Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension

Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension

Progress in Cardiovascular Diseases 55 (2012) 161 – 171 www.onlinepcd.com Computed tomography and cardiac magnetic resonance imaging in pulmonary hyp...

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Progress in Cardiovascular Diseases 55 (2012) 161 – 171 www.onlinepcd.com

Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension Gerin R. Stevens a,⁎, Nadia Fida a , Javier Sanz b b

a Montefiore-Einstein Center for Heart and Vascular Care, Albert Einstein College of Medicine, Bronx, NY The Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY

Abstract

Recent advances in imaging technology have allowed for better temporal and spatial resolution in cardiovascular imaging. The idea of a “one-stop shop” for anatomical and functional cardiopulmonary and vascular assessment in patients with pulmonary hypertension is very appealing since diagnostic, prognostic, and therapeutic response can be measured. Modalities, such as computed tomography (CT) and cardiac magnetic resonance (CMR), are better suited to image the right heart and associated structures in multiple projections allowing for threedimensional data sets and image reconstruction. This review will focus on the use of CT and CMR in the assessment of the right ventricle and pulmonary structures as they relate to pulmonary vascular disease. (Prog Cardiovasc Dis 2012;55:161-171) © 2012 Elsevier Inc. All rights reserved.

Keywords:

Hypertension; Pulmonary; Computed tomography; Magnetic resonance imaging; Right ventricle

Pulmonary circulation under normal physiologic conditions is a low-resistance, high-capacitance system allowing the right ventricle (RV) to maintain its stroke volume performing one sixth of the work of the left ventricle. 1 With increasing afterload and diminished vascular elasticity due to pulmonary hypertension (PH), the coupling of the RV–pulmonary circuit is disrupted leading to RV hypertrophy, eventual dilatation and impaired contractility. 2 Since RV failure is the most common cause of death in PH, 3 identifying early signs of right heart disease is paramount to treatment. While two-dimensional transthoracic echocardiography is the most readily available technology for initial screening and assessment of PH, it is limited by acoustic windows, the irregular geometry of the RV and the inability to quantify indexes of RV function. Modalities Statement of Conflict of Interest: see page 169. ⁎ Address reprint requests to Gerin R. Stevens, MD, PhD, Center for Advanced Cardiac Therapy, Montefiore Medical Center, Greene Medical Arts Pavilion, 3400 Bainbridge Avenue—7th Floor, Bronx, NY 104672490, USA. E-mail address: gstevens@montefiore.org (G.R. Stevens).

0033-0620/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pcad.2012.07.009

such as computed tomography (CT) and cardiac magnetic resonance (CMR), are better suited to image the right heart and associated structures in multiple projections allowing for three-dimensional data sets and image reconstruction. 4,5 Our discussion will focus on the use of CT and CMR in the assessment of the RV and pulmonary structures as they relate to pulmonary vascular disease.

Computed tomography CT of the chest is an important part of the evaluation for patients with PH. 6,7 The current generation of 64-slice (and higher) multidetector CT (MDCT) scanners allow for better spatial (versus CMR) and temporal (versus older scanners) resolution, shorter scanning times and breath-holds, and electrocardiogram (ECG)-gated acquisition for detailed cardiac structural analysis. 8 The use of intravenous iodinated contrast further permits assessment of ventricular volumes, ejection fraction, and vascular structures. The specific protocols for image acquisition are beyond

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Abbreviations and Acronyms AA = ascending aorta ce-MRA = contrast-enhanced magnetic resonance angiography CMR = cardiac magnetic resonance CT = computed tomography CTE = chronic thromboembolic DCE = delayed contrast enhancement

the scope of this review, but are well described elsewhere. 9,10 Thus, the systematic evaluation of cardiac, pulmonary, and vascular structures with image reconstruction makes MDCT a favorable singletest modality. Cardiovascular assessment

