Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit
2015; Lippincott Williams & Wilkins; Volume: 131; Issue: 10 Linguagem: Inglês
10.1161/circulationaha.114.006972
ISSN1524-4539
AutoresAnton Vonk Noordegraaf, François Haddad, Harm Jan Bogaard, Paul M. Hassoun,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoHomeCirculationVol. 131, No. 10Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBNoninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit Anton Vonk Noordegraaf, MD, PhD, Francois Haddad, MD, Harm J. Bogaard, MD, PhD and Paul M. Hassoun, MD Anton Vonk NoordegraafAnton Vonk Noordegraaf From Pulmonary Diseases (A.V.N., J.H.B.) and Physics and Medical Technology (A.V.N.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Division of Cardiovascular Medicine, Department of Medicine and Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA (F.H.); and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD (P.M.H.). , Francois HaddadFrancois Haddad From Pulmonary Diseases (A.V.N., J.H.B.) and Physics and Medical Technology (A.V.N.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Division of Cardiovascular Medicine, Department of Medicine and Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA (F.H.); and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD (P.M.H.). , Harm J. BogaardHarm J. Bogaard From Pulmonary Diseases (A.V.N., J.H.B.) and Physics and Medical Technology (A.V.N.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Division of Cardiovascular Medicine, Department of Medicine and Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA (F.H.); and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD (P.M.H.). and Paul M. HassounPaul M. Hassoun From Pulmonary Diseases (A.V.N., J.H.B.) and Physics and Medical Technology (A.V.N.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Division of Cardiovascular Medicine, Department of Medicine and Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA (F.H.); and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD (P.M.H.). Originally published10 Mar 2015https://doi.org/10.1161/CIRCULATIONAHA.114.006972Circulation. 2015;131:899–913Noninvasive imaging plays a key role in both the diagnosis and management of patients with pulmonary hypertension (PH). In recent years, there have been 2 major changes in perspective of imaging in PH. The first was the realization that imaging should focus on the evaluation of not only the pulmonary pressures but also the cardiopulmonary unit (Figure 1).1,2 The second was the emergence of multimodality imaging with a complementary role for echocardiography, magnetic resonance (MRI), computed tomography, and positron emission tomography (PET).2–7 These techniques not only help in the diagnosis of PH but also help identify factors that determine risk and prognosis and gauge therapeutic effects on right ventricular (RV) function in patients with pulmonary arterial hypertension (PAH). Although echocardiography is the mainstay in the assessment of hemodynamic and ventricular function in PH, MRI has emerged as the gold standard for quantifying volumes, function, and flow in the right side of the heart.2–7 PET is also offering novel insights into perfusion and blood flow, metabolism, neurohormonal activation, and other molecular processes in the right side of the heart but is used mainly for research at this time. Catheterization of the right side of the heart remains the gold standard for defining PH and assessing hemodynamics both at rest and with exercise. Invasive assessment of cardiac output (CO) may, however, have limited accuracy when assumed instead of measured oxygen consumption is used to derive CO (eg, using the Fick method) or when thermodilution is used in the setting of a low-CO state.8–10Download figureDownload PowerPointFigure 1. Overview of multimodality assessment of the cardiopulmonary unit. Emphasis in evaluation has shifted for assessment of pulmonary vascular disease alone to assessment of the cardiopulmonary unit. Echocardiography, magnetic resonance imaging, positron emission tomography, computed tomography angiography (not drawn), and catheterization of the right side of the heart are complementary in the assessment of the cardiopulmonary unit.This review covers RV imaging studies performed in the field of PH and discusses recent advances in echocardiography and cardiac MRI and PET imaging for detailed assessment of RV function. The review starts with a discussion of important physiological considerations and unmet needs in imaging research of the right side of the heart in PH. Computed tomography angiography, which plays an important role in evaluating chronic thromboembolic PH, is not discussed extensively in this review.Physiological ConsiderationsAlthough PH is a syndrome affecting the pulmonary vasculature, survival of patients with PH is closely