Pulmonary hypertension: echocardiographic assessment

1 840 Pulmonary arterial hypertension (PAH)is defined as a mean Pulmonary artery pres-sure (PAP) of > 25 mmHg at rest, or > 30mmHg during exercise. However, the diag-nosis of PAH does not imply necessarilyright ventricular (RV) dysfunction, neithera clinically relevant condition. Echocardio-graphic assessment of PAH includes twodifferent issues: detection of elevated PAPvalues and functional evaluation of theright of Pulmonary hypertensionCorrelation between Doppler and cath-eter measurement of Pulmonary arterysystolic pressure. Noninvasive pulmonaryartery systolic pressure (PASP) is deter-mined by measuring the peak systolic pres-sure gradient of the right ventricle to theright atrium, according to the simplifiedBernoulli equation. Adding the mean rightatrial pressure (RAP) to the transtricuspidpressure gradient one can predict the RVsystolic pressure, which approximates prevalence of tricuspid regurgita-tion increases as PAP increases.

2 Berger tricuspid regurgitation in 80%of patients with PASP > 35 mmHg and inroughly 96% of those > 50 mmHg. Unfor-tunately, not all patients with detectable tri-cuspid regurgitation will have velocity pro-files suitable for measurement, rangingfrom 442 to 96%3, as a consequence of fac-tors that limit accurate visualization of ve-locity profile, such as disease severity, obe-sity and hyperinflated has been reported a variable correla-tion between transthoracic Dopplerechocardiography (TTE) and right heartcatheterization measurements of PASP, de-pending on the underlying disease, lungconditions, and time from TTE examina-tion to catheter measurement, ranging in patients with cardiac dis-ease1,4, to in patients with advancedlung disease2. Furthermore, in the latterpopulation, despite a significant correla-tion, a discordance > 10 mmHg betweenestimated and measured PASP was presentin 52% of patients, resulting in a poor pos-itive predictive value for the diagnosis ofPAH, with confirmation of PAH by rightheart catheterization in only one half ofthose patients in whom TTE suggested itspresence.

3 Finally, despite a good correla-tion between transthoracic echocardiogra-phy and right heart catheterization mea-surement of PASP, widely reported in sev-eral studies, the diagnostic performancecharacteristics of TTE should be consid-ered, with sensitivity and specificity valuesstrongly depending on the threshold valueused as a cut-off point, PAH severity, andKey words:Doppler;Echocardiography;Prognosis ; Pulmonary hypertension . 2005 CEPI Susanna SciomerDipartimento diScienze Cardiovascolarie RespiratorieUniversit degli Studi La Sapienza Policlinico Umberto IViale del Policlinico, 15500161 hypertension : echocardiographicassessmentSusanna Sciomer, Roberto Badagliacca, Francesco FedeleDepartment of Cardiovascular and Respiratory Sciences, La Sapienza University, Rome, ItalyPulmonary arterial hypertension (PAH) is a clinical condition characterized by elevated vascularresistance, associated with a poor prognosis and usually diagnosed in late stage.

4 Echocardiographicassessment of PAH includes early disease detection and functional heart evaluation, in order to in-troduce a more accurate surveillance at an early stage of the disease and to contribute to prognosticstratification of advanced disease. Detection involves Pulmonary artery systolic pressure (PASP) esti-mation. There is no clear consensus on defining normal distribution, but a PASP of 36 mmHg has beenwidely assumed as a cut-off value for mild PAH, requiring a more aggressive surveillance to detectfurther progression. Functional heart evaluation requires an accurate characterization of morpho-logic and hemodynamic changes, secondary to PAH development, which involves description of di-mensional parameters, ventricular interdependency, intracardiac flow patterns, and right ventricu-lar systolic performance. A valid assessment of these issues results in a useful evaluation of cardiacfunction, supporting clinical context in defining heart failure condition.

5 (Ital Heart J 2005; 6 (10): 840-845)conditions limiting the capability of detecting and mea-suring the velocity profile. Moreover, the positive andnegative predictive values of Doppler-estimated PASP depend not only on sensitivity and specificity, butmainly on differences in the prevalence of PAH in thepatient population. Overall, the attention should be fo-cused on the accuracy of Doppler-estimated PASP(possibly within 10 mmHg of right heart catheteriza-tion measurement), particularly in those patients withborderline values for PAH values and clinical implications. Right heartcatheterization is currently used as the gold standardfor firmly establish the hemodynamic status, althoughthere is no clear consensus as to what value of PAP isneeded for PAH diagnosis. Various threshold valueshave been proposed for PAH diagnosis, based on meanPAP or PASP, ranging from 18 mmHg5,6of mean PAPat rest to 20 mmHg7-9and 25 mmHg7,10, or a restingPASP > 30 mmHg6,7.

