dimensional echocardiography to detect - Wiley Online Library

Clin Physiol Funct Imaging (2016)

doi: 10.1111/cpf.12398

Discriminatory ability of right atrial volumes with two- and three-dimensional echocardiography to detect elevated right atrial pressure in pulmonary hypertension Ellen Ostenfeld1, Anna Werther-Evaldsson2, Henrik Engblom1, Annika Ingvarsson2, Anders Roijer2, €ran R adegran2 and Marcus Carlsson1 Carl Meurling2, Johan Holm2, Go 1

Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, and 2Department of Clinical Sciences Lund, Cardiology, Section for Heart Failure and Valvular Disease, Skane University Hospital, Lund University, Lund, Sweden

Summary Correspondence Ellen Ostenfeld, Department of Medical Imaging and Physiology, Skane University Hospital, SE-22185 Lund, Sweden E-mail: [email protected]

Accepted for publication Received 13 July 2016; accepted 30 September 2016

Key words echocardiography; inferior vena cava; pulmonary hypertension; right atrial pressure; right atrial volume; three-dimensional

Aims Pulmonary hypertension (PH) patients have high mortality due to right ventricular failure. Predictors of poor prognostic outcome are increased right atrial volume (RAV) and elevated mean right atrial pressure (mRAP). Our aim was to determine whether RAV measured with 2D echocardiography (2DE) and 3D echocardiography (3DE) can detect elevated mRAP in patients evaluated for PH. Methods Of 85 patients prospectively evaluated for PH, 44 patients (63  15 years, 57% female) had 2DE, 3DE and right heart catheterization within 48 h and were in sinus rhythm. Maximum (RAVmax) and minimum (RAVmin) volumes were measured with 3DE. 2D maximum RAV and RA area, inferior vena cava diameter and collapsibility were measured. Invasive mRAP > 8 mmHg was predefined as elevated. Results RAVmax and RAVmin correlated with mRAP (r = 0
40 and r = 0
35, P8 mmHg was 0
75 (P = 0
004) for RA area and 0
76

© 2016 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

4 Assessment of right atrial pressure, E. Ostenfeld et al.

Table 2

Clinical characteristics. PH population n = 44

3DE Maximum right atrial volume, ml m Minimum right atrial volume, ml m RHC Cardiac index, l min 1 m 2 Systolic pulmonary arterial pressure, mmHg Mean pulmonary arterial pressure, mmHg Pulmonary artery wedge pressure, mmHg Right ventricular systolic pressure, mmHg Right ventricular end-diastolic pressure, mmHg Mean right atrial pressure, mmHg Pulmonary vascular resistance, Woods units 2DE Fractional area change of the right ventricle, % Peak systolic tricuspid annular tissue velocity, cm s 1 Tricuspid annular plane systolic excursion, mm Inferior vena cava diameter, mm Inferior vena cava respiratory collapse, % Right atrial area, cm2 Right atrial major diameter, cm Right atrial minor diameter, cm Right atrial maximum volume, ml m 2 Tricuspid regurgitant gradient, mmHg

2 2

48
3  20
8 (16
2–98
4) 31
4  19
7 (6
8–85
2) 2
6  0
6 (1
7–3
9) 72
5  18
5 (22–112) 44
2  10
8 (12–74) 10
0  4
0 (3–20)

the curve was neither significant for IVC diameter (P = 0
09) nor for collapsibility (P = 0
4). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting elevated mRAP with 3DE RAV and 2DE maximum RA volume using the optimal thresholds from our study, as well as inferior cava measurements, are shown in Table 4. The corresponding results when using normal values of RAVmax < 47 ml m 2 and RAVmin < 20 ml m 2 from earlier studies are also included in Table 4. Increased RA maximum volume assessed with 3DE or 2DE, as well as RA area, all have higher predictive value of elevated mRAP than IVC diameter and collapsibility (Table 4).

71
1  18
9 (19–109) 11
8  4
8 (0–24) 8
1  4
4 (0–19) 7
7  3
7 (1
4–17
2) 24
2  12
6 (2
7–49
8) 10
7  2
8 (6
5–17
6) 17
1  4
5 (9–29) 19
8  5
6 (10–36) 39
8  20
4 (3
7–80) 25
9 6
0 4
9 49
0

   

7
0 (15
7–42
9) 0
8 (4
7–7
9) 0
8 (3
5–6
8) 19
3 (23
6–99
7)

63
8  20
4 (23–105
8)

PH, pulmonary hypertension; 3DE, three-dimensional echocardiography; RHC, right heart catheterization; 2DE, two-dimensional echocardiography. Data expressed as mean  SD, with range in parentheses.

