is isolated from the surrounding myocardium and provides a fast means to simultaneously electrify both ventricles to stimulate contraction. In humans the Purkinje system starts at the level of the atrioventricular (AV) node, branches via the right and left bundle bundles and fans subendocardically, spreading in a caudal way to the right and left ventricles and then ascends towards the base of the heart. It is difficult to accurately trace the distal connections of the bundle-branch system because the Purkinje fibers penetrate the subencocardioum and myocardium for varying distances, depending on the species [16][17][18]. The QRS wave of the electrocardiogram corresponds to the electrical activation of the Purkinje system and is referred to as depolarization. It is thought that the electrical impulse follows a radial distribution from endocardium to epicardium, after which repolarization follows, giving rise to the T wave. Interpretation of the QRS complex follows from understanding of how depolarization takes place: from the septum, towards the apex, to both ventricles and eventually the base of the heart [19,20]. The spatial sequence of the repolarization process has never been fully explained.

Assumptions Revisited
Interpretation of QRS and T waves of the ECG are based on several assumptions: 1) The myocardium is an homogenous structure; 2) radial distribution, from the endocardium to the epicardium, is the basis of the electrical propagation through the myocardium; 3) mechanical activation of the myocardium topographically follows sequence of its electrical activation; 4) the T wave reflects the electrical recovery phase of the myocardium, the repolarization; 5) blood flow in the aortic arch is laminar.
In the next paragraphs, several considerations are put forward that question these assumptions.

The myocardium is not an homogenous structure
Recent discovery of the myocardium as a continuous double helical structure which folds on itself has been a major breakthrough [21,22]. Manual dissection of the myocardial anatomy as a continuous single band (Figures 1 and 2) questions the classical division of the right and left ventricles as unrelated structures. Actually, the myocardium is formed by a superposition of muscular layers that are complexly interwoven [23] (Figures 3a and 3b). As an example, the interventricular septum is formed by an endocardial helical descendent muscular segment that crosses at approximately a 60º angle with the ascendant epicardial one ( Figure 4). Recently,   automated analysis of myocardial fibre orientation by diffusion tensor magnetic resonance multi-resolution tractography imaging has confirmed the continuous double helical ventricular myocardial fibre arrangement [24][25][26] (Figure 5). Thus, the complexity of ventricular myofibre direction, which had challenged anatomists and physiologists for centuries [27,28] can be explained by the spatial architecture of a double helicoid. The anatomical findings of Torrent-Guasp are therefore confirmed.

Radial distribution is not the basis of the electrical propagation from the endocardium to epicardium
Study of propagation of the electrical impulse that triggers contraction of the myocardial fibres was developed before the helical structure of the myocardium was known. The concept of radial propagation from the endocardium to the epicardium stems from the belief that the Purkinje system penetrates the cardiac muscle from the endocardium towards the epicardium (Figures 6a and 6b). This has provided the basis of the ECG interpretation following a radial depolarization process [19]. But in fact the Purkinje system in humans is subendocardial [29] and does not penetrate the myocardium. This differs from other species (birds) in which Purkinje fibres do penetrate the full thickness of the myocardium, and explains the very high cardiac frequencies attained (1200 pm) [30].
It is well established that propagation throughout myocardial fibers is anisotropic, meaning that it preferentially follows the longitudinal arrangement of the rod-like shaped myocytes, and that propagation velocity in this direction is maximum [31]. In the face of the complex interwoven ventricular anatomy of the helical heart it seems unlikely that the endocardial stimulus follows a radial distribution to the epicardium crossing muscular layers which are differently oriented, therefore in a non-anisotropic pathway. But how can we explain the well-known timing of endocardial to epicardial propagation? The answer lies in the helical anatomy and the sequential activation, first via the subendocardial descendent segment, followed by subsequent activation of the epicardial ascendant segment, as first suggested by Torrent-Guasp [21] and shown in the laboratory using microcrystals oriented according to the helical segments [32] (Figure 7) and myocardial 3D displacement fields captured with DENSE MRI [33]. A recent computer model of propagation of the helical model [34] also supports this pattern of electromechanical propagation.