The use of retrospective ECG gating has ECG = electrocardiogram allowed for more accurate IVRT = isovolumic relaxation quantification of ventricutime lar volumes and ejection fraction that correlate well LV = left ventricle with CMR with minimal MDCT = multidetector intra- and inter-observer computed tomography variability. 11-13 Bi- and NPV = negative predictive multi-phasic contrast invalue jection protocols can be used to optimally visuaPA = pulmonary artery lize right and left heart PH = pulmonary hypertension structures, including the coronary arteries if PPV = positive predictive needed. 14,15 Although value retrospective ECG gating PVR = pulmonary vascular typically requires a higher resistance radiation dose, recent RHC = right heart technical developments catheterization allow for large reductions in radiation dose without RV = right ventricle compromising diagnostic RVEF = right ventricular accuracy. 16 ejection fraction There are multiple TR = tricuspid regurgitation studies using CT of the thorax to look for useful VMI = ventricular mass index measures to diagnose WHO = World Health PH. 4 Chan et al demonOrganization strated that several parameters were predictive of PH of varying etiologies independent of age, sex, pulmonary capillary wedge pressure, and body size (body surface area, thoracic diameter, and ascending aorta [AA] diameter). 17 Specifically, dilatation of the main pulmonary artery (PA) ≥29 mm had a sensitivity and specificity for the detection of PH of 77.4% and 89.6%, respectively. However correlation of main PA diameter with mean PA pressure by right heart catheterization (RHC) varies widely and may depend on the severity of disease. 17,18 The main PA to AA diameter ratio N1.0 was 86.8% sensitive and 79.2% specific for a diagnosis of PH. 17 Additionally, the PA/AA diameter ratio correlated strongly with RHC-

derived mean PA pressure (R 2 =0.45, pb0.001), which was enhanced when combined with echocardiographyderived RV systolic pressure (R 2 =0.55, pb0.001), giving a 96% specificity and 59% sensitivity to detect PH. 19 In patients with connective tissue disease, however, the PA/ AA diameter ratio showed only modest correlation with hemodynamic quantification of PH. 20 Others have found that CT-measured PA volumetric analysis normalized to body surface area correlates highly with mean PA pressure (r=0.89, pb0.05), although this was a small sample size of patients with sleep apnea. 21 In patients being evaluated for lung transplantation, the strongest correlation with mean PA pressure was seen by combining the cross-sectional areas of the main and left main PA indexed to body surface area (r=0.81, p=0.0001). 22 ECG-gated MDCT measures of RV and left ventricular (LV) wall thickness and dimensions have also been studied. RV hypertrophy suggests that exposure to chronic pressure overload and septal bowing into the LV during systole (pressure overload) or diastole (volume overload) are important markers of RV strain (Fig 1). 10 Regions of the RV demonstrated changes in structure and function in patients with PH, most notably at the infundibulum, with compensatory regional wall hypertrophy regardless of right-sided filling pressures. 23 Simon et al described that wall stress of the infundibulum is no different between compensated and decompensated patients with PH, but those with decompensated disease demonstrated increased infundibular end-systolic wall thickness. 23 Others have shown that increased RV free wall, RV/LV free wall ratio, and RV/LV lumen ratio are also predictive of PH. 17 The

Fig 1. Axial CT scan image of a patient with pulmonary hypertension. This is a four-chamber view in diastole. Note the massive RA, RV hypertrophy, RV enlargement, and septal bowing into the LV cavity causing reduced LV volume. RA, right atrium; RV, right ventricle; LV, left ventricle.

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strongest predictor of PH in this series was a lumen ratio ≥1.28 with a sensitivity of 85.7% and a specificity of 86.1% (OR =28.8). 17 Groves et al demonstrated that contrast reflux into the inferior vena cava and hepatic veins on first-pass contrastenhanced CT was a strong marker for tricuspid regurgitation (TR) having 90.4% sensitivity and 100% specificity when compared to echocardiography. 24 They further demonstrated excellent correlation between semiquantitative grading of TR with systolic PA pressure measured by RHC (r = 0.69, p b0.001). 24 Subsequently, others have shown that high-grade contrast reflux was significantly associated with a diagnosis of PH (OR 5.41, 2.95–9.94 95% CI, p b0.001) in a large retrospective cohort. 25 Findings of right heart disease may be dependent upon contrast injection rate, but have high negative predictive values (83%–100%) at both low and high injection rates. 26 Evaluation of specific PH types Pulmonary venous hypertension (World Health Organization [WHO] group 2) is the most common cause of PH

