Haemodialysis: Effects of acute decrease in preload on tissue Doppler imaging indices of systolic and diastolic function of the left and right ventricles

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Haemodialysis: effects of acute decrease in preload on tissue Doppler imaging indices of systolic and diastolic function of the left and right ventricles

Abdenasser Drighil

¹

*, John E. Madias

^2,3

, James W. Mathewson

⁴

, Hanane El Mosalami

¹

, Nadia El Badaoui

¹

, Beenyouness Ramdani

⁵

, and Ahmed Bennis

¹

1

Department of Cardiology, Ibn Rochd University Hospital, Casablanca, Morocco;

²

Mount Sinai School of Medicine of the New York University, New York, NY, USA;

³

Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, USA;

⁴

St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; and

⁵

Department of Nephrology, Ibn Rochd University Hospital, Casablanca, Morocco

Received 12 June 2007; accepted after revision 9 September 2007; online publish-ahead-of-print 27 March 2008

AimsConventional echocardiographic (ECHO) parameters of left ventricular (LV) and right ventricular (RV) systolic and diastolic function have been shown to be load-dependent; however, the impact of preload reduction on tissue Doppler (TD) parameters of LV and RV function is incompletely understood.

The aim of this study was to examine the effect of acute preload reduction by haemodialysis (HD) on conventional (ECHO) and TD imaging (TDI) indices of systolic and diastolic function of the left and right ventricles.

Methods and resultsSeventeen chronically uremic patients (age 31+10 years), without overt heart disease underwent conventional 2D and Doppler ECHO together with measurement of longitudinal mitral and tricuspid annular motion velocities. Fluid volume removed by HD was 2706+1047 cm³. Haemodialysis led to reduction in LV end-diastolic volume (P,0.0001), end-systolic volume (P,0.001), peak early (E wave) transmitral flow velocity (P¼0.0001), and the ratio of early to late Doppler velocities of diastolic mitral inflow (P¼0.021). For the LV, early diastolic (E0) TDI velocities and the ratio of early to late TDI diastolic velocities (E0/A0) only on the septal side of the mitral annulus decreased significantly after HD (P¼0.0001 and P¼0.009, respectively). In a subgroup of seven patients who sustained significantly larger fluid volume loses following HD, E0 and the ratio of E0/A0 at the lateral side of mitral annulus also decreased suggesting a greater resistance of the lateral annulus to preload changes. Systolic velocities decreased after HD on both sides of mitral annulus (septal 6.90+1.10 vs. 5.97+1.48 cm/s,P¼0.006; lateral 8.68+2.67 vs. 6.94+1.52 cm/s, P¼0.011). For the RV, systolic tricuspid annular velocities decreased (13.45+1.47 vs.11.73+ 1.90 cm/s, P¼0.002) together with early diastolic velocities after HD (13.95+2.90 vs.10.62+ 2.45 cm/s,P¼0.0001). Both systolic and early diastolic tricuspid annular velocities correlated directly with fluid removal (P,0.01).

ConclusionThis study shows that both systolic and diastolic TDI velocities of the LV and RV are preload- dependent. However, the lateral mitral annulus is more resistant to preload changes than either the septal mitral annulus or the lateral tricuspid annulus.

KEYWORDS

Tissue Doppler immaging;

Haemodialysis;

Left ventricular function;

Right ventricular function

Introduction

Echocardiography (ECHO) is an established method for the assessment of left ventricular (LV) and right ventricular (RV) function. Most conventional ECHO parameters of LV

and RV systolic and diastolic function are known to be load- dependent.

^1–3

Recently, the results of a number of exper- imental and clinical studies showed that the measurement of mitral annular velocities using tissue Doppler imaging (TDI) is a simple and reliable method for the assessment of global (longitudinal) systolic and diastolic LV function.

^4–6

Also TDI systolic and diastolic velocities of the tricuspid annulus correlated with RV global systolic and diastolic func- tion.

⁷

However, in spite of multiple previous studies,

^8–17

the

*

Corresponding author: Hay Sadri, Group 5, 54th street, N 56, Casablanca, Morocco. Tel:þ212 64237566.

E-mail address: sdrighil@gmail.com

&

The Author 2008.

For permissions please email: journals.permissions@oxfordjournals.org.

doi:10.1093/ejechocard/jen125

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impact of preload reduction on TDI parameters is still incom- pletely understood. First, to our knowledge the effect of preload reduction on TDI parameters of RV function is not well known. Secondly, there is no consensus as to the effects preload reduction has on tissue Doppler (TD) indices of LV diastolic function. Some studies have demon- strated preload independence

^8–13

whereas others

^14–17

suggest the opposite. These discrepancies are thought to be mainly due to the heterogeneity of the studied popu- lations. For example, the reduction of TDI diastolic par- ameters following preload reduction observed in a study by Agmon

¹⁴

was attributed to the presence of LV systolic dys- function. For example, Ishizaka et al.

