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Defining normal variables of right ventricular size and function in pulmonary hypertension: an echocardiographic study
  1. A López-Candales,
  2. K Dohi,
  3. N Rajagopalan,
  4. K Edelman,
  5. B Gulyasy,
  6. R Bazaz
  1. Cardiovascular Institute at the University of Pittsburgh, Pittsburgh, PA, USA
  1. Dr A López-Candales, University of Pittsburgh, Cardiovascular Institute, Scaife 560, 200 Lothrop Street, Pittsburgh, PA 15213-2582, USA; lopezcandalesa{at}upmc.edu

Abstract

Background: Right ventricular (RV) fractional area change and tricuspid annular plane systolic excursion (TAPSE) are recognised methods for assessing RV function. However, the way in which these variables are affected by varying degrees of pulmonary hypertension (PH) has not been well characterised.

Methods: RV end-systolic area (RVESA), RV end-diastolic area (RVEDA), pulmonary artery systolic pressure (PASP) and TAPSE were collected from a database of 190 patients who had been referred to the PH clinic for evaluation.

Results: The mean (SD) age of the study population was 56 (17) years; 82 men were included with a mean (SD) PASP of 54 (33) mm Hg (range 16–150), RVESA of 14 (9) cm2, RVEDA of 24 (9) cm2, RV fractional area change of 44 (18)% and TAPSE of 2.06 (0.69) cm. Receiver-operating characteristic curves identified TAPSE <2.01 cm, RV fractional area change <40.9%, RVESA >12.3 cm2 and RVEDA >23.4 cm2 as abnormal values with PH. Finally stratification of patients into sub-groups according to their PASP allowed means and standard deviations to be reported for each echocardiographic variable.

Conclusion: This analysis provides a range of normal variables of RV size and function, not previously published, that can be used in routine evaluation and follow-up of patients with PH.

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Pulmonary hypertension (PH) is a disease of the pulmonary circulation where the pressure increase in the lungs causes increased resistance and afterload for the right ventricle (RV), but the condition manifests as compromised cardiac output due to RV dysfunction. RV dysfunction has an important independent bearing on prognosis in patients with PH.1 2 However, accurate assessment of RV function is difficult because of the ventricle’s complex structure and physiology.35 Despite these limitations, transthoracic echocardiography continues to be widely used for evaluation of patients with PH. The initial examination is usually used to exclude left ventricular dysfunction, valvular abnormalities and congenital heart disease, and Doppler techniques are used to detect and quantify pulmonary pressures initially as well as for subsequent follow-up.68

Box 1

Knowledge about the role of the right ventricle in health and disease historically has lagged behind that of the left ventricle. Consequently, little attention has been devoted to how right ventricular dysfunction may be best detected and measured.

In a recent report published by the National Heart, Lung, and Blood Institute, there is a need to understand how to better define normal parameters of right ventricular function. Critical information is required to determine the most sensitive and specific variables to describe abnormal right ventricular function.

Voelkel et al. Circulation 2006;114:1883–91

Even though RV function is crucial in determining clinical outcomes, a clear notion of what constitutes normal versus abnormal function remains poorly defined. Furthermore, as recently stated in a publication by the National Heart, Lung, and Blood Institute, a proportionately limited amount of information exists on RV impairment in various disease states and how it affects outcomes when compared with the left ventricle.9 Consequently, this panel suggested that not only is the RV an important contributor but also further understanding of RV size and function is of pivotal importance.9 Specifically, critical information is required to determine the most sensitive and specific variables for describing abnormal RV function, particularly when we still use an RV fractional area change (RVFAC) of less than 32%, defined by the investigators of the Survival And Ventricular Enlargement (SAVE) echocardiography sub-study, to identify an abnormal RV function.10

Box 2

Size and function of the right ventricle are not only indicators of the severity and chronicity of pulmonary hypertension but impose an additional cause of symptoms and reduced longevity. Right ventricular function is the most important determinant of longevity in patients with pulmonary arterial hypertension.

Voelkel et al. Circulation 2006;114:1883–91

Unfortunately, many clinicians rely on visual assessment of RV size and function rather than using a more systematic approach to interpret RV performance. Therefore, the goal of this study was to provide normal values of echocardiographic variables regarding RV size and function that can be routinely applied in the evaluation of patients with PH. To accomplish this, we evaluated RV area, RVFAC and tricuspid annular plane systolic excursion (TAPSE) in patients with various degrees of pulmonary artery systolic pressure (PASP); these variables are well-known markers of RV function, which are easily obtainable and reproducible.

Box 3

  • Pulmonary hypertension is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) rises above normal levels and may become life threatening.