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and it results from chronic elevations in left-sided filling pressures of any etiology. 27 Therefore, imaging to assess for structural and valvular causes of elevated left atrial pressure is crucial to the evaluation of PH. Pulmonary venous hypertension is evident as interstitial edema with interlobular septal thickening, centrilobular nodular opacities and/or pleural effusions. 18 PH due to lung disease or hypoxia is classified as WHO group 3. 28 Parenchymal lung disease, pulmonary nodules, extracardiac shunts, and bronchial and vascular diameters can readily be seen by CT. 9 Chronic obstructive lung disease and interstitial lung disease represent the most common diagnoses in this group and are associated with a high risk of morbidity and mortality. 29 High-resolution CT is recommended to characterize the extent of parenchymal disease, but MDCT images reconstructed with 1-mm slice thicknesses are comparable. 8 Findings of chronic lung disease include emphysematous destruction, honeycombing, ground-glass attenuation, and pruning of peripheral arteries. 30 PH due to chronic thromboembolic (CTE) disease (WHO group 4) typically shows variable lung parenchymal attenuation (“mosaic pattern”) due to shunting of

Fig 2. Axial CT scan images of the chest following the administration of intravenous contrast. Upper panels (A, C, E) represent CT pulmonary angiogram windows. Lower panels (B, D, F) represent corresponding lung windows. Ground glass infiltrates are noted in both upper lobes (B). The main PA is enlarged (*) and areas of hypodensity and soft tissue thickening along right and left main PA, which extend into numerous segmental pulmonary branches, are consistent with chronic pulmonary embolism (arrows in C and E). A mosaic pattern is evident as areas of variable attenuation in the lung fields (D, F).

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blood flow away from regions of chronic arterial occlusion (Fig 2). 4,31 Filling defects seen by CT angiography may be complete or partial, eccentric, and even calcified, although this is rare. 32,33 Previous pulmonary infarction may also be evident. 34 Cardiovascular magnetic resonance CMR is the current gold standard for structural and functional assessment of the right heart and it allows for simultaneous evaluation of the lungs and pulmonary circulation. Studies show minimal intra- or inter-observer variability, providing an accurate and reproducible testing modality. 35 Cardiac evaluation Quantification of RV and LV volumes and ejection fraction does not only offer quantitative information on ventricular performance (Fig 3A) but, importantly, preliminary data suggest potential prognostic value in PH. In a study of 64 patients with idiopathic PH, van Wolferen et al reported that the presence of an RV enddiastolic volume index ≥ 84 ml/m 2 or an LV end-diastolic volume index ≤40 ml/m 2 was independently associated with decreased survival at 1 year. 36 More recently, RV ejection fraction was identified as an independent predictor of time to clinical worsening (defined as death, decompensated right heart failure, initiation of prostacyclin, or lung transplantation) in 58 patients with PH of different etiologies when controlling for exercise capacity, serum levels of brain natriuretic peptide, and RHC measurements. 37

The ratio of RV to LV mass or ventricular mass index (VMI) has been well correlated with mean PA pressure (r=0.81, CMR and RHC obtained within 2–14 days), with a significant difference between normal subjects and those with PH (0.5 ± 0.2 versus 0.9±0.2, pb0.01). 38 In this small group of 26 patients referred for evaluation of PH (7 without PH), VMI N0.6 conferred a sensitivity and specificity of 84% and 71%, respectively, for detecting PH. 38 In a group of 81 patients with connective tissue disease, VMI was strongly correlated with mean PA pressure (r = 0.69, p b0.001) and pulmonary vascular resistance (PVR; r=0.78, pb 0.001) with a sensitivity and specificity for PH diagnosis of 85% and 82%, respectively, at a VMI ≥ 0.45. 20 Survival was significantly reduced 3 years after CMR measured VMI N 0.75 (p= 0.04), with marked separation of the curves at less than 1 year. 20 Gan and coauthors analyzed RV diastolic dysfunction in patients with PH (n=25) versus healthy controls (n=11). 39 The majority of PH patients were New York Heart Association class III with severe PH and RV hypertrophy (RV mass index 40.7± 16.4 versus 19.5±4.2 g/m 2). Using phase-contrast velocity encoding, they measured the isovolumic relaxation time (IVRT; interval between pulmonic valve closure and tricuspid valve opening) normalized to R-R interval to account for differences in heart rate. They also measured early peak filling rate (E) and atrial-induced filling rate (A) normalized to RV enddiastolic volume to quantify the RV diastolic function (E/A ratio). IVRT was approximately 4.5 times longer in patients with PH (pb0.001) while E was reduced or absent and A was more pronounced in PH patients versus controls (E/A ratio 1.1±0.7 versus 5.3± 4.9, pb0.001, respectively).

