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Cardiac MRI as a diagnostic tool in pulmonary hypertension Khadija Alassas1, Patricia Mergo2, El-Sayed Ibrahim3, Charles Burger4, Robert Safford1, Pragnesh Parikh1 & Brian Shapiro*1
ABSTRACT: Pulmonary hypertension is characterized by alterations in the viscoelastic properties of the pulmonary arteries, leading to increased pulmonary arterial stiffness and elevated pressures. Early detection and accurate quantification of pulmonary hypertension are limitations to conventional noninvasive imaging and may have therapeutic implications. Cardiac MRI provides important information that can aid the clinician, particularly relating to morphologic right ventricular alterations and quantification of stiffness, as well as providing a novel prognostic framework. The pulmonary artery (PA) represents a large conduit vessel and, with its continuous expansion and recoil (e.g., pulsatility), serves to propel blood into the smaller pulmonary vasculature and dampens downstream pressure to a near steady flow at the level of the capillary [1–5]. The normal pulmonary vascular bed is characterized by low resistance and high capacitance [6]. Various disease states (Box 1), including those found in group 1 pulmonary arterial hypertension (PAH; e.g., idiopathic PAH, familial PAH, connective tissue diseases and portopulmonary hypertension, among others), may lead to pulmonary endothelial dysfunction, thickening and fibrosis of the intima and media, which may ultimately culminate in increased small-vessel resistance and worsened vascular damage [2,7,8]. This occurrence is coupled with the loss of the normal elastic fibers in the larger PA along with collagen replacement and stiffening [9]. The PA subsequently becomes dilated and rigid [4,10,11] and elevated pulmonary pressure ensues. Higher PA pressures are required to overcome the increased pulmonary vascular resistance (PVR; [mean PA pressure - PA occlusion pressure]/cardiac output) and worsened capacitance (e.g., oscillatory or pulsatile flow) [12,13]. It is believed that increased small-vessel PVR and loss of elasticity of the larger conduit PA contribute to the progression of pulmonary vascular disease [4,14]. A vicious cycle ensues when the increased PA stiffness and pressures cause a higher right ventricular (RV) workload, followed subsequently by RV dysfunction and failure. Changes to PA stiffness may also impact RV–PA coupling. As the pulsatility of the PA decreases (e.g., worsened compliance), the velocity of the pulse wave through the PAs increases (e.g., pulsewave velocity [PWV]), although the flow is reduced [15]. The resultant return of reflected waves earlier in the cardiac cycle adds to the increased RV afterload [16]. The abnormal loading, combined with the earlier return of reflected waves and increased PVR, are all detrimental to the ventricular–vascular coupling by unfavorably taxing the already ejecting RV [17]. Thus, changes to the proximal PA have a critical role in the pathophysiology of PAH. The changes to the PA stiffness are also reflected by PA pulse pressure and capacitance (stroke volume/pulse pressure), which are
KEYWORDS
• cardiac MRI • pulmonary artery • pulmonary hypertension • pulsatility • tagging
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA Department of Radiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA 3 Division of Nephrology & Hypertension, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA 4 Division of Pulmonary Medicine, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA *Author for correspondence: Tel.: +1 904 783 6351; [email protected] 1 2
10.2217/FCA.13.97 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(1), 117–130
part of
ISSN 1479-6678
117
Review Alassas, Mergo, Ibrahim et al. Box 1. Classification of pulmonary hypertension. Group 1 ●● Pulmonary arterial hypertension (e.g., idiopathic, familial, associated with connective tissue disease, toxins, HIV and portal hypertension) Group 2 ●● Pulmonary venous hypertension from left-sided disease Group 3 ●● Pulmonary disease (e.g., emphysema, interstitial lung disease and sleep disordered breathing) Group 4 ●● Chronic thromboembolic pulmonary hypertension Group 5 ●● Miscellaneous
markers for pulsatility and are reliably measured by right heart catheterization (RHC). Studies have consistently demonstrated that the large vessel proximal circulation contributes approximately 20% of total pulmonary vascular compliance [18–20]. Mahapatra et al. provided supportive data that low capacitance, defined as a value 3 Wood units and pulmonary capillary wedge pressure ≤15 mmHg [23,24]. At the point that PAH occurs,
Figure 1. Quantification of left and right ventricular size and function by cardiac MRI. (A) Diastolic and (B) systolic still-frame images from short-axis (base to apex) imaging from steady-state free precession sequence. Left ventricular endocardium (red) and epicardium (green) are traced along with right ventricular endocardium (yellow) in end diastole and end systole in order to calculate enddiastolic and end-systolic volume, as well as left ventricular mass. Ejection fraction is quantified by the formula: ([end-diastolic volume - end-systolic volume]/enddiastolic volume) × 100 and expressed as a percentage. Adapted with permission from [89].
