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European Journal of Heart Failure 2005 7(5):829-833; doi:10.1016/j.ejheart.2004.09.008
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© 2004 European Society of Cardiology

Echocardiographic evaluation of left ventricular end-systolic elastance in the elderly

Domenico de Santisa, Pasquale Abetea,*, Gianluca Testaa, Francesco Cacciatoreb, Gianluigi Galiziaa, Dario Leoscoa, Luisa Viatia, Vincenzo Del Villanoa, David Della Mortea, Francesca Mazzellaa, Nicola Ferrarab and Franco Rengoa,b

a Cattedra di Geriatria-Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche Universitá degli Studi di Napoli "Federico II", Via S. Pansini, 5, 80131 Naples, Italy
b Istituto scientifico di Telese Terme Fondazione Salvatore Maugeri, IRCCS, Benevento, Italy

* Corresponding author. Tel.: +39 081 746 2270; fax: +39 081 746 2339. E-mail address: p.abete{at}unina.it


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
Background: The aging heart is characterized by structural changes, which are implicated in the development of left ventricular diastolic dysfunction. However, important changes in systolic function may also occur. Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular—arterial interaction.

Aim: To evaluate left-ventricular Ees in elderly subjects compared with adult control subjects.

Methods: We studied dilated (DA, n=14) and hypertensive (HA, n=21) cardiomyopathy patients, and both adult control (A, n=25; age 55.6±6.6 years) and elderly (E, n=25; age 76.3±7.1 years) subjects without clinical–instrumental evidence of cardiovascular disease. M-mode, two-dimensional, and pulsed Doppler echocardiogram were performed. Doppler-derived indices of diastolic function were assessed and Ees was calculated by a modified single-beat method.

Results: Ees was reduced in dilated cardiomyopathy (1.32±0.10 mm Hg/ml) and increased in hypertensive cardiomyopathy (3.12±0.33 mm Hg/ml) patients compared to age-matched control subjects (1.96±0.26 mm Hg/ml; p<0.01 and p<0.05, respectively). More importantly, Ees was higher in the elderly (2.52±0.70 mm Hg/ml) than in the adult control group (p<0.05) and was linearly correlated with age (r2=0.639; p<0.0001).

Conclusion: Age-related increase in Ees, together with diastolic dysfunction, may lead to aging heart decompensation.

Key Words: Elastance • Elderly • Echocardiography • Diastole

Received February 6, 2004; Revised September 10, 2004; Accepted September 20, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
Congestive heart failure (CHF) in the elderly is characterized by a high percentage of patients with preserved ejection fraction, who have a prognosis similar to those patients with a low ejection fraction [1,2]. This may be due to diastolic dysfunction [3–5]. On the other hand, human aging is associated with vascular stiffening that is matched by ventricular systolic stiffening, leading to an abnormal ventricular–arterial interaction [6]. One of the major determinant of cardiac systolic function and ventricular–arterial interaction is the "end-systolic pressure–volume relation" (ESPVR) and its slope "elastance" (Ees).

Enhancement of afterload in the elderly may contribute to decompensation in the aging heart by further prolonging diastolic relaxation and by altering ventricular filling, with a subsequent increase in diastolic pressure [7]. It should also be noted that these haemodynamic modifications are very frequent in elderly hypertensive patients, in whom diastolic hypertension and aging alterations act in a synergistic way [8].

It has recently been demonstrated, that in patients with heart failure and normal ejection fraction, end-systolic elastance increases more than would be expected due to hypertension and aging [9]. Moreover, elderly normotensive patients showed an end-systolic elastance similar to the age-matched young normotensive patients.

Thus, the present study aimed to evaluate differences in end-systolic elastance (Ees) between adult control and elderly subjects, without clinical–instrumental evidence of cardiovascular disease, using a non-invasive echocardiographic method. In addition, Ees values in both adult control and elderly subjects will be compared with those from dilated and hypertrophic cardiomyopathy patients.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
We prospectively studied 85 subjects consecutively recruited from the outpatients clinic of our department. The subjects were divided into four patients groups, as follows. Dilated cardiomyopathy patients (<65 years old, n=14) had chronic NYHA II–III symptoms, ejection fraction less than 50%, no evidence of regional wall motion abnormalities or valvular disease at echocardiography, and of significant coronary artery disease at angiography. Hypertensive cardiomyopathy patients (<65 years old, n=21) had left ventricular hypertrophy (cardiac mass/body surface area ≥125 g/m2 ), no evidence of regional wall motion abnormalities or valvular disease at echocardiography, and no significant coronary artery disease at exercise stress test. Control adult (<65 years old, n=25) and elderly subjects(≥65 years, n=25) had normal ejection fraction, no evidence of regional wall motion abnormalities, left ventricular hypertrophy or valvular disease at echocardiography, and no significant coronary artery disease at exercise stress test. All patients were in sinus rhythm at the electrocardiogram.

