General description of procedure, equipment, technique

The prevalence of heart failure (HF) is increasing in the Western World. Current efforts aim to identify HF at its earliest and preclinical stages to begin treatment and prevent deterioration before the symptoms escalate.

Cardiac magnetic resonance (CMR) is likely to continue playing an important role in improving diagnostic evaluation and management of patients at risk for HF. CMR, which involves no radiation, is considered the gold standard technique for the measurements of left ventricular (LV) and right ventricular (RV) volumes, mass, and ejection fraction (EF).

Unlike echocardiography, CMR has the ability to obtain high-resolution tomographic imaging in arbitrary planes. CMR is particularly useful for the evaluation of LV function in patients with limited acoustic windows and poor-quality echocardiograms. In addition, using different pulse sequences with and without gadolinium contrast, CMR can characterize myocardial tissue, assess myocardial viability, and help diagnose specific cardiomyopathies.

The emergence of T₁ mapping further improves our knowledge and the clinical assessment of myocardial diffuse fibrosis. T₁ mapping will also help to improve therapeutic strategies and enable a more direct monitoring of their effect to improve clinical outcomes. In this chapter, the current evidence supporting the use of CMR in the diagnostic and risk stratification of patients with HF will be reviewed.

Indications and patient selection

CMR has recently been proposed as a comprehensive and unique diagnostic tool in the clinical arena for the diagnosis and management of patients with HF. Cardiac remodeling and functions has been used successfully as a surrogate end point for HF in clinical trials.

Contraindications

One major limitation is that the current implanted pacemakers or defibrillators are not compatible with magnetic resonance imaging (MRI), although, this limitation may be obviated by the development of newer devices. The risk of nephrogenic sclerosing fibrosis must also be considered when deciding whether to administer gadolinium-based contrast agents to patients with renal dysfunction.

Details of how the procedure is performed

Cine movie images for the evaluation of LV systolic function are most often obtained with steady state free precession (SSFP) imaging by displaying the same myocardial slice at different points within the cardiac cycle. CMR can provide clear delineation of the endocardial borders owing to its high spatial resolution (up to 1.5 mm × 1.5 mm in plane resolution), and CMR without contrast enhancement provides highly accurate and reproducible assessment of myocardial mass, chamber volumes, and LV and RV function without the need for geometric assumptions.

Late gadolinium enhancement (LGE) is probably the most widely used and investigated CMR technique for determining etiology, as well as a prognosis in the setting of cardiomyopathy. Enhanced (white) regions indicate areas of gadolinium accumulation and suggest the presence of inflammation, fibrosis, or scar tissue when specific T1-weighted pulse sequences are performed.

Phase contrast velocity imaging has been shown to measure mitral inflow and pulmonary venous velocities accurately with validating against Doppler echocardiography. CMR phase contrast imaging also assesses blood flow volume throughout the cardiac cycle and measures mitral valve early diastolic flow (E) and atrial contraction flow (A).

CMR tagging is a technique by which a radiofrequency pulse is applied to the LV myocardium in the form of grid lines. The tagged grid deforms as the saturated myocardium moves throughout the cardiac cycle, allowing regional strain to be visualized and quantified.

Interpretation of results

Assessment of LV systolic function

CMR is currently considered the gold standard technique for the measurements of LV and RV volumes, mass, and ejection fraction. These features lead to very high intrareader and interreader reproducibility when assessing LV volumes and LV ejection fraction (LVEF), with coefficients of variation less than 5%.

Cine loop can measure several parameters, including LVEF, systolic wall thickness, stroke volume, and cardiac index, as an expression of systolic function of the heart. LVEF is the most widely accepted expression of global LV function and the most robust determinant of adverse outcomes in the setting of either ischemic or nonischemic cardiomyopathy.

LVEF is especially important in clinical settings where a precise cut-off value for a therapy is required, such as in patients considered for implantable cardiac defibrillator therapy. LVEF is also used as a surrogate end point for reserve remolding in biventricular pacing and in drug trials with regard to systolic HF.

Myofiber orientation of myofibers changes smoothly across the LV wall; from a left-handed helix in the subepicardium and circumferential orientation in the midwall, to a right-handed helix in the subendocardium. The LV systolic deformation is a complex 3-dimensional motion, characterized by radial thickening, circumferential and longitudinal shortening, and a wringing motion with counter directional rotation of the basal and apical LV in order to eject blood from the ventricle.

Among these fibers, circumferential fibers are predominant and circumferential shortening is a main determinant of LV stroke volume. Global measures are insensitive to reductions in regional performance, where even a normal LVEF can obscure significant underlying regional dysfunction. Thus, measures of regional function, such as quantification of myocardial strain and torsion, have emerged as more accurate tools for defining degrees of myocardial disease.

