The emerging role of magnetic resonance imaging and multidetector computed tomography in the diagnosis of dilated cardiomyopathy
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Magnetic resonance imaging and multidetector computed tomography are new imaging methods that have much to offer clinicians caring for patients with dilated cardiomyopathy. In this article we briefly describe the clinical, pathophysiological and histological aspects of dilated cardiomyopathy. Then we discuss in detail the use of both imaging methods for measurement of chamber size, global and regional function, for myocardial tissue characterisation, including myocardial viability assessment, and determination of arrhythmogenic substrate, and their emerging role in cardiac resynchronisation therapy.
KeywordsDilated cardiomyopathy Magnetic resonance imaging MRI Multidetector computed tomography MDCT
The term “cardiomyopathy” identifies a heterogeneous group of cardiac diseases characterised by direct myocardial involvement leading to impaired cardiac function. Since the term was introduced by Harvey and Brigden in the 1960s, substantial progress has been made, in terms of understanding the pathophysiological substrate, underlying causes and peculiarities, and most importantly, in defining a classification system for cardiomyopathies. Primary cardiomyopathies include those with genetic, acquired or mixed causes, and refer to a disease that is predominantly limited to the myocardium, whereas secondary cardiomyopathies are characterised by myocardial involvement that is part of a generalised or diffuse systemic disorder. In addition, several cardiovascular diseases not regarded as cardiomyopathies may also affect the myocardium, causing systolic or diastolic dysfunction and hampering differentiation from heart muscle diseases . Although with the current arsenal of diagnostic imaging tools, the diagnosis of cardiomyopathies has been facilitated, in many cases the correct diagnosis remains challenging and sometimes elusive. Nevertheless, these techniques have significantly contributed towards an increased awareness of cardiomyopathies among clinicians, and they have an increasing impact on patient management and risk stratification. Transthoracic echocardiography is currently the first-line imaging technique for the diagnosis, evaluation and decision-making in cardiomyopathy patients. In the last decade, magnetic resonance imaging (MRI) and, to a lesser extent, multidetector (or multirow) computed tomography (MDCT) have become increasingly important in the diagnosis of cardiomyopathies. In particular, the comprehensive approach of MRI, including non-invasive tissue characterisation, makes it indispensable in the work-up of many cardiomyopathies.
Pathophysiological and histological aspects
Independently of the underlying cause, DCM is characterised by an increase in ventricular chamber size. As demonstrated by the Frank-Starling mechanism, this serves as a first compensatory step aiming to maintain an appropriate stroke volume. However, above a critical sarcomere stretch, the efficiency of interaction between actin and myosine filaments decreases, resulting in impairment of stroke volume. Myocardial fibre elongation increases the ventricular radius, causing eccentric ventricular hypertrophy, with decreased wall thickness to chamber diameter ratio and increased ventricular sphericity. According to the Laplace law, these changes increase significantly myocardial wall stress with increased oxygen demand and subsequent worsening of the left ventricular (LV) systolic performance . The main histological features of DCM are myocyte elongation, myocardial apoptosis and hypertrophy of the remaining myocytes . Additionally, there is an excessive collagen deposition and decreased capillary density, with both reactive (interstitial and perivascular) and reparative (replacement) patterns of fibrosis [7, 8]. Myocardial fibrosis is considered the result of damage due to microvascular ischaemia and myocardial wall inflammation. The cellular and extracellular changes result in a normal, thinned or slightly thickened myocardial wall (Fig. 1).
MRI and MDCT
Even if MDCT is not yet considered as a first-line imaging technique for the evaluation of LV performance and volumes, it is important to mention that in patients undergoing an MDCT examination for coronary artery evaluation, reliable information about cardiac morphology and function can be obtained without any additional radiation exposure [34, 35, 36, 37]. Although nowadays the prospective trigger mode is preferable because of the significant reduction in irradiation dose, reliable data regarding ventricular volumes and function can be obtained using retrospective electrocardiogram (ECG) gating. Several papers reported good agreement among MDCT and echocardiography, and MRI and invasive catheter ventriculography, with good interobserver agreement [38, 39, 40, 41].
Cardiac volumes and ventricular function
As the LV ejection fraction is the strongest prognostic determinant in heart failure patients, while LV volume and mass are independent predictors of mortality and morbidity, a first primordial step in assessing DCM patients is the reliable quantification of the severity of chamber dilatation and dysfunction. Often stroke volumes are within normal limits or only modestly decreased despite the severely impaired ejection fraction. The LV enlargement may furthermore dilate the mitral valve ring, dislocate the papillary muscles, and impair leaflet coaption, thereby causing mitral valve regurgitation and putting additional load on the already diseased ventricle (Fig. 1). Except for mildly dilated forms of DCM, the LV and/