How to Identify Latent Systolic Dysfunction and Post Operative Risk in Patients with Mitral Incompetence and Normal Ejection Fraction?

doi:10.4236/wjcs.2011.12003

Paper Menu >>

Journal Menu >>

World Journal of Cardiovascular Surgery, 2011, 1, 11-17

doi:10.4236/wjcs.2011.12003 Published Online December 2011 (http://www.SciRP.org/journal/wjcs)

How to Identify Latent Systolic Dysfunction and Post

Operative Risk in Patients with Mitral Incompetence

and Normal Ejection Fraction?

Galal Eldin Nagib Elkilany1, Maryam De Groef2, Ibrahim Kabbash3

1Adult Cardiology Department, Medical School, Tanta University, Tanta, Egypt

2SOAS, London, UK

3Public Health and Statistics, Tanta, Egypt

E-mail: [email protected]

Received October 25, 2011; revised November 27, 2011; accepted Decembe r 6, 2011

Abstract

Purpose: To study the significance of impaired positive peak rate of left ventricular (LV) pressure develop-

ment (MR + dp/dt) and global systolic strain (GLPSS) values in patients presented with significant mitral

incompetence (MR) in coronary artery disease (CAD) and early dilated cardiomyopathy (DCM) with normal

ejection fraction (EF). Methods: A description of LV contractile behavior requires measurement of the abil-

ity of the ventricle to develop force (pressure) and to shorten. Hence, performance of the ventricle as a pump

assessed in the present study by measuring the pressure developed by the ventricle (Left ventricular +dP/dt is

estimated from MR jet as the rate of pressure rise from 1 to 3 m/sec) and shortening assessed by GLPSS (this

Doppler technology allowed measurement of LV systolic strain for the entire length of LV myocardium).

GLPSS and MR + dp/dt were calculated in 30 consecutive patients (mean age was 55 ± 12 years) character-

ized by echocardiographic evidence of moderate or severe MR (in CAD and DCM patients) and normal EF

(mean LV Ejection Fraction of 50.9% ± 5.9%) and compared with those obtained in 35 consecutive controls

(age 54.7 ± 11.4 years) with normal echocardiographic study of the heart. Results: The mean values of MR

+dp/dt and GLPSS averaged from the 3 apical views, differed significantly in DCM and CAD patients

(characterized by significant MR with normal EF) compared with control group, (MR + dp/dt = 733 ± 170

mmhg/s and GLPSS –13% ± 1.3%) versus (1420 ± 210 mmhg/s and −19.5% ± 3.3%) for patients versus

control, respectively, p < 0.001. A depressed values of MR + dp/dt were highly correlated with GLPSS val-

ues in patients with CAD and DCM, r = 0.78. The combined use of 2D Strain (<−13%) and MR dp/dt (<900

mmhg/s) in the presence of MR (grade II or more) had 89% sensitivity and 92% specificity for detection of

patients at risk of post-operative major cardiac events after MR and coronary artery bypass surgery. Conclu-

sions: Latent LV systolic dysfunction could be defined noninvasively by depressed peak MR + dp/dt and

GLPSS in the echocardiography laboratories.

Keywords: Mitral Incompetence, Systolic Dysfunction, MR dp/dt, Global Strain

1. Introduction

The most commonly used index of LV contractile func-

tion is the EF which represents volume strain (change in

volume divided by initial volume). However, the EF is

influenced by acute or short-term as well as chronic al-

terations in preload, afterload and contractility. A full

assessment of the contractile behavior of the ventricle

requires the combined use of indices that reflect LV sys-

tolic performance, function, and contractility, as well as a

consideration of global and regional function [1].

Load-sensitive measures of systolic function, including

fractional area change, fractional shortening, ejection frac-

tion, and positive peak rate of LV pressure development.

Load-insensitive measures of systolic function, including

the preload recruitable stroke work relationship and the

end-systolic P-V relationship. Regional wall motion as-

sessed by circumferential shortening velocity suggested

enhanced circumferential fiber contractility in LVH, but

tissue Doppler imaging, used to assess longitudinal func-

G. E. N. ELKILANY

tion, was not different between controls and LVH groups.

