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Remarkably, non-invasive cardiology did not begin with ultrasound but rather as investigations into systolic time . Indeed, studies on the duration of systole began in 1875 with Garrod who showed that the left ventricular ejection time [LVET] – the time that the aortic valve is open and ejecting blood – varies inversely with heart rate . In 1904, Bowen used the carotid pulse tracing to measure left ventricular ejection in man . Subsequently, in 1923, Katz and Feil described a technique of deconstructing systole into sub-components using simultaneous recordings from a phonocardiogram, electrocardiogram [ECG] and the pulse of a central artery such as the common carotid artery [1, 4-8].
Using the aforementioned analysis of the ECG and common carotid pulse, systole can be reduced into two distinct time periods [9, 10] – the pre-ejection period [PEP] and the LVET. PEP is defined as the period of time between the onset of electrocardiographic systole and the opening of the aortic valve. As above,the LVET begins with the aortic valve opening and terminates at its closure –marked by the onset of the second cardiac sound, or the dichrotic notch in the pulse tracing of a central artery [see figure 1] [1, 7, 8].
Electromechanical Systole or QS2
The summation of the PEP and LVET gives the total time of systole – electromechanical systole. As it is bounded by a Q wave and the second heart sound, the duration of total systole has been dubbed ‘QS2’ . QS2 is remarkably constant – even across a wide variety of cardiac disorders [7, 9-11]. Perhaps the most clinically relevant change in QS2 occurs in response to inotropes; increased inotropic state is reliably reflected by a decrease in QS2, whereas a decreased inotropic state prolongs QS2 [5, 7]. These findings are true whether or not the inotropes are intrinsic – such as anxiety or pheochromocytoma, or extrinsic – such as the provision of digitalis or adrenalin [5, 7, 10, 11].
The Pre-Ejection Period
As seen in the figure, the PEP begins with electrical systole and ends when the aortic valve opens and ejects blood into the arterial tree. Classically, the opening of the aortic valve has been defined as the upstroke in the pulse waveform of the common carotid artery. There is a small delay between the upstroke of pressure in the central aorta and the common carotid by 18-20 milliseconds  but there have been multiple validations equating the duration of the LVET to the pressure upstroke in the central aorta and carotid arteries [1, 7, 8]. Additionally, the PEP may be defined by relating the onset of systole on the electrocardiogram to both M-mode of the aortic valve  as well as Doppler of the aortic outflow tract [12, 13] and the carotid artery .
The PEP, essentially, reflects the time the ventricle is in isovolumic contraction; accordingly, the PEP is prolonged when myocardial contractility is impaired and the change in pressure with respect to time [dP/dt] is low [1, 5, 7, 8]. Interestingly, PEP also rises when stroke volume falls acutely probably because there is less myocardial fiber stretch and less contraction potentiation via the Frank-Starling Mechanism . Classically, stroke volume has been measured via indicator-dilution methods, but the rise in PEP in response to a fall in stroke volume has also been confirmed more recently using impedance cardiography and Doppler-derived cardiac output .
Left Ventricular Ejection Time
As above, the LVET represents the duration that the aortic valve is open and ejecting blood. When corrected for heart rate, the LVET shows a direct relationship with stroke volume [SV]. For example, early studies that employed indicator-dye dilution techniques to measure SV revealed striking correlations between SV and LVET in healthy controls and heart failure patients [9, 11]. LVET also tracked SV changes in response to head-up tilt and tourniquet application to mimic venous pooling . Further, in patients with pulsus paradoxus and confirmed tamponade physiology, inspiratory changes in LVET followed SV . These data matched earlier animal studies [16, 17]. Additionally, in patients with varying stroke volume secondary to complete heart block, LVET tracked stroke volume exceedingly well .
Nevertheless an absolute LVET cannot guarantee an absolute stroke volume; the reasons for this are multi-factorial but lie within the relationship between ejection time, ventricular volume and competing hemodynamic influences such as afterload and contractility [9, 19, 20]. One can think of the LVET as being directly related to the ‘distance’ of myocardial fiber shortening and indirectly related to the ‘velocity’ of fiber shortening [i.e. time is distance divided by velocity]. Consider the provision of dobutamine to a patient with dilated cardiomyopathy; this should increase contractility, lower afterload and, consequently, increase the ‘distance’ of myocardial fiber shortening. While this is expected to increase LVET, the extent to which dobutamine also augments the velocity of shortening will reduce the time required to traverse the greater distance – affecting less change in the LVET.
The PEP-to-LVET Ratio
Across numerous cardiac populations, the most robust metric for predicting LV performance has been PEP/LVET as this static ratio predicts LV ejection fraction especially well [5, 8]. A normal ratio is such that the PEP occupies about one-third of the LVET duration. When the PEP increases relative to the LVET beyond about 45%, there is a strong likelihood that the LVEF is less than 40-45% [1, 7]. This has been demonstrated more recently using standard TTE  as well as carotid artery Doppler . Interestingly, changes in SV in response to upright position and diuresis [12, 15] are marked by an increase in the PEP/LVET ratio.
Application in the ICU
The corrected systolic flow time [cSFT] is, effectively, the LVET corrected for heart rate. Like the studies of LVET in the 1960s and 70s described above, changes in cSFT have been used successfully as a surrogate for SV when assessing the slope of a patient’s Starling curve in response to provocative maneuvers [22,23]. Given that both PEP and LVET diverge in response to changes in LV preload, perhaps the PEP/LVET ratio may better refine hemodynamic prediction with Doppler ultrasound in the ICU.
Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he also the creator and author of a free hemodynamic curriculum at heart-lung.org
2. Garrod, A.H., On some points connected with the circulation of the blood, arrived at from a study of the sphygmograph-trace. Proceedings of the Royal Society of London, 1875. 23(156-163): p. 140-151.
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9. Weissler, A.M., R.G. Peeler, and W.H. Roehll Jr, Relationships between left ventricular ejection time, stroke volume, and heart rate in normal individuals and patients with cardiovascular disease. American heart journal, 1961. 62(3): p. 367-378.
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14. Polak, J.F., et al., Left ventricular ejection time derived from the common carotid artery Doppler waveform: association with left ventricular ejection fraction and prediction of heart failure. Journal of ultrasound in medicine, 2015. 34(7): p. 1237-1242.
16. Remington, J.W., W. Hamilton, and R.P. Ahlquist, Interrelation between the length of systole, stroke volume and left ventricular work in the dog. American Journal of Physiology-Legacy Content, 1948. 154(1): p. 6-15.
18. Harley, A., C.F. Starmer, and J.C. Greenfield, Pressure-flow studies in man. An evaluation of the duration of the phases of systole. The Journal of clinical investigation, 1969. 48(5): p. 895-905.
19. Shaver, J.A., et al., The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time. The Journal of clinical investigation, 1968. 47(1): p. 217-230.
21. Kelm, D.J., et al., Fluid overload in patients with severe sepsis and septic shock treated with early-goal directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock (Augusta, Ga.), 2015. 43(1): p. 68.