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Central diastolic pressure exponential decay constant and subendocardial flow supply

Salvi, Paoloa; Salvi, Luciab; Parati, Gianfrancoa,c

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doi: 10.1097/HJH.0000000000001439
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An imbalance between myocardial oxygen supply and demand represents a possible cause of myocardial ischemia, even in the absence of atherosclerotic coronary artery disease. In such a perspective, the term ‘type 2 myocardial infarction’ has been proposed [1]. This is a relatively common condition, especially in the elderly [2], in critically ill patients, in patients undergoing major noncardiac surgery [3–5] and may be a cause of myocardial ischemia in patients under acute high-altitude exposure [6,7]. The incidence of myocardial infarction ‘type 2’ and of myocardial injury due to this pathogenetic mechanism tends to increase with age; after the age of 75, this type of myocardial infarction is more frequent than ‘type 1’ (i.e. the myocardial infarction related to intraluminal thrombus in coronary arteries [2]. Despite its relatively high incidence in clinical practice, the occurrence of myocardial injury due to this mechanism is often difficult to face and manage by physicians, including cardiologists and internists, as little is known about the specific etiopathogenetic mechanisms that trigger this type of myocardial damage. Moreover, there are virtually no universally adopted methods to noninvasively assess the relationship between oxygen myocardial demand and supply in clinical practice.

With the aim to fill this gap, a useful index was introduced by Buckberg and Hoffman at the beginning of the 1970s known as subendocardial viability ratio (SEVR) [8,9]. This index reflected the subendocardial oxygen supply and demand ratio and was defined invasively by analyzing left ventricular (LV) and aortic pressure curves. The introduction of transcutaneous arterial tonometry has provided, albeit with major limitation [10,11], a new approach to noninvasively determine the subendocardial oxygen supply and demand ratio through a simple and easy test, based only on central pulse waveform analysis [12].

The area under the LV (or aortic) pressure waveform in systole [estimated by systolic pressure–time index (SPTI)], from the onset of ventricular systole to the dicrotic notch, represents the LV afterload and defines cardiac work. Thus, SPTI directly correlates with myocardial oxygen needs and mainly depends on LV ejection time, ejection pressure and myocardial contractility.

On the other hand, the area between the ascending aorta and LV pressure curve in diastole [estimated by diastolic pressure–time index (DPTI)] represents the factor that influences the coronary blood flow in diastole and maintains adequate subendocardial blood supply during the diastolic phase of the cardiac cycle. Therefore, the DPTI : SPTI ratio represents an indirect estimate of the balance between oxygen subendocardial supply and needs.

What parameters affect subendocardial flow supply? Diastolic time is certainly one of the main factors we should consider in the evaluation of the balance between myocardial flow supply and demand, as subendocardial blood flow occurs almost exclusively during diastole due to extravascular compressive forces developed during the systolic contraction. Diastolic time is strictly linked to heart rate (HR), thus controlling HR represents an important factor regulating subendocardial viability. Actually, the regulation of HR is a consolidated element in the treatment of coronary heart disease. However, a prolonged diastolic time (i.e. a reduced HR) does not always warrant an appropriate subendocardial flow. Together with the ‘time’ function, it is necessary to consider the ‘pressure’ function too. In fact, subendocardial coronary flow does not only depend on diastolic time but also on aortic diastolic blood pressure (DBP) and on the pressure gradient in diastole between coronary arteries intravascular pressure and LV pressure. In undamaged coronary conditions, coronary arterial pressure equals that in ascending aorta. When coronary perfusion pressure is decreased, autoregulation breaks off in subendocardial layers [13]. Once autoregulation is deranged, myocardial blood flow becomes pressure dependent. Vasodilatation in small coronary vessels cannot adequately compensate for the reduced perfusing pressure, and this may result in ischemia.

A proper assessment of blood pressure (BP) during diastole requires the evaluation of at least two elements: first, the BP levels at the end of diastole, and second, the decay of BP during diastole, that is the speed and the mode by which the pressure decreases during the diastolic phase of cardiac cycle.

The study published by Hashimoto and Ito [14] in this issue of the Journal of Hypertension focused the spotlight on the role of aortic diastolic pressure decay in the evaluation of myocardial viability. The relationship between aortic stiffness, central BP decay in diastole and SEVR was investigated in patients with uncomplicated hypertension.

An inverse association between aortic pulse wave velocity and SEVR has been clearly shown in this study [14]. Anyhow, this study provides a further and substantial contribution to clarifying the relationship between arterial stiffness and myocardial ischemia. To investigate the putative causal relationship between aortic stiffening and reduced subendocardial oxygen supply and demand ratio, the authors performed a mediation analysis. This type of statistical analysis helps to quantify the influence of a potential mediator on the association between a candidate mechanism and the hypothesized outcome. Although not providing direct proof of causality when such analysis uses cross-sectional data, this method can nevertheless provide evidence to support the occurrence of causal mechanisms in biological processes. The mediation analysis showed that 75% of the observed inverse relationship between aortic pulse wave velocity and SEVR was mediated by diastolic pressure decay index, suggesting that arterial stiffening causes an accelerated diastolic decay of the aortic pressure; thus, a reduction in the area under the diastolic phase of BP curve, resulting in a reduction in SEVR.

