What is the role of CMR in the diagnosis and management of pulmonary hypertension?

Cardiovascular magnetic resonance (CMR) is a valuable tool to evaluate patients with pulmonary hypertension (PH). A comprehensive CMR study often includes cine imaging to assess left and right ventricular (RV) size and function; late gadolinium enhancement (LGE) imaging to characterize the myocardial tissue and identify pathological processes within it; magnetic resonance angiography to evaluate the anatomy of the aorta, pulmonary artery and systemic/ pulmonary veins; and velocity encoded imaging to quantify shunt fractions, cardiac output, and pulmonary artery stiffness. A comprehensive CMR study not only has the potential to differentiate between different categories of PH but also provide important insights into RV function and prognosis. Accurate categorization of PH is integral to the management of these patients given the fact that the treatment choice depends on the underlying etiology. It is increasingly recognized that RV failure secondary to chronically elevated afterload is often the cause of death in pulmonary hypertension. The complex shape of the right ventricle makes it very challenging to reproducibly quantify its size and ejection fraction using conventional imaging modalities such as echocardiography. These parameters can be accurately quantified using CMR because geometric assumptions about the shape of the ventricle are not required and the endocardium is clearly defined ¹. Several investigators have shown that RV ejection fraction and RV end-diastolic volume are predictors of prognosis in individuals with PH ^{2, 3}, as are parameters of left ventricular morphology and function ² and also those which are related to pulmonary artery stiffness ⁴.

Does the presence of LGE in the insertion point influence your clinical management of these patients?

There is growing evidence that may patients with PH have mid-myocardial wall LGE at the RV insertion points with or without associated enhancement of the inter-ventricular septum ^{3, 5, 6, 7}. In fact, the prevalence of LGE in patients with diagnosed PH seems to be relatively common, ranging between 69-98% of the population ^3,6,7,8. The presence of LGE at the insertion points has been shown to be sensitive (83%) and specific (94%) for the diagnosis of PH ⁹ and has been previously shown to be associated with time to clinical worsening ³. When the LGE of the insertion points is more extensive and extends into the septum, it may be a stronger predictor of mortality than just LGE of the insertion points ⁸. However, no studies have shown that the presence of LGE in PH is an independent predictor of mortality.

The mechanism of LGE in PH is poorly understood. At this time, there is probably enough evidence to conclude that the presence of LGE in PH is not typically secondary to scar or ischemia. Although chronic inducible RV ischemia has been documented in patients with PH, it is likely secondary to the high RV systolic pressures and increased myocardial wall stress leading to impaired coronary perfusion during systole. There is, however, no evidence of reversible myocardial ischemia within either the insertion points or interventricular septum on stress scintigraphy in patients with PH ¹⁰. The RV insertion points are regions which come to bear a considerable amount of mechanical stress. In PH, these stresses are magnified due to the remodeling of the right ventricle and the continued high inter-chamber pressures, and can be manifest as paradoxical septal displacement. In fact, the presence of LGE in the septum has been associated with paradoxical septal motion ⁶. One theory put forth for the explanation of LGE is that it accumulates in areas of increased mechanical stress which in PH would be the insertion points and septum. What is not clear in this hypothesis is where the gadolinium actually accumulates. We know that gadolinium can accumulate in areas of expanded extracellular space caused by fibrosis, protein infiltration, and collagen deposition. Bradlow ¹¹ examined the heart of a patient with idiopathic PH who had evidence of RV insertion point LGE on CMR. They discovered areas of myocardial disarray and increased collagen and fat deposition between fiber bundles, a finding that is histologically described as plexiform fibrosis. They proposed that the architecture of the RV insertion point and interventricular septum is exaggerated in PH, since neither myocardial disarray nor the presence of collagen in this area is abnormal per se, by RV remodeling and shear forces from the paradoxical motion of the interventricular septum leading to contrast pooling in this area. They further postulated that this explanation could account for the mid-myocardial distribution of LGE in patients with PH and why the quantity of LGE correlates with RV mass and volumes ^{6, 7}. Yet another explanation for the LGE (especially when it is isolated to the RV insertion points) is that it represents through-plane partial volume effect from contrast trapping in the acute angles of the right ventricular cavity adjacent to where it inserts into the left ventricle. Regardless of the underlying mechanism of RV insertion point LGE, it is clear that the finding occurs commonly in severe PH complicated by significant RV dilation and dysfunction.