related to RV function.1,11–14 The RV initially adapts to the increased afterload by increasing its wall thickness and contractility. These mechanisms are, however, often insufficient, and RV dysfunction eventually occurs. After the recent Fifth World Symposium on Pulmonary Hypertension, a definition of failure of the right side of the heart secondary to PH was adopted: "Right heart failure in the setting of PH can be defined as a complex clinical syndrome due to a suboptimal delivery of blood or elevated systemic venous pressure at rest or exercise as a consequence of elevated RV afterload."2 The proposed definition takes into account both the systolic and diastolic characteristics of function of the right side of the heart, as well as physiological demands such as exercise.In understanding RV adaptation to PH, one important metric that takes into account both contractility and afterload is ventriculo-arterial coupling. When in PH the increased pulmonary vascular afterload is matched by an adaptive increase in RV contractility, the RV is said to be coupled to the pulmonary arterial circulation.15 Altered ventriculo-arterial coupling occurs with increasing afterload, with some patients showing a better compensation or adaptability than others. Most of the metrics of RV function used in clinical practice today are a reflection of ventriculo-arterial coupling rather than contractility (load-independent measure).16 In fact, although contractility is increased in patients with PH, RV ejection fraction (RVEF), RV strain, or tricuspid plane annular excursion is often decreased.15,16 In addition, a recent study has also highlighted the importance of serial assessment of function of the right side of the heart in PAH, with patients with stable ventricular function showing good long-term outcomes.12 In comparisons of RV and left ventricular (LV) adaptation to pressure overload, one important distinction is the fact that the right side of the heart dilates early and that eccentric hypertrophy is, by far, the most common RV geometry. In the left side of the heart, both concentric hypertrophy and eccentric hypertrophy occur in response to systemic hypertension, and myocardial fibrosis is more common.17 Finally, although the focus is often placed on the RV, ongoing studies will determine whether right atrial function adds independent prognostic information in PH or failure of the right side of the heart.Unmet Needs in Noninvasive Imaging of the Cardiopulmonary Unit in PHAlthough imaging of the cardiopulmonary unit is a routine part of clinical evaluation, several unmet needs in the field remain (summarized in Table 1), which span from defining normal scaled reference values, to refining the definition of exercise-induced PH (EIPH), to developing integrative diagnostic and prognostic scores, to determining the best surrogate end point for research, and to developing novel physiological management strategies in PH. We anticipate that several of these questions will be answered within the next 5 to 10 years.Table 1. Selected Unmet Needs in the Assessment of the Right Side of the HeartFieldUnmet Research Need in ImagingReference valuesTo establish normal scaled values for chambers of the right side of the heart in echocardiography (adjusted for age, sex, level of activity)Physiological indexesTo establish the best index of contractility, to determine physiological bases of deformation indexes, to determine and standardize methods to assess myocardial deformation, to develop better indexes to assess the septal contribution of the function of the right side of the heart, and to better determine the role of atrial function in patients with right heart disease.ScreeningTo develop novel imaging scores for screening patients at risk of PH that may incorporate strain imaging parameters, to develop and validate scores to identify patients with increased PVR in disease of the left side of the heart, and to standardize exercise or stress testing for screening of PH screening purposesPathophysiologyTo determine the best imaging correlate(s) for fibrosis of the right side of the heart and to refine molecular imaging of the right heart. This would be useful to predict recovery and arrhythmia potential in disease of the right side of the heart. Multimodality imaging will help in the search of genetic and epigenic factors modulating RV adaptation in PH by identifying better-defined phenotypes.PrognosisTo validate simple and reproducible imaging-based prediction scores in PAH. This will provide a better perspective of the complementary value of novel circulating biomarkers and will be useful for randomization or propensity matching.Physiological based therapeutic managementTo determine how a physiology-based approach that incorporates metabolism, fibrosis, and ventriculo-arterial coupling can help tailor