  • Symptoms of pulmonary hypertension include shortness of breath with minimal exertion, fatigue, chest pain, dizzy spells and fainting.

  • Pulmonary hypertension is often misdiagnosed and has often progressed to late stage by the time it is accurately diagnosed. It has been historically chronic and incurable with a poor survival rate. However, new treatments are available which have significantly improved prognosis.

METHODS

Study population

We reviewed our database of patients who had been referred to the University of Pittsburgh, Presbyterian Hospital PH programme from January 2004 to September 2006. We looked for patients who had a complete echocardiogram with PASP estimated on an adequate tricuspid regurgitation signal.3 We collected RV end-systolic and end-diastolic areas, RVFAC and TAPSE, well-known markers of RV function, from 108 patients with various degrees of abnormal PASP who were referred for evaluation to the PH programme at the University of Pittsburgh echocardiography laboratories. Patients with an irregular heart rhythm such as atrial fibrillation, previous myocardial infarction, resting wall motion abnormalities, cardiomyopathy and moderate to severe valvular heart disease were not included in the analysis.

Box 4

The Cardiovascular Institute’s Pulmonary Hypertension Program at the University of Pittsburgh Medical Center is one of the most experienced in the United States. Linked closely with the Advanced Heart Failure Center, it receives patient referrals from Pennsylvania, Ohio, West Virginia, Western New York and Western Maryland. About 250 new patients are seen by this programme annually. This programme also works closely with the Systemic Sclerosis Center, Comprehensive Lung Center, and Liver Transplantation Program at the University of Pittsburgh Medical Center.

As pulmonary arterial hypertension can result from many disease processes, all patients with suspected pulmonary arterial hypertension at the University of Pittsburgh Medical Center undergo a detailed and comprehensive assessment. This includes blood tests, echocardiograms, six-minute walk tests, pulmonary function tests, CT scans, cardiac MRI, perfusion lung scans, pulmonary angiograms and cardiac catheterization. After diagnosis, a plan of medical or surgical treatments is tailored to each patient’s individual case.

We collected the same echocardiographic variables from a group of 82 consecutive patients referred for a clinical echocardiogram for reasons other than PH, who had a complete study with normal biventricular function and an adequate tricuspid regurgitation signal showing normal PASP. The same exclusion criteria used for patients with PH was used to select the patients with normal PASP.

None of the patients included in the final analysis were inpatients admitted with haemodynamic instability or a clinical suspicion of acute pulmonary embolism. Data from both groups, totalling 190 patients, were consecutively collected and included for final analysis. The institutional review board of the University of Pittsburgh Medical Center approved the study.

Standard echocardiography

All patients underwent a complete transthoracic echocardiographic study including two-dimensional, colour flow and spectral Doppler using a GE-Vingmed Vivid 7 system (GE Vingmed Ultrasound, Horten, Norway). Standard two-dimensional echocardiographic evaluation of RV size and function was performed as routinely.11 As seen in fig 1, RV size was calculated by tracing the endocardium at the end of diastole (RVEDA) and at the end of systole (RVESA) as suggested by the American Society of Echocardiography in order to calculate RVFAC as previously reported11 12:

Figure 1 (A,B) Four-chamber end-systolic still-frame view. Endocardial tracing is carried out along the endocardium of the right ventricle to measure the right ventricular end systolic area. (C,D) Four-chamber end-diastolic still-frame view. Similarly, endocardial tracing is carried out along the endocardial border of the right ventricle to measure the right ventricular end diastolic area.

RVFAC  =  ((RVEDA − RVESA)/RVEDA) ×100%

An additional measure of RV function was used: the motion and excursion of the tricuspid annulus.1214 As shown in fig 2A, the M-mode cursor is oriented at the junction between the lateral portion of the tricuspid annulus and the RV free wall. Then maximal TAPSE is obtained by measuring total excursion, as seen in fig 2B.15

Figure 2 (A) The M-mode cursor is placed at the junction of the lateral tricuspid annulus and the right ventricular free wall from the four-chamber view to obtain the recording seen in (B). (B) Maximal tricuspid annular plane systolic excursion (TAPSE) is shown.

Colour-flow Doppler imaging was obtained with the standard colour-encoding system with the patient in the left lateral decubitus position from the apical four-chamber view to determine the tricuspid regurgitation signal. PASP was estimated as described by the American Society of Echocardiography.16 17

Figure 3 Calculation of the systolic pressure gradient between the right ventricle and the atrium using the tricuspid regurgitation signal (see box 5).

Box 5

Calculation of the systolic pressure gradient between the right ventricle and the atrium using the tricuspid regurgitation signal.

