Prevalence and Prognostic Value of Left Ventricular Diastolic Dysfunction in Idiopathic and Heritable Pulmonary Arterial Hypertension

Abstract

Background:

Little is known about the association between left ventricular (LV) diastolic dysfunction and outcomes in patients with idiopathic or heritable pulmonary arterial hypertension (PAH). Our rationale was to investigate the prevalence of LV diastolic dysfunction, and its association with disease severity and outcomes, in patients with idiopathic or heritable PAH.

Methods:

Using the Cleveland Clinic Pulmonary Hypertension Registry, we identified subjects with heritable or idiopathic PAH who underwent Doppler echocardiography and right-sided heart catheterization. Echocardiographic diastolic parameters were assessed in each patient.

Results:

A total of 61 patients met the inclusion criteria (idiopathic 85%, heritable 15%). The age at the time of echocardiography was 48.3 ± 18 years, 84% of the subjects were women, and 48% were on PAH-targeted therapies. Normal LV diastolic function, impaired relaxation, and pseudonormalization were seen in 10%, 88%, and 2% of the patients, respectively. Peak early diastolic (peak E) velocity was directly associated with LV end-diastolic volume and cardiac index and inversely associated with the degree of right ventricular dilation, right atrial pressure, and pulmonary vascular resistance. Peak E velocity was associated with mortality adjusted for age and sex (hazard ratio [HR], 1.5; 95% CI, 1.1-2 per 10 cm/s decrease; P = .015) and age, sex, 6-min walk distance, and cardiac output (HR, 1.8; 95% CI, 1.2-2.9 per 10 cm/s decrease; P = .01).

Conclusions:

LV diastolic dysfunction of the impaired relaxation type is observed in the majority of patients with advanced idiopathic or heritable PAH. A decrease in transmitral flow peak E velocity is associated with worse hemodynamics and outcome.

Several authors have reported a high prevalence of impaired left ventricular (LV) relaxation (diastolic dysfunction grade I) in patients with pulmonary arterial hypertension (PAH).^1‐3 Little is known, however, about its association with severity of disease and outcomes in patients with idiopathic or heritable PAH, since most of the studies were done on subjects with chronic thromboembolic disease or included a heterogeneous group of patients with PAH.

Impaired LV relaxation in PAH is commonly attributed to decreased LV compliance as a result of right-to-left interventricular septal displacement^1,2 or reduced LV preload.^4,5 Studies comparing echocardiographic with hemodynamic data have noted an association between the degree of PAH and the presence of LV diastolic dysfunction,^3,6,7 but limited information exists about the prognostic value of parameters that measure LV diastolic function.⁸

We sought to investigate the LV diastolic function in patients with idiopathic or heritable PAH, using Doppler echocardiography, and compare the results with hemodynamic data obtained by right-sided heart catheterization (RHC). Our hypothesis is that LV diastolic dysfunction is common and correlates with severity of disease and outcomes in patients with idiopathic or heritable PAH.

Materials and Methods

Study Design and Inclusion Criteria

This study was approved by the Cleveland Clinic institutional review board (protocol approval number: 10-1127). Informed consent was waived. We identified subjects by using the Cleveland Clinic Pulmonary Hypertension Registry. A total of 1,329 individuals underwent RHC. We selected patients with hemodynamic criteria for PAH (pulmonary artery occlusion pressure [PAOP] ≤ 15 mm Hg, pulmonary vascular resistance [PVR] ≥ 3 Wood units)⁹ who also had FEV₁/FVC ≥ 0.6 and total lung capacity ≥ 60%. Of those, we only included patients with either idiopathic or heritable PAH and no other medical conditions known to be associated with PAH (n = 140). Each of these patients underwent a careful selection process that included extensive testing to exclude other causes of pulmonary hypertension (additional data in e-Appendix 1). No patient had evidence of coronary artery disease or LV systolic, mitral, or aortic valvular dysfunction. We only included patients who had Doppler echocardiography performed within 2 months of the RHC and after the year 2004, to be sure that the echocardiography studies were accessible for off-line review. In addition, each patient was independently reviewed by two pulmonary hypertension specialists. We excluded all patients in whom both physicians were not in complete agreement about the diagnosis. All selected patients were in sinus rhythm at the time of the echocardiography. The presence or absence of LV diastolic dysfunction on echocardiography was not part of the inclusion or exclusion criteria.