LV hypertrophy (LVH) represents the commonest condi-

tion whereby load-sensitive measures of contractility can

be misinterpreted [2]. The contraction of excess sar-

comeres may mask subnormal function of cardiomyocytes

in the presence of LVH by maintaining normal wall

shortening and thickening values. Furthermore, radial and

circumferential fiber contractility is preserved in LVH, but

longitudinal fiber function may be impaired, possibly due

to the effects of subendocardial ischemia [3].

We hypothesized that load-sensitive methods of as-

sessing cardiac contractility, which rely on circumferen-

tial or radial fiber function, such as the ejection fraction

(EF), fractional shortening (FS), fractional area change

(FAC), and the myocardial velocity of LV circumferen-

tial shortening (Vcf), may overestimate cardiac contractil-

ity in the presence of mitral incompetence and that load-

insensitive contractility indexes derived from Global

Strain and MR dp/dt (rate of pressure development)

analysis would better reflect and predict cardiac contrac-

tility at the cardiac myocyte level.

2. Subjects

Of the 65 individuals evaluated, 30 patients had signifi-

cant MR allowing dp/dt measurement and were included

in this study (ischaemic 18 and non-ischaemic 12). Most

patients were in New York Heart Association Class II

(69%) and the remaining were class III NYHA. 35

served as control.

3. Methods

A description of LV contractile behavior requires

measurement of the ability of the ventricle to develop

force (pressure) and to shorten. Hence, performance of

the ventricle as a pump assessed in the present study

by measuring the pressure developed by the ventricle

(Left ventricular + dp/dt is estimated from MR jet as

the rate of pressure rise from 1 to 3 m/sec) and short-

ening assessed by GLPSS (this Doppler technology

allowed measurement of LV systolic strain for the en-

tire length of LV myocardium which is normalized and

do not require correction for LV size). GLPSS and MR

+ dp/dt were calculated in 30 consecutive patients

(mean age was 55 ± 12 years) characterized by echo-

cardiographic evidence of moderate or severe MR (in

CAD and DCM patients) and normal EF (mean LV

Ejection Fraction of 50.9% ± 5.9%) and compared

with those obtained in 35 consecutive controls (age

54.7 ± 11.4 years) with normal echocardiographic

study of the heart Figure 1.

Figure 1. Bulls eye technique (automated function imaging algorithm) generated from apical 2, 3 and 4 chamber views illus-

trated the impaired global longitudinal peak systolic strain (GLPSS) of −13% in patient with significant mitral incompetence

but normal ejection fraction (EF = 51%), note that : MR + dp/dt = 645 mmhg/s only.

G. E. N. ELKILANY

The automated function imaging (AFI) algorithm non-

invasively tracks and analyzes peak systolic strain based

on 2D strain: Digital loops were acquired from apical 2-,

3- and 4-chamber views and a line was traced along the

LV endocardium (Figure 1). Around this line, the soft-

ware selected natural acoustic markers moving with the

tissues automatic frame by frame tracking of these

markers during the heart cycle yielded a measure of con-

tractility along the selected region of interest.

GLPSS and MR + dp/dt were calculated in 30 con-

secutive patients (mean age was 55 ± 12 years) (Figures

2-3).

4. Statistics Used

The collected data were tabulated and statistically ana-

lyzed using SPSS software statistical package version 17.

Figure 2. Global Longitudinal Peak Systolic Strain in 4

chamber view is below normal values (−14%) inspite of

normal EF by 2 Dimensional echocardiography [Biplane

Technique].

Figure 3. Left ventricular dp/dt is estimated from mitral

regurgitation (MR) jet as the rate of pressure rise (RPR)

from 1 to 3 m/sec. Isometric Contraction was estimated as

pre-ejection time minus Q-first sound (S1).

For quantitative variables, mean and standard deviation

were calculated. Because of small sample size of each

studied categories, non parametric tests of significance

were used. Kruskal-Wallis test was used to compare be-

tween mean values of studied groups if they were more

than two and Mann-Whitney test to compare two groups.

Wilcoxon singed rank test was used to compare mean

values of EF% before and after the intervention. Cate-

gorical variables were represented as number and per-

centage and Monte Carlo test was used as test of signifi-

cance. The level of significance was adopted at p < 0.05.