For the time being, we are left with the impression that the presence of LGE is clinically important in PH but our understanding of why and when it is most important remains to be determined. Furthermore, it must still be determined how the presence of LGE in PH should influence clinical decision-making.

References

1. Addetia K, Bhave NM, Tabit CE, Gomberg-Maitland M, Freed BH, Dill KE, Lang RM, Mor-Avi V, Patel AR. Sample size and cost analysis for pulmonary arterial hypertension drug trials using various imaging modalities to assess right ventricular size and function end points. Circ Cardiovasc Imaging. 2014 Jan;7(1):115-24.
2. Van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007 May;28(10):1250-7.
3. Freed BH, Gomberg-Maitland M, Chandra S, Mor-Avi V, Rich S, Archer SL, Jamison EB Jr, Lang RM, Patel AR. Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension. J Cardiovasc Magn Reson. 2012 Feb 1;14:11.
4. Stevens GR, Garcia-Alvarez A, Sahni S, Garcia MJ, Fuster V, Sanz J. RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness. JACC Cardiovasc Imaging. 2012 Apr;5(4):378-87.
5. McCann GP, Beek AM, Vonk-Noordegraaf A, van Rossum AC. Delayed contrast-enhanced magnetic resonance imaging in pulmonary arterial hypertension. Circulation. 2005 Oct 18;112(16):e268.
6. Blyth KG, Groenning BA, Martin TN, Foster JE, Mark PB, Dargie HJ, Peacock AJ. Contrast enhanced-cardiovascular magnetic resonance imaging in patients with pulmonary hypertension. Eur Heart J. 2005 Oct;26(19):1993-9.
7. Sanz J, Dellegrottaglie S, Kariisa M, Sulica R, Poon M, O'Donnell TP, Mehta D, Fuster V, Rajagopalan S. Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension. Am J Cardiol. 2007 Aug 15;100(4):731-5.
8. Swift AJ, Rajaram S, Capaner D, Elliot C, Condliffe R, Wild JM, Kiely DG. LGE Patterns in pulmonary hypertension do not impact overall mortality. JACC Cardiovasc Imaging. 2014 Dec; 7(12): 1209-17.
9. Swift AJ, Rajaram S, Condliffe R, Capener D, Hurdman J, Elliot CA, Wild JM, Kiely DG. Diagnostic accuracy of cardiovascular magnetic resonance imaging of right ventricular morphology and function in the assessment of suspected pulmonary hypertension. J Cardiovasc Magn Reson.2012 Jun 21;14:40.
10. Rich JD, Ward RP. Right-ventricular function by nuclear cardiology. Curr Opin Cardiol. 2010 Sep;25(5):445-50.
11. Bradlow WM, Assomull R, Kilner PJ, Gibbs JS, Sheppard MN, Mohiaddin RH. Understanding late gadolinium enhancement in pulmonary hypertension. Circ Cardiovasc Imaging. 2010 Jul;3(4):501-3.

Keywords: Animals, Aorta, Blood Pressure, Cardiac Output, Cause of Death, Cicatrix, Collagen, Echocardiography, Endocardium, Extracellular Space, Gadolinium, Heart, Heart Ventricles, Humans, Hypertension, Pulmonary, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Myocardial Ischemia, Prevalence, Prognosis, Pulmonary Artery, Pulmonary Veins, Research Personnel, Stress, Mechanical, Systole, Ursidae, Ventricular Function, Right, Ventricular Septum

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