¹⁸

suggested that failing hearts are more sensitive to load changes. In other studies,

^19,20

reductions in TDI parameters in the presence of normal systolic and diastolic function were attributed to sensitivity of normal hearts to loading conditions. Nagueh et al.

¹⁹

suggested that the presence of normal and enhanced relaxation state uncovers E

⁰

load-dependency, whereas when LV relaxation was impaired, E

⁰

was load-independent.

During haemodialysis (HD), patients are subjected to acute intravascular volume depletion due to ultraﬁltration; there- fore, these patients constitute an interesting group for the study of acute preload reduction and its impact on these new ECHO parameters. Therefore, the aim of the present study was to examine the effect of HD-mediated acute intra- vascular volume reduction on mitral and tricuspid annular longitudinal motion measured by TD and thus evaluate preload dependence of these variables in a homogeneous group of young chronic uremic patients with no overt heart disease and normal systolic LV and RV function under- going the same HD protocol.

Methods Patients

After having obtained informed consent, 17 randomly recruited patients with end-stage renal failure (mean duration of chronic HD¼11+5 years, creatinine¼10.8+3.2 mg/dL, and BUN¼ 177+51 mg/dL) volunteered for participation in the study. All were receiving twice weekly bicarbonate based HD lasting 5 h, using polysulphone capillaries and bicarbonate dialysate containing 138 mmol/L of Na^þ, 2.0 mmol/L K^þ, 1.75 mmol/L Ca^þþ, and 0.5 mmol/L Mg^þþ. Four patients were receiving antihypertensive drugs (Ca^þþ antagonists, two, angiotensin-converting enzyme inhibitors, one, and angiotensin II receptor antagonist, one). Hae- modialysis was uncomplicated and resulted in urea rate reduction (URR)¼82.38+9.73% (66.66–98.20). For each patient during HD, we attempted to reach his or her respective ‘dry weight’ deﬁned as the lowest weight that could be tolerated without the develop- ment of symptoms or hypotension.²¹

Exclusion criteria included patient age.50, atrial fibrillation, LV systolic dysfunction which we defined as an LV ejection fraction (EF) ,50%, RV dysfunction, systolic pulmonary hypertension.50 mmHg, more than a small pericardial effusion, acute intercurrent illness, neoplasia, history of coronary artery disease, myocardial infarction, or significant valvular disease (more than mild aortic/mitral/tricuspid/pulmonary stenosis or more than a mild degree of aortic/

mitral/tricuspid/pulmonary regurgitation).

Study variables

The following variables were measured for all patients before and after HD: weight, total ﬂuid volume removed (FVR), heart rate,

and blood pressure. In addition, each subject had blood drawn for serum electrolytes.

Echocardiography

Two-dimensional ECHO and Doppler studies were performed immediately before and after HD, using a Phillips* Sonos 5500 ultra- sonographic machine equipped with a 3.5 MHz transducer. In addition to TDI variables, we made several additional measurements that served to confirm significant fluid volume losses following HD.

These included LV end-diastolic and end-systolic dimensions (LVEDD, LVESD) using standard M-mode, LV end-diastolic and end- systolic volumes (LVEDV, LVESV) and EF using Simpson’s method as recommended by the American Society of ECHO.²²In addition, we measured the maximum antero-posterior linear end-systolic left atrial dimension from the parasternal long-axis 2D view, and calcu- lated left atrial volume using the cube method formula: 4/3pr³(r¼ d/2), wheredthe antero-posterior dimension.²³

The pulsed Doppler transmitral flow velocity profile was obtained from the apical four-chamber view with the sample volume posi- tioned just below the mitral leaflet tips. The following parameters were evaluated: peak transmitral flow velocity in early diastole (peakE), peak transmitral flow velocity in late diastole (peakA), E/Aratio, and theEdeceleration time (DT).

Doppler tissue imaging (TDI) was performed in the four-chamber view, with the mitral and tricuspid annular planes perpendicular to the ultrasound beam. A 5 mm pulsed TD sample volume was placed at the septal⁶and lateral^24,25aspects of the mitral annulus, and at the lateral aspect of the tricuspid annulus. Care was taken to elimin- ate Doppler inﬂow and noise signals. Measurements were made of peak systolic (S⁰), peak early diastolic (E⁰), and late peak diastolic myocardial velocities (A⁰), and theE⁰/A⁰ratio at both the septal and lateral mitral and tricuspid annulus. Tracings were recorded at a sweep speed of 100 mm/s,²⁶and measurements were averaged over a minimum of three separate heart beats.

