Assessment of left ventricular diastolic function by radionuclide ventriculography in patients with chronic heart failure and reduced ejection fraction

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Hodnocení diastolické funkce levé komory pomocí radionuklidové ventrikulografie u pacientů s chronickým srdečním selháním a sníženou ejekční frakcí

Cíl práce:
Zjistit, zda u pacientů s chronickým srdečním selháním a sníženou ejekční frakcí korelují parametry diastolické funkce levé komory hodnocené radionuklidovou ventrikulografií (RNVG) s parametry získanými dopplerovskou echokardiografií (ECHO).

Soubor a metodika:
RNVG a ECHO byly provedeny u 40 pacientů (36 mužů a 4 žen) s CHSS (EF LK < 50 %). K posouzení diastolické funkce levé komory byly použity pro RNVG: PFR (peak filling rate [% SV/sec]), TFR – time to peak filling rate (ms), pro ECHO: vrcholová rychlost časného transmitrálního diastolického toku (E), rychlost pozdního diastolického toku (A) měřených pulzní dopplerovskou echokardiografií a vypočtený poměr E/A a vypočtený průměr rychlostí diastolického pohybu septálního a laterálního mitrálního anulu (E´) měřených tkáňovou dopplerovskou echokardiografií a vypočtený poměr E/E´. RNVG a ECHO byly provedeny týž den.

Výsledky:
Průměrný poměr E/A byl dle ECHO 1,21 (medián 0,85) a E/E´ 9,0 (medián 8,40). Průměrný PFR byl 421,7 (medián 371,0) % SV/sec a průměrný TPF byl 198,7 ms (medián 169,5). TPF koreloval významně s E/A (r = -0,34, p = 0,030), korelace TPF k E´ (r = -0,27, p = 0,082) nedosáhla statistické významnosti, poměr PFR/věk koreloval s E/E´ (r = -0,31, p = 0,05).

Závěr:
U pacientů s chronickým srdečním selháním a sníženou ejekční frakcí byly nalezeny významné korelace mezi některými parametry diastolické funkce levé komory hodnocené pomocí radionuklidové ventrikulografie a dopplerovské echokardiografie.

Klíčová slova:
diastolická funkce – dopplerovská echokardiografie – radionuklidová ventrikulografie – srdeční selhání se sníženou ejekční frakcí

Authors: Jan Naar ¹; Filip Málek ¹; Otto Lang ²; Otakar Bělohlávek ³; Jana Vránová ⁴; Tomáš Mráz ¹; Eva Mandysová ¹; Petr Neužil ¹
Authors place of work: Department of Cardiology, Cardiocenter, Na Homolce Hospital, Prague, head prof. MUDr. Petr Neužil, CSc., FESC ¹; Department of Nuclear Medicine, Královské Vinohrady Faculty Hospital, Prague, head MUDr. Otto Lang, Ph. D. ²; Department of Nuclear Medicine, Na Homolce Hospital, Prague, head doc. MUDr. Otakar Bělohlávek, CSc. ³; Department of Medical Biophysics and Informatics, Third Faculty of Medicine, Charles University, Prague, dean prof. MUDr. Michal Anděl, CSc. ⁴
Published in the journal: Vnitř Lék 2014; 60(2): 110-113
Category: Original Contributions

Summary

Study objective:
To compare parameters of diastolic function as assessed by radionuclide ventriculography (RNVG) and Doppler echocardiography (ECHO) in the patients with chronic heart failure and reduced ejection fraction (HF REF).

Patients and methods:
RNVG and ECHO were performed on the same day in 40 patients with systolic chronic HF, NYHA II and III, with LV EF < 50 % and sinus rhythm, followed at tertiary HF clinic. Diastolic function was assessed by RNVG using parameters: PFR (peak filling rate [% SV/sec]), TFR – time to peak filling rate (ms), and by ECHO using pulse Doppler parameters: the peak Doppler velocities of early (E) and late diastolic flow (A), the E/A ratio, the calculated mean of the early (E´) diastolic velocity of septal and lateral mitral annulus measured by tissue Doppler imaging, and the E/E´ ratio.

Results:
The mean PFR was 421.7 (median 371.0) % SV/sec and TPF was 198.7 ms (median 169.5), the mean E/A ratio was 1.21 (median 0.85) and the E/E´ ratio was 9.0 (median 8.40). TPF correlated significantly (inverse correlation) with the E/A ratio (r = -0.34, p = 0.030), and not significantly with E´ (r = -0.27, p = 0.082), the PFR/age ratio correlated with the E/E´ ratio (r = -0.31, p = 0.05).

Conclusion:
Significant correlations of parameters of diastolic function as assessed by radionuclide and Doppler studies were identified in the HF REF patients.