M-mode, two-dimensional echocardiography, and cardiac Doppler studies were performed using a phased-array echo-Doppler system equipped with 2.5- or 3.5-MHz transducer (Philips, Sonos 5500). The following parameters were monitored: left atrial diameter (LAD, cm), left ventricular end-diastolic diameter (LVEDD, cm), left ventricular end-systolic diameter (LVESD, cm), left ventricular mass (according to the formula of Devereux and Reichek [10]) (LVM, g), peak early diastolic flow velocity peak (Peak E, cm/s), peak late diastolic flow velocity peak (Peak A, cm/s), ratio between heights of early and late diastolic flow velocity peak (E/A ratio), isovolumic relaxation time (IVRT, ms), deceleration time (DT, ms), stroke volume (SV, ml), ejection fraction (EF, %), ratio of pre-ejection period (R-wave->flow-onset) to total systolic period (R-wave->end-flow) with the time at onset and termination of flow defined from the aortic Doppler waveform (t). Stroke volume was measured from proximal aorta pulse-wave Doppler-flow (apical 5 chamber view) and aortic cross sectional area. Ejection Fraction was calculated using the standard dimension cubed formula (LVEDD3–LVESD3/LVEDD3). Intraobserver and interobserver variability of Doppler echocardiographic variables was less than 5% in our laboratory The study protocol was approved by the University of Naples "Federico II" Institutional Review Board and conforms with the principles outlined in the Declaration of Helsinky. Informed consent was obtained from all the participating patients.

Left ventricular end-systolic elastance (Ees) was calculated by a modified single-beat method [11], employing systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) arm-cuff pressures, echo-Doppler stroke volume (SV), echo-derived ejection fraction (EF) and an estimated normalized ventricular elastance at arterial end-diastole (ENd): Ees(sb)=[Pd–(ENd(est)xPsx0.9)[/(ENd(est)xSV) where ENd(est)=0.0275–0.165xEF+0.3656x(Pd/Pes)+0.515xENd(avg) where ENd(avg) is given by a seven-term polynomial function: ENd(avg)=–i=0 aixtiNd where ai are (0.35695, –7.2266, 74.249, –307.39, 684.54, –856.92, 571.95, –159.1) for i=0 to 7, respectively. Our study methodology was based on the equation developed by Chen et al. [11]. The authors show a group of regression results for 43 baseline comparisons between invasive Ees and the single-beat non-invasive Ees(sb) estimate. The regression equation was: Ees=0.78xEes(sb)+0.55 (r=0.81, SEE=0.50, p<0.0001). The mean difference was 0.03 mm Hg/ml (95% confidence interval: –0.14–0.19). Thus, the method did not show systematic bias, and 80% estimate errors fell below 0.6 mm Hg. The authors also show combined baseline and post-dobutamine data, extending the range of Ees comparisons nearly twofold and improving the strength of the estimated error at 0.64, with a mean error of 0.43±0.5 and with 75% estimate errors falling within 0.6 mm Hg/ml of the measured value.

Data in the text and tables are presented as mean±S.D. Between-group comparisons were performed by ANOVA with Bonferroni "post hoc" test for multiple comparisons. Correlation between Ees and age was determined by linear regression analysis. A p value less than 0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
3.1. Clinical parameters
Table 1 describes the clinical characteristics of the adult (dilated and hypertensive cardiomyopathy and control) and elderly groups. No significant differences in sex, weight, height and BSA were found among the groups except for the age of the elderly group (p<0.01 vs. other groups) and HR in the dilated cardiomyopathy group (p<0.05 vs. other groups).


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  		Table 1 Clinical characteristics and echocardiographic measurements in dilated cardiomyopathy, control, hypertensive cardiomyopathy and elderly groups

 
3.2. Echocardiographic and Doppler measurements
LAD was significantly greater in the dilated cardiomyopathy group than in all other groups. As expected, LVEDD and LVESD in dilated cardiomyopathy and LVM in hypertensive cardiomyopathy were significantly greater than in the other groups (p<0.01). Peak A, IVRT, and DT were significantly higher (p<0.05) while E/A ratio was significantly lower (p<0.05) in the elderly and hypertensive cardiomyopathy groups than in the control and dilated cardiomyopathy groups. This reflects an abnormal diastolic relaxation. Peak E was significantly higher in the dilated cardiomyopathy group than the other groups (p<0.01) reflecting a pseudonormalized diastolic pattern (Table 1).

3.3. Elastance measurements
Table 2 shows the parameters necessary to calculate Ees. As expected, SBP and DBP were significantly higher in the hypertensive cardiomyopathy group (p<0.01), whereas SV and EF were significantly lower in the dilated cardiomyopathy group (p<0.01) than the other groups. The ratio of pre-ejection period to total systolic period with the time at onset and termination of flow (t) was significantly larger in the dilated cardiomyopathy (p<0.01) and significantly smaller in the elderly group and the hypertensive cardiomyopathy group (p<0.05) than in the adult control group. These parameters lead to a reduced elastance in the dilated cardiomyopathy group (p<0.0001) and an increased elastance in the elderly group and in the hypertensive cardiomyopathy group(p<0.01) compared to the control group (see Table 2 and Fig. 1). Accordingly, Ees and age were linearly correlated when control adults and elderly were analyzed together (y=0.24+0.03x; r2=0.639; p<0.0001) (Fig. 2).


