Author + information
- Received August 30, 2001
- Revision received March 29, 2002
- Accepted April 17, 2002
- Published online July 17, 2002.
- Ehtisham Mahmud, MD, FRCP(C)*,
- Ajit Raisinghani, MD, FACC*,
- Alborz Hassankhani, MD, PhD*,
- H.Mehrdad Sadeghi, MD*,
- G.Monet Strachan, RDCS*,
- William Auger, MD*,
- Anthony N DeMaria, MD, MACC* and
- Daniel G Blanchard, MD, FACC*,* ()
- ↵*Reprint requests and correspondence:
Dr. Daniel G. Blanchard, UCSD Medical Center, Division of Cardiology, 200 West Arbor Drive, San Diego, California 92103-8411, USA.
Objectives This study was designed to determine a quantitative relationship between right ventricular (RV) pressure overload and left ventricular (LV) diastolic filling characteristics in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Background Right ventricular pressure overload in patients with CTEPH causes abnormal LV diastolic filling. However, a quantitative relationship between RV pressure overload and LV diastolic function has not been established.
Methods We analyzed pre- and postoperative diastolic mitral inflow velocities and right heart hemodynamic data in 39 consecutive patients with CTEPH over the age of 30 (55 ± 11 years) with mean pulmonary artery pressure >30 mm Hg who underwent pulmonary thromboendarterectomy (PTE).
Results After PTE, mean pulmonary artery pressure (mPAP) decreased from 50 ± 11 to 28 ± 9 mm Hg (p < 0.001) while cardiac output (CO) increased from 4.4 ± 1.1 to 5.7 ± 0.9 l/m (p < 0.001). Mitral E/A ratio (E/A) increased from 0.74 ± 0.22 to 1.48 ± 0.69 (p < 0.001). E/A was < 1.25 in all patients pre-PTE. After PTE, all patients with E/A >1.50 had mPAP <35 mm Hg and CO >5.0 l/min. E/A correlated inversely with mPAP (r = 0.55, p < 0.001) and directly with CO (r = 0.53, p < 0.001).
Conclusions E/A is consistently abnormal in patients with CTEPH and increases post-PTE. Moreover, E/A varies inversely with mPAP and directly with CO. Following PTE, E/A >1.5 correlates with the absence of severe pulmonary hypertension (mPAP >35 mm Hg) and the presence of normal cardiac output (> 5.0 l/m).
Both primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension (CTEPH) are associated with abnormal left ventricular (LV) diastolic filling (1,2). In patients with CTEPH, Dittrich et al. (2)found a relationship between Doppler indexes of LV diastolic function and distortion (flattening) of the interventricular septum. They demonstrated that the abnormal LV diastolic function seen in a right ventricular (RV) pressure overload state was a consequence of ventricular interaction that was largely mediated through the interventricular septum. However, a quantitative relationship between the degree of pulmonary hypertension and LV diastolic filling has never been established.
The group of patients with CTEPH who undergo successful pulmonary thromboendarterectomy (PTE) provides a unique opportunity to evaluate the relationship between diastolic mitral flow indices and the severity of pulmonary hypertension. We undertook this study to compare the pre- and postoperative diastolic transmitral Doppler flow characteristics in patients with CTEPH who were undergoing PTE. Our goal was to define the quantitative relationship between transmitral E/A and both pulmonary artery (PA) pressure and cardiac output (CO) in patients with CTEPH.
The transthoracic echocardiograms and right heart hemodynamic data of 39 consecutive patients over age 30 with surgically accessible CTEPH were examined. The study group was composed of 24 men and 15 women with a mean age of 55 ± 11 years (range 30 to 82 years). All patients had chronic longstanding symptoms of cardiopulmonary disease and were classified as New York Heart Association class III or IV. Each patient had evidence of right-sided heart disease on physical examination, including elevated jugular venous pressure, palpable right ventricular heave, hepatomegaly or a pronounced P2 on auscultation. Patients diagnosed with surgically accessible CTEPH by previously described criteria (3)who underwent successful PTE were included in this study.
All patients underwent right heart catheterization within 48 h of preoperative echocardiography. Patients who had a mean pulmonary artery pressure (mPAP) of <30 mm Hg, were <30 years of age, had a suboptimal echocardiographic examination or had a right heart catheterization performed more than 48 h before or after the preoperative echocardiogram were excluded from the study. Following PTE, echocardiograms and right heart catheterization data were obtained and analyzed. Right heart catheterization data were obtained in the surgical intensive care unit within 72 h of the postoperative echocardiogram.
All patients underwent a standard echocardiographic examination, including two-dimensional and M-mode imaging, pulsed and continuous wave Doppler and color Doppler recordings. In addition, a contrast echocardiogram was performed by injecting agitated saline into the left antecubital vein (4). Commercially available echocardiographic instruments with 2.0 to 4.0 MHz transducers were used for two-dimensional imaging. Pre- and postoperative diastolic transmitral flow velocities were recorded in the standard apical four-chamber view of the heart. The sample volume was positioned at the mitral leaflet tips. No corrections were made for the angle between the interrogating Doppler beam and apparent mitral inflow but this angle was estimated to be <20° in all cases. Heart rate and atrioventricular conduction (PR interval) were determined from the electrocardiogram at the time of the Doppler echocardiographic studies.