All measurements were made by a single observer (A.D.), blinded to the patient’s identity but not to pre-, and post-HD status. The interobserver variability of measurements of TDI ECHO parameters was 0.4+1% (mean+SD), and the intraobserver variability was 0.2+0.7% in our previous study.¹⁷

Statistical analysis

Data are reported as mean+SD. Analysis employed thet-test for paired data. Pearson’s correlation coefﬁcient for linear regression analysis was used to determine study variable percent change (D%) resulting from HD.P,0.05 was considered as statistically sig- niﬁcant. The SPSS 11.5 (version 11.5, SPSS Inc, Chicago, Illinois) and Origin statistical packages were used.

Table 1 Baseline characteristics of subjects

Characteristics Frequency

Male/female 8/9

Age (year) 31+10 (17–48)

Systemic hypertension 3 (17.6%)

Diabetes 0

Average duration of chronic HD (year) 11+5 (2–21) Cause of end-stage renal failure

Glomerulonephritis 7 (41%)

Nephrosclerosis 1(6%)

Obstructive 1(6%)

Hereditary 1(6%)

Unknown 6(35%)

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Results

Haemodynamics and conventional Doppler echocardiographic parameters

The baseline demographic characteristics of the 17 subjects are shown in Table 1, and their measured pre- and post-HD laboratory values in Table 2. Following HD, systolic and dias- tolic blood pressure did not change but serum potassium, urea, creatinine, and body weight all decreased (all, P

,

0.05). Heart rate increased after HD (78

+18 vs. 87+

19 bpm, P

¼

0.001). Fluid volume removed by HD averaged 2706

+1047 cc. There was a strong correlation between

FVR and

D% in weight (r¼

0.978, P

¼

0.0001).

ECHO changes are noted in Table 3. After HD, LVEDD, LVESD, RV end-diastolic diameter, PAPS, LV end-systolic and end- diastolic volumes, and LA volume all signiﬁcantly decreased (all, P

,

0.01), but the LVEF remained unchanged.

After HD, peak mitral E and A velocities decreased and E DT increased. Peak mitral inﬂow E wave velocity correlated with FVR adjusted for pre-HD weight obtained by dividing FVR by pre-HD weight (r

¼

0.622, P

¼

0.013). The E/A ratio of the mitral inﬂow decreased signiﬁcantly after HD.

Five patients had evidence of impaired LV relaxation at base- line, with an E/A ratio of

,1. Three separate additional

patients had an E/A ratio of

,1 after HD. All patients with

E/A

,

1 before HD had the same pattern after HD.

Finally, the E/E

⁰

ratio at the lateral side of mitral annulus decreased signiﬁcantly (P

¼

0.003) after HD and was unchanged at the septal side of mitral annulus.

Tissue Doppler imaging systolic and diastolic variables

Table 4 and Figures 1 and 2 summarize the measured TDI vel- ocities for the LV and RV. The peak systolic velocities (S

⁰

) at

Table 3 Echocardiographic parameters before and after

haemodialysis

Parameter Pre-HD Post-HD P-value

LV end-diastolic volume (mL)

85.2+27.9 61.5+24.8 0.0001 LV end-systolic volume

(mL)

37.4+15.2 30.2+13.6 0.001 LV ejection fraction 70.1+9.9 68.1+9.4 0.13 LA diameter (mm) 37.96+3.90 30.62+3.38 0.0001 LA volume (cm³) 29.46+8.19 15.56+5.43 0.0001 RV end-diastolic

diameter (mm)

24.03+3.55 21.31+2.94 0.001 PA systolic pressure

(mmHg)

35.69+7.53 20.96+6.65 0.0001

LA, Left atrium; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.