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  		Table 2 Elastance measurements in the dilated cardiomyopathy, control, hypertensive cardiomyopathy and elderly groups

 


Figure 1
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  		Fig. 1 Left ventricular end-systolic elastance (Ees) in the dilated cardiomyopathy, control, hypertensive cardiomyopathy and elderly groups (*p<0.01 vs. all groups; §p<0.05 vs. adult control).

 


Figure 2
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  		Fig. 2 Relationship between left ventricular end-systolic elastance (Ees) and age.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusions
 Acknowledgments
 References
 
4.1. Ees in the aging heart
Echocardiographic data from our study shows an increase in Ees in elderly normotensive subjects when compared to adult controls and, more importantly, Ees was linearly correlated with age. Ees was highest in hypertensive cardiomyopathy and lowest in dilated cardiomyopathy. Why Ees is higher in the elderly than in normotensive adult controls? Elastance depends on active contractions and diastolic relaxation, in addition passive structural factors including increased left ventricular mass, reduced myocyte content, apoptosis and increased cross-linking of collagen are important [6]. This is particularly true in the aging heart, in which passive structural and geometric changes significantly contribute to the increase in Ees. Aging is characterized by structural changes such as fibrosis and cross-linking of collagen [12,13], and by vascular stiffening [14]. These factors may contribute to cardiac loading by determining an age-related hypertensive-response during exercise and, therefore, a higher Ees [6,9,15,16]. It should be noted that, Kawaguchi et al. [9] using similar methodology, did not demonstrate an effect of aging on left ventricular elastance. However, the mean age of elderly patients in the Kawaguchi study was lower than in the present study (65±11.5 vs. 76.4±7.2 years) and, furthermore, the patients were receiving pharmacological treatment (Ca channel blocker or β-blocker drug, diuretics, nitrates). However, in the present study the elderly patients were not on treatment with cardiac active drugs, which, may influence the Ees value.

4.2. Diastolic dysfunction in the aging heart
Echocardiographic evaluation showed an increase in peak A, IVRT and DT in the elderly normotensive subjects, confirming the age-related diastolic dysfunction observed in several other studies [6,18–20]. These haemodynamic modifications are related to morphological and functional changes occurring in the heart at advancing age (increased myocyte size, myocardial collagen content increase with an augmented stability of collage fiber crosslinks, reduction of calcium ion uptake by the sarcoplasmic reticulum and modification of myosin isoenzyme composition) [13]. Our study confirms that diastolic alterations observed in hypertensive cardiomyopathy patients are similar to those observed in elderly patients [17,20]. Thus, the effects of aging on diastolic filling are similar to the effects of hypertension [21].

4.3. Association of Ees increase and diastolic dysfunction in the aging heart
Thus, the aging heart seems to be characterized by diastolic dysfunction and increased Ees. How do these two pathophysiological conditions influence cardiovascular homeostasis in the aging heart? First of all, age-related increase in vascular stiffening [15,16] may be responsible for the enhancement of the basal afterload independent of blood pressure, with a consequent increase in end-systolic pressure–volume ratio. On the other hand, it is well documented that blood pressure is higher in older versus younger subjects during maximal aerobic exercise [22–24] and this is responsible for the steeper pressure–volume relation slope, i.e. Ees. The increase in Ees is characterized by a significant reduction in stroke volume with little modification in afterload. Furthermore, an increased Ees may worsen diastolic dysfunction in the aging heart, through further limited filling and raised diastolic pressure [7]. In addition, increased Ees and diastolic dysfunction may increase myocardial oxygen consumption for a given SV and this might limit metabolic reserve, especially in patients with coronary artery disease [15]. Moreover, some studies have indicated a reduced coronary flow reserve in the elderly [25]. It can be hypothesized that pressure–volume curves in the aging heart may be steeper and similar to those observed in patients with heart failure and normal EF [6,9,26]. In other words, diastolic dysfunction may be a determinant in the failing of the Frank–Starling mechanism in the aging heart and, therefore, for small volume increase an exceeding pressure increase with consequent higher values of end-systolic pressure–volume would be observed. From these considerations, it is clear that the occurrence of precipitating factors, such as paroxysmal atrial fibrillation or an acute increase in blood pressure, could lead to acute heart failure condition in the aging heart, without apparent cardiac disease.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
Acknowledgments
 References
 
It is concluded that the aging heart is characterized not only by diastolic dysfunction but also by increased Ees. Both diastolic dysfunction and increased Ees may contribute to failure of the aging heart in response to an acute increase in blood pressure or the presence of tachyarrhythmias. This may explain the mechanism by which acute heart failure may occur in the elderly even in the absence of any cardiac disease. Doppler echocardiography can be considered an useful tool to evaluate both diastolic function and Ees in the elderly.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
References
 
This study was supported by Ministero della Istruzione, Università e Ricerca Scientifica MIUR (PRIN 2001).


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 

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