Right heart catheterization
All patients underwent right heart catheterization within 48 h of preoperative echocardiography. Right heart catheterization was performed in the standard manner in the cardiac catheterization laboratory (5)with a 7.5F Swan Ganz (Baxter Healthcare Corporation, Santa Ana, California) catheter inserted into the right internal jugular vein. Pressure transducers were routinely balanced and positioned at the level of the right atrium. Resting phasic and electrical mean pressures were recorded on paper at 50 mm/s from the right atrium, right ventricle, PA and pulmonary capillary wedge positions. Cardiac output was obtained by the thermodilution method (mean of three injections) and pulmonary vascular resistance (PVR) was calculated by using the standard formula (6). The same data were obtained postoperatively in the surgical intensive care unit within 72 h of the postoperative echocardiogram.
Data are expressed as mean ± SD. Correlation coefficients with related p values are reported. A two-tailed Student ttest for paired populations was used to compare pre- and post-PTE measurements of transmitral diastolic filling parameters, CO, mPAP and mean pulmonary capillary wedge pressure (PCWP). Logarithmic regression analysis was applied to the data comparing transmitral E/A with mPAP and with CO. All statistical analyses were performed with Statview 5.0 software (SAS Institute, Cary, North Carolina).
The echocardiographic measurements and right heart catheterization data for the group are summarized in Table 1. As noted, there was a significant change in early diastolic mitral filling post-PTE, with an increase of the peak E-wave velocity from 52.5 ± 20.5 cm/s to 82.5 ± 18.5 cm/s (p < 0.0001). As a result, the mitral E/A increased from 0.74 ± 0.22 to 1.48 ± 0.69 (p < 0.0001). This was accompanied by significant improvement in CO (p < 0.0001), reduction in PVR (p < 0.0001) and mPAP (p < 0.0001), as well as an increase in the PCWP (p = 0.04). The E-wave deceleration time (DT) and pressure half-time (PHT) both decreased after surgery, although the p value did not reach statistical significance (DT: 216 ± 60 ms vs. 193 ± 34 ms, p = 0.26; PHT: 63 ± 15 ms vs. 54 ± 11 ms, p = 0.12). Figures 1 and 2⇓⇓show a representative example of E/A reversal and reduction of interventricular septal distortion and flattening pre- and post-PTE.
Mitral E/A correlated inversely with mPAP (r = 0.55, p < 0.001) and directly with CO (r = 0.53, p < 0.001) (Fig. 3). Statistical analysis showed a best fit with a nonlinear logarithmic model rather a linear one. Of note, the mitral E/A was <1.25 in all patients pre-PTE. Post-PTE, E/A >1.5 consistently predicted the absence of severe pulmonary hypertension (i.e., all such patients had a mPAP <35 mm Hg) and the presence of a normal CO (>5 l/m) (Fig. 4).
This study shows that Doppler-derived indices of LV diastolic filling dynamics (i.e., the peak transmitral E-wave velocity and the E/A ratio) increase quickly after resolution of pulmonary hypertension in patients with CTEPH who undergo successful PTE. In addition, our data demonstrate that this relationship between RV pressure overload and LV diastolic dysfunction is quantitative rather than merely qualitative. Specifically, there is a nonlinear logarithmic association between E/A and mean PA pressure as well as between E/A and CO in this population. This study demonstrates that transmitral diastolic flow is affected in a predictable manner in patients with CTEPH. In addition, we have found that normalization of E/A following PTE is a strong marker of successful surgery.
Why does RV pressure overload affect diastolic mitral inflow? Right ventricular pressure overload causes flattening and leftward displacement of the interventricular septum. Distortion of LV cavity geometry could limit early diastolic filling. This could be further diminished in cases of severe tricuspid regurgitation in which early diastolic trans-tricuspid volume dwarfs the transmitral volume. Indeed, we have recently found a strong correlation between the difference in filling pressures (RAP − PCWP) and the degree of septal flattening in CTEPH (7).
It is not difficult to assume that the abnormally low E/A ratio in CTEPH represents a variant of abnormal LV relaxation caused by hypertrophy and abnormal relaxation of the interventricular septum (a sort of “segmental” LVH). Echocardiographically, the interventricular septum is often markedly flattened in CTEPH, and the LV appears compressed. This only adds to the impression that LV diastolic filling must be impaired by massive RV enlargement and septal hypertrophy. It is important to note, however, that the change in LV shape in CTEPH is the result of long-term remodeling rather than acute compression, because complete surgical pericardiectomy in these patients produces absolutely no significant change in cardiac geometry or filling pressures (8).