5. Results

The mean values of MR + dp/dt and GLPSS averaged

from the 3 apical views, differed significantly in DCM

and CAD patients (characterized by significant MR with

normal EF) compared with control group, (MR + dp/dt =

733 ± 170 mmhg/s and GLPSS –13% ± 1.3%) versus

(1420 ± 210 mmhg/s and −19.5% ± 3.3%) for patients

versus control, respectively, p < 0.001.

The combined use of 2D Strain(<−13%) and MR dp/dt

(<900 mmhg/s) in the presence of MR (>grade II/IV) had

89% sensitivity and 92% specificity for detection of pa-

tients at risk of post-operative major cardiac events fol-

lowing mitral repair and/or coronary artery bypass sur-

gery (Figure 4).

6. dp/dt

After cardiac surgery, EF and + dp/dt were significantly

improved (p < 0.001) in the group of patients character-

ized by an average pre operative value of dp/dt > 900

mmhg/s overall, with no difference between the ischemic

and non-ischemic groups (Figure 5).

However, a depressed values of MR + dp/dt pre opera-

tively were highly correlated with post operative depres-

sion of EF in patients with CAD and DCM, r = 0.790, p

= 0.001, Figure 6.

7. Global Logitudinal Peak Systolic Strain

(GLPSS)

Global strain was calculated as the average of maximum

strain in all LV segments. in order to test if global strain

could express the ideal LV systolic function in compari-

son with 2 dimensional & real time 3 dimensional echo-

cardiography. GLPSS averaged from the 3 apical views

(Bulls-eye display), differed significantly in patients with

left ventricular systolic dysfunction (depressed values of

dp/dt in DCM and ischemic MR) compared with control

patients (GLPSS –13%) versus (−19.5%) for patients vs

control, respectively, (p < 0.0001) (Figure 7).

G. E. N. ELKILANY

Figure 4. Recipient-observer characteristic curve: showed

high incidence of major cardiac events (cardiac death in-

cluded) among patients with significant mitral incompe-

tence and depression of Global strain (GLPSS) as well as

low MR + dp/dt values. Note that: patients represented by

blue line who have pre operative low global systolic strain

and depressed dp/dt values Showed severe depression of

cardiac function (EF < 25%) and high incidence of major

cardiac events post operatively on 140 days follow up (in-

spite of normal EF pre operatively).

In intermediate term follow up (140 days), a depressed

values of GLPSS had 89% sensitivity and 92 specificity

for prediction of patients prone to develop severe LV

systolic dysfunction (EF of ≤30% - 35%) post opera-

tively and patients at risk for major cardiac events (car-

diac death, acute heart failure, pumonary edema, fre-

quent hospitalization for progressive heart failure symp-

toms, need for cardiac re synchronization therapy, re-

vascularization, and/or need for cardiac transplantation).

8. Discussion

Our study shows for the first time that echocardiographic

assessment of Global Strain and MR + dp/dt is a useful

predictor of Intermediate-term clinical outcome in ischemic

and non-ischemic mitral incompetence.

This is consistent partly with previous work from

Oguz E. et al., showing that LV dp/dt-rise was the single

variable significantly different between CRT (cardiac

resynchronization therapy) responders and non-respond-

ers (defined by the change in NYHA-class) [4].

Moreover, there is limited information regarding whether

an acute hemodynamic response to CRT (assessed as

percent change of the baseline dp/dt) is associated with a

favorable clinical course, and whether there are cardiac

substrate specific outcome in ischemic and non-ischemic

cardiomyopathy. However, recent work has indicated

that acute beneficial hemodynamic changes are sustained

at a 6-month follow-up [5].

Furthermore, Tournoux et al., concluded that acute in-

Figure 5. Correlation between EF% before intervention and dp/dt, r = 0.598, p = 0.001.

G. E. N. ELKILANY15

Figure 6. Correlation between EF% after intervention and dp/dt, r = 0.790, p = 0.001.

50.00 60.00 70.00 80.00

EF%

10.00

12.50

15.00

17.50

20.00

22.50

25.00

AFI

Figure 7. Correlation between EF% and AFI (GLPSS) among studied control.

crease in LV dp/dt (Δdp/dt) by Doppler echocardiogra-

phy is a relatively simple non-invasive test for the acute

haemodynamic response after CRT implantation.