118
Future Cardiol. (2014) 10(1)
significant vascular damage has already likely occurred. The pathobiology is complex and includes upregulation of vasoconstrictor and proliferative mediators (e.g., endothelin-1) and downregulation of vasodilators, such as nitric oxide and prostacyclins [23,25,26]. During the early stages of disease development, there is a potentially reversible role of PAH-specific therapies. Disease progression produces a severe pulmonary vasculopathy characterized by vascular obstruction by intraluminal cellular proliferation, vascular smooth muscle hypertrophy and in situ thrombosis. Left unabated, irreversible vascular remodeling occurs, resulting in severe PAH and RV dysfunction [27–30]. Initially, the RV wall thickens, but with continued high pulmonary pressures, dilatation and failure ultimately occur. Cardiac MRI (CMR) is well suited in the evaluation of PAH for a variety of reasons [31–33]. It serves as the reference standard for assessing RV morphology and function, particularly in cases where the RV is poorly visualized or characterized by echocardiography. Further advances have led to its use for a variety of additional reasons, which will be the focus of this review. Cardiovascular MRI ●●RV morphology & function
Cine imaging using steady-state free precession sequences is now considered the ‘gold standard’ to assess RV size and function [34–36]. CMR has many advantages over echocardiography in that there is no need for complex mathematical assumptions to determine RV size and function. Furthermore, CMR provides higher image quality that is less dependent on the operator’s skills and is not limited by the existence of an appropriate acoustic window, as in echocardiography [16,37]. A stack of short axis images are obtained from base to apex and the endocardial RV is traced in end systole and end diastole (Figure 1). This can also be performed using an axial data set, which may further enhance accuracy [38–41]. The RV end-systolic and end-diastolic volume (EDV) are then calculated. The RV stroke volume (difference between RV EDV and RV endsystolic volume) and ejection fraction (EF; stroke volume/EDV) can also be calculated [38]. Using these measurements, the RV size and function can be stratified as normal or abnormal and can be used for risk stratification [42,43]. At this point, semiquantitative stratification into normal, mildly, moderately or severely abnormal is unknown for CMR. If RV mass is desired, the
future science group
Cardiac MRI as a diagnostic tool in pulmonary hypertension
27 mm
Systole
SAX
Diastole
4Ch
RV epicardial border is also traced (interventricular septum [IVS] is excluded by convention), and this volume is multiplied by the myocardialspecific density (1.05 g/cm3). This measurement, particularly when referenced to left ventricular (LV) mass, is highly correlated to pulmonary pressures and is predictive of mortality [42,44–46]. Structural and functional RV alterations occur in the latter stages of PAH, and correlate with disease progression and prognosis. RV dilatation, which occurs with perpetually increased pulmonary pressures and tricuspid regurgitation, has been shown to be a poor marker of outcome when RV EDV exceeds 84 ml/m2 [35,42]. In addition, RV EF is highly predictive of poor prognosis. A recent study using CMR in 100 consecutive patients with PAH demonstrated that with every standard deviation drop in RV EF, there was a greater than twofold increased risk in mortality [47]. Given the reliability of volumetric or mass measurements, CMR assessment of RV size, function and mass have been used as end points in a number of pharmaceutical drug trials using sildenafil [48] and bosentan [49]. These studies provided evidence that CMR is not only a reliable and cost-effective end point for clinical studies, but that RV morphologic and functional parameters are highly predictive of outcome and therapeutic effectiveness; for example, pulmonary hypertension (PH) patients treated with bosentan for 12 months underwent repeat CMR. Only those patients who had improved
Review
Figure 2. D-shaped ventricular septum. With marked right ventricular pressure overload, the interventricular septum bows leftward and encroaches into the left ventricular cavity, at times causing impaired left ventricular filling. Still-frame images are shown in systole and diastole from a steady-state free precession cardiac MRI sequence. Also note the severe right ventricular enlargement. Arrow represents the right ventricle. 4Ch: Four-chamber long axis; SAX: Short axis at mid-ventricle.
