Int J Cardiovasc Imaging DOI 10.1007/s10554-015-0682-2

ORIGINAL PAPER

Evaluation of right and left heart mechanics in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy Murat Sunbul1 • Tarik Kivrak2 • Erdal Durmus3 Bedrettin Yildizeli4 • Bulent Mutlu1



Received: 7 April 2015 / Accepted: 13 May 2015 Ó Springer Science+Business Media Dordrecht 2015

Abstract The aim of the present study was to evaluate of the right and left heart mechanics by two-dimensional (2D) speckle tracking echocardiography (STE) in chronic thromboembolic pulmonary hypertension (CTEPH) patients before and after pulmonary thromboendarterectomy (PTE). A total of 40 consecutive CTEPH patients (mean age 49.3 ± 13.5 years, 27 female) were included. 2D STE was performed in all patients before, and 3 months, after PTE. 12 months of prognostic data were also recorded via the use of telephone calls. Postoperative 6-minute walk test (6MWT) distances were significantly longer than preoperative values (410.5 ± 61.5 vs. 216.6 ± 131.4 m, p \ 0.001). Postoperative left ventricular (LV) and right ventricular (RV) systolic functions (LV EF, TAPSE, RVS) were similar compared to preoperative values. While postoperative RV, right atrial (RA) and systolic pulmonary artery pressure measurements were significantly lower, LV and left atrial (LA) measurements were higher than preoperative values. Postoperative LV and RV global longitudinal strain (GLS) measurements were significantly higher than preoperative values. Postoperative LV global radial and circumferential strain measurements were

& Murat Sunbul [email protected] 1

Department of Cardiology, Marmara University School of Medicine, Fevzi Cakmak Mahallesi, Muhsin Yazicioglu Caddesi, No: 10, Ustkaynarca/Pendik, Istanbul, Turkey

2

Department of Cardiology, Sivas Numune Hospital, Sivas, Turkey

3

Department of Cardiology, Silifke State Hospital, Mersin, Turkey

4

Department of Thoracic Surgery, Marmara University School of Medicine, Istanbul, Turkey

similar to preoperative values. While postoperative RA reservoir and conduit functions were significantly higher, postoperative LA reservoir and conduit functions were similar to preoperative values. Correlation analysis revealed that baseline 6MWT distances were correlated with LV GLS, RV GLS, and RA reservoir and conduit functions in the preoperative and postoperative periods. 2D STE indices may help the clinician in assessing the effect of PTE on cardiac functions and may also be used for followup data in CTEPH patients. Keywords Chronic thromboembolic pulmonary hypertension  Ventricular functions  Atrial functions  Speckle tracking echocardiography  Pulmonary thromboendarterectomy

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease caused by abnormal organization of thromboembolic material in the pulmonary arteries [1]. It is rare, and occurs in 2–4 % of patients after acute pulmonary embolism [2]. Persistent macrovascular obstruction, small vessel arteriopathy, several mediators, and vasoconstriction are the main causes of its clinical consequences. Although several treatment methods have been developed, CTEPH morbidity and mortality remain high. Pulmonary thromboendarterectomy (PTE) is the primary treatment choice for the disease, which mainly affects the right ventricle (RV), but also causes impairment in left ventricular (LV) function [3]. Left atrial (LA) and right atrial (RA) data are limited in CTEPH patients. Two-dimensional (2D) speckle tracking echocardiography (STE) is an advanced method that provides an objective

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quantification of myocardial function [4]. Although it has often been used to assess LV function, to date it has rarely been used for evaluation of RV and atrial functions [5–7]. Previous studies have demonstrated that 2D STE is a useful method for the evaluation of LV function in CTEPH patients before and after PTE [8]. Preoperative RV myocardial deformation parameters have been associated with 6-minute walk test (6MWT) distances in patients with CTEPH [6]. However, 2D STE has not previously been used to evaluate RV and atrial functions before and after PTE. The aim of the present study was to evaluate of the right and left heart mechanics in CTEPH patients before and after PTE, using 2D STE.