Fig 3. CMR imaging in a patient with severe PH. (A) Short-axis cine view. The RV is dilated and hypertrophied with the ventricular myocardium outlined in dark red. The LV cavity is compressed with the endocardium outlined in bright red and the epicardium outlined in green. A pericardial effusion is noted by the asterisks. (B, C) Phase-contrast CMR image of the main PA trunk (outlined in red) showing both anatomy (B) and flow velocity (C). Ao, aorta; LV, left ventricle; PA, pulmonary artery; RV, right ventricle. Reproduced with permission from Stevens, et al. 53

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Furthermore, IVRT was directly related to RV mass index (r=0.56; p=0.005), PVR (r=0.74; pb0.0001), and NTproBNP level (r=0.70, pb0.001) and inversely to cardiac index (r = − 0.70; p b0.001) and RVEF (r = − 0.69; p b0.001). Repeat assessment 50 min after the acute administration of 50 mg oral sildenafil (i.e., decrease in afterload) revealed a significant reduction in IVRT (p b0.0001) and improvement in RVEF (p= 0.008). 39 Biventricular relaxation abnormalities have also been shown in patients with severe PH with mean tricuspid and mitral E/A ratios of 0.8±0.5 and 0.8±0.6, respectively (Fig 4). Interestingly, ventricular dyssynchrony was also suggested in this cohort by a time delay between mitral and tricuspid E and A waves. 40 Several groups have evaluated alterations in LV geometry as a consequence of RV pressure overload. Interventricular septal flattening or convex bowing into the LV has been extensively assessed. 40-43 An early

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study by Marcus et al compared 12 patients with PH and 14 healthy controls. 41 Abnormal septal bowing into the LV occurred during early diastole, indicative of a high RV to LV transseptal pressure gradient, with reduced LV versus RV filling. No relationships between septal curvature and invasive pressures or CMR-derived RV volumes or RVEF were seen, but this may be due to the small cohort size and/or timing between RHC and CMR studies (not provided by authors). In another study of 40 patients (median interval between CMR and RHC was 1 day), interventricular septal position was related to the degree of PH. Abnormal septal position in systole had 86% sensitivity, 91% specificity, 96% positive predictive value (PPV), and 71% negative predictive value (NPV) for PH detection, whereas abnormal septal position in diastole had 100% sensitivity and 100% NPV, but reduced specificity of 64% (PPV 88%), for a mean PA pressure ≥30 mm Hg. 40 Others went on to specifically quantify the degree of curvature of the interventricular septum, defined as the reciprocal of the radius. 43 Roeleveld and colleagues studied 39 patients referred for evaluation of PH who had CMR and RHC within the same week. 43 They found a strong correlation between systolic PA pressure and septal curvature (r=0.77, pb0.001) deriving an average systolic PA pressure value N67 mm Hg when leftward septal bowing was observed. Dellegrottaglie et al measured endsystolic LV interventricular septal and LV free wall curvature using CMR in 61 patients with known or suspected PH and compared to same-day RHC studies (Fig 5). 42 A septal/free wall curvature ratio of 0.67 yielded a sensitivity of 87% and a specificity of 100% for detection of RV systolic pressure N40 mm Hg with excellent intra(r=0.97) and inter-observer (r=0.95) reproducibility. Delayed contrast enhancement

Fig 4. Phase-contrast MR sequence applied perpendicular to the flow across mitral and tricuspid valves. The red and blue lines represent the trace of the mitral valve (MV) and tricuspid valve (TV) on magnitude image (B) and flow measurements to time (R-R interval) on image (A). Both ventricles have impaired relaxation (E/A b1), but the RV is worse than the LV. The time delay of 94 ms between the two E waves reveals asynchrony between the two ventricles. 40 RV, right ventricle; LV, left ventricle. Reproduced with permission from Alunni, et al. 40