Measurements and Calculations

We selected the RHC and Doppler echocardiogram pair that was first performed at our institution. Echocardiographic measurements were obtained by experienced observers unaware of the patients’ clinical status. All echocardiographic determinations were compared with the ones originally reported at the time of the study. In case of discrepancies, another physician reviewed the echocardiographic images and a consensus was obtained. We obtained all the traditional echocardiographic (two-dimensional [2D] and Doppler) measurements following American Society of Echocardiography recommendations.¹⁰

Transmitral flow measurements included peak early diastolic velocity (peak E velocity), peak late diastolic velocity (peak A velocity), E/A ratio, and deceleration time of the E velocity. Pulmonary vein flow determinations (feasible in 46 patients) consisted of peak systolic velocity (peak S velocity), peak anterograde diastolic velocity (peak D velocity), S/D ratio, and peak velocity in late diastole (peak Ar velocity). Tissue Doppler measurements (available in 25 patients) were early (e′) and late (a′) diastolic velocities and E/e′ and e′/a′ ratios at the septal and lateral areas of the mitral annulus.

Abnormal function was divided in three grades, following recommendations from the American Society and European Association of Echocardiography (grade I: impaired LV relaxation; grade II: pseudonormal LV filling; and grade III: restrictive LV filling).⁶ When indicated, Valsalva maneuver was performed to distinguish a “true-normal” from a pseudonormal diastolic filling pattern. A detailed description of the methodology used to obtain echocardiographic parameters is in e-Appendix 1.

Statistics

Two-group comparisons were performed by Student t test or Mann-Whitney U test when appropriate. For three or more groups comparison we used one-way analysis of variance with Bonferroni correction. Categorical data were compared using Fisher exact test. We used linear regression analysis to compare continuous variables. Survival was assessed by Kaplan-Meier methodology. Time 0 was the date at the time of the initial echocardiogram. The end of follow-up was December 2009 or the time of the recipient’s death (or transplantation, when a combined end point was used). Survival differences between patients with peak E wave ≥ 60 cm/s or < 60 m/s was assessed using log-rank test. A cutoff of 60 cm/s was chosen as it was the closest round value from the peak E wave median. Cox proportional hazards modeling, adjusted by age and sex, was used for survival analysis of echocardiographic variables as predictors of death. When appropriate, we also adjusted the analyses for other previously identified predictors of survival.^11,12 Death of the study participants was ascertained by reviewing our records and querying the US Social Security Death Index. All P values reported are two-tailed. A P value of < .05 was considered significant. The statistical analyses were performed using the statistical package SPSS, version 17 (SPSS Inc).

Results

Overall Characteristics of the Patients

A total of 61 patients with either idiopathic (n = 52, 85.2%) or heritable (n = 9, 14.8%) PAH were included in the study. New York Heart Association (NYHA) functional class was II, III, and IV in 31%, 49%, and 20% of the patients, respectively. The age (mean ± SD) at the time of the echocardiography was 48 ± 18 years, and 84% of the subjects were women. Forty-eight percent of the patients were on PAH-targeted therapies at the time of echocardiography (phosphodiesterase 5 inhibitors, nine patients [15%]; endothelin receptor antagonists, five patients [8%]; prostacyclin analogs, 15 patients [25%]). Hemodynamic characteristics are shown in Table 1.

Table 1.

—Hemodynamic Parameters in All Patients (N = 61) and in Those With (n = 55) or Without (n = 6) LV Diastolic Dysfunction

Parameter	All Patients (mean ± SD)	Normal Diastolic Function (mean ± SD)	Diastolic Dysfunction Grade ≥ I (mean ± SD)	P Value (Mann-Whitney Test)
HR, beats/min	86 ± 14	82 ± 19	85 ± 13	.66
Systolic ABP, mm Hg	125 ± 20	128 ± 12	125 ± 21	.71
Diastolic ABP, mm Hg	79 ± 12	75 ± 9	80 ± 13	.28
RA, mm Hg	11 ± 6	6 ± 3	12 ± 6	.04
Systolic PAP, mm Hg	86 ± 19	84 ± 12	86 ± 19	.95
Diastolic PAP, mm Hg	38 ± 13	34 ± 9	39 ± 13	.34
Mean PAP, mm Hg	54 ± 14	51 ± 9	54 ± 14	.77
PAOP, mm Hg	10 ± 4	13 ± 4	9 ± 4	.04
Cardiac index, L/m/m2	2.1 ± 0.7	2.9 ± 0.4	2 ± 0.6	.001
TPG, mm Hg	44 ± 15	38 ± 7	45 ± 15	.22
PVR, Wood units	13 ± 6	7 ± 1	13 ± 6	.002

ABP = arterial BP; HR = heart rate; LV = left ventricular; PAOP = pulmonary artery occlusion pressure; PAP = pulmonary artery pressure; PVR = pulmonary vascular resistance; RA = right atrial; TPG = transpulmonary gradient.