Materials and methods A total of 57 consecutive patients with a diagnosis of CTEPH who underwent PTE between March 2010 and December 2013 were recruited. Our study was designed prospectively, and 12 months of prognostic data were also recorded via the use of telephone calls. All study participants underwent a complete transthoracic echocardiography for evaluation of bi-ventricular and atrial functions with 2D STE, and the 6MWT was performed for evaluation of functional capacity, according to recent guidelines [9]. PTE was performed according to the standard procedures described previously [10], and transthoracic echocardiography and 6MWT were repeated at the 3-month follow-up visit. Patients with a history of coronary artery disease, significant valvular disease (moderate-tosevere aortic or mitral stenosis, or regurgitation), left-sided heart failure, or poor echogenicity (five patients), patients who died in the perioperative period (six patients died from reperfusion injury, one died of fatal hemorrhage, and one died as a result of cardiac tamponade), and those who did not attend the 3-month follow-up visit (four patients) were excluded from the study. Data relating to the remaining 40 CTEPH patients were included in the analysis. The investigation complied with the principles outlined in the Declaration of Helsinki, and was approved by the local ethics committee. All participants gave written informed consent before taking part. Standard transthoracic echocardiography Standard transthoracic echocardiography was performed by a single experienced cardiologist with an ultrasound system (Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway). Data acquisition was performed with a 3.5-MHz transducer at a depth of 16 cm in the parasternal and apical views (standard parasternal short-axis from midventricular level, apical long-axis, two-chamber, and four-chamber images).

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Standard M-mode, 2D, and color-coded TDI images were obtained during breath hold, stored in cine loop format from three consecutive beats, and transferred to a workstation for further offline analysis (EchoPAC 6.1; GE Vingmed Ultrasound AS). Gain settings, filters, and pulse repetitive frequency were adjusted to optimize color saturation, and a color Doppler frame scanning rate of 100–140 Hz was used for color TDI images and greyscale images at a frame rate of 44–82 frames/s. Conventional echocardiographic measurements were performed in accordance with the American Society of Echocardiography guidelines recommendations [11]. LV ejection fraction (EF) was calculated using the biplane Simpson’s method. Tricuspid annular plane systolic excursion (TAPSE) was calculated from the apical four-chamber view of the longitudinal excursion of the lateral tricuspid annulus toward the RV apex. Myocardial performance index (MPI) was calculated from time intervals obtained from Doppler recording of tricuspid and pulmonary flow as: (isovolumetric contraction time ? isovolumetric relaxation time)/pulmonary ejection time. RV myocardial systolic velocity was measured by pulsed tissue Doppler imaging from the apical four-chamber view. Systolic pulmonary artery pressure (sPAP) was calculated by measuring the peak systolic gradient from the peak velocity of the continuous-wave Doppler of the tricuspid regurgitation jet by using the Bernoulli equation. Speckle tracking imaging All of the images were recorded with a frame rate of at least 50 frames/s to allow for reliable operation of the software (EchoPAC 6.1; GE Vingmed Ultrasound AS). The average frame rate of the speckle tracking images for atria and ventricles are 54 and 52 frames per second, respectively. Multidirectional analysis of LV strain (in the radial, circumferential, and longitudinal directions) and RV global longitudinal strain (GLS) were performed using 2D STE, as previously described (12, 13). The speckles, natural acoustic markers equally distributed within the myocardium, can be detected and tracked on standard grayscale 2D images. Myocardial strain can be calculated by measuring the change of the position of the speckles within a myocardial segment along the cardiac cycle. The assessment of LV GLS was performed by applying 2D STE to the apical two-, three-, and four-chamber views of the LV, and the LV was divided into six segments in each apical view. The value of LV GLS was derived from the average of the six segmental peak systolic longitudinal strain values (Fig. 1a, b). The assessment of RV GLS was performed by applying 2D STE to the apical four-chamber view of the RV, and RV free wall (basal, mid, and apical segments) endocardial borders were manually traced at the

Int J Cardiovasc Imaging

Fig. 1 Left ventricular global longitudinal strain image in a patient with chronic thromboembolic pulmonary hypertension during preoperative period (a) and postoperative period (b), left atrial functions in

a patient with chronic thromboembolic pulmonary hypertension during preoperative period (c) and postoperative period (d)

end systolic frame by software. The value of RV GLS was derived from the average of the three segmental peak systolic longitudinal strain values (Fig. 2a, b). The assessment of LV global circumferential strain (GCS) and global radial strain (GRS) was performed by applying 2D

STE to the parasternal short-axis views of the LV. The midventricular short-axis of the LV was divided into six segments, and the values of GRS and GCS were derived from the average of the six segmental peak systolic strain values (Fig. 3a–d).