Key words:
diastolic function – Doppler echocardiography – heart failure with reduced ejection fraction – radionuclide ventriculography

Introduction

Radionuclide studies showed significant correlation of the parameters of diastolic function as assessed by radionuclide ventriculography (RNVG) with parameters obtained by Doppler echocardiography (ECHO) in the patients with heart failure with preserved ejection fraction (HF REF) [1,2]. An assessment of diastolic function in subjects with systolic heart failure brings important prognostic information: subjects with reduced ejection fraction and advanced diastolic dysfunction have worse outcome and higher natriuretic peptides levels [3]. Doppler echocardiography and tissue Doppler imaging are standard methods for the non-invasive assessment of left ventricular diastolic function [4]. The assessment of left ventricular diastolic function using another method might be of advantage in the subjects with poor echocardiographic images.

The aim of the present study was to compare the parameters of diastolic function as assessed by RNVG and ECHO in the patients with chronic heart failure and reduced ejection fraction (HF REF).

Patients and methods

RNVG and ECHO were performed on the same day in 40 patients (36 men and 4 women) with systolic chronic heart failure (CHF), functional class according to New York Heart Association (NYHA) II and III, left ventricular ejection fraction (LV EF) < 50 % and sinus rhythm. All subjects were followed at tertiary HF clinic at Na Homolce Hospital, Cardiovascular Center. The mean age of the patient cohort was 64 years.

All patients signed inform consent and approval for the study was granted by Local Board Ethics Committee Na Homolce Hospital in 2010.

Patients were treated with optimal medical therapy including betablockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists for at least six months before study entry. Ischemic etiology of CHF was present in 22 patients, 18 subjects had dilated cardiomyopathy. Patients with valvular heart disease as a primary cause of CHF were not included in the study. Patients with moderate to severe functional mitral regurgitation were not included in the study too. Cardioverter defibrilator was implanted in 36 patients (90 %) in the past. The mean LV EF as assessed by dual-mode echocardiography (Simpson´s method) was 30 %.

Gated equilibrium radionuclide ventriculography (RNVG) was realized using standard protocol in the Department of Nuclear Medicine and the acquired data were interpreted by a specialist in Nuclear Cardiology. Patient’s red blood cells (RBCs) were radiolabeled and electrocardiograph gated cardiac scintigraphy was obtained. Data were collected from several hundred cardiac cycles to generate an image set of the beating heart that was presented as a single, composite cardiac cycle [5,6]. The administered activity was 570 MBq and autologous RBCs were labeled with 99mTc using the in vivo techniques. Acquisition was performed by a gamma camera interfaced to a dedicated computer. SPECT E. CAM, Siemens, system and Biomedical 101NR, Biomedical Systems, Inc. were used.

Diastolic function was assessed by RNVG using parameters: PFR (peak filling rate [% EDV/sec]), TPF – time to peak filling (ms). The normal values for PFR and TPF vary according to different published reports, normal values are usually: PFR > 250 % EDV/sec and TPF < 150 ms [1].

Echocardiography studies were realized on the same day as RNVG and the results were interpreted by two specialists. An echocardiographic examination of the each patient was performed using a broadband transducer with a transmitting frequency from 1.7 to 4.0 MHz on commercially available equipment (GE Vivid 7, USA).

Doppler echocardiography is widely used for the noninvasive assessment of diastolic filling of the left ventricle [7]. Mitral flow is dependent on multiple factors, tissue Doppler imaging (TDI) of mitral annular motion corrects the influence of myocardial relaxation on transmitral flows [8]. Diastolic function was assessed by ECHO using pulse Doppler parameters: the peak velocities of early (E) and late (A) diastolic flow, the E/A ratio, the calculated mean of the early (E´) diastolic velocity of the septal and lateral mitral annulus measured by tissue Doppler imaging, and the E/E´ ratio.

Spearman´s correlation coefficient was used for the statistical analysis.

Results

The parameters of diastolic function obtained by ECHO and RNVG are shown in the table (p. 111). As shown in the table, mean PFR was 421.7 (median 371.0) % SV/sec and TPF was 198.7 ms (median 169.5), mean E/A ratio was 1.21 (median 0.85) and E/E´ ratio was 9.0 (median 8.40). Peak filling rate is influenced by age and TPF is influenced by heart rate. PFR/age ratio and TPF/HR ratio were used for further evaluation.

**Tab. 1. Parameters of diastolic function as assessed with Doppler echocardiography and radionuclide ventriculography**

Correlation of parameters of diastolic function as assessed by RNVG and ECHO are shown in the figures. TPF correlated significantly (inverse correlation) with the E/A ratio (fig. 1) and not significantly with E´ (inverse correlation). PFR/age ratio correlated with the E/E´ ratio significantly (fig. 2).

**Fig. 1. Correlation of time to peak filling with the E/A ratio**

**Fig. 2. Correlation of time to peak filling rate/age ratio with E/E’ ratio**

Discussion

In the present study, significant correlations of parameters of diastolic function as assessed by radionuclide and Doppler studies were identified in the HF REF patients.