The administration of an intravenous gadolinium-based contrast agent and imaging 10–20 min later allows for delayed contrast enhancement (DCE) analysis of the myocardium. While traditionally this has been related to myocardial fibrosis or infarction, the significance of DCE in patients with PH is not yet clear. Blyth et al demonstrated DCE at the RV septal insertion points and interventricular septum in 23 of 25 patients with PH of which 16 also demonstrated abnormal septal bowing. 44 Strong correlations were seen between DCE extent and RV mass index (r=0.68, pb0.001), RVEF (r=−0.76, pb0.001), and mean PA pressure (r=0.67, pb0.001). Subsequent studies showed the same pattern of DCE at RV insertion points as well as in the septum. McCann et al found a similar correlation between DCE and RVEF (r=−0.63, p=0.001), but they did not see a relationship with PA pressures. 45 In a multivariate analysis by Sanz et al, systolic PA pressure was an independent predictor of DCE in a single center cohort of 55 patients with known or

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Fig 5. Septal-to-free wall curvature calculation. Two points—junction 1 (J1) and junction 2 (J2)—are initially positioned at the junctions between the IVS and the free wall. Two additional points are then marked in the middle portion of the IVS (M1) and the free wall (M2). The radius of the CIVS (RIVS) is derived by applying the three-point circle method. J1, J2, and M2 are used similarly to derive the radius of the CFW (RFW). 42 IVS, interventricular septum, CIVS, curvature of the interventricular septum; CFW, curvature of the free wall. Reproduced with permission from Dellegrottaglie et al. 42

suspected PH of different etiologies (OR 1.23, 95% CI 1.08–1.40, p=0.002). 46 They also developed an “insertion enhancement score” of different patterns of DCE (Fig 6). 46 In a prospective 2-center study of 38 patients with suspected PH versus 10 age- and sex-matched healthy controls, DCE was identified in 31 of 32 patients with PH, 1 of 6 suspected, but absent PH, and none of the controls. 47 Interestingly, in this cohort, VMI and RV mass index were strongly correlated with DCE mass (r= 0.70 [pb0.001] and r=0.58 [pb0.001], respectively), and remained independent predictors of DCE mass after multiple linear regression analyses. In a recent study, Freed et al. 37 found that DCE of the RV insertion points in patients with PH of varied etiologies was a univariate predictor of poor outcome at 10.2± 6.3 months, but lost significance in a multivariate analysis. Together, these studies suggest that DCE relates to severity of disease as measured by the amount of RV remodeling and might be useful prognostically. Pulmonary artery evaluation Main PA imaging by phase-contrast velocity encoded CMR has allowed the quantification of PA flow velocities and areas, as well as the cardiac output (Fig 3B, C). A reduced stroke volume index (≤25 ml/m 2) has been

Fig 6. Representative examples of myocardial DCE involving the septal right ventricular insertion points and various values of insertion enhancement scores. The bottom row displays DCE images. The top row shows still frames from the cine loops in matching slice positions. The cine images were used to help differentiate true DCE from nearby nonmyocardial structures, such as cavity or epicardial fat. The left ventricle (LV) and right ventricle (RV) are labeled in panel A for reference. (A, B) Insertion enhancement score=1 (inferior insertion point; arrow). (C, D) Insertion enhancement score=2 (both insertion points; arrows). (E, F) Insertion enhancement score=3 (isolated inferior insertion point and anterior insertion point extending into anterior septum; arrows). (G, H) Insertion enhancement score=4 (both insertion points are involved, with extension into the anterior and inferior septum; arrows). 46 Reproduced with permission from Sanz et al. 46

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Table 1 Indexes of PA stiffness Parameter

Units

Formula

Definition

Pulsatility Compliance Capacitance Distensibility Elastic modulus Stiffness index β