Fig. 2 Right ventricular global longitudinal strain image in a patient with chronic thromboembolic pulmonary hypertension during preoperative period (a) and postoperative period (b), right atrial functions

in a patient with chronic thromboembolic pulmonary hypertension during preoperative period (c) and postoperative period (d)

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Fig. 3 Left ventricular global radial and circumferential strain images in a patient with chronic thromboembolic pulmonary hypertension during preoperative period (a–c) and postoperative period (b–d)

For the LA and RA speckle tracking analysis, LA- and RA-focused images in the apical four-chamber view were obtained. For 2D STE analysis, a line was manually drawn along the LA and RA endocardial border of the apical fourchamber view after contraction, when the LA and RA were at minimum volume, using the point-and-click approach, as previously described [12, 13]. The software then automatically generated additional lines near the atrial epicardium and mid-myocardial line, with the narrowest region of interest (ROI). The ROI then included the entire LA and RA myocardial wall, and a click feature increased or decreased the widths between the endocardial and epicardial line for thicker or thinner walls, respectively. The software generated strain curves for each atrial segment. The value of peak early and late diastolic longitudinal strain were determined as LA, or RA reservoir and conduit function (Figs. 1c, d, 2c, d).

pressure)/cardiac index] were calculated. Cardiac output was measured by the Fick equation. Statistical analysis Statistical analyses were performed using the SPSS 16.0 statistical package for Windows. Continuous data were expressed as mean ± standard deviation (SD), while categorical data were presented as number of patients. A Chi square test was used for comparison of categorical variables. Statistical comparisons of quantitative data were performed by paired sample t test, student t test, or Mann–Whitney U test. Pearson’s or Spearman’s correlation analysis was performed to explore relationships between 6MWT, right heart catheterization data, and 2D STE indices. A value of p \ 0.05 was considered statistically significant. Reproducibility

Right-heart catheterization Right-heart catheterization was performed by a Swan Ganz catheter using femoral venous access with hemodynamic and fluoroscopic guidance before standard echocardiographic examination for all patients, to confirm the diagnosis of pulmonary hypertension and to distinguish hemodynamic mechanisms before PTE. Measurements were obtained at end-expiration and averaged over three to five beats. Mean PAP and pulmonary vascular resistance [(mean PAP—mean pulmonary capillary wedge

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The analyses were repeated twice 1 day later, by the same observer, in order to assess intraobserver variability, which was calculated by the average difference between the ten measurements realized. A second independent observer repeated the analyses for the assessment of interobserver variability, which was calculated as the absolute difference divided by the average of the two observations for all parameters. The intraobserver and interobserver variabilities were 5.6 and 6.8 % for LA, 6.1 and 7.3 % for RA, 5.8 and 7.1 % for LV, and 6.6 and 7.8 % for RV, respectively.

Int J Cardiovasc Imaging

Results Data obtained from 40 CTEPH patients were included in the analysis. The mean age of the study participants was 49.3 ± 13.5 years. A total of 13 patients were male (mean age 49.0 ± 14.2 years), while 27 patients were female (mean age 49.5 ± 13.4 years) (p = 0.908). Postoperative 6MWT distances were significantly longer than preoperative values (410.5 ± 61.5 vs. 216.6 ± 131.4 m, p \ 0.001). Only one patient died due to a cerebrovascular event during the 12 months of follow-up. Baseline right heart catheterization data are listed in Table 1, and a comparison of transthoracic echocardiographic parameters of the study participants is shown in Table 2. Postoperative LV and RV systolic functions (LV EF, TAPSE, RVS) were similar to preoperative values. While postoperative RV, RA, and sPAP measurements were significantly lower, LV and LA measurements were higher than preoperative measurements. A comparison of cardiovascular hemodynamics and 2D STE parameters of the study population is shown in Table 3. Preoperative cardiovascular hemodynamics, including heart rate and blood pressure, were similar to postoperative measurements. Speckle tracking analysis revealed that postoperative LV and RV GLS measurements were significantly higher than preoperative values. Postoperative LV GRS and GCS measurements were similar to preoperative values. While postoperative RA reservoir and conduit functions were significantly higher than, postoperative LA reservoir and conduit functions were similar to, preoperative values. We evaluated the patients with regard to whether there was an increase in the deformation parameters after PTE (Table 4). While almost half of patients had increased RV and RA deformation parameters by over 20 % compared to the preoperative values, a quarter of patients had increased LV and LA deformation parameters by over 20 % compared to the preoperative values. We evaluated the correlation between baseline 6MWT distances and 2D STE measurements (Table 5). Correlation analysis revealed that these 6MWT distances were correlated with LV GLS, RV GLS, and RA reservoir and RA conduit functions in the preoperative and postoperative periods. However, we did not find any correlation between Table 1 Baseline right heart catheterization data of the study population (n = 40) Mean pulmonary artery pressure (mmHg)