Echocardiographic Evaluation

General Measurements:

Echocardiography was performed 1.5 ± 7 weeks from the RHC. Left heart cavities were small, with biplane right-over-left atrial and ventricular volume ratios of 3.3 ± 3.4 and 2.3 ± 1.4, respectively. Eccentricity index was higher in early diastole than in end diastole (1.8 ± 0.6 vs 1.3 ± 0.2, P < .001) (Fig 1). Right ventricle was dilated in 98% of the patients (mild, 15%; moderate, 28%; moderate to severe, 20%; severe, 37%) and the same percentage had right ventricular (RV) dysfunction (mild, 15%; moderate, 27%; moderate to severe, 27%; and severe, 31%). Tricuspid regurgitation was present in 98% of the patients (trivial, 7%; mild, 29%; moderate, 32%; and severe, 32%). Tricuspid jet velocity and estimated RV systolic pressure (n = 59) were 4.4 ± 0.7 m/s and 86 ± 24.1 mm Hg, respectively. Other measured echocardiographic parameters are shown in Table 2.

Figure 1.

Eccentricity index. A, M mode at the level of LV papillary muscles in parasternal long axis view. There is marked RV dilation, early diastolic septal flattening, and PE. B-D, Measurements of eccentricity index in the parasternal short axis view at the level of the LV papillary muscles. B, End diastole; C, end systole; D, early diastole. Arrowheads in each panel point the interventricular septum. bpm = beats/min; HR = heart rate; LV = left ventricular; PE = pericardial effusion; RV = right ventricular.

Table 2.

—Two-Dimensional Echocardiographic Measurements in All Patients (N = 61) and in Those With (n = 55) or Without (n = 6) LV Diastolic Dysfunction

Measurement	All Patients	Normal Diastolic Function (mean ± SD)	Diastolic Dysfunction Grade ≥ I (mean ± SD)	P Value (Mann-Whitney Test)
Interventricular septum, cm	1.2 ± 0.9	1.1 ± 0.3	1.3 ± 1	.72
Posterior wall septum, cm	1.2 ± 0.9	1.1 ± 0.3	1.2 ± 1	.72
LA diameter, cm	3.5 ± 0.7	3.8 ± 0.5	3.4 ± 0.7	.26
LA volume index, mL/m2	18 ± 9	26 ± 12	18 ± 8	.026
RA volume index, mL/m2	48 ± 26	40 ± 12	49 ± 27	.51
RA/LA ratio	3.3 ± 3.4	1.7 ± 0.7	3.5 ± 3.6	.17
LV EDV, mL	48 ± 19	62 ± 21	47 ± 18	.07
RV EDV, mL	94 ± 40	85 ± 19	95 ± 42	.83
RV/LV EDV ratio	2.3 ± 1.4	1.6 ± 0.8	2.4 ± 1.5	.12
Eccentricity index (end systole)	1.3 ± 0.2	2.2 ± 1.1	2.3 ± 0.9	.65
Eccentricity index (early diastole)	2.3 ± 0.9	1.9 ± 0.8	1.8 ± 0.5	.97
Eccentricity index (end diastole)	1.8 ± 0.6	1.2 ± 0.1	1.3 ± 0.3	.20

Pericardial effusion was observed in eight patients (mild in five and moderate in three subjects). EDV = end-diastolic volume; LA = left atrium; RV = right ventricular. See Table 1 legend for expansion of other abbreviations.

LV Diastolic Dysfunction Evaluation:

We observed normal diastolic function, impaired relaxation, and pseudonormalization pattern in 10%, 88%, and 2% of the patients, respectively (Fig 2). Diastolic parameters measured are shown in Table 3. There were no differences in age (P = .16), sex (P = .58), race (P = .8), or heart rate (P = .66) between patients with or without LV diastolic dysfunction.

