Estimation of Elevated Systolic Pulmonary Artery Pressure Using Right Ventricular Isovolumic Relaxation Time

INTRODUCTION

Pulmonary hypertension (PH) is a pathophysiological disorder that complicates the majority of cardiovascular and respiratory diseases.^[1] Non-invasive assessment of systolic pulmonary artery pressure (sPAP) is routine investigation in echocardiography laboratories using tricuspid regurgitation (TR) peak velocity (TRVmax) and Bernoulli’s equation. However, there are certain limitations of this method. In 20% of healthy population and up to 70% of patients with chronic obstructive pulmonary disease, assessment of TR jet is difficult.^[2,3] There can be underestimation of sPAP mostly due to the underestimation of mean right atrial pressure (mRAP) and TRVmax. Simplified Bernoulli’s equation may underestimate the right ventricle (RV) to the right atrial (RA) pressure gradient since an inertial component of complete Bernoulli’s equation is neglected. In patients with severe TR, early equalisation of RV and RA pressures underestimates the RV-RA gradient.^[4] Studies have shown that RV isovolumic relaxation time (IVRT) is a reliable tool to predict sPAP with good correlation.^[5-7] Pulsed Doppler tissue imaging (DTI) is an excellent echocardiographic technique that provides information on the velocities and intervals from the myocardial wall.^[8] The RV IVRT is the time interval from closure of the pulmonary valve to opening of the tricuspid valve and it can be measured using DTI. It is sensitive to changes in PAP and heart rate (HR).^[9] This study was designed to evaluate the feasibility and accuracy of RV IVRT for predicting elevated sPAP.

MATERIAL AND METHODS

Echocardiographic evaluation

The echocardiographic study was done in patients with clinical suspicion of PH or known to have PH. The study was done using Philips iE33 [(F.3) with Vision 2007–Vision 2012 software] echocardiography machine (PureWave cardiac sector S5-1 [1–5 MHz] probe). Patients underwent routine transthoracic echocardiographic examination with standard measurements including sPAP estimation using TRVmax and Bernoulli’s equation. mRAP was estimated from the dimensions of the inferior vena cava and its inspiratory collapse.^[11] IVC diameter <2.1 cm and collapse >50% correlate with normal mRAP of 0–5 mmHg (average 3 mmHg). IVC diameter <2.1 cm with <50% collapse and IVC diameter >2.1 cm with >50% collapse correspond to an intermediate RAP of 5–10 mmHg (average 8 mmHg). IVC diameter >2.1 cm with <50% collapse suggests a high RAP of 15 mmHg.^[4,12] TDI measurements were done from a 2 mm sample volume from the apical window at the right lateral corner of the tricuspid annulus, as described by Caso et al.^[6] The resulting velocities were recorded at a sweep speed of 100 mm/s. DTI ejection time (tET) was obtained between onset and cessation of S-wave (peak systolic tricuspid annular velocity). RV IVRT was measured as a time interval between the end of the systolic S’ wave and the beginning of the diastolic E’ wave. Isovolumic contraction time (IVCT) was measured between cessation of A’-wave and onset of S-wave [Figure 1]. To account for beat-to-beat variations in HR, an average of three consecutive cycles was obtained. As RV IVRT is HR dependent, adjusted RV IVRT₀ was calculated as RV IVRT/√RR. Myocardial performance index (MPI-TDI) was calculated as the sum of IVCT and IVRT divided by ejection time (iVCT+IVRT)/(ET). An alignment between the tricuspid annulus motion and the ultrasound beam was kept as parallel as possible. High-frequency signals were excluded by the appropriate filter setting. Optimisation of gain setting was done to allow a clear tissue signal with minimal background noise. RV systolic function was assessed using S’ wave and TAPSE. RV systolic dysfunction was defined by S’ <9.5 cm/s and a tricuspid annular plane systolic excursion <17 mm.^[13] All Doppler echocardiographic and TDI recordings were obtained at end expiration.

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Figure 1:

Tissue Doppler imaging of the lateral tricuspid annulus showing measurement of isovolumic contraction time, isovolumic relaxation time, ejection time, tricuspid annular systolic velocity (S), tricuspid annular early (E’) and late diastolic velocities (A’).

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RESULTS

Right ventricular IVRT measured by tissue Doppler imaging and sPAP

The average RV IVRT and adjusted RV IVRT were 67.29 ± 22.2 ms and 75 ± 24.47 (36–136 ms), respectively. There was a strong correlation between IVRT and sPAP in our population (r = 0.69, P < 0.0001) which did not improve with adjustment for HR, IVRT/√RR (r = 0.61, P < 0.0001). A cutoff of 43 ms IVRT showed a sensitivity and specificity of 89% and 93%, respectively, for the prediction of elevated sPAP (as defined sPAP ≥39 mmHg) [Figure 2].