PA 47 mm
Ao
Figure 3. Pulmonary artery enlargement. (A) Long- and (B) short-axis imaging of the main PA and ascending Ao using still-frame images (end diastole) from a steady-state free precession cardiac MRI sequence. In addition to the main PA being severely enlarged (47 mm), it is significantly larger when compared with the ascending Ao (27 mm). Ao: Aorta; PA: Pulmonary artery.
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www.futuremedicine.com
119
Review Alassas, Mergo, Ibrahim et al. PAH
Diastole
Systole
Normal
Figure 4. Pulmonary artery pulsatility. A short-axis image of the main pulmonary artery (PA; 1 cm distal to the pulmonary valve, indicated by dotted circle and arrow) using a phase-contrast cardiac MRI flow sequence in (A) a normal patient, as well as (B) someone with moderate PAH. Images are displayed at end systole (top) and end diastole (bottom). PA pulsatility is calculated as: ([PA systolic area - PA diastolic area]/PA diastolic area) × 100 and expressed as a percentage. Larger values represent better compliance and PA elasticity. In this case, the normal patient had a pulsatility calculated at 53 versus 18% for the PAH patient. PAH: Pulmonary arterial hypertension.
RV systolic function were found to gain clinical benefit from the drug [49]. The degree of RV pressure and/or volume overload may be readily apparent by determining the severity of LV septal bowing (or curvature). With right-sided pressure overload, the IVS is flattened or pushed leftward (e.g., D-shaped) [50], thus compromising LV diastolic filling and accentuating ventricular interaction (e.g., ventricular interdependence) [51]. The presence and severity of this septal configuration is strongly correlated to the severity of PAH (r = 0.77; p 29 mm or a ratio of PA:aorta cross-sectional areas >1.0 (Figure 3) [54].
future science group
Cardiac MRI as a diagnostic tool in pulmonary hypertension
future science group
Box 2. Pulmonary artery stiffness calculations. ●● Pulsatility: relative change in lumen area during cardiac cycle: ^ Max area - Min areah
Min area
# 100
●● Distensibility: relative change in lumen area for a change in pressure: ^ Max area - Min areah
# 100
^ Pulse pressure # Min areah ●● Compliance: absolute change in lumen area for a change in pressure: ^ Max area - Min areah
Pulse pressure
●● Capacitance: change in volume per change in pressure: Stroke volume Pulse pressure
●● Elastic modulus: pressure change for a relative change in lumen area: ^ Pulse pressure # Min areah ^ Max area - Min areah Max: Maximum; Min: Minimum.
not simultaneously) with similar study design as mentioned above [13]. These patients had highly variable diagnostic etiologies to explain their PH. Subjects were subdivided into the following subgroups: Systole
Diastole
276 249 222 195 Flow (m/s)
In addition to PA size, stiffness indices provide additional information that indicates diagnostic and therapeutic implications. Invasive [22] or noninvasive [21] calculation of capacitance (e.g., change in volume per change in pressure; stroke volume/pulse pressure) is a very strong predictor of death. For example, a value below 0.81 ml/mmHg predicted a high mortality rate versus a value >2 ml/mmHg, which predicted universal survival in patients with PAH [22]. The compliance of the PA is reflected by arterial distensibility or pulsatility, and may be accurately detected by CMR [57]. As an example, Figure 4 depicts the cross-sectional PA in systole and diastole in a normal subject compared with that of a patient with PAH. As observed in preliminary studies, patients with severe PAH have larger cross-sectional areas and markedly reduced pulsatility ([maximal PA area - minimal PA area]/minimal PA area) compared with normal controls [14]. While most PA stiffness indices (Box 2) require invasive hemodynamic catheterization, pulsatility of the PA can be assessed by CMR alone. CMR is well suited to evaluate pulsatility of the proximal PA, which is a surrogate for PA stiffness. Several studies have evaluated the utility and accuracy of PA pulsatility using phase-contrast CMR [14,57–60]. In a retrospective review, Sanz et al. evaluated 42 patients with at least moderate or severe PAH with CMR who also underwent RHC within several days and compared them with patients ultimately found to have no PH by RHC [55]. They evaluated a variety of measurements including PA crosssectional area, pulsatility, acceleration time (AT; time from beginning of upslope in systole to the peak systolic flow), and ejection time (ET; time from beginning to end of systole), which is shown in a normal PA profile in Figure 5. Compared with controls, patients with PAH had greater PA size (maximal PA area 11.8 ± 3.7 vs 7.1 ± 2.8 cm 2; p
Cardiac MRI as a diagnostic tool in pulmonary hypertension Khadija Alassas1, Patricia Mergo2, El-Sayed Ibrahim3, Charles Burger4, Robert Safford1, Pragnesh Parikh1 & Brian Shapiro*1