the management of acute and chronic failure of the right side of the heart. Specifically for surgical planning for end-stage PAH, determine whether strain imaging or markers of fibrosis can help identify which patients would benefit from heart-lung or double-lung transplantation.Three-dimensional imaging, including a 3-dimensional print model, may also guide patient-tailored interventional therapy.Surrogate end pointsTo determine whether function of the right side of the heart would be a better surrogate end point for phase 2 clinical trials than hemodynamic measuresPAH indicates pulmonary arterial hypertension; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; and RV, right ventricular.EchocardiographyOverview of Echocardiographic EvaluationTransthoracic echocardiography is the mainstay in the assessment patients with PH.18,19 Basic assessment of the cardiopulmonary unit by echocardiography involves assessment of cardiac chamber size; metrics of RV function such as tricuspid annular plane systolic excursion, fractional area change, and myocardial performance indexes; valvular regurgitation or function; pulmonary hemodynamics; and septal curvature, which can integrate metrics on ventricular interdependence.16,20,21Table 2 summarizes normative values for the measures of function of the right side of the heart, and Figure 2 illustrates some of these measures.16,22–31 As discussed in the following paragraphs, myocardial deformation imaging is also emerging as a useful modality for imaging the right side of the heart.Table 2. Selected Useful Functional Metrics for the Right Ventricular–Pulmonary Arterial Unit Obtained By EchocardiographyMetricReferencesCommentsSystolic phase indexes RVEF>50%< 35% often considered as moderate RV systolic dysfunction RVFAC>35%Less than 25% denotes moderate RV systolic dysfunction TAPSE>18 mmAbnormal value suggested in ASE guideline <16 mmRVMPI–pulsed tissue<0.55Nongeometric index of global systolic and diastolic function. Pseudonormalized values have been reported in patients with severe RV dysfunctionDeformation indexes Global long. strain<−25%Severe often if >−15% by speckle tracking. RV values need to be better defined for clinical practice; average normal value around −2/s (longitudinal) Peak systolic SR…Ill defined Peak diastolic SRIll definedVelocity metrics IVA…Depends on methodology; usually >2 m/s2 (considered less load dependent) S velocity>12 cm/sDiastolic metrics IVRT (TDI) corrected 55%sHVF VTI/(sHVF VTI+dHVF VTI) 8 mm HgPulmonary flow Pulmonary AT> 93 msHas been shown useful to screen for PHAdapted from several references.22,24–30 ASE indicates American Society of Echocardiography; AT, acceleration time; d, diastolic; HV, hepatic vein; HVF, hepatic vein flow; IVA, myocardial acceleration during isovolumic contraction; IVRT, isovolumic relaxation time; long, longitudinal; PH, pulmonary hypertension; RAP, right atrial pressure; RV, right ventricular; RVEF, right ventricular ejection fraction; RVFAC, right ventricular fractional area change; RVMPI, right ventricular myocardial performance index; s systolic; S velocity, tissue Doppler systolic velocity; SR, strain rate; TAPSE, tricuspid annular systolic excursion; TDI, tissue Doppler imaging; and VTI velocity-time integral.Download figureDownload PowerPointFigure 2. Basic echocardiographic measures of the cardiopulmonary unit. A, A 4-chamber view with measures of right ventricular (RV) end-diastolic and end-systolic areas (RVEDA and RVESA), as well as 2-dimensional (2D) tricuspid plane annular excursion (TAPSE) and right atrial (RA) area. B, A representative tracing of an M-mode–derived TAPSE. C, The important measure of the eccentricity (EI), a metric of septal curvature. D, Pulmonary flow Doppler signal and the presence of a pulmonary notch, which is reflective of pulmonary vascular disease. E, A tricuspid regurgitation (TR) signal and the measure of the maximal TR velocity at the modal frequency (used to derive the RV–RA pressure [RAP] gradient). F, A representative hepatic vein flow signal. AcT indicates acceleration time; AR, atrial reversal; D, diastole; eRAP, estimated RAP; LA, left atrium; LV, left ventricle; Pej, ejection period; PEP, pre-ejection period; RVMPI, right ventricular myocardial performance index; RVSP, right ventricular systolic pressure; S, systole; SR, systolic reversal; and TRdur, TR duration.Several pearls are important in evaluating the cardiopulmonary unit by echocardiography. The most important pearl in evaluating patients with PH is that the focus of the study should not be limited to evaluation of RV systolic pressures (RVSPs) but rather should include evaluation of both systolic and diastolic parameters of the right side of the heart.22 This is especially important because prognosis in PH is strongly related to function of the right side of the