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Figure 2:

(a) Correlation between right ventricle isovolumic relaxation time and sPAP (r = 0.69, P < 0.0001). (b) ROC curve for predicting systolic pulmonary artery pressure of 40 mmHg or higher. Area under the curve 0.956 (95% CI 0.916–0.995).

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DISCUSSION

The PAP reflects both the left and right heart functions and thus has diagnostic, therapeutic, and prognostic values for patients with cardiac and pulmonary diseases. The most widely accepted and employed echocardiographic method for the estimation of PAPs relies on the measurement of TRVmax. Often times, TR is not sufficient to perform this measurement and this method is appropriate in 75–80% of patients.^[3,14,15] With the advent of technology, TDI has also been used in defining PH.^[7] It has been found that TDI is superior to the blood flow Doppler since it reflects the functional status of the myocardium directly and is less affected by background noise and the loading condition. In the specific study, we investigated an alternative echocardiographic method for the estimation of increased sPAP.

In his study, Burstin has concluded that sPAP could be estimated non-invasively by measuring the time interval between the pulmonary valve closure to the onset of tricuspid flow using phonocardiography and pulse tracings.^[16] TDI is a newer technique that provides the assessment of myocardial motion and time intervals throughout the cardiac cycle.^[17] In this study, we found a strong positive correlation between RV IVRT measured by TDI and sPAP estimated from TRVmax. This result is consistent with numerous Doppler catheterisation studies conducted from 1967 to 2016 [Table 3].^{[3,5-9,15,18-22]} All these studies compared RV IVRT measured by TDI with pulmonary artery systolic pressure measured invasively at catheterisation laboratory. We estimated pulmonary artery systolic pressure noninvasively by adding the estimated mean RAP (as per IVC diameter and respirophasic variation) and RV to RA pressure gradient from TR. It has been shown that TR peak pressure gradient correlates significantly with sPAP.^[18,23,24] Our results are consistent with Cabrita et al. who studied the correlation between IVRT and systolic PAP measured through echocardiography, in which they found a strong correlation between IVRT and sPAP [Table 3].^[8] They found that a cutoff of 75 ms IVRT showed a sensitivity and specificity of 94 and 97%, respectively, for the prediction of PH (as defined PASP >39 mmHg). Fourteen out of 90 patients in our study had normal sPAP. This could be the result of underestimation of mRAP based on IVC diameter respirophasic variation.

RV systolic function was assessed using tricuspid S’ wave and TAPSE. The effects of the RV systolic function were also investigated in this correlation. The correlation between RV IVRT and sPAP was higher in patients with preserved RV systolic function than with RV dysfunction. It has been shown that RV IVRT gets prolonged during RV dysfunction even in the absence of PAH.^[10] It appears that RV dysfunction reduces the rate of the RV pressure drop during relaxation, increasing the diastolic PAP and lengthening the RV IVRT. Therefore, it indicates that RV dysfunction may perturb the evaluation of sPAP using RV IVRT.

Abbas et al. demonstrated an inverse relationship between IVRT and RAP in a Doppler catheterisation study in 21 patients, with 80% sensitivity and 87.7% specificity for IVRT 59 ms to predict RAP 8 mmHg.^[25] It means an increase in mRAP should shorten IVRT. Yoshifuku et al. also described RV IVRT to be pseudonormalised in patients with elevated RAP during acute right ventricular myocardial infarction.^[26] In our study, we found a positive correlation between RAP and RV IVRT. RAP was higher in patients with PAH. This is probably because the increase in RAP was a consequence of elevated right ventricular filling pressures in our population, which is consistent with a study by Bre´chot et al., as opposed to Abbas and Yoshifuku et al. patients where the principle mechanism was RV failure.^[27] Correlation between RV IVRT and sPAP was further improved when patients with elevated RAP were excluded from the study [Table 2].

As IVRT is HR dependent, it was adjusted for HR by dividing IVRT by root of RR time interval (IVRT/√RR). In our study, there was a strong correlation between IVRT with sPAP and did not improve when IVRT was corrected for HR as described by others.^[5-7,9,19] This is probably because HR was in the same range in our population, and corrected rIVRT may be useful in case of extreme HR.

The imaging technique plays an important role in the measurement of RV IVRT that accurately reflects pulmonary pressure. Proper placement of the Doppler sample volume at the lateral tricuspid annulus and also its accurate alignment to the long axis is essential. As a non-invasive method, IVRT was able to distinguish between patients with and without PH, regardless of the aetiology. Since DTI has wide availability, the signal is easy to obtain in almost all patients; more studies remain to be done with prospectively validating tissue Doppler techniques and its incorporation into clinical practice.

CONCLUSION

The calculation of IVRT by DTI is a simple and feasible method. It correlates well with sPAP. Hence, RV IVRT can be used as an alternative to TR derived sPAP in the absence of TR. This method should be used as screening in patients at risk for PH, monitoring the disease progression and the effect of treatment. Care has to be taken while assessing patients with RV dysfunction and elevated mRAP.