53.8 ± 13.4

Right atrial pressure (mmHg)

12.4 ± 6.9

Cardiac output (L/min)

4.1 ± 1.2 2

Cardiac index (L/min/m ) Pulmonary vascular resistance (Wood units) Data are presented as mean ± SD

2.3 ± 0.6 10.2 ± 5.0

postoperative 6MWT distances and 2D STE measurements (p [ 0.05 for all parameters). We also evaluated the correlation between baseline right-heart catheterization data and baseline 2D STE indices. Mean PAP, RA pressure, and pulmonary vascular resistance were correlated with some of baseline 2D STE indices (Table 6). We did not find any correlation of baseline cardiac output and/or cardiac index with baseline 2D STE indices.

Discussion In the present study, we showed that postoperative LV GLS, RV GLS, and RA reservoir and conduit functions were significantly higher than preoperative measurements, while LV and RV systolic functions (LVEF, TAPSE, RVS) did not change. To the best of our knowledge, this is the first study to evaluate the effect of PTE on bi-ventricular and atrial functions in CTEPH patients using 2D STE. Long-term exposure of pulmonary hypertension (PH) causes intimal hyperplasia, which leads to increased pulmonary vascular resistance. Several inflammatory mediators, such as prostacyclin and endothelin-1, are associated with pulmonary vasoconstriction, hypercoagulability, smooth-muscle hypertrophy, and vascular remodeling [14]. As a result, persistent PH triggers RV pressure overload, which leads to functional and morphologic modification of both ventricles. PH usually affects RV and leads to RV dilatation and RV systolic dysfunction. RV functions are a strong predictor of survival in PH patients [15]. Therefore, assessment of RV functions is important in the workup of CTEPH patients. In our study, we demonstrated that RV end-diastolic diameter, RA area, sPAP, and grade of tricuspid regurgitation significantly improved after PTE, in accordance with the results of previous studies [16, 17]. Conversely, conventional functional parameters of RV (TAPSE, RVS, MPI) were not changed after PTE, although those factors were the most important parameters of clinical improvement in previous reports [17, 18]. Right ventricular functions of CTEPH patients increased after PTE. Although TAPSE is an easy method for evaluation of RV function, and is also associated with RV systolic function, it is not useful for the follow-up of RV functional improvement in the postoperative period [19]. There are several explanations for this. The rocking motion pattern of the entire heart causes an abnormal elevated TAPSE value in the preoperative period; cardiac chambers are widely affected by PTE; the postoperative normalization of the rocking motion pattern results in decreased TAPSE value. Giusca et al. [19] reported that TAPSE demonstrated a bi-phasic response with an early decrease in the postoperative period, and continuing improvement in the postoperative late period. In our study, postoperative

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Int J Cardiovasc Imaging Table 2 Comparison of transthoracic echocardiographic parameters of the study population

Preoperative (n = 40)

Postoperative (n = 40)

p

LVEDD (mm)

42.3 ± 5.5

45.0 ± 4.1

0.001

LVESD (mm)

25.7 ± 4.0

27.3 ± 4.2

0.028

LVEDV (ml)

40.3 ± 11.0

58.9 ± 11.2

Evaluation of right and left heart mechanics in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy.

The aim of the present study was to evaluate of the right and left heart mechanics by two-dimensional (2D) speckle tracking echocardiography (STE) in ...
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