Maximum velocity of the tricuspid regurgitant jet and then using the modified Bernoulli equation.

p = 4V2

In the example in fig 3, the maximum tricuspid regurgitation signal is 2.3 m/s; therefore, the pressure gradient between the right ventricle and the atrium is 21 mm Hg. The final calculation depends on an estimated value of the right atrial pressure that is conventionally based on both the size of the inferior vena cava and the change in calibre of this vessel with respiration. In a normal patient, 5–10 mm Hg is usually considered normal. Therefore, in this example the final pulmonary artery systolic pressure is 31 mm Hg.

To be able to report means and standard deviations for the RV echocardiographic variables used in this study, we stratified the patient population according to a PASP severity index previously reported by our laboratory.18

Statistical analysis

All echocardiographic variables were calculated using the commercially available software EchoPAC PC V6.00 (GE Vingmed Ultrasound) and determined by a single observer. Three measurements were collected for each variable, and the mean (SD) of each variable was used for comparison analysis using the two-tailed Student t test for paired and unpaired data. Linear regression analysis was used to examine relations between various dependent variables. Univariate analysis between PASP and other echocardiographic variables was also performed. The ability of the measured echocardiographic variables of RV size and systolic function to detect an abnormal PASP greater than 40 mm Hg, considered as abnormal, was assessed using receiver-operating characteristic curves to provide optimal values for each variable and areas under the curve (AUCs), which were compared by the method of Hanley and McNeil.19 Finally, a stepwise multiple linear regression analysis was performed to determine the independent predictive value of the echocardiographic variables with respect to PH. p<0.05 was considered significant.

Results

Patient analysis

In the population studied, patients with PH (mean (SD) age 60 (15) years with a mean PASP of 74 (30) mm Hg) were older than patients with normal PASP (mean (SD) age 50 (16) years (p<0.001) with a mean PASP of 28 (6) mm Hg). Almost the same number of male patients was found in each group (43 vs 40, respectively). Patients with PH included six with end-stage liver disease and portopulmonary hypertension, six with valvular disease, 12 with connective tissue disorders, 15 with cardiomyopathy, 34 with end-stage pulmonary disease, and 35 with idiopathic PH.

Right ventricle in pulmonary hypertension

As expected, patients with PH had significantly larger RVESA (19 (9) cm2), RVEDA (35 (9) cm2), lower RVFAC (35 (16)%), and lower TAPSE (1.68 (0.65) cm) than patients with normal PASP (RVESA 8 (4) cm2 (p<0.001), RVEDA 18 (5) cm2 (p<0.001), RVFAC 56 (13)% (p<0.001), TAPSE 2.54 (0.49) cm (p<0.001)).

Using the data from the 190 patients included in this study, we first examined the correlation between RV areas and PASP and found a positive correlation (r = 0.74 (p<0.001) for RVESA and PASP as seen in fig 4A; r = 0.66 (p<0.001) for RVEDA and PASP as seen in fig 4B). Consequently, when we look at the relationship between RVFAC and PASP, a negative correlation is seen, as shown in fig 5A (r = −0.67, p<0.001). Finally, a similar negative correlation is seen between TAPSE, another marker of RV function, and PASP (r = −0.63, p<0.001, as seen in fig 5B). Simply stated, as the degree of PH increases, both indices that describe RV size increase correspondingly, and consequently lower values for RV systolic function, described by either RVFAC or TAPSE, are seen.

Figure 4 (A) Correlation between pulmonary artery systolic pressure (PASP) and right ventricular end systolic area (RVESA) (r = 0.74). (B) Correlation between PASP and right ventricular end diastolic area (RVEDA) (r = 0.66).
Figure 5 (A) Negative correlation between pulmonary artery systolic pressure (PASP) and right ventricular fractional area change (RVFAC) (r = −0.67). (B) Negative correlation between PASP and tricuspid annular plane systolic excursion (TAPSE) (r = −0.63).

Receiver-operating characteristic curves were useful for indicating values that can be considered either normal or abnormal. In the population studied, TAPSE <2.01 cm (AUC of 0.852, fig 6A), RVFAC <40.9% (AUC of 0.846, fig 6B), RVESA >12.3 cm2 (AUC of 0.879, fig 6C) and RVEDA >23.4 cm2 (AUC of 0.814, fig 6D) were all abnormal values when the studied variable of interest was a PASP greater than 40 mm Hg, indicating PH.