(P = 0
003) for maximum RA volume determined on 2DE (Table 3). The optimal ‘threshold’ value was calculated to be 36 ml m 2 for 2DE maximum RA volume. The area under

Discussion This study shows that RAV assessed with 2DE or 3DE, as well as RA area, has better discriminatory ability to detect mRAP above 8 mmHg than either IVC diameter or collapsibility in patients evaluated for PH. IVC diameter and collapsibility did not reach a significant AUC for the diagnostic purposes of predicting elevated mRAP. In effect, combining RAV with IVC diameter decreased the accuracy compared with RAV alone. Of note, the maximum RA volume from 2DE had similar diagnostic accuracy for detecting elevated mRAP as 3DE, but with higher sensitivity and lower specificity. Thus, the presented data suggest that IVC measurements are of limited use in the evaluation of PH patients and that 2DE or 3DE for the quantification of systolic maximum RAV, as well as RA area, has higher discriminatory ability to detect elevated mRAP. RA volumes and mRAP AUC (0
77) for 3DE RAVmax to detect invasively measured increased mRAP in this study was similar to that detected (0
78) by Patel et al.’s (2011) study in patients with acute left heart failure, but the correlation was slightly weaker in our study (r = 0
40 versus 0
51). The difference may be explained by pathophysiological differences between patients with acute heart failure and PH patients. In PH patients, elevated pressure, as well as to some degree volume overload, has often

Figure 2 Comparison of normal and patients without and with elevated mean right atrial pressure. Mean and 95% CI of 3DE right atrial maximum (RAVmax, a) and minimum (RAVmin, b) volume in a normal population (n = 15) and in pulmonary hypertension (PH) patients with normal (n = 23) and elevated mean right atrial pressure (mRAP) (n = 21). **P15 mmHg) therefore we cannot extrapolate the influence on RAV and IVC in these situations. Inferior vena cava and mRAP Correlation of IVC with mRAP in our population is in concordance with earlier studies reporting a weak relation (Simonson Table 3 Linear regression analyses and area under the curve to detect mean right atrial pressure above 8 mmHg. r-value

P-value

AUC

P-value

0
40 0
35

0
007 0
019

0
77 0
74

0
003 0
006

0
41 0
28 0
42

0
007 0
078 0
005

0
66 0
42 0
76

0
09 0
368 0
003

0
40

0
008

0
75

0
004

3DE RAVmax (ml m 2) RAVmin (ml m 2) 2DE IVC diameter (mm) IVC collapsibility (%) RA maximum volume (ml m 2) RA area (cm2)

Linear regression analyses (with r- and P-value) and area under the curve (AUC with P-value) for two-dimensional (2DE) and threedimensional (3DE) echocardiography compared with invasively measured mean right atrial pressure (mRAP) >8 mmHg.

Table 4

Sens Spec PPV NPV Accu

& Schiller, 1988; Nagueh et al., 1996). Using IVC diameter above 20 mm to predict elevated mRAP had less than moderate diagnostic accuracy even in combination with IVC collapsibility 31 ml m 2

IVCd > 20 mm

IVCc < 50%

IVCd > 20 mm or IVCc 35%

RAVmax > 57 ml m 2 or IVCd >20 mm

RAVmax > 47 ml m 2*

RAVmin > 20 ml m 2*

2DE max RAV > 36 mL m 2

0
57 0
92 0
86 0
71 0
76

0
91 0
39 0
58 0
82 0
64

0
52 0
62 0
58 0
57 0
57

0
65 0
33 0
48 0
50 0
49

0
70 0
29 0
48 0
50 0
49

0
45 0
67 0
56 0
56 0
56

0
76 0
57 0
64 0
71 0
67

0
67 0
70 0
67 0
70 0
68

1
00 0
09 0
50 1
00 0
52

0
91 0
57 0
66 0
87 0
73

IVCc, IVC collapsibility; IVCd, IVC diameter; Accu, accuracy; NPV, negative predictive value; PPV, positive predictive value; Sens, sensitivity; Spec, specificity. Sensitivity, specificity, predictive value and accuracy of three-dimensional (3DE) right atrial maximum and minimum volumes (RAVmax and RAVmin) and inferior vena cava (IVC) measurements and two-dimensional right atrial maximum volume (2DE max RAV) for predicting invasively measured mean right atrial pressure (mRAP) >8 mmHg. *Upper normal values from Aune et al., (2009). © 2016 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Assessment of right atrial pressure, E. Ostenfeld et al. 7