In the Cox proportional hazard model, change in dp/dt

was the only significant predictor of event-free survival

after adjustment (HR 1/4 0.95 per unit dp/dt change, P

1/4 0.0176). Other clinical variables kept in the model

(serum creatinine, etiology of the cardiomyopathy, per-

cent change in EF acutely after CRT, and percent change

in ESV acutely after CRT), were not significant predic-

tors after adjustment [6].

The Previous works concluded that ventricular con-

tractility as measured by dp/dt max is a predictor of

outcome in patients with heart failure [7].

In the present study, MR + dp/dt and Global Strain

(utilizing automated function imaging algorithm) were

G. E. N. ELKILANY

calculated in 65 subjects (30 patients and 35 controls)

and EF measured by 2 and 3 dimensional echocardi-

ography [biplane and tri-plane geometry], providing a

more accurate measure of the extent of global and re-

gional dysfunction of the left ventricle even in the pres-

ence of apparently normal ejection fraction.

Acute and intermediate-term hemodynamic improve-

ment due to revascularization or/and mitral valve surgery

were correlated to basic pre operative normal values of

dp/dt and minimally reduced GLPSS values, with mini-

mal chance for time-dependent changes in factors such

as pre-load to confound the analysis.

In this study , measurements of Global peak systolic

strain had excellent correlation with LVEF (derived from

2 & 3 dimensional echocardiography) and of great help

in identifying patients at risk of major cardiac events

when rate of pressure development was also depressed.

This observation has important diagnostic and therapeu-

tic implications and lead to improvement in non invasive

risk stratification for individual patients with significant

mitral incompetence and borderline LVEF.

In accordance with our study, a recent study conducted

by Edvardsen, revealed that: Global strain correlated

well with total infarct size; a global strain value less than

−11.7% in absolute values had very good sensitivity and

specificity to predect infarct size including more than

18% of the total LV [8].

Indeed, in CAD patients LVEF showed a poor correla-

tion to infarct size by MRI. One possible reason is that

LVEF describes the global LV function, where as the

infarcted area and reduced function is regional. A de-

crease in LVEF is supposes that several LV segments or

large area of infarcted myocardium are involved. Meth-

ods that measure LV regional function could therefore be

more sensitive measures than EF to identify systolic

dysfunction, and the assessment of myocardial strain has

been shown to be superior to wall motion analysis in

CAD and is fundamentally a regional technique [9].

In mitral valve incompetence, measures such as ejec-

tion fraction (EF) are load-dependent and the increased

preload may enhance EF despite a subtle decrease in

contractility. By the time EF is low, there may already

have been irreversible myocardial damage [10].

In addition, in the pathophysiology of heart failure,

exercise echocardiography reveals complex abnormali-

ties of both systolic and diastolic ventricular function

Involving Torsion, Untwist, and Longitudinal Motion

[11].

9. Clinical Implication

Although the measure used in this study was made in the

immediate pre-operative period, one could speculate that

such a measure made intra-procedurally could facilitate

selecting an optimal patient for mitral valve surgery and

CABG who are at risk of post operative major cardiac

events.

Additionally, measure of dp/dt may also prove useful

in selecting patients at high risk of post operative severe

left ventricular systolic dysfunction and cardiac death

and need for post-procedural CRT/Defibrillator device

implantation.

10. Limitation

Technical aspects is of crucial importance in the present

study; surgeon experience could affect the results posi-

tively or negatively; complete revascularization and op-

timal mitral valve repair surgery is not a simple proce-

dure for all cardiac surgeon, and if done by expert hands

will improve cardiac function (+ dp/dt & GLPSS) spe-

cially in patients who had a large ischemic although vi-

able myocardium preoperatively.

In addition, the etiology of mitral incompetence and

type of mitral valve surgery play an important role in our

results.

Finally, tachyarrhthymias affect global longitudinal

peak systolic strain values.