heart; moreover, pulmonary pressures may decrease when function of the right side of the heart deteriorates and can thus be deceiving in the estimation of severity.2 A second pearl is that not all cases of increased right-sided systolic pressures are caused by PH; for example, pulmonary stenosis or a double-chambered RV can cause elevation of RVSP in the absence of PH. A third and associated pearl is that the cause of an increased RVSP does not necessarily lie within the pulmonary circulation per se. Rather, in many patients, the increase in RVSP relates to increased pulmonary venous pressure. Findings such as LV hypertrophy and increased left atrial size represent common and practical clues that strongly sway the diagnosis of PH toward pulmonary venous hypertension. A forth pearl in the assessment of PH is that, in the presence of severe hypertrophy or severe PA enlargement, a congenital cause of PH should be excluded and strong consideration for MRI should be given. Finally, in the presence of hypoxemia, evaluation of a right-to-left shunt through a patent foramen ovale should always be considered in the differential.The following sections highlight recent controversies with regard to the noninvasive evaluation of pulmonary hemodynamics, the renewed interest in the use of exercise stress testing in the evaluation of PH, the use of scores to differentiate patients with PH and increased pulmonary vascular resistance (PVR) from patients with normal PVR, and the growing interest in the field of myocardial deformation imaging.Controversies in Screening Patients for PHThere has been controversy recently about whether echocardiography is a useful screening method or is accurate for the evaluation of PH.20,32–37 Although earlier studies demonstrated an excellent correlation between echocardiographic estimates and pulmonary pressures measured invasively, the strength of this correlation has been challenged in recent studies.20,32,33,35–37 For example, in the landmark clinical study by Yock and Popp,37 there was an excellent association between Doppler and catheterization-derived RVSP of the right side of the heart, with a correlation coefficient of 0.93 and a standard error of the estimate of 8 mm Hg. In more recent studies by Fisher et al,34 the strength of this correlation has been challenged. These investigators found lower correlation coefficients, and in >52% of the patients, there was a >10-mm Hg estimated difference between the 2 techniques (n=63). The key question in interpreting these studies, however, is whether the quality of the signals (eg, Doppler envelope) was always appropriate for analysis. In addition, screening for PH does not necessarily require accurate prediction of pulmonary pressures; one index could be adequate for screening but not allow accurate prediction of pulmonary pressures. This brings us to another important pearl for the evaluation of PH, which is the fact that adequate screening should take into account multiple parameters, for example, estimates of pressures, pulmonary acceleration time, the presence or absence of a pulmonary notch, or septal curvature (systolic D shape of the LV), or supporting evidence of PH such as RV enlargement, an increase in isovolumic relaxation time, and, if further validated, a decrease in strain or strain-rate index (Table 3).21,38–41 Moreover, in future studies, screening algorithms should be tested in patients with very mild pulmonary vascular disease to identify the most reliable early markers of pulmonary vascular disease and dysfunction of the right side of the heart.Table 3. Useful Parameters and Formulas for PH Screening by EchocardiographyParametersIndexesAssessment of pulmonary pressures by Doppler echocardiography (gradients)RVSP=4×TRV2+RAPMPAP=4×peak PRV2DPAP=4×PRVED2+RAPMPAP=2 mm Hg+0.59 RVSPEstimation using pulmonary flowMPAP=79−0.45(AT)Septal curvatureSystolic septal flattening reflects anatomic, hemodynamic, electric ventricular interdependenceSupporting evidenceRV enlargement, ↑ RV IVRT, ↑ RAPExercise-induced PHEmerging field but signal acquisition may be difficultInvestigationalOngoing studies on RV strain and strain-rate imagingAT indicates acceleration time; DPAP, diastolic pulmonary artery pressure; IVRT, isovolumic relaxation time; MPAP, mean pulmonary artery pressure; PH, pulmonary hypertension; PRV, pulmonary regurgitation velocity; PRVED, pulmonary regurgitation end-diastolic velocity; RAP, right atrial pressure; RV, right ventricular. RVSP, right ventricular systolic pressure; and TRV, tricuspid regurgitation velocity. Adapted from several references.18,19,28,42,43Differentiating Patients With Increased PVRAnother important interest in the evaluation of PH has been differentiating patients with normal from those with increased PVR. Two different approaches have been described in the literature. The