% mm 2/mm Hg mm 3/mm Hg %/mm Hg mm Hg n/a

maxA−minA/minA [(maxA−minA)/PP]*100 sV/PP [(maxA−minA)/PP*minA]*100 PP*minA/(maxA−minA) ln(sPAP/dPAP)/[(maxA−minA)/minA]

Relative change in lumen area during one cardiac cycle Absolute change in lumen area for a given change in pressure Change in volume associated with a given change in pressure Relative change in lumen area for a given change in pressure Pressure change driving a relative increase in lumen area Slope of the function between distending arterial pressure and arterial distension

dPAP, diastolic pulmonary artery pressure; maxA, maximal area; mina: minimal area; PP, pulse pressure; sPAP, systolic pulmonary artery pressure. Reproduced with permission from Sanz et al. 52

associated with increased 1-year mortality in idiopathic PH. 36 Sanz et al. found excellent correlations between average PA velocity and mean PA pressure, systolic PA pressure and PVRI (r = −0.73, − 0.76, and −0.86, respectively; pb0.001). Strong correlations were also seen for measures of PA area and PA pressures and PVRI (r=0.56–0.73). There were significant differences be-

tween those with PH and those without PH and both average PA velocity (b11.7 cm/s; sensitivity of 92.9% and specificity of 82.4%) and minimum PA area (≥6.6 cm 2; sensitivity of 92.9% and specificity of 88.2%) were useful to detect PH. 48 The simultaneous assessment of both cardiac and pulmonary circulation in a single test offers advantages in

Fig 7. PA stiffness in different patient subgroups. Median values and interquartile ranges (error bars) for pulmonary artery pulsatility (A), compliance (B), capacitance (C), distensibility (D), elastic modulus (E), and stiffness index β (F) in the different patient subgroups. *pb0.05 in comparison with patients with no pulmonary hypertension (PH). †pb0.05 in comparison with patients with exercise-induced pulmonary hypertension (EIPH). PA=pulmonary artery. 52 Reproduced with permission from Sanz et al. 52

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the study of PH. The combined presence of an enlarged PA (increased minimum area) and reduced RVEF increases the accuracy of CMR to diagnose PH in comparison with either abnormality alone. 49 Moreover, Garcia-Alvarez et al developed, in 80 patients with known or suspected PH and same-day RHC, a noninvasive method for the quantification of pulmonary vascular resistance based on the measurement of RVEF and average PA velocity. 50 In a separate validation cohort (n= 20), CMR-derived values demonstrated a strong correlation (r = 0.84; p b0.001) and good agreement (mean bias −0.54±2.80 Wood units, limits of agreement −6.02/4.94) with invasive determinations. When combined with RHC data, PA and RV assessment also can be employed to study ventriculo-arterial coupling, demonstrating the expected increase in RV contractility in early PH stages with subsequent failure to match the progressive increases in afterload and severe uncoupling in advanced disease. 51 Measures of PA stiffness are abnormal in patients with PH and convey reduced functional capacity and increased risk of mortality. 52-57 Only pulsatility can be measured using CMR alone; the other indexes of stiffness require hemodynamic data (Table 1). In 94 patients with same-day RHC and CMR testing, Sanz et al found highly correlated curvilinear relationships between measures of PA stiffness and systolic PA pressure between those with PH at rest, exercise-induced PH (normal PA pressures at rest), and those with normal hemodynamics at rest and with exercise (Fig 7). 52 Furthermore, PA pulsatility (also referred to as elasticity) b 40% detected PH at rest with a sensitivity of 93% and a specificity of 63%. 52 We and others have shown that PA elasticity is independently related to 6-min walk distance, 53,54 and a value b20% predicted a 6-min walk distance b400 m