11. References

[1] M. K. Karunanithi and M. P. Feneley, “Single-Beat De-

termination of Preload Recruitable Stroke Work Rela-

tionship: Derivation and Evaluation in Conscious Dogs,”

Journal of the American College of Cardiology, Vol. 35,

2000, pp. 502-513.

doi:10.1016/S0735-1097(99)00566-5

[2] B. A. Carabello, “Evolution of the Study of Left Ven-

tricular Function: Everything Old Is New Again,” Circu-

lation, Vol. 105, 2002, pp. 2701-2703.

doi:10.1161/01.CIR.0000021240.86593.9D

[3] N. H. Andersen and S. H. Poulsen, “Evaluation of the

Longitudinal Contraction of the Left Ventricle in Normal

Subjects by Doppler Tissue Tracking and Strain Rate,”

Journal of the American Society of Echocardiography,

Vol. 16, No. 7, 2003, pp. 716-723.

doi:10.1016/S0894-7317(03)00325-0

[4] E. Oguz, B. Dagdeviren, T. Bilsel, O. Akdemir, I. Er-

dinler, A Akyol, T. Ulufer, T. Tezel and K. Gurkan,

“Echocardiographic Prediction of Long-Term Response

to Biventricular Pacemaker in Severe Heart Failure,”

European Journal of Heart Failure, Vol. 4, No. 1, 2002,

pp. 83-90. doi:10.1016/S1388-9842(01)00188-X

[5] P. Steendijk, S. A. Tulner, J. J. Bax, P. V. Oemrawsingh,

G. B. Bleeker, L. van Erven, H. Putter, H. F. Verwey, E.

E. van der Wall and M. J. Schalij, “Hemodynamic Effects

of Long-Term Cardiac Resynchronization Therapy: Analy-

sis by Pressure Volume Loops,” Circulation, Vol. 113,

G. E. N. ELKILANY

2006, pp. 1295-1304.

doi:10.1161/CIRCULATIONAHA.105.540435

[6] F. B. Tournoux, C. Alabiad, D. Fan, A. A. Chen, M.

Chaput, K. Heist, T. Mela, M. Mansour, V. Reddy, J. N.

Ruskin, M. H. Picard and J. P. Singh, “Echocardiographic

Measures of Acute Haemodynamic Response after Car-

diac Resynchronization Therapy Predict Long-Term

Clinical Outcome,” European Heart Journal, Vol. 28, No.

9, 2007, pp. 1143-1148. doi:10.1093/eurheartj/ehm050

[7] T. J. Kolias, K. D. Aaronson and W. F. Armstrong, “Dop-

pler-Derived dp/dt and 2 dp/dt Predict Survival in Con-

gestive Heart Failure,” Journal of the American College

of Cardiology, Vol. 36, No. 5, 2000, pp. 1594-1599.

doi:10.1016/S0735-1097(00)00908-6

[8] M. D. Thor Edvardsen, “Early Prediction of Infarct Size

by Strain after Coronary Perfusion, Cardiovascular Sur-

gery 2007,” ACC 9/12/2007, American College of Cardi-

ology Foundation.

[9] T. Edvardsen, B. L. Gerber, J. Garot, D. A. Bluemke, J. A.

Lima and O. A. Smiseth, “Quantitative Assessment of In-

trinsic Regional Myocardial Deformation by Doppler

Strain Rate Echocardiography in Humans: Validation

against Three-Dimensional Tagged Magnetic Resonance

Imaging,” Circulation, Vol. 106, 2002, pp. 50-56.

doi:10.1161/01.CIR.0000019907.77526.75

[10] J. L. Harrison and B. D. Prendergast, “Mitral Valve Re-

pair: Benefits of Early Intervention and Future Pros-

pects,” European Journal of Cardiology, Vol. 5, No. 30,

2007.

[11] Y. T. Tan, F. Wenselburger, E. Lee, et al., “The Patho-

physiology of Heart Failure with Normal Ejection Frac-

tion: Exercise Echocardiography Reveals Complex Ab-

normalities of Both Systolic and Diastolic Ventricular

Function Involving Torsion, Untwist, and Longitudinal

Motion,” Journal of the American College of Cardiology,

Vol. 54, No. 1, 2009, pp. 36-46.

doi:10.1016/j.jacc.2009.03.037