Figure 6 Receiver-operating characteristic curves (solid lines) with confidence intervals (dashed lines) are seen for abnormal echocardiographic values for right ventricular (RV) size and systolic function when PASP was greater than 40 mm Hg. (A) Tricuspid annular plane systolic excursion (TAPSE) <2.01 cm is abnormal; (B) RV fractional area change (RVFAC × 100) <39.8% is abnormal; (C) RV end-systolic area (RVESA) >15.4 cm2 is abnormal; (D) RV end-diastolic area (RVEDA) >23.4 cm2 is abnormal. AUC, area under the curve.

A stepwise linear regression analysis showed that, of all the variables used in the study, RVFAC appears to be more closely related to PASP than TAPSE and RV areas, as shown in table 1.

Table 1 Multiple linear regression analysis of parameters on pulmonary hypertension

Finally, stratification of patients into sub-groups according to their PASP, as described in the Methods section (group 1, patients with PASP  =  36–50 mm Hg; group 2, PASP  =  51–75 mm Hg; group 3, PASP > 75 mm Hg), allowed means and standard deviations to be reported for each echocardiographic variable (fig 7). This analysis was useful for better discrimination of values according to the increase in PASP.

Figure 7 Box plot images showing mean (SD) for tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) end-systolic area (RVESA), RV end-diastolic area (RVEDA) and RV fractional area change (RVFAC) in patients with normal pulmonary artery systolic pressures as well as in patients with different degrees of pulmonary hypertension: group 1, patients with pulmonary artery systolic pressure (PASP)  =  36–50 mm Hg; group 2, PASP  =  51–75 mm Hg; group 3, PASP > 75 mm Hg.

Discussion

The results of our analyses provide for the first time a range of normal echocardiographic variables, including RV areas, RVFAC and TAPSE, that are useful in the assessment of RV performance. These results are of utmost importance, as clinicians have traditionally relied on subjective visual assessments of RV size and function, derived from two-dimensional echocardiography, to estimate RV performance.20 21 The catastrophic consequences of these visual interpretations without an objective basis was recently addressed by The National Heart, Lung, and Blood Institute, who urged researchers to better define normal parameters of RV function,9 as unrecognised RV failure adversely affects clinical outcomes.1 10 11 2225 The systematic use of reliable echocardiographic variables that are readily available will undoubtedly help clinicians to identify early RV dysfunction so that other diagnostic and therapeutic interventions can be promptly implemented. As no published data on normal parameters of RV size and function are currently available, the results of this study will be useful for identifying early changes in RV size and function in order to institute more aggressive therapeutic intervention.

What is known on the topic of right ventricular dysfunction

  • It has an important independent bearing on prognosis in pulmonary hypertension

  • Accurate assessment of function is limited by the ventricle’s complex structure and physiology

  • Despite limitations, transthoracic echocardiography is widely used in evaluation of pulmonary hypertension by:

    • Estimating pulmonary artery systolic pressure

    • Visually assessing size and function

What this study adds

Previously unreported normal values for:

  • Right ventricular area

  • Right ventricular fractional area change

  • Tricuspid annular plane systolic excursion

Traditionally, echocardiography has been mainly used to estimate PASP by calculating the systolic pressure gradient between the RV and atrium from the maximum velocity of the tricuspid regurgitant jet, by using the modified Bernoulli equation and then adding to this value the estimated right atrial pressure based on both the size of the inferior vena cava and the change in its calibre with respiration.16 17 However, results from the Primary Pulmonary Hypertension Study Group show that, in up to 14% of all cases, an adequate Doppler signal of tricuspid regurgitation might not be obtained, leading to underestimation of PASP.26 Therefore, additional echocardiographic measures are needed that may help both sonographers and clinicians to identify RV size and function abnormalities in PH.

It may be argued that these findings represent a snapshot in the continuum of possible PASPs. However, the correlations obtained in this study are acceptable and suggest a linear relationship between PH and indices of RV size and function. One limitation is a lack of knowledge about duration of PH in these patients. As with many other studies involving patients with PH, the non-specific nature of symptoms, as well as the subtlety of signs found in less advanced cases, often makes it difficult to determine the actual duration of the disease process. However, as our goal was to provide normal values of routine echocardiographic variables of RV size and function, we analysed the commonly used RV areas, RVFAC and TAPSE in patients with varying degrees of abnormal PASP and compared them with data obtained from patients without PH at the time of the examination.

In summary, these results provide a range of normal variables of RV size and function, not previously published, that can be used in the routine evaluation and follow-up of patients with PH, with the implication that, by knowing and applying these variables, we will be able to determine RV dysfunction earlier and therefore diagnose PH earlier.

REFERENCES

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Footnotes

  • Funding: AL-C is supported by an American Society of Echocardiography Outcomes Research Award.

  • Competing interests: None.

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