The analysis of central diastolic pressure decay by using an exponential decay equation is not a novelty, having been already proposed and validated in the 1970s [15,16]. Hashimoto and Ito [14], in their study, used a reliable and easy method to quantify and measure the BP decay in diastole, by measuring the exponential decay constant (λ). The authors provide further confirmations that the gradual reduction of BP during diastole may be described using an exponential decay curve, by the equation: P(t) = P0e−δt, where P0 is the diastole starting pressure, t is the interval from the beginning of the diastole and λ is the exponential decay constant. The shape of this hypothetical decay is related with aortic characteristics.

Actually, the occurrence of a strong association between arterial stiffness and myocardial ischemia is well known [12,17–19], and high values of carotid–femoral pulse wave velocity, indicative of aortic stiffening, were demonstrated to be an independent risk factor for ischemic cardiovascular disease [20,21]. Aortic stiffness indeed appears to be an important factor affecting subendocardial oxygen supply and demand balance. An alteration in the viscoelastic properties of the arterial system causes a stiffening in the arterial wall in the aorta and large elastic arteries. Under this condition, the amount of stroke volume stored by the aorta during the systolic ejection time decreases. As a consequence, aortic systolic BP (SBP) increases and aortic DBP decreases (Fig. 1). An increase in SBP related to an increase in LV afterload leads to a rise in cardiac work and consequently to an increase in LV mass and myocardial oxygen needs. On the other hand, the reduction in DBP in the aorta may cause a reduction in subendocardial blood flow supply. Moreover, the development of LV hypertrophy and progression toward the resulting LV failure predispose to an increase in LV diastolic pressure and to a prolongation in isometric contraction time, further reducing the diastolic subendocardial pressure gradient and perfusion time.

How aortic stiffening affects subendocardial viability.

Furthermore, arterial stiffness causes a higher speed in pulse wave transmission through the arterial system, giving rise also to earlier return of backward pressure waves to the ascending aorta. The early superimposition of forward and backward waves in the protomesosystolic phase of the cardiac cycle, produces a further increase in SBP and, thus, in myocardial oxygen demand.

Arterial stiffening affects the decay in BP during diastole in at least two ways (Fig. 2). First, as we have seen above, in normal conditions during the LV contraction a great quantity of blood remains ‘stored up’ in the aorta and large elastic arteries, to be released afterward (Windkessel effect) so that proper pressure values are maintained in diastole as well. Thus, we can consider the aorta as a pump that guarantees a normal supply of blood in diastole. When the normal viscoelastic properties of large arteries are somehow altered, a failure in the aortic pump function during diastole occurs. As a consequence, DBP undergoes a rapid decay during diastole (Fig. 2, upper images). Second, with arterial stiffening, reflected waves return earlier in the ascending aorta and largely overlap with the forward wave during the systolic phase. This leads to a further rapid decay of BP in diastole (Fig. 2, lower images). In summary, with the same BP values in tele-systole and tele-diastole, a rapid diastolic pressure decay is associated with lower values of mean DBP. Since subendocardial oxygen supply depends on the area below the diastolic phase of arterial pulse waveform in ascending aorta, a rapid decay of BP in diastole is associated with lower subendocardial oxygen supply.

Blood pressure waveforms (a) in a young healthy adult with normal viscoelastic properties of aorta (left panels) and (b) in a hypertensive patient with increased aortic stiffness (right panels). The upper panels show the pressure waveform resulting from the interaction between left ventricle and large elastic arteries (forward wave, recorded at ascending aorta). The lower panels show the overall arterial pulse wave at ascending aorta, resulting from overlapping of forward wave and backward waves. The latter are also shown separately at the bottom in the figure. Arrows highlight the aortic diastolic pressure decay. BP, blood pressure; aortic PWV, carotid–femoral pulse wave velocity.

A major limitation in the Hashimoto and Ito's [14] study concerns the evaluation of SEVR. The DPTI (as described by Buckberg and Hoffman) is represented by the area between the aortic and LV pressure curves in diastole. Nevertheless, LV diastolic pressure and isometric contraction time are not taken into account when this index is assessed as done by Hashimoto and Ito with the SphygmoCor device, thus DPTI (and as consequence, the SEVR) is overestimated with this approach [10,11]. Furthermore, the method used in this study to assess the central diastolic pressure exponential decay constant (λ) may be questionable. Usually the pulse pressure waveform is characterized by a dicrotic notch, corresponding to the closure of the aortic valve, followed by a dicrotic wave. When recording BP waves in ascending aorta, a dicrotic wave is almost always present, with variable magnitude, sometimes being quite prominent. However, in this study, the authors analyze the diastolic phase of pulse waveform starting from the end-SBP, thus disregarding the presence of the dicrotic wave. Several artifacts can contribute to attenuate the magnitude of dicrotic waves. In this article, the analysis of pulse waves was carried out on the ensemble-averaged aortic pulse waveform. However, the overlapping of waves characterized by different cardiac cycle duration may cause the disappearance of the dicrotic notch and may lead to an unavoidable attenuation of the dicrotic wave. Moreover, the presence of signal filters and the low sampling rate of the SphygmoCor device used (128 Hz, i.e. a sample every 7.8 ms) may contribute to reduce the amplitude of the dicrotic wave. To solve the problem represented by the presence of the dicrotic waves, some authors suggested to consider only the BP decay during last two-thirds of the diastolic phase [15,22].