The topographic sequence of electrical activation of the myocardium (QRS) is unrelated to the sequence of electromechanical activation
Electrical propagation via Purkinje system, which is responsible for the QRS complex, is indeed a very fast event, usually 80 ms [35]. No mechanical activity is observed at that time. Therefore, QRS reflects the quick electrification process of the ventricular myocardium rather than  Figure 6: a) the radial theory of electrical propagation from subendocardium to subepicardium, based on b) the intramyocardial penetration of the Purkinje system thought to occur in humans [19].
LVP dP/dt Figure 7: Explanation of the endocardial to epicardial activation in the helical heart [32]. Microcrystals have been implanted at the endocardium, aligned with the descendant segment, and at the epicardium, aligned with the ascendant segment. Note that the sequence of events of propagation has an endocardiumepicardium direction through the helical anatomy.
the effects of propagation through myocytes, which is a much slower process (300-400 ms). It is well known that electrical diffusion follows a septum-apex-base direction [36]. The rapid electrification of the heart is mediated through the conduction system fibres of the Purkinje network. Purkinje fibers are surrounded by a fine fibrous sheath that progressively loses its interaction with the working myocardium [37], and once the electrical stimulus has been delivered at the cardiac muscle, in a way that is still poorly understood [38] electromechanical anisotropic propagation through myocardium follows.
Existing evidence suggests that the starting point in the myocardium is not a single one, but two topographically different areas appear to be the recipients of the electrical stimulus: at the level of the infundibulum of the right ventricle and the base of the left ventricle [39][40][41]. From the moment the electrical impulse attains the myocardium, the electromechanical impulse anisotropically follows the myocardial fibre tracts, first from base of the heart, where it proceeds to the subendocardium (descendant helical segment) and later the subepicardium (ascendant helical segment) in a sequence that explains systole (counterclockwise twist of the base of the heart and clockwise twist of the apex) and diastole, which reverses these torsion movements [42][43][44] (Figure 8).

The T wave Coincides with the Electromechanical Activation
Correlation between the myocardial mechanical activity and the T wave reveals a temporal coincidence (Figures 9, 10a and  10b). Indeed, propagation of the electromechanical stimulus, as assessed by magnetic resonance imaging [46] and speckle tracking echocardiography [47,48] reveals a close overlap between the muscular activity and the T wave.

Blood flow in the aortic arch is laminar
Several studies have shown that both the heart and the vessels connected to it twist with each heartbeat [49]. The vortical structure and dynamics of the ventricular myocardial band continue into the aortic arch and arteries. The blood spirals through the aorta and beyond, into the arterial tree and all the way to the pre-capillaries (Figure 13a). And arterial endothelial cell orientation closely follows these blood flow patterns [50]. This type of vortical charge movement is similar to that taking place in a coil or solenoid (Figure 13b). From the electrical engineering perspective, this should amplify the electromagnetic field produced by the heart.  [40,45]. A) Isotopic blood pool image of the ventricles in LAO view. In circle the left ventricular cavity. B) A pig heart has been unwrapped, dissected and rewrapped. In blue, the right ventricle -which corresponds to the right segment; in red, the basal portion of the left ventricle, which corresponds to the left segment. C) A four chamber section of a heart, as described in figure 3A, which illustrates the position of the basal loop of the helical heart: blue -right segment-and red -left segment. Number 1 to 5 correspond to the Fourier analysis of ventricular motion during ventricular activation: 1) the first portion to be activated is at the level of the pulmonary infundibulum, beneath the pulmonary valve. At that time no signal from the left ventricle is elicited; 2) The signal from the right ventricle increases and there is a minor dot at the basal portion of the left ventricle indicating the initial process of activation; 3 and 4) The right ventricle signal is increasingly expanding to the right ventricle and the basal portion of the left is now activated, but the signal has not propagated to the body left ventricle. 5) Eventually the full myocardium of the right ventricle is fully activated as is the left ventricle.  Figure 9: Time course of transmural myocardial fiber strain correlated with the T wave. Note that there is a temporal coincidence with both events [46]. Stonebridge and Brophy performed direct angioscopic examination in the lower extremities and found that the inner surface of the arteries is organized in a series of spiral folds that sometimes protrude into the lumen. These folds are probably a consequence of spiral blood flow. Vortexing blood was actually observed with fiber optics in the region of these endoluminal folds. It was suggested that this type of vortex flow may be more efficient, requiring less energy for the blood to move through the distal tapering and branching arterial system [51]. Rifled gun barrels cause bullets to spin, making them more stable in flight and therefore improving accuracy. In the vessels the blood appears to form its own grooved conduits to support torsional flow. The spiral folds are not found in excised arteries or cadavers; they are dynamic features of living tissues.
Physiological helices may help to stabilize flow by reducing turbulence, preserving energy, and protecting vessels from atherosclerosis [52].