first uses multiple approximation formulas that estimate pulmonary capillary wedge pressure and CO, and the other uses a score that focuses on key differentiating features.18,19 The first approach has the advantage of being simpler but is limited by the cumulative effects of several measuring errors. The second approach has the advantage of taking into account remodeling, hemodynamics, and epidemiological features but does not lead to quantification of PVR. In a recent study, Opotowsky et al44 developed a simple score based on left atrial size, the ratio of E to e′, and acceleration time or the presence of a pulmonary notch to discriminate patients with increased PVR. Of note, patients with left-sided heart failure without increased PVR are often much older with more comorbidities, as was shown by Thenappan et al.45 Validation of these scores by several research groups is currently underway.EIPH and Dynamic Testing in PHIn recent years, there have been several key studies on exercise testing in patients with PH. The renewed interest in exercise in PH is based on the premise that, although patients may have normal pulmonary pressures at rest, any increase in these pressures with exercise would be significantly higher than in healthy control subjects. Previously, EIPH was defined as a mean pulmonary arterial pressure (mPAP) >30 mm Hg with exercise; however, this definition was abandoned because it does not take into account changes in CO. On the basis of both invasive and noninvasive data, several investigators have now shown that the mPAP-CO relationship can be approximated by a linear relationship.46–49 This is unlike the systemic circulation in which several slopes are needed to describe the systemic pressure–CO relationship. In control subjects, the slope of the mPAP-CO relationship is usually 3 mm Hg·min·L−1 or an mPAP >30 mm Hg at a CO of 10 L/min (approximation because the slope does not perfectly intersect the zero origin) could be considered a potential criterion. Patients with higher-than-normal mPAP deserve a clinical evaluation to exclude the 2 major causes of EIPH: conditions of the left side of the heart (eg, dynamic mitral insufficiency) or increased PVR (eg, PAH or late closure of an atrial septal defect).There are several noteworthy studies in the literature; here, we chose to highlight three recent studies. Grünig et al46 showed in a large multicenter study that relatives of patients with PAH had a significantly higher pulmonary hypertensive response with exercise compared with control subjects and that this was higher in patients with BMPR2 mutations. In their study, PH was defined by a tricuspid regurgitation velocity jet >3.08 cm/s based on a 90% value of control subjects. This study was followed by the study by D'Alto et al,52 which showed that patients with New York Heart Association class I or II scleroderma without evidence of PH at rest had a greater incidence of EIPH, defined as the upper limits of control subjects (13%). Furthermore, they demonstrated that the slope of change in the relationship between PASP and cardiac index was significantly greater than normal. In the field of degenerative mitral regurgitation, Magne et al53 also recently showed that EIPH, defined as an RVSP >60 mm Hg with exercise, better discriminates patients who progress to symptomatic disease compared with rest RVSP. Although these results are very promising, some challenges remain as we move forward such as proving the feasibility and reproducibility of these tests in clinical practice and standardizing the pulmonary pressure–CO or pulmonary pressure–cardiac index slope criteria. In addition, demonstrating a potential value when added to a multiparameter screening approach would be an important step at this time.Further insight into RV function during (endurance) exercise was provided by a recent study by La Gerche et al.54 Whether it was due to EIPH or prolonged volume loading, the authors showed that, immediately after an endurance race, RV volumes increase and functional measures (ie, tricuspid plane annular excursion and RVEF) decrease, whereas LV volumes decrease and LV function remains unaltered. Reflective of a degree of cardiac injury during endurance exercise, B-type natriuretic peptide and troponin levels increased after a race and correlated with reductions in RVEF. Although RV function mostly recovered by 1 week after the race, evidence of localized fibrosis was demonstrated in the interventricular septum of 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF than those with normal cardiovascular magnetic resonance. The long-term clinical significance of these findings requires further study but may include the generation of arrhythmias.Myocardial Deformation Imaging of the RV: Holy Grail or Flavor du JourIn a recent editorial, Reichek55 noted that