Figure 2.

Diastolic function evaluated with pulse Doppler of the mitral inflow. A, Normal diastolic function (peak E wave velocity [E] over peak A wave velocity [A] ratio > 1). B, Impaired LV relaxation (E/A ratio < 1). C, Pseudonormal LV filling pattern (during normal respiration E/A ratio > 1). D, During Valsalva maneuver there is reversal of the ratio (E/A ratio < 1) due to LV preload reduction. See Figure 1 legend for expansion of abbreviations.

Table 3.

—Echocardiographic Evaluation of Diastolic Parameters

Location	Measurement	Mean ± SD
Transmitral flow (n = 61)	Peak E velocity, cm/s	58 ± 17
	Peak A velocity, cm/s	74 ± 20
	E/A ratio	0.83 ± 0.3
	E deceleration time, ms	225 ± 55
Pulmonary vein flow (n = 46)	Peak S velocity, cm/s	50 ± 10.3
	Peak D velocity, cm/s	38 ± 10.5
	S/D ratio	1.4 ± 0.3
	Peak A velocity	29 ± 5.8
Tissue Doppler (n = 25)	Lateral e′ velocity, cm/s	11 ± 4.5
	Lateral a′ velocity, cm/s	12 ± 4.3
	Lateral e′/a′ ratio	1 ± 0.5
	Lateral E/e′ ratio	6.7 ± 3.9
	Septal e′ velocity, cm/s	8.1 ± 4.1
	Septal a′ velocity, cm/s	8.8 ± 3.1
	Septal e′/a′ ratio	1 ± 0.4
	Septal E/e′ ratio	9.7 ± 6.5

Few patients had mitral color M mode to measure propagation velocity or reliable echocardiographic evaluation to precisely measure intraventricular relaxation time. A = late diastolic; D = anterograde diastolic; E = early diastolic; S = systolic.

Comparison of LV Diastolic Function With 2D Echocardiographic Parameters:

Patients with LV diastolic dysfunction had significantly smaller left atrial (LA) volume index (P = .03) and a trend toward a lower LV end-diastolic volume (P = .07) than subjects with normal diastolic function (Table 2). No correlation was found between diastolic LV wall thickness and mitral flow velocities. Peak E velocity was directly associated with the LV end-diastolic volume (R = 0.37, P = .004), LA volume index (R = 0.49, P < .001), and inversely associated with RV over LV volume ratio (R = 0.35, P = .007) and right atrial (RA) over LA volume ratio (R = 0.37, P = .005). Peak A velocity was directly associated with LA volume index (R = 0.29, P = .03) and inversely associated with RA over LA volume ratio (R = 0.31, P = .02). E/A ratio directly related to LV end-diastolic volume (R = 0.3, P = .02).

Eccentricity index at late systole, early diastole, and late diastole did not vary significantly in patients with or without LV diastolic dysfunction. In addition, the eccentricity indexes were not associated with peak E velocity, peak A velocity, or E/A ratio. Patients with normal or mild RV dysfunction had a trend to have higher peak E velocity than subjects with more severe degrees of dysfunction (70 ± 22 vs 56.1 ± 15 cm/s, P = .06). Patients with normal to mild RV dilation had higher peak E velocities than patients with more severe degrees of dilation (73 ± 19 vs 56 ± 15, P = .02).

Comparison of LV Diastolic Parameters With NYHA Functional Class and Use of PAH-Targeted Therapies

When patients were divided by NYHA functional class (II-IV), no statistical difference was noted in diastolic parameters assessed by transmitral flow, pulmonary vein flow, or tissue Doppler (data not shown). The E/A ratio was 0.97, 0.81, and 0.79 for NYHA functional class II, III, and IV, respectively (P = .32).

Individuals receiving PAH-targeted therapy covered more distance on 6-min walk test than patients on no therapy (375 m vs 283 m, P = .003), suggesting less severe disease. Hemodynamic and echocardiographic variables did not significantly differ between the groups. Patients on PAH-targeted therapy had higher E/A ratio than patients on no therapy (0.91 vs 0.75, P = .04); nevertheless peak E velocity did not vary between the groups (no treatment, 54.4 cm/s vs on treatment, 60.6 cm/s; P = .15).