Table 2 Study variables before and after haemodialysis

Variable Pre-HD Post-HD P-value

Potassium (mM/L) 5.59+0.99 3.77+0.74 0.0001

urea (mg/mL) 177+ 51 31+18 0.0001

Creatinine (mg/dL) 10.8+ 3.2 3.3+1.6 0.0001 Systolic BP (mmHg) 133+25.9 130+24.7 0.403 Diastolic BP (mmHg) 77+13 75+14 0.565 Heart rate (bpm/min) 78+18 87+19 0.001 Body weight (kg) 49.8+ 13.0 47.2+12.3 0.0001

Table 4 Doppler measurements before and after haemodialysis

Before HD After HD % Change P-value

Lateral mitral annulus

Myocardial systolic wave (cm/s) 8.67+2.67 6.94+1.52 216.64+18.5 0.011

E⁰peak velocity (cm/s) 13.94+2.92 13.70+4.06 24.07+28.5 0.458

A⁰peak velocity (cm/s) 9.71+2.84 9.13+3.12 22.01+31.4 0.482

E⁰/A⁰ratio 1.52+0.44 1.57+0.64 5.80+54.88 0.724

Septal mitral annulus

E⁰/A⁰ratio 1.12+0.39 0.88+0.28 216.13+29.18 0.009

Tricuspid annulus

E⁰/A⁰ratio 0.96+0.39 0.71+0.21 218.53+26.07 0.023

Mitral inﬂow

PeakE(cm/s) 96.54 +23.13 63.65+16.33 231.33+22.84 0.0001

PeakA(cm/s) 87.08+23.20 69.14+15.51 217.82+18.85 0.005

E/Aratio 1.14+0.32 0.94+0.25 215.09+23.16 0.021

DT 145.38+39.07 174.61+46.12 26.66+45.49 0.024

LV ﬁlling pressure

E/E⁰(septal) 11.69+3.55 10.56+3.56 26.51+24.29 0.256

E/E⁰(lateral) 7.11+1.55 5.21+1.64 223.55+31.36 0.003

LV, Left ventricle; IVRT, isovolumetric relaxation time; DT, deceleration time.

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the septal and lateral mitral annulus and at the lateral tri- cuspid annulus fell, respectively, by 13, 16, and 12%

(P-values, respectively,

¼

0.006, 0.011, and 0.002). Although we found a signiﬁcant correlation between

D% in tricuspid

systolic velocities and FVR adjusted for pre-HD weight (r

¼

0.499, P

¼

0.041), there was no significant correlation between systolic velocities of LV and FVR. Also, we did not find a significant correlation between systolic velocities of LV and RV and the heart rate.

Early diastolic velocities (E

⁰

) also decreased signiﬁcantly at the tricuspid annulus and septal side of mitral annulus.

The

D% in

E

⁰

at the septal mitral annulus and E

⁰

at the tricus- pid annulus correlated positively with FVR adjusted for pre-HD weight (respectively, r

¼

0.654, P

¼

0.006; and r

¼

0.532, P

¼

0.034). E

⁰

velocities at the lateral side of the mitral annulus remained unchanged in 10 patients, but

signiﬁcantly decreased in seven (Figure 1); the latter were characterized by greater volumes of ﬂuid removed (2850

+

1210 vs. 2600

+960 cc,

P

¼

0.03). The

D% in

E

⁰

at the lateral mitral annulus correlated also positively with FVR adjusted for pre-HD weight (r

¼

0.47, P

¼

0.05).

A

⁰

at tricuspid and at both sides of mitral annulus did not change after HD. The E

⁰

/A

⁰

ratio of septal mitral annulus and tricuspid annulus decreased signiﬁcantly after HD (P

¼

0.009 and P

¼

0.023, respectively). The E

⁰

/A

⁰

at lateral mitral annulus remained unchanged in 10 patients and decreased in the seven patients who had a decrease in theirE

⁰

(P

¼

0.02).

Discussion

To our knowledge, this study is the ﬁrst to comprehensively examine the acute affects of HD on RV and LV systolic and

Figure 1 Haemodialysis-related changes in mitral annular systolic and diastolic parameters. Before and after haemodialysis values in indi- vidual patients. Difference assessed by pairedt-test. Mean observations before and after haemodialysis as horizontal line+1SD.

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diastolic function using TDI variables in a homogeneous group of uremic young patients with normal systolic function and no known coronary artery disease. First, we conﬁrmed preload dependence of conventional parameters of LV dias- tolic function including peak E, peak A, E/A ratio, and DT.