Systolic wall thickening (SWT), a radial thickening, is calculated by end-systolic wall thickness (ESWT) and end-diastolic wall thickness (EDWT): %SWT = (ESWT－EDWT)/EDWT×100%. The assessment of SWT is a validated technique for the evaluation of regional LV myocardial function.

Assessment of LV diastolic function

Epidemiology studies report that 40% to 50% of patients with HF have preserved EF. HF with preserved EF is generally found in the elderly aged >65 years old, particularly in the elderly >80 years old, and they are not predominantly but prominently female (50% to 70%).

Care must be taken to specific cardiac remodeling patterns and abnormalities, such as hypertrophic cardiomyopathy (HCM), hypertensive heart disease, and infiltrative cardiomyopathy (e.g., amyloid). Echocardiography remains the standard modality for assessment of diastolic function, although, novel CMR technique can also provide useful information on myocardial performance in diastole.

E normalized to in vivo mitral septal tissue velocity (Ea) measured using CMR phase contrast imaging provides a strong correlation and good agreement with mean pulmonary capillary wedge pressure measured by invasive cardiac catheterization (correlation coefficient = 0.8). Nonetheless, CMR may be an option for evaluation of diastolic function in patients with adequate echo imaging.

Assessment of LV remodeling

As heart disease progresses into HF, the heart remodels and cardiac function deteriorates before symptoms become clinically evident. Limitation of LVEF is not a direct measure of myocardial deformation, and LVEF assesses only changes in cavity volumes during systole and diastole.

Compared with the traditional measures, direct evaluation of cardiac structure and mechanical behavior might provide further insight into cardiac structure and function, particularly in patients with preserved EF. It is well recognized the association between LV mass and adverse cardiovascular outcomes and even sudden death.

CMR is currently considered to be the clinical gold standard for assessment of LV mass owing to its high reproducibility and close correlation with autopsy results. The reproducibility and accuracy of volumetric measurements using CMR is superior to those of echocardiography.

The LV remodeling pattern is classified into the following four mutually exclusive groups on the basis of LV mass and the mass-cavity ratio as a mass-to-volume (M/V) ratio (Figure 1): concentric hypertrophy (increased mass and increased relative wall thickness), eccentric hypertrophy (increased mass and normal relative wall thickness), concentric remodeling (normal mass and increased relative wall thickness), and normal geometry (normal mass and normal relative wall thickness).

Performance characteristics of the procedure (applies only to diagnostic procedures)

Determining etiology cases of HF using CMR

In HF patients with decreased LV systolic function, accurate differentiation between ischemic and nonischemic HF has important therapeutic and prognostic implications. Cardiac catheterization with coronary angiography is the gold standard for determining the presence and severity of coronary artery disease.

Patients with ischemic cardiomyopathy often have regional myocardial thinning or regional wall motion abnormality corresponding to coronary artery territories. Diffuse hypokinesis tends to be more global with nonischemic cardiomyopathies.

Occasionally, this differentiation is not precise. A unique property of CMR is its ability to provide detailed myocardial tissue characterization in a way that helps clinicians determine the etiology of a given cardiomyopathy.

In addition to the detection of ischemic cardiomyopathy, the pattern of delayed enhancement may differ in different causes of nonischemic cardiomyopathy. When hyperenhancement is present, ischemic disease can be found in the endocardium.

Isolated midwall or epicardial hyperenhancement strongly suggests a “nonischemic” etiology. In ischemic cardiomyopathy, the transmural extent of LGE is predictive of not only myocardial wall recovery after revascularization but also adverse LV remodeling.

Myocardial infarct size is an independent prognostic factor for HF, arrhythmic events, and cardiac mortality. The typical pattern of hyperenhancement is shown in Figure 2.

In ischemic cardiomyopathy, LGE in anatomic regions corresponds to coronary artery territories. Nonischemic dilated cardiomyopathy generally has a typical midwall linear LGE pattern, which is commonly located in the ventricular septum.

Patients with HCM reveal a patchy distribution involving the midwall hypertrophic regions. Cardiac amyloidosis frequently shows diffuse global subendocardial LGE. Myocarditis typically affects the epicardial quartile of the ventricular wall. Sarcoid is found isolated in the mid myocardial wall or epicardium, and Anderson-Fabry disease in the basal inferolateral wall.