6 A mean PAP > 25 mmHg is themost often cut-off value used in recent PAH clinical tri-als. The Third World Symposium on PAH held inVenice in 2003 defined mild PAH as a resting Dopplerestimated PASP between 36 and 50 mmHg, assuming afixed 5 mmHg RAP11, but a value > 36 mmHg is notrarely reported in otherwise normal subjects. In a recentlarge scale TTE study of 15 596 healthy subjects, Mc-Quillan et a mean RV to right atrial gradi-ent of mmHg (range 5 to 47 mmHg), equiv-alent to a mean PASP of mmHg, assuming afixed 10 mmHg RAP. An increase in PASP was associ-ated with age, body mass index and male sex, support-ing the use of age- and body mass index-corrected val-ues in establishing the normal pressure range, since aPASP > 40 mmHg was found in 6% of healthy subjects> 50 years of age and in 5% of healthy subjects with abody mass index > 30 kg/m2. Possible explanations for mildly elevated PASP de-tected by TTE include the following physiological andtechnical considerations: an increase in Pulmonary vas-cular resistance (PVR) and decreased left ventricular(LV) compliance with aging; an increase in cardiac out-put, and therefore in Pulmonary pressure, associatedwith a higher body mass index, unless there is an ac-companying decrease in PVR; presence of a stable mildPAH, associated with underlying conditions such aspulmonary obstructive disease; discovery of an earlyprogressive PAH; overestimation of the Doppler-esti-mated PASP in a patient with true normal , in diagnosing PAH attention should be fo-cused on the clinical relevance of the patient s condi-tions, which represents the final objective of a diagnos-tic test.

7 Thus, the clinical suspicion of PAH should befurther investigated in a hierarchical diagnostic frame-work, comprehensive of RV function evaluation, andnot limited to a PASP Doppler determination. Functional evaluation of the right ventricleMorphologic evaluation. Morphologic descriptioncomprises right side chamber dimension evaluation andpericardial effusion description. To assess RV dimen-sions, important preliminary considerations are need-ed. The right ventricle is a structurally complex cavitythat changes greatly in geometry, orientation and spa-tial relationship with the left ventricle, when pressureand/or volume overload conditions occur. Thus, RV di-mension evaluation is both technically and conceptual-ly difficult to study in a quantitative manner. The mostdifficult approach to evaluate RV dimensions is repre-sented by volume determination, so there is poor corre-lation with RV volume as measured by angiography13,14or nuclear alternative approach to assess RV size consistson simple linear dimension measurements.

8 Unfortu-nately, several limitations affect this kind of evaluation,greatly related to particular RV shape, thereby affectingthe recorded diameters. As a result, these measure-ments should be useful to alert to the possibility of RVdilation and hence that the right ventricle needs to beevaluated in a different manner. A robust dimensionalmeasurement is mandatory in this context. It is recog-nized that hemodynamic conditions or clinical outcomeare the best endpoints available for defining severity ofmorphologic changes, so attention should be focusedon pathophysiologic considerations regarding ventricu-lar interdependency and hemodynamic impairment,reason whereby comparison of relative RV and LV sizemay be more useful. Thus, under PAH conditions the pat-tern of abnormal septum motion, more closely reflect-ing RV hemodynamics, affects LV geometry and can bewell expressed by an eccentricity index. In a cohort ofpatients with pressure or volume overload, Ryan et LV geometry defining the LV eccentricity in-dex (in parasternal short axis, LV index = D2/D1,where D1 is the diameter perpendicular to and bisect-ing the septum, and D2 is the diameter perpendicular toD1 and parallel to the septum) at end-diastole (LVd in-dex) and end-systole (LVs index).

9 This index has beensubsequently evaluated in clinical trials (Table I)17-20. Ina multicenter, randomized, unblinded study assessingthe effect of epoprostenol infusion in idiopathic PAHpatients, as compared with conventional therapy alone,Hinderliter et a baseline LVd index signifi-cantly related to baseline mean PAP, mean RAP, car-diac index (p < ), and exercise capacity (p < ).At the end of the 12-week treatment period, epo-prostenol therapy was associated with an improvementof both LVd and LVs indexes. Raymond et the associations between TTE findings and theclinical outcomes at the end of 1-year open-label peri-od of the same cohort of patients evaluated by Hinder-liter et al. The LVd index was identified by univariateanalysis as the only dimensional parameter significant-S Sciomer et al - Pulmonary hypertension : echocardiographic assessment841ly associated with the composite endpoint of death ortransplantation (p = ).

10 Gali et , further, ex-amined a subgroup of PAH patients enrolled in theBREATHE-1 study22, a multicenter, randomized,placebo-controlled trial. The objective of the study wasto evaluate the effect of 16-week bosentan therapy onTTE parameters. Bosentan therapy improved LV ec-centricity index in both diastole and systole, althoughno statistical significance was dimensional TTE parameter, easy to obtainand no time-consuming, is represented by the right atri-al area index. Right atrial enlargement denotes highRAP, as a consequence of elevated RV diastolic pres-sure and functional tricuspid regurgitation. The rightatrial area index has been identified as a strong predic-tor of adverse clinical outcome (Table I)17-20. In thestudy of Raymond et right atrial area index cor-related closely with RAP (r = , p < ) and wasidentified by multivariate analysis as an independentpredictor of the composite endpoint of death or trans-plantation (p = ).