Relationship of LV Diastolic Function With Hemodynamics Parameters

Patients with LV diastolic dysfunction had worse hemodynamic profile than patients with normal diastolic function (lower cardiac index and higher RA pressure, transpulmonary gradient, and PVR) (Table 1). Peak E velocity was inversely associated with PVR (R = 0.26, P = .05), RA pressure (R = 0.27, P = .04), and RA minus PAOP (R = 0.34, P = .009). Peak E velocity was directly associated with cardiac index (R = 0.35, P = .007) but not with PAOP, mean pulmonary artery pressure (PAP), or transpulmonary gradient. Peak A velocity was not significantly associated with any hemodynamic parameter. E/A ratio was inversely associated with RA pressure (R = 0.31, P = .02) and RA pressure minus PAOP (R = 0.38, P = .003) and directly associated with cardiac index (R = 0.32, P = .014). Septal e′, septal and lateral a′, e′/a′, and E/e′ were not associated with RA pressure, mean PAP, cardiac index, transpulmonary gradient, or PVR.

Outcomes

Mean survival (censored for lung transplantation, n = 5) was 54 (95% CI, 45.9-62.9) months. At 1, 2, 3, and 5 years the survival was 78%, 70%, 66%, and 60%, respectively. When adjusted by age and sex, we did not identify a difference in survival in patients with (any degree) or without LV diastolic dysfunction (P = .62). Transmitral flow E/A ratio showed a nonsignificant trend for predicting adjusted mortality (HR, 7.7; 95% CI, 0.92-50) per 0.1 decrease, P = .06). Peak E velocity was associated with adjusted mortality (HR, 1.5; 95% CI, 1.1-2 per 10 cm/s decrease; P = .015). When peak E velocity was dichotomized in ≥ 60 and < 60 cm/s, a peak E velocity < 60 cm/s was associated with adjusted mortality (HR, 2.7; 95% CI, 1.1-6.7; P = .028). Kaplan-Meier analysis with log-rank test is shown in Figure 3. Peak E velocity < 60 cm/s continued to be predictive of mortality after adjusting for RV function (normal, mild, moderate, moderate to severe, and severe impairment) (HR, 3.85; 95% CI, 1.3-11.3; P = .014).

Figure 3.

Kaplan-Meier survival analysis. Kaplan-Meier survival analysis using peak E wave velocity of < 60 and ≥ 60 cm/s. Log rank statistics showed P = .03. Cum = cumulative.

When adjusted for mean PAP, RA pressure, and cardiac index,¹³ E/A ratio was a significant predictor of mortality (P = .03). When adjusted by age, sex, 6-min walk distance, and cardiac output,¹¹ E/A ratio and peak E velocity were associated with mortality (P = .04 and P = .01, respectively). None of the variables measured by tissue Doppler predicted adjusted mortality.

Discussion

In the present study we demonstrated that the majority of patients with severe idiopathic or heritable PAH have grade I (impaired LV relaxation) diastolic dysfunction. Other grades of LV diastolic dysfunction were very rare and a few patients with less advanced PAH disease have normal diastolic function. Transmitral flow peak E velocity, which is a simple echocardiographic measure to obtain, was inversely associated with the ratio of right-to-left atrial and ventricular chambers, PVR, and RA pressure. More importantly, peak E velocity was associated with mortality (whether lung transplantation was included as end point) even when adjusted for several variables known to predict survival in patients with PAH.

Several authors have previously noted the high prevalence of LV diastolic dysfunction in patients with PAH.^1‐3,14 However, most of these studies included patients with chronic thromboembolic disease or a heterogenous group of patients with PAH. In our cohort, which consisted of carefully selected patients with hemodynamic criteria for PAH,⁹ we observed that nine out of 10 patients had impaired LV relaxation (grade I diastolic dysfunction) by echocardiographic criteria, with redistribution of the LV filling from early to late diastole. Only one patient had grade II (pseudonormal filling) LV diastolic dysfunction.

Impaired relaxation has been predominantly attributed to displacement of the interventricular septum toward the left ventricle, predominantly during early diastole, due to negative left-to-right transseptal pressure gradient,^15,16 leading to decrease in LV compliance.^{1,2,14,17‐19} Other causes include an increase in RV tension that leads to prolonged RV myocardial shortening with abnormal relaxation of the interventricular septum that impairs RV systole and LV diastole,^1,20 decrease in LV torsion,²¹ delay in early diastolic LV untwisting,²² reduction in the preload,^4,5,21 diastolic asynchrony in the anterior-lateral or apical regions,^23,24 and intrinsic disease of the left ventricle.^25‐27

In our study, as well as others,^2,14 septal displacement (measured as eccentricity index) was predominantly observed in systole and early diastole, possible decreasing LV compliance and explaining impaired LV relaxation. However, unlike other investigations,⁷ we did not observe a relationship between eccentricity indices and parameters of LV diastolic dysfunction. Interestingly, tissue Doppler analysis provided no data to suggest a myocardial abnormality.