Our study has several limitations. From the logistic issues, it was not possible to record echo Doppler studies and radionuclide studies simultaneously. Both methods were used on the same day. Patients were instructed not to change their regular medication and stayed fasting before ECHO and RNVG studies. Other limitations get alone with each method.

Doppler echocardiography is widely used for the noninvasive assessment of diastolic filling of the left ventricle. Mitral flow is dependent on multiple interrelated factors including heart rate, atrial and ventricular compliance and left atrial pressure [9]. Tissue Doppler imaging of the mitral annulus during diastole has been proposed for assessment of cardiac function. The velocity of the earliest diastolic motion measured by pulse-wave TDI is not dependent on pressure gradient as is blood flow [8].

Radionuclide ventriculography has several limitations too. Many studies have demonstrated a negative correlation between age and PFR and a positive correlation between heart rate and PFR in normal subjects [10]. Thus the age and heart rate of the patient must be considered when diastolic measurements are assessed. In patients with impairment of LV systolic function, PFR is reduced in proportion to the fall in ejection fraction [11].

On the other hand, radionuclide studies have some advantages. The major advantages of the radionuclide ventriculography is its ability to measure relative volume changes with time without the geometric assumptions necessary with contrast angiographic and echocardiographic techniques. Other advantages include: lack of dependence on patient anatomy, production of data in a digitized format ready for computer processing and high reproducibility [5,6]. This was a reason, why studies in different clinical settings put back the interest in the assessment of diastolic function by radionuclide ventriculography.

In one study, the assessment of LV diastolic function in the patients with subclinical hypothyroidism was useful in prediction of response to levothyroxine replacement [12]. However, not parameters of diastolic dysfunction including PFR and TPF but ejection fraction were predictive for new heart failure onset and mortality in asymptomatic patients referred for RNVG for cardiac function evaluation [13].

Our result showed that radionuclide studies may be used for cardiac function assessment in the patients with systolic heart failure. The RNVG might be indicated with HF REF subjects with poor echocardiographic images.

Assoc. Prof. Filip Málek, M.D., Ph.D., MBA

filip.malek@homolka.cz

Department of Cardiology, Na Homolce Hospital, Cardiovascular Center, Prague

www.homolka.cz

Doručeno do redakce dne 6. 8. 2013

Přijato po recenzi dne 16. 9. 2013

Zdroje

1. Clements I, Sinak L, Gibbons R et al. Determination of diastolic function by radionuclide ventriculography. Mayo Clin Proc 1990; 65(7): 1007–1019.

2. Magorien D, Shaffer P, Bush C et al. Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. Circulation 1983; 67(4): 844–853.

3. Yu CM, Sanderson JE, Shum IO et al. Diastolic dysfunction and natriuretic peptides in systolic heart failure. Higher ANP and BNP levels are associated with the restrictive filling pattern. Eur Heart J 1996; 17(11): 1694–1702.

4. Ommen SR, Nishimura NA, Appleton CP et al. Clinical Utility of Doppler Echocardiography and Tissue Doppler Imaging in the Estimation of Left Ventricular Filling Pressures. A Comparative Simultaneous Doppler-Catheterization Study. Circulation 2000; 102(15): 1788–1794.

5. Scheiner J, Sinusas A, Wittry MD et al. Society of Nuclear Medicine Procedure Guideline for Gated Equilibrium Radionuclide Ventriculography, version 3.0, approved June 15, 2002. Available on: <http://interactive.snm.org/docs/pg_ch01_0403.pdf>.

6. Hesse B, Lindhardt TB, Acampa W. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging 2008; 35(4):851–885. Available on: .

7. Oh JK, Appleton CP, Hatle LK et al. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997; 10(3):246–270.

8. Sohn DW, Chai IH, Lee DJ et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997; 30(2): 474–480.

9. Choong CY, Hermann HC, Weyman AE et al. Preload dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am Coll Cardiol 1987; 10(4): 800–808.

10. Miller T, Grossman S, Schectman H et al. Left ventricular diastolic filling and its association with age. Am J Cardiol 1986; 58(6): 531–535.

11. Ishibashi M, Yasuda T, Rocco T et al. Evaluation of left ventricular diastolic function using an ambulatory radionuclide monitor: relationship to left ventricular systolic performance. Am Heart J 1990; 120(1): 96–103.

12. Brenta G, Mutti LA, Schnitman M et al. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. Am J Cardiol 2003; 91(11): 1327–1330.

13. Wisniacki N, Gowda V, Dar O et al. Does diastolic function evaluated with radionuclide ventriculography predict mortality, hospitalization and the development of new onset heart failure? Nucl Med Commun 2003; 24(6): 707–713.