^1,27

Pre-HD intravascular volume expansion leads to a high preload, which may mask impairment of early diastolic filling. Haemodialysis acutely reduces preload, resulting in decreased peak early filling velocities that may unmask delayed relaxation not apparent prior to HD. In our study, HD unmasked delayed relaxation in three patients whose mitral inflow pattern was pseudonormal. Second, we demonstrated that TDI E

⁰

and E

⁰

/A

⁰

ratio at the septal side of mitral annulus and E

⁰

, and E

⁰

/A

⁰

at the tricuspid annulus were also preload-dependent and directly correlated to FVR. In 10 of our patients, TDI E

⁰

and E

⁰

/A

⁰

ratios did not change after HD suggesting that the lateral mitral annulus is more resistant to acute changes in preload than are the

septal mitral and tricuspid annulae. However, in the remain- ing seven in whom signiﬁcantly larger volumes of dialysate were removed, the same TDI variables decreased signiﬁ- cantly, thus suggesting that the lateral annulus is also preload-dependent. Graham et al.,

¹²

in patients with normal LV systolic function, found no signiﬁcant reduction in E

⁰

after HD at either the lateral or the septal mitral annulus. In their study, the average volume of ﬂuid removed by HD was only1600 cc compared with 2700 cc in our study. Our results agree with the ﬁndings of Agmon et al.,

⁷

who in a cohort of patients, with high prevalence of coronary heart disease (69%) and heart failure (15%), found that E

⁰

velocities at both the septal and lateral sides of mitral annulus were load-dependent when the average FVR was 3100 cc. Also, Hung et al.

²⁸

demonstrated that TDI indices of LV diastolic function changed depending on the extent of loading alterations. Furthermore, in a study performed in dogs, Firstenberg et al.

²⁰

found that large changes in preload resulted in reductions in E

⁰

. In all these studies, in spite of the heterogeneous nature of the patient population, the only variable that changed signifi- cantly from one study to the next was the amount of volume removed. Therefore, our findings suggest that TDI diastolic parameters are preload-dependent, even in the presence of delayed relaxation or normal systolic LV func- tion, and that this dependency correlates directly and mainly with the volume of fluid removed. Small reductions in preload may not unmask this dependency. Hence, we believe that discrepancies among existing studies may be due more to the amount of volume removed than to the populations studied. The reason for the difference in preload dependency between the lateral and septal aspects of mitral annulus may be related to a greater sensi- tivity of the septal side of the mitral valve to right ventricle compliance changes compared with the lateral wall of the stiffer left ventricle.

We also found that TDI systolic velocities of LV and RV were preload-dependent. Galetta et al.

¹⁵

demonstrated a decrease in TDI systolic LV velocities after HD. Also, Pela et al.

²⁹

found a reduction in systolic velocities of the RV and LV after an experimental protocol in which preload was reduced in healthy subjects in the absence of any changes in afterload. The changes in systolic myocardial velocities following preload reduction could be explained on the basis of the Frank–Starling mechanism.

³⁰

However, we found that

D% in tricuspid annular systolic velocities

correlated with FVR, whereas this was not observed for the mitral annular systolic velocities. This result may be explained by the fact that in uremic patients, the decrease in systolic velocities of LV might also represent a marker of myocardial dysfunction likely related to changes in myocar- dial collagen, tissue water content, size and orientation of myocardial cells, or change of serum ionized calcium con- centration after HD.

^31,32

Limitations

Our study population was small (N

¼

17). Nevertheless, we carefully controlled for age, underlying disease, and HD con- ditions. Most of the changes we observed were highly signiﬁ- cant with the exception that the lateral mitral annulus is insensitive to small or moderate levels of preload reduction.

It is possible that there would be less apparent insensitivity

Figure 2 Haemodialysis-related changes in tricuspid annular

velocities. Difference assessed by pairedt-test. Mean observations before and after haemodialysis as horizontal line+1SD.

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of the lateral mitral annulus if a larger cohort of patients had been studied. In addition, we could not control the volume of dialysate removed because we did not consider it ethical to hold the FVR constant. Instead, we followed a standard protocol to dialyze until each patient reached his/her dry weight (vide ‘Methods’). The changes observed in this study may reflect the load sensitivity of ECHO par- ameters in young and relatively healthy patients and may not be directly applicable to patients with significant co-morbid conditions and more severe structural heart disease. The echocardiographer who made the measure- ments and calculations could not be blinded to the pre- or post-HD condition since the HD sessions in our study started early in the morning and finished in the afternoon.

This last limitation is common to other HD studies cited.

^12,14

Finally, even though the echocardiographer was not blinded to the pre- or post-HD condition, the results should not be affected because he was blinded to the patient’s identity and to the results of the pre-HD ECHO.

Conclusion

Our study shows that systolic and diastolic TDI velocities of the LV and RV are preload-dependent. Vigorous HD may unmask early diastolic dysfunction in young patients with chronic uraemia. Therefore, when assessing RV and LV systo- lic and diastolic function both pre- and post-HD using TDI ECHO, observers must carefully note the FVR before con- cluding that HD has not unmasked LV diastolic dysfunction.

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