It should also be noted that central arterial pressure waves were not directly recorded but were rather the output of a transfer function analysis on a peripheral pulse waveform, derived by a tonometric radial artery recording. According to this approach, central pressure waveforms are not directly measured but are rather the output of an applied algorithm. The results of this study should, thus, be verified by using invasive recording of aortic pressure waveforms and subsequent pulse wave analysis focalized on the diastolic phase of the cardiac cycle.

Despite these limitations, the study of Hashimoto and Ito [14] provides important information with possible clinical relevance, by highlighting the role of central diastolic pressure decay induced by arterial stiffening in the pathophysiology of ischemic myocardial disease. The diastolic pressure exponential decay constant (λ) might, thus, deserve to be included between the main parameters considered in the central pulse wave analysis. In such a perspective, however, a better standardization of the method to evaluate this parameter should be achieved.


Conflicts of interest

P.S. is a consultant for DiaTecne s.r.l., manufacturer of the arterial pulse wave analysis system, PulsePen.


1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Circulation 2012; 126:2020–2035.
2. Shah AS, McAllister DA, Mills R, Lee KK, Churchhouse AM, Fleming KM, et al. Sensitive troponin assay and the classification of myocardial infarction. Am J Med 2015; 128:493–501.
3. Devereaux P, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med 2011; 154:523–528.
4. Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA 2012; 307:2295–2304.
5. Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology 2014; 120:564–578.
6. Salvi P, Revera M, Faini A, Giuliano A, Gregorini F, Agostoni P, et al. Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide. Hypertension 2013; 61:793–799.
7. Caravita S, Faini A, Bilo G, Revera M, Giuliano A, Gregorini F, et al. Ischemic changes in exercise ECG in a hypertensive subject acutely exposed to high altitude. Possible role of a high-altitude induced imbalance in myocardial oxygen supply-demand. Int J Cardiol 2014; 171:e100–e102.
8. Buckberg GD, Fixler DE, Archie JP, Hoffman JI. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 1972; 30:67–81.
9. Hoffman JI, Buckberg GD. The myocardial oxygen supply:demand index revisited. J Am Heart Assoc 2014; 3:e000285.
10. Salvi P, Parati G. Aortic stiffness and myocardial ischemia. J Hypertens 2015; 33:1767–1771.
11. Chemla D, Nitenberg A, Teboul JL, Richard C, Monnet X, le Clesiau H, et al. Subendocardial viability ratio estimated by arterial tonometry: a critical evaluation in elderly hypertensive patients with increased aortic stiffness. Clin Exp Pharmacol Physiol 2008; 35:909–915.
12. Salvi P. Pulse waves. How vascular hemodynamics affects blood pressure. 2nd ed.Heidelberg, Germany: Springer Nature; 2017.
13. Canty JMJ. Coronary pressure-function and steady-state pressure-flow relations during autoregulation in the unanesthetized dog. Circ Res 1988; 63:821–836.
14. Hashimoto J, Ito S. Central diastolic pressure decay mediates the relationship between aortic stiffness and myocardial viability: potential implications for aortosclerosis-induced myocardial ischemia. J Hypertens 2017; 35:2034–2043.
15. Simon AC, Safar MA, Levenson JA, Kheder AM, Levy BI. Systolic hypertension: hemodynamic mechanism and choice of antihypertensive treatment. Am J Cardiol 1979; 44:505–511.
16. Bourgeois MJ, Gilbert BK, Donald DE, Wood EH. Characteristics of aortic diastolic pressure decay with application to the continuous monitoring of changes in peripheral vascular resistance. Circ Res 1974; 35:56–66.
17. O’Rourke MF. How stiffening of the aorta and elastic arteries leads to compromised coronary flow. Heart 2008; 94:690–691.
18. Watanabe H, Ohtsuka S, Kakihana M, Sugishita Y. Coronary circulation in dogs with an experimental decrease in aortic compliance. J Am Coll Cardiol 1993; 21:1497–1506.
19. Watanabe H, Ohtsuka S, Kakihana M, Sugishita Y. Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery. Cardiovasc Res 1992; 26:1212–1218.
20. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39:10–15.
21. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 2010; 121:505–511.
22. Messerli FH, Frohlich ED, Ventura HO. Arterial compliance in essential hypertension. J Cardiovasc Pharmacol 1985; 7 (Suppl 2):S33–S35.
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