Outcomes (applies only to therapeutic procedures)

SWT quantitatively measured by CMR in patients with normal LVEF is independently associated with subsequent development of HF and adverse cardiovascular events. An increase in LV mass is the most important finding of cardiac remodeling, and confers a substantially increased risk for incident HF (Figure 3)

A: Cumuloative event rates for coronary heart disease patients by quartiles of left ventricular mass/voume; B: cumulative event rates for heart failure events by interveals of LV mass (body size-adjusted)

The M/V ratio has also been demonstrated to be a strong predictor of incident cardiovascular events in the population-based studies. The high M/V ratio is also related to a decline in LV systolic function expressed as a circumferential myocardial strain and assessed circumferential myocardial strain assessed by CMR. Therefore, cardiac hypertrophy is a major predictor of HF, and HF therapy should target not only systolic HF but also diastole HF.

LGE patterns obtained by CMR can provide detailed diagnostic information on myocardial viability. The presence of CMR LGE identifies a subset of nonischemic cardiomyopathy patients with an 8-fold higher risk of an index composite outcome of HF hospitalization, appropriate ICD firings, and cardiac death compared with those without LGE (Figure 4).

Late gadolinium enhancement and Kaplan-Meiler event-free survival curve

In nonischemic dilated cardiomyopathy, the presence of myocardial LGE is associated with a 3-fold increase in hospitalization because of HF and cardiac death, and a 5-fold increase in sudden cardiac　death and ventricular arrhythmias. In HCM, LGE is strongly associated with arrhythmia and remains significantly associated with subsequent sudden cardiac death.

Moreover, LGE is significantly and independently associated with adverse cardiac events in patients with cardiac amyloidosis and those who receive aortic valve replacement. Recent studies report the additional prognostic value of LGE in patients with hypertensive and those with diabetes mellitus who are free from any cardiac symptoms and those who have preserved EF.

Another merit of LGE is quantification of heterogeneous tissue in fibrosis at the peripheral area (gray zone). The gray zone has been arbitrarily defined on late enhancement CMR images as myocardium with intermediate signal intensity enhancement between normal and scarred/fibrotic myocardium.

This area is strongly correlated with ventricular arrhythmia inducibility and postmyocardial infarction mortality in ischemic cardiomyopathy. The use of this “gray zone” in ischemic cardiomyopathy and other types of cardiomyopathies further expands the assessment and the quantification of hyperenhanced myocardium for purposes that go beyond pure quantification of myocardial fibrosis.

These identifications may significantly improve risk stratification strategies in a high-risk population. Accordingly, CMR with late postgadolinium myocardial enhancement sequences will provide a more accurate and precise analysis in myocardial tissue composition.

Alternative and/or additional procedures to consider

Tagged CMR has been accepted as a reference method to measure regional myocardial function and the LV wringing motion expressed as circumferential strain (Ecc) and torsion. In a large population, concentric remodeling is associated with a decline in LV systolic function evaluated by midwall Ecc.

It is also found in the association between carotid intima-media thickness and decreased myocardial systolic (Ecc) and diastolic strains measured by CMR tissue tagging, which considers that atherosclerosis-related alterations in LV function occur much earlier than previously anticipated.

During ejection, the subendocardial and subepicardial layers shorten simultaneously, resulting in rotation of the apex and base in the counterclockwise and clockwise directions, respectively, when viewed from the apex. Systolic torsion may limit myocardial energy consumption and minimize transmural gradients of fiber stress and oxygen demand, resulting in more efficient LV contraction.

During isovolumic relaxation, torsional unfolding (untwisting) occurs and contributes to diastolic suction and reduction of LV pressure. Several studies demonstrate enhanced LV torsion with preserved EF in patients with hypertension, diabetes, aortic stenosis, LV hypertrophic cardiomyopathy, and also in elderly volunteers.

Reduced subendocardial function would result in less opposition to the dominant epicardium, and finally result in elevated rotation. Since the changes in LV torsion occur before irreversible tissue damage, it may be considered to be an early indicator of systolic dysfunction. Direct evaluation of strain and torsion thus provides further insight into cardiac structure and function, and mechanical behavior over and above traditional measures of functional assessment.

Measuring myocardial fibrosis with T1 mapping

LGE relies on the difference in signal intensity between the fibrotic and normal myocardium, and it is used as a reference. Myocardial fibrosis is often diffuse, particularly in nonischemic cardiomyopathy. Thus, fibrosis may not be evident without regionality.

More recently, the modified Look-Locker inversion recovery (MOLLI) sequence has been developed and enabled us to perform myocardial T₁ mapping with high spatial resolution by using CMR scanners. T1 mapping technique directly measures the underlying T1 relaxation times of the different areas of the myocardium.

This method allows signal quantification on a standardized scale, which is closely correlated to the extracellular myocardial volume content and quantified diffuse myocardial fibrosis. Therefore, the composition of each myocardial slice can be analyzed as a T1 distribution histogram, which gives more accurate description of the myocardial tissue composition (Figure 5).