there have been several hundred publications on RV myocardial imaging over the past few years. Considering this impressive body of literature, an obvious question is, How does myocardial deformation imaging affect screening or prediction of outcome in patients with PH? As shown in Figure 3A, there are 4 essential components of myocardial imaging: velocities, displacement, strain (normalized deformation), and strain rate.42,57 Either spatial or temporal integration or derivation links the different concepts together. Methodologically, imaging can be accomplished with either tissue Doppler imaging or speckle tracking. Tissue Doppler imaging appears to be ideal for determining velocity profiles (Figure 3B), whereas speckle tracking imaging may be superior for strain and strain-rate imaging. In addition, global strain of the ventricle can be assessed by manually measuring 2-dimensional changes in entire wall segments. The measures that have captured more attention include global RV strain, peak systolic strain rate, and early diastolic strain rate (Figure 3C and 3D). Analysis of right strain or strain rate involves a comparison of peak values, timing of deformation, or comparative left values. Although very interesting conceptually, the technology used to derive these measures makes several assumptions; thus, quality control cannot be overemphasized in the interpretation of the results.58,59 Ongoing studies will determine the best methodology to use for strain measurements.Download figureDownload PowerPointFigure 3. Myocardial deformation and velocity imaging of the right side of the heart. A, The relationship between different concepts of myocardial deformation and velocities. The concepts are related to each other through spatial and temporal integration or derivation. Adapted from Gjesdal and Edvardsen.56 © 2011, Gjesdal and Edvardsen. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. B, A representative tissue Doppler velocity profile of the basal right ventricular (RV) wall with the different maximal velocities, ie, systolic (s), early diastolic (e), and late diastolic (a), as well as acceleration during the isovolumic contraction period (IVA) and time measures useful to measure the tissue Doppler–derived RV myocardial performance index (RVMPI). C, Superposed speckle tracking tracing on the right ventricle with numbers representing segmental peak strain. D, The strain-time curve of the different signals. Strain rate is not represented. Tissue Doppler appears to be superior for generation of velocity profiles, whereas speckle tracking appears to provide more reliable strain and strain-rate data (still a matter of debate, however). ApL indicates apex lateral; ApS, apex septum; BIS, basal interventricular septum; BL, basal lateral; GLS, global longitudinal strain; IVA, isovolumic acceleraton; IVC, isovolumic contraction; IVR, isovlumic relaxation time; MIS, mid interventricular septum; and ML, mid lateral.For screening purposes, Kittipovanonth et al40 have shown that, in patients with early PH (n=30), both RV peak strain and strain rate were significantly lower than in control subjects (n=40), whereas there were no significant differences in RV dimension, tricuspid plane annular excursion, RV fractional area change, or RV myocardial performance indexes. In an earlier study by Rajdev et al,41 RV free wall strain was significantly lower than in control subjects, whereas there were no difference in strain rate measures. Future studies are needed to determine the sequence of change in deformation imaging in patients with early pulmonary vascular disease.Fine et al60 recently published the largest study investigating the value of strain imaging in PH (n=406 patients with PH) for outcome prediction. They demonstrated that peak longitudinal free wall strain was independently associated with outcome, along with log N-terminal brain natriuretic peptide levels and World Health Organization functional class. Several key messages emerge from their study. First, outcome prediction in PAH can probably be simplified by the use of quantitative indexes of RV function. Second, strain measurement could offer a simpler metric in the echocardiographic evaluation of the RV. One of the merits of their study is the inclusion of all the usual 2-dimensional and time indexes of RV function. An important implication of this study is that this could help improve randomization between studies and potentially help tailor therapy in intermediate-risk groups. Table 4 places the study of Fine et al in context with recent outcome studies in PAH.3–5,60–63Table 4. Selected Outcome Studies Using Quantitative Echocardiographic Measures in Patients With PAHStudyYearn*Comment on the StudyYeo et al63199853First study to demonstrate the prognostic value of RVMPI
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