(sensitivity 82% and specificity 94%), which is a marker of poor outcome. 53,54,58 Furthermore, PA elasticity ≤16% in patients with PH was a strong predictor of cardiopulmonary mortality at 4 years (p=0.006). 57 Recently, we have demonstrated an independent relationship between PA stiffness and markers of RV adaptation to chronic pressure overload in 124 patients having CMR and RHC within 1 week. Increased PA stiffness indexes were independently associated with reduced RVEF, increased RV hypertrophy and dilatation, along with a higher workload (RV stroke work index) after multivariate adjustment including PVRI (steady afterload) or mean PA pressure (distending pressure). 55 This suggests that RV adaptation to chronic pressure overload is determined not only by resistance (steady afterload) but also by PA stiffness (pulsatile load). At the present time, the majority of PA stiffness indexes utilize a combination of invasive and noninvasive data, which appears to be the most useful method of understanding RV adaptation to chronic PH. Pulmonary angiography While MDCT angiography and digital subtraction angiography are useful for establishing a diagnosis of CTEPH, standard contrast-enhanced magnetic resonance angiography (ce-MRA) allows for accurate imaging of the pulmonary vasculature to the level of the segmental arteries. 59 In a retrospective study of 53 patients with CTE disease and 36 controls, ce-MRA had an overall sensitivity of 98% and a specificity of 94% for diagnosing CTE disease (PPV 96%, NPV 97%), however, it was best at detecting lobar and segmental disease. 60 Additional findings on ce-MRA include dilated bronchial arteries as a result of increased flow from obstruction in the

Table 2 Advantages and disadvantages of CT and CMR for the evaluation of PH Advantages

Disadvantages

Contraindications

MDCT

High temporal resolution High spatial resolution 3D data set Fast acquisition (10–15 s) Technically simple Good safety profile

Ionizing radiation Iodinated contrast Intermediate cost Relatively limited experience Immobility (scanner) Immobility (patient)

Allergy to iodine Pregnancy Renal insufficiency (relative) Arrhythmia (relative; for RV evaluation)

CMR

High temporal resolution High spatial resolution High contrast resolution 3D data set Good penetration Unlimited spatial orientation Large field of view Versatility Reproducibility Good safety profile

Magnetic field Technically complex High cost Relatively limited experience Immobility (magnet) Immobility (patient)

Avoid gadolinium if GFR ≤30 ml/min/1.73 m 2 Ferromagnetic devices Brain vascular clips Intraocular metal Infusion pumps Neurostimulators Pacemakers/AICD Clinical instability Claustrophobia (relative) Obesity (relative) Pregnancy (relative)

MDCT, multidetector computed tomography; CMR, cardiac magnetic resonance; 3D, 3-dimensional; GFR, glomerular filtration rate; AICD, automatic internal cardioverter–defibrillator.

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pulmonary arteries. In addition, the contrast first-pass through the pulmonary vasculature can be imaged with time-resolved ce-MRA at the expense of decreases in spatial resolution. This enables quantification of additional functional parameters such as the contrast transit time (prolonged in the presence of PH) 61 or the evaluation of lung perfusion with promising preliminary results. 62,63 59

Future directions Both CT and CMR have limitations making it difficult to use either modality ubiquitously (Table 2). The main limitations for CT include exposure to ionizing radiation and iodinated contrast. However, as discussed earlier, multiple dose reduction techniques are being implemented, further expanding the potential applications of CT. CMR is limited by current contraindications for ferromagnetic items (although novel magnetic resonancecompatible devices are also under different stages of development), claustrophobia, and a rare, but possible risk of nephrogenic systemic fibrosis after exposure to gadolinium-based contrast agents in patients with a glomerular filtration rate ≤30 ml/min/1.73 m 2. The possibility of performing invasive hemodynamic measurements simultaneously to the CMR evaluation with dedicated interventional equipment 64,65 also opens new possibilities for the in vivo evaluation of cardiovascular adaptation to PH. Moreover, preliminary reports indicate the feasibility of studying pulmonary ventilation with CMR, 66 potentially allowing for ventilation–perfusion evaluation in CTEPH without the need of radioisotopes. Conclusions Recent advances in imaging technology have allowed for better temporal and spatial resolution in cardiovascular imaging. The idea of a “one-stop shop” for anatomical and functional cardiopulmonary assessment in patients with PH is very appealing since diagnostic, prognostic, and therapeutic response can be measured. As other fields advance providing safer contrast agents and CMRcompatible devices, perhaps the current limitations will no longer apply. Statement of Conflict of Interest None of the authors have any conflicts of interest or relationships with industry to disclose. References 1. Apostolakis S, Konstantinides S. The right ventricle in health and disease: insights into physiology, pathophysiology and diagnostic management. Cardiology. 2012;121:263-273.

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