ABSTRACT: Pulmonary hypertension is characterized by alterations in the viscoelastic properties of the pulmonary arteries, leading to increased pulmonary arterial stiffness and elevated pressures. Early detection and accurate quantification of pulmonary hypertension are limitations to conventional noninvasive imaging and may have therapeutic implications. Cardiac MRI provides important information that can aid the clinician, particularly relating to morphologic right ventricular alterations and quantification of stiffness, as well as providing a novel prognostic framework. The pulmonary artery (PA) represents a large conduit vessel and, with its continuous expansion and recoil (e.g., pulsatility), serves to propel blood into the smaller pulmonary vasculature and dampens downstream pressure to a near steady flow at the level of the capillary [1–5]. The normal pulmonary vascular bed is characterized by low resistance and high capacitance [6]. Various disease states (Box 1), including those found in group 1 pulmonary arterial hypertension (PAH; e.g., idiopathic PAH, familial PAH, connective tissue diseases and portopulmonary hypertension, among others), may lead to pulmonary endothelial dysfunction, thickening and fibrosis of the intima and media, which may ultimately culminate in increased small-vessel resistance and worsened vascular damage [2,7,8]. This occurrence is coupled with the loss of the normal elastic fibers in the larger PA along with collagen replacement and stiffening [9]. The PA subsequently becomes dilated and rigid [4,10,11] and elevated pulmonary pressure ensues. Higher PA pressures are required to overcome the increased pulmonary vascular resistance (PVR; [mean PA pressure - PA occlusion pressure]/cardiac output) and worsened capacitance (e.g., oscillatory or pulsatile flow) [12,13]. It is believed that increased small-vessel PVR and loss of elasticity of the larger conduit PA contribute to the progression of pulmonary vascular disease [4,14]. A vicious cycle ensues when the increased PA stiffness and pressures cause a higher right ventricular (RV) workload, followed subsequently by RV dysfunction and failure. Changes to PA stiffness may also impact RV–PA coupling. As the pulsatility of the PA decreases (e.g., worsened compliance), the velocity of the pulse wave through the PAs increases (e.g., pulsewave velocity [PWV]), although the flow is reduced [15]. The resultant return of reflected waves earlier in the cardiac cycle adds to the increased RV afterload [16]. The abnormal loading, combined with the earlier return of reflected waves and increased PVR, are all detrimental to the ventricular–vascular coupling by unfavorably taxing the already ejecting RV [17]. Thus, changes to the proximal PA have a critical role in the pathophysiology of PAH. The changes to the PA stiffness are also reflected by PA pulse pressure and capacitance (stroke volume/pulse pressure), which are
KEYWORDS
• cardiac MRI • pulmonary artery • pulmonary hypertension • pulsatility • tagging
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA Department of Radiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA 3 Division of Nephrology & Hypertension, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA 4 Division of Pulmonary Medicine, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA *Author for correspondence: Tel.: +1 904 783 6351; [email protected] 1 2
10.2217/FCA.13.97 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(1), 117–130
part of
ISSN 1479-6678
117
Review Alassas, Mergo, Ibrahim et al. Box 1. Classification of pulmonary hypertension. Group 1 ●● Pulmonary arterial hypertension (e.g., idiopathic, familial, associated with connective tissue disease, toxins, HIV and portal hypertension) Group 2 ●● Pulmonary venous hypertension from left-sided disease Group 3 ●● Pulmonary disease (e.g., emphysema, interstitial lung disease and sleep disordered breathing) Group 4 ●● Chronic thromboembolic pulmonary hypertension Group 5 ●● Miscellaneous
markers for pulsatility and are reliably measured by right heart catheterization (RHC). Studies have consistently demonstrated that the large vessel proximal circulation contributes approximately 20% of total pulmonary vascular compliance [18–20]. Mahapatra et al. provided supportive data that low capacitance, defined as a value 3 Wood units and pulmonary capillary wedge pressure ≤15 mmHg [23,24]. At the point that PAH occurs,
Figure 1. Quantification of left and right ventricular size and function by cardiac MRI. (A) Diastolic and (B) systolic still-frame images from short-axis (base to apex) imaging from steady-state free precession sequence. Left ventricular endocardium (red) and epicardium (green) are traced along with right ventricular endocardium (yellow) in end diastole and end systole in order to calculate enddiastolic and end-systolic volume, as well as left ventricular mass. Ejection fraction is quantified by the formula: ([end-diastolic volume - end-systolic volume]/enddiastolic volume) × 100 and expressed as a percentage. Adapted with permission from [89].