What does the T wave Reflect?
The ECG tracing reflects changes in the electromagnetic activity of the heart. It is usually detected by electrodes placed on the chest, but an identical signal can also be detected at a distance by a sensitive magnetometer (SQUID detector) [53][54][55] (Figure 11). Any mechanical activity is invariably associated with an electromagnetic field [56] and electromechanical propagation through the myocardium should have its electromagnetic correlate. We believe that the T wave might reflect the electromagnetic field associated with the mechanical activity of the working myocardium and the blood motion. In fact, this has been shown in magnetic resonance studies, where myocardial and blood motion induces the so called the magnetohydrodynamic effect, a signal superimposed on the T wave of the ECG. This effect makes it challenging to synchronize the MRI scan with the ECG [57][58][59]. In such tracings, the magnetohydrodynamic effect waves closely overlap the T wave, as seen in Figure 12.
Cellular depolarization, repolarization and myocardial electromechanical activation: do they reflect the same phenomena?
Much of the equivocal concepts in ECG interpretation probably stem from the fact that the electrophysiological events shown in a single cell have been equated with the electromechanical events occurring at the myocardial level. The terms cellular depolarization and repolarization have been assumed to have electromechanical correlates. And this is probably a major source of confusion. In order to clarify these issues, a new way to interpret the ECG events is suggested (Table 1).

Implications
In the light of the new ventricular anatomy and function [60] interpretation of the ECG should be revisited. The terms depolarization and repolarization should best be limited to cell physiology rather than to myocardial activity. This new vision -and division-of the electrical and electromechanical phenomena brings up questions regarding the    (a) (b) Figure 13: a) Vortical flow pattern in the aortic arch. The heart electricity is thought to be conducted through the circulatory system by ions in the blood, and the conductor itself is moving helically. b) From an electrical engineering perspective, this resembles a coil or a solenoid that amplifies the electromagnetic output.   nature of ECG changes in health and disease and opens the way to future research.

Summary
Depolarization and repolarization are electrophysiological terms that describe changes in a single cell´s membrane potential due to ionic movements. Membrane potentials transiently change from inside negative to positive due to influx of positive ions into the cell while activated, and reverse to attain the resting state.
These phenomena have been extrapolated from a cellular level to the entire myocardium to form the basis for the interpretation of the electrocardiogram (ECG). Thus, the QRS complex of the ECG is thought to reflect the depolarization and the T wave the repolarization.
The sequence of events that explains the morphology of the QRS is the electrical activation of the myocardium beginning with the pacemaker cells in the sinoatrial node. The wave of depolarization spreads out through the atrium, passes through the atrioventricular node and down into the left and right bundle of His to the respective Purkinje fibers for each side of the heart, and then to the endocardium at the apex of the heart, then finally throughout the ventricular epicardium. The T wave is deemed to reflect the electrical events associated with recovery from this process.
The myocardium has traditionally been viewed as a homogenous morphological structure. However, discovery of the complex anatomical 3D configuration of the ventricles as a double helix, known as the helical ventricular myocardial band (HVMB), prompts a reconsideration of the origin of the T wave.
The 3D-helical model of the heart has been confirmed. Its electrical, electromechanical and functional implications are the basis for a new interpretation of the T wave. We believe that the T wave might reflect the electromagnetic field associated with the mechanical activity of the working myocardium and the vortical motion of the blood through the aortic arch.

P wave 50 ms
Electromagnetic field corresponding to the atrial activation

QRS complex 80 ms
Electromagnetic field corresponding to the ventricular electrical delivery (via Purkinje) to sites of initial ventricular propagation T wave 300-400 ms Electromagnetic field associated with ventricular electromechanical propagation and/ or blood motion Table 1: Proposed interpretation of the ECG phenomena.