Obviously, there are additional causes of low E/A. These include hypovolemia (9), age (10), increased heart rate (11)and movement of the Doppler sample volume from the mitral leaflet tips to the level of the mitral annulus (12). In this study, we excluded any patient under the age of 30. In addition, pre- and post-PTE heart rates were basically identical, and we were careful to position the sample volume at the mitral leaflet tips in all cases. This leaves the possibility of hypovolemia (or “underfilling” of the LV). It is noteworthy that the PCWP was in the low normal range preoperatively, and actually rose by approximately 17% post-PTE. This finding may be confounded by intra- and postoperative hydration, blood transfusions and variations in pressure measurements, but it is still possible that a component of the low preoperative E/A stems from underfilling of the LV. Also of note, it was the E-wave velocity that changed most after PTE; the A-wave velocity was relatively constant. Thus, RV overload does not merely cause a shift from early to late diastolic LV filling, but more of an absolute decrease in early filling without late diastolic compensation (corresponding with a low stroke volume and cardiac output preoperatively). With removal of the PA thrombi and improved CO (and increased PCWP) post-PTE, this underfilling is corrected and the E/A increases.
With resolution of pulmonary hypertension following PTE, transmitral diastolic flow improves in a predictable manner. Not surprisingly, this correlates with improvement in the CO. In fact, all patients in this group with successful PTE had restoration of normal cardiac output postoperatively. In this population, an E/A ratio of >1.50 predicted the resolution of severe pulmonary hypertension and the presence of normal CO post-PTE. Before PTE, all patients with severe pulmonary hypertension had an E/A ratio of <1.25. Therefore, obtaining the simple measurement of E/A can aid in determining the presence of pulmonary hypertension when a TR envelope is not measurable (i.e., the finding of E/A >1.5 in an adult over 30 years old makes severe pulmonary hypertension very unlikely). The E/A ratio can also be used as an added parameter to judge the hemodynamic success of PTE. In the occasional cases when endocardial definition is poor and echocardiographic CO is not feasible postoperatively, the presence of E/A >1.5 suggests a normal CO.
Transthoracic echocardiography and right heart catheterization were not simultaneous; up to 48 h elapsed between them in this study. However, because the underlying medical condition in all patients was chronic pulmonary hypertension and no major hemodynamic events occurred between the time of catheterization and echocardiography, we believe that simultaneous echocardiography and right heart catheterization would not have yielded substantially different results. Post-PTE right heart catheterization data were obtained in the intensive care unit by various operators and thus may be susceptible to variability in these measurements. In addition, we did not include measurement of pulmonary venous spectral Doppler because of severe right atrial enlargement and resultant distortion of the posterior atrial structures (especially the area of the right upper pulmonary vein ostium).
Another limitation is that the study group consisted only of patients with CTEPH. Therefore, these findings should be extrapolated to other RV pressure overload states with caution. Finally, we did not directly measure left atrial or LV filling pressures. Pulmonary capillary wedge pressure is a reasonably accurate surrogate of left atrial pressure (13), however, and none of the patients studied had evidence of pulmonary veno-occlusive disease, mitral stenosis, or more than mild mitral regurgitation.
Transmitral diastolic blood flow is consistently abnormal in patients with severe CTEPH. The E/A ratio is uniformly low in patients over age 30 with severe CTEPH, and the ratio consistently increases following successful PTE. Moreover, E/A varies inversely with mean pulmonary hypertension and directly with CO. In these patients, E/A >1.5 signaled the absence of severe pulmonary hypertension (defined as mPAP >35mm Hg) and the presence of normal CO (>5.0 l/m).
☆ This work was supported in part by a grant from the UCSD Academic Senate Committee on Research.
Presented in part at the American College of Cardiology Annual Scientific Session, March 1999.
- cardiac output
- chronic thromboembolic pulmonary hypertension
- deceleration time
- E/A ratio
- left ventricular
- mean pulmonary artery pressure
- pulmonary artery
- pulmonary capillary wedge pressure
- pressure half-time
- pulmonary thromboendarterectomy
- pulmonary vascular resistance
- right ventricular
- Received August 30, 2001.
- Revision received March 29, 2002.
- Accepted April 17, 2002.
- American College of Cardiology Foundation
- Louie E.K.,
- Rich S.,
- Brundage B.H.
- Dittrich H.C.,
- Chow L.C.,
- Nicod P.H.
- Snider A.R.,
- Dorts T.A.,
- Silverman N.H.
- Gregoratos G.
- Shabetai R.,
- Bhargava V.
- Sadeghi H.M.,
- Mahmud E.,
- Raisinghani A.,
- Sawhney N.,
- DeMaria A.N.,
- Blanchard D.G.
- Blanchard D.G.,
- Dittrich H.C.
- Berk M.R.,
- Xie G.,
- Kwan O.L.,
- et al.
- Batson G.A.,
- Chandrasekhar K.P.,
- Payas Y.,
- Rickards D.F.