118
Future Cardiol. (2014) 10(1)
significant vascular damage has already likely occurred. The pathobiology is complex and includes upregulation of vasoconstrictor and proliferative mediators (e.g., endothelin-1) and downregulation of vasodilators, such as nitric oxide and prostacyclins [23,25,26]. During the early stages of disease development, there is a potentially reversible role of PAH-specific therapies. Disease progression produces a severe pulmonary vasculopathy characterized by vascular obstruction by intraluminal cellular proliferation, vascular smooth muscle hypertrophy and in situ thrombosis. Left unabated, irreversible vascular remodeling occurs, resulting in severe PAH and RV dysfunction [27–30]. Initially, the RV wall thickens, but with continued high pulmonary pressures, dilatation and failure ultimately occur. Cardiac MRI (CMR) is well suited in the evaluation of PAH for a variety of reasons [31–33]. It serves as the reference standard for assessing RV morphology and function, particularly in cases where the RV is poorly visualized or characterized by echocardiography. Further advances have led to its use for a variety of additional reasons, which will be the focus of this review. Cardiovascular MRI ●●RV morphology & function
Cine imaging using steady-state free precession sequences is now considered the ‘gold standard’ to assess RV size and function [34–36]. CMR has many advantages over echocardiography in that there is no need for complex mathematical assumptions to determine RV size and function. Furthermore, CMR provides higher image quality that is less dependent on the operator’s skills and is not limited by the existence of an appropriate acoustic window, as in echocardiography [16,37]. A stack of short axis images are obtained from base to apex and the endocardial RV is traced in end systole and end diastole (Figure 1). This can also be performed using an axial data set, which may further enhance accuracy [38–41]. The RV end-systolic and end-diastolic volume (EDV) are then calculated. The RV stroke volume (difference between RV EDV and RV endsystolic volume) and ejection fraction (EF; stroke volume/EDV) can also be calculated [38]. Using these measurements, the RV size and function can be stratified as normal or abnormal and can be used for risk stratification [42,43]. At this point, semiquantitative stratification into normal, mildly, moderately or severely abnormal is unknown for CMR. If RV mass is desired, the
future science group
Cardiac MRI as a diagnostic tool in pulmonary hypertension
27 mm
Systole
SAX
Diastole
4Ch
RV epicardial border is also traced (interventricular septum [IVS] is excluded by convention), and this volume is multiplied by the myocardialspecific density (1.05 g/cm3). This measurement, particularly when referenced to left ventricular (LV) mass, is highly correlated to pulmonary pressures and is predictive of mortality [42,44–46]. Structural and functional RV alterations occur in the latter stages of PAH, and correlate with disease progression and prognosis. RV dilatation, which occurs with perpetually increased pulmonary pressures and tricuspid regurgitation, has been shown to be a poor marker of outcome when RV EDV exceeds 84 ml/m2 [35,42]. In addition, RV EF is highly predictive of poor prognosis. A recent study using CMR in 100 consecutive patients with PAH demonstrated that with every standard deviation drop in RV EF, there was a greater than twofold increased risk in mortality [47]. Given the reliability of volumetric or mass measurements, CMR assessment of RV size, function and mass have been used as end points in a number of pharmaceutical drug trials using sildenafil [48] and bosentan [49]. These studies provided evidence that CMR is not only a reliable and cost-effective end point for clinical studies, but that RV morphologic and functional parameters are highly predictive of outcome and therapeutic effectiveness; for example, pulmonary hypertension (PH) patients treated with bosentan for 12 months underwent repeat CMR. Only those patients who had improved
Review
Figure 2. D-shaped ventricular septum. With marked right ventricular pressure overload, the interventricular septum bows leftward and encroaches into the left ventricular cavity, at times causing impaired left ventricular filling. Still-frame images are shown in systole and diastole from a steady-state free precession cardiac MRI sequence. Also note the severe right ventricular enlargement. Arrow represents the right ventricle. 4Ch: Four-chamber long axis; SAX: Short axis at mid-ventricle.