In the present study, patients with normal diastolic function had less severe PAH, supported by a higher cardiac index and lower RA pressure and PVR. Moustapha et al² showed that impaired LV relaxation was more commonly observed in patients with estimated RV systolic pressure by echocardiography of ≥ 60 mm Hg. The authors also reported a negative correlation between estimated RV systolic pressure and E/A ratio.² Other studies have shown an inverse relationship between diastolic parameter and PAH severity.⁷ More importantly, this ratio was found to track with the hemodynamic improvements observed after pulmonary thromboendarterectomy or initiation of PAH-targeted therapy.^18,28,29

A variety of clinical, echocardiographic, and hemodynamic variables with prognostic value have been identified, but very limited information exists about the usefulness of diastolic function parameters to predict outcomes in patients with PAH. Galiè et al²⁹ found that patients with PAH treated with the endothelin receptor antagonist bosentan had improvement in mitral flow peak E velocity and E/A ratio. Ruan and Naguen³ described an increase in mitral E/A ratio, PV systolic filling fraction, septal e′, and lateral E/e′ ratio with PAH-targeted therapies. Eysmann et al⁸ found that mitral E/A ratio ≤ 1 correlated with poor survival in a small number of patients with relatively short follow-up. In our study, we found that E/A ratio was higher in patients receiving PAH-targeted therapy and that peak E velocity significantly predicted mortality when adjusted by age and sex and RV function. E/A ratio remained an independent predictor of mortality even when adjusted by variables suggested by the National Institutes of Health¹³ and Humbert et al.¹¹

Strengths of this study are (1) rigorous selection of study participants to form a homogenous group of patients with advanced PAH diagnosed by RHC, (2) meticulous review of echocardiographic studies, and (3) precise data on outcome. Limitations include: (1) Doppler echocardiography was not performed simultaneously with RHC but within 2 months; (2) few Tricuspid Annular Plane Systolic Excursion (TAPSE)³⁰ measurements were available for analysis; (3) the use of diuretics and/or vasodilators in a few patients could have temporally reduced the value of the PAOP, thus meeting the inclusion criteria; and (4) the study group consisted only of patients with advanced idiopathic or heritable PAH, thus, the results might not be generalizable to other pulmonary hypertension causes or milder disease. It is likely that a less severely affected cohort of patients with idiopathic or heritable PAH might have a lower prevalence of impaired relaxation.

In summary, impaired relaxation is expected in patients with advanced idiopathic and heritable PAH and should not motivate the diagnosis of left-sided heart disease (diastolic dysfunction). The observations noted in our study are clearly different from those observed in individuals with LV diastolic dysfunction, elevated PAOP, and enlarged left atrium, in whom pulmonary hypertension is likely a passive or reactive response to the elevated LV filling pressures. In patients with advanced idiopathic and heritable PAH, abnormal LV filling is more apt to be related to other mechanisms. The presence of grade II or III LV diastolic dysfunction is seldom seen in idiopathic and heritable PAH; thus, a diagnosis other than idiopathic PAH should be considered. The traditional belief that the LV diastolic dysfunction is associated with LA enlargement is not upheld by our observations in patients with idiopathic and heritable PAH, in whom a smaller LA is associated with impaired relaxation of the LV.

Conclusions

LV diastolic dysfunction of the impaired relaxation type is observed in the majority of patients with advanced idiopathic or heritable PAH. A decrease in transmitral flow peak E velocity is associated with worse hemodynamics and outcome.

Abbreviations

A

late diastolic

D

anterograde diastolic

E

early diastolic

HR

hazard ratio

LA

left atrial

LV

left ventricular

NYHA

New York Heart Association

PAH

pulmonary arterial hypertension

PAOP

pulmonary artery occlusion pressure

PAP

pulmonary artery pressure

PVR

pulmonary vascular resistance

RA

right atrial

RHC

right-sided heart catheterization

RV

right ventricular

S

systolic