Causes of right atrial dilatation While increased RA area is predictor of outcome in PH (Raymond et al., 2002), altered RA sphericity index with 3DE is associated with clinical deterioration (Grapsa et al., 2012). In the failing right ventricle, due to pressure or volume overload, elevated end-diastolic pressure propagates to the RA and the RA size increases (Lang et al., 2005). In our population, mean grade of tricuspid regurgitation was merely mild to moderate and the trans-tricuspid gradient highly elevated up to 64 mmHg (Table 2), indicating that pressure overload is the predominant cause of RAV enlargement in our study. Though, it indicates the complexity of RAV enlargement in PH patients. Whether RA is assessed with the newer 3DE method or with the more routinely used 2D methods seems to be of less importance in our study, while the discriminatory ability of IVC appears to be less useful to detect elevated mRAP. Limitations As a result of RA being farther from the probe, the relatively low spatial resolution to image RA with 3DE compared with the ventricles is a limitation in the endocardial visualization with 3DE. The software used for 3DE is designed for left ventricular assessment, which anatomically differs from the RA. Considering these limitations, intra- and interobserver variabilities of 3DE were low with intraclass correlation coefficients above 0
9 and biases below 5%. The variability is similar to that in a previous study (Grapsa et al., 2012) and suggests that reproducibility of 3DE measurements is high. 3DE can therefore be used for repetitive measurements (Grapsa et al., 2012). Echocardiography and invasive measurements were not performed simultaneously in all patients, and therefore, the hemodynamic values can differ. On the other hand, a majority of patients had examinations performed in direct adjacency, which minimizes the change in rehydration status. No patient had massive tricuspid regurgitation, and no patient had high cardiac output. Therefore, this study does not investigate the relationship between mRAP and RAV in these patients. Mean RA pressure (mRAP) from RHC was used in comparisons with echocardiography. According to the international guideline, mRAP was measured as the average of all pressure phases over several heart beats and respiratory cycle during free unforced breathing (Kovacs et al., 2014; Galie et al., 2016). This evens out the respiratory variations in pressure shown in previous studies (Boerrigter et al., 2012). Our population had an average mRAP of 8
1 mmHg with a mean systolic pulmonary arterial pressure of 73 mmHg. No patients were fasting prior to RHC, yet a majority of patients were medicated with diuretic, ranging from low-dose thiazide to high-dose loop diuretics in combination with aldosterone

receptor antagonists (Table 1). Also, a high proportion of our patients were on at least one PH-dedicated treatment. The intensive medication could be an explanation to the relative low mRAP in relation to the high pulmonary pressure. PH patients often have shortness of breath and hence have difficulties with breath-hold. In this study, we trained them in the breath-hold technique before acquiring 3DE. This can explain the high feasibility of 3DE acquisition during breathhold. Newer 3DE techniques with no requirement of breathhold during recording might facilitate acquisition. Yet we did not experience breathing artefacts, because 3DE was acquired in the best acoustic window obtained in the unforced breathing cycle and not necessarily at end expirations.

Conclusions Enlarged RAV measured with either 2DE or 3DE, as well as RA area, has better discriminatory ability to detect elevated mean RA pressure than IVC diameter and collapsibility in patients with PH. In contrast, even if the IVC diameter correlates with mRAP, it lacks a significant diagnostic discriminatory power to detect elevated mRAP in our material. The prognostic value related to volumes of the RA remains to be investigated.

Ethical approval The study was performed in accordance with the Declaration of Helsinki, and the ethical committee of Region Sk ane approved the study protocol (EPN Dnr 2004/621, EPN Dnr 2010/114, EPN Dnr 2010/248, EPN Dnr 2011/777).

Acknowledgements The authors thank Skane University Hospital, Region Sk ane, Lund University.

Conflict of interests The authors declare that they have no competing interests. Corresponding author has been lecturer at Philips’ courses in 3D echocardiography, but no potential conflicts of interest have been identified.

Authors’ contributions EO and MC are responsible for the conception of the study. MC, EO, GR, JH, AR and CM have designed the study and drafted the manuscript. EO, AWE, HE and GR have interpreted the data. All have revised the manuscript critically for important intellectual content and approved the final manuscript. The authors met the full criteria and requirements for authorship.

© 2016 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

8 Assessment of right atrial pressure, E. Ostenfeld et al.

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© 2016 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.