Comparison of late gadolinium enhanced studies with corresponding T, maps and T, values distribution histograms in different cardiomyopathies

T1 distribution might be useful for identifying specific myocardial patterns, such as diffuse myocardial fibrosis, specific myopathies, and the gray zone. This would help us detect the greater number of patients with lower cardiovascular risk who have subclinical myocardial changes before the onset of diastolic and systolic dysfunction.

No prospective studies with a larger population have been conducted, although the results of T1 mapping might provide appropriate therapeutic strategies, which will lead to decreased the morbidity in patients with HF.

Complications and their management

Nephrogenic systemic fibrosis is progressive and can be associated with a fatal outcome. There is still no definitive cure. Gadolinium contrast medium should be avoided in patients with reduced kidney function or kidney failure (either chronic or acute), and hepatorenal syndrome (a condition involving reduced function of liver and kidneys). Updated safety information for medical devices can be found at http://www.scmr.org/Education/Documents-and-guidelines.html

What’s the evidence?

Rathi, VK, Doyle, M, Yamrozik, J. “Routine evaluation of left ventricular diastolic function by cardiovascular magnetic resonance: a practical approach”. J Cardiovasc Magn Reson. vol. 10. 2008. pp. 36(This study highlights certain key points for evaluation of mitral valve flow to assess diastolic function using phase contrast velocity imaging, and E:A ratio and deceleration time calculated from CMR and Doppler echocardiography showed excellent agreement.)

Paelinck, BP, deRoos, A, Bax, JJ. “Feasibility of tissue magnetic resonance imaging: a pilot study in comparison with tissue Doppler imaging and invasive measurement”. J Am Coll Cardiol. vol. 45. 2005. pp. 1109-116. (Combining early mitral velocity (E) and early diastolic septal velocity (Ea) allowed similar estimation of filling pressure by CMR and Doppler echocardiography in patients with hypertensive heart disease and absence of valvular regurgitation, in good agreement with invasive measurement.)

Bluemke, DA, Kronmail, RA, Lima, JA. “The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study”. J Am Coll Cardiol. vol. 52. 2008. pp. 2148-55. (The association between stroke and coronary heart disease may be mediated through concentric ventricular remodeling, whereas incident heart failure was most closely associated with very high levels of LV mass.)

Rodriguez, CJ, Diez-Roux, AV, Mora, A. “Left ventricular mass and ventricular remodeling among Hispanic subgroups compared with non-Hispanic blacks and whites: MESA (Multi-ethnic Study of Atherosclerosis)”. J Am Coll Cardiol. vol. 55. 2010. pp. 234-42. (This article nicely shows LV remodeling pattern on the basis of LV mass and mass-cavity ratio as a mass-to-volume (M/V) ratio and demonstrated that a higher prevalence of LV hypertrophy and abnormal LV remodeling was observed among Mexican-origin Hispanics, despite a lower prevalence of hypertension.)

Mahrholdt, H, Wagner, A, Judd, RM. “Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies”. Eur Heart J. vol. 26. 2005. pp. 1461-74. (This article reviews the potential of delayed contrast enhanced CMR to distinguish between ischemia and nonischemic cardiomyopathy as well as to differentiate nonischemic etiologies.)

Bello, D, Shah, DJ, Farah, DM. “Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy”. Circulation. vol. 108. 2003. pp. 1945-53. (In this study, for heart systolic failure patients with beta-blockers, gadolinium enhanced CMR predicts the response in LV function and remodeling.)

Wu, KC, Weiss, R, Thiemann, DR. “Late gadolinium enhancement bycardiovascular magnetic resonance heralds an adverse prognosis in nonischemic cardiomyopathy”. J Am Coll Cardiol. vol. 51. 2008. pp. 2414-21. (In this study, the presence of CMR LGE identifies a subset of nonischemic cardiomyopathy patients with an 8-fold higher risk of an index composite outcome of HF hospitalization, appropriate ICD firings, and cardiac death compared with those without LGE.)

Mewton, N, Liu, CY, Croisille, P. “Assessment of myocardial fibrosis with cardiovascular magnetic resonance”. J Am Coll Cardiol. vol. 57. 2011. pp. 891-903. (This review summarized the advantages and limitations of CMR for the assessment of myocardial fibrosis.)

Shehata, ML, Cheng, S, Osman, NF. “Myocardial tissue tagging with cardiovascular magnetic resonance”. J Cardiovasc Magn Reson. vol. 11. 2009. pp. 55(This review presents an in-depth discussion on the current clinical applications of CMR myocardial tagging and the increasingly important role of this technique for assessing subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes.)

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