PA 47 mm
Ao
Figure 3. Pulmonary artery enlargement. (A) Long- and (B) short-axis imaging of the main PA and ascending Ao using still-frame images (end diastole) from a steady-state free precession cardiac MRI sequence. In addition to the main PA being severely enlarged (47 mm), it is significantly larger when compared with the ascending Ao (27 mm). Ao: Aorta; PA: Pulmonary artery.
future science group
www.futuremedicine.com
119
Review Alassas, Mergo, Ibrahim et al. PAH
Diastole
Systole
Normal
Figure 4. Pulmonary artery pulsatility. A short-axis image of the main pulmonary artery (PA; 1 cm distal to the pulmonary valve, indicated by dotted circle and arrow) using a phase-contrast cardiac MRI flow sequence in (A) a normal patient, as well as (B) someone with moderate PAH. Images are displayed at end systole (top) and end diastole (bottom). PA pulsatility is calculated as: ([PA systolic area - PA diastolic area]/PA diastolic area) × 100 and expressed as a percentage. Larger values represent better compliance and PA elasticity. In this case, the normal patient had a pulsatility calculated at 53 versus 18% for the PAH patient. PAH: Pulmonary arterial hypertension.
RV systolic function were found to gain clinical benefit from the drug [49]. The degree of RV pressure and/or volume overload may be readily apparent by determining the severity of LV septal bowing (or curvature). With right-sided pressure overload, the IVS is flattened or pushed leftward (e.g., D-shaped) [50], thus compromising LV diastolic filling and accentuating ventricular interaction (e.g., ventricular interdependence) [51]. The presence and severity of this septal configuration is strongly correlated to the severity of PAH (r = 0.77; p 29 mm or a ratio of PA:aorta cross-sectional areas >1.0 (Figure 3) [54].
future science group
Cardiac MRI as a diagnostic tool in pulmonary hypertension
future science group
Box 2. Pulmonary artery stiffness calculations. ●● Pulsatility: relative change in lumen area during cardiac cycle: ^ Max area - Min areah
Min area
# 100
●● Distensibility: relative change in lumen area for a change in pressure: ^ Max area - Min areah
# 100
^ Pulse pressure # Min areah ●● Compliance: absolute change in lumen area for a change in pressure: ^ Max area - Min areah
Pulse pressure
●● Capacitance: change in volume per change in pressure: Stroke volume Pulse pressure
●● Elastic modulus: pressure change for a relative change in lumen area: ^ Pulse pressure # Min areah ^ Max area - Min areah Max: Maximum; Min: Minimum.
not simultaneously) with similar study design as mentioned above [13]. These patients had highly variable diagnostic etiologies to explain their PH. Subjects were subdivided into the following subgroups: Systole
Diastole
276 249 222 195 Flow (m/s)
In addition to PA size, stiffness indices provide additional information that indicates diagnostic and therapeutic implications. Invasive [22] or noninvasive [21] calculation of capacitance (e.g., change in volume per change in pressure; stroke volume/pulse pressure) is a very strong predictor of death. For example, a value below 0.81 ml/mmHg predicted a high mortality rate versus a value >2 ml/mmHg, which predicted universal survival in patients with PAH [22]. The compliance of the PA is reflected by arterial distensibility or pulsatility, and may be accurately detected by CMR [57]. As an example, Figure 4 depicts the cross-sectional PA in systole and diastole in a normal subject compared with that of a patient with PAH. As observed in preliminary studies, patients with severe PAH have larger cross-sectional areas and markedly reduced pulsatility ([maximal PA area - minimal PA area]/minimal PA area) compared with normal controls [14]. While most PA stiffness indices (Box 2) require invasive hemodynamic catheterization, pulsatility of the PA can be assessed by CMR alone. CMR is well suited to evaluate pulsatility of the proximal PA, which is a surrogate for PA stiffness. Several studies have evaluated the utility and accuracy of PA pulsatility using phase-contrast CMR [14,57–60]. In a retrospective review, Sanz et al. evaluated 42 patients with at least moderate or severe PAH with CMR who also underwent RHC within several days and compared them with patients ultimately found to have no PH by RHC [55]. They evaluated a variety of measurements including PA crosssectional area, pulsatility, acceleration time (AT; time from beginning of upslope in systole to the peak systolic flow), and ejection time (ET; time from beginning to end of systole), which is shown in a normal PA profile in Figure 5. Compared with controls, patients with PAH had greater PA size (maximal PA area 11.8 ± 3.7 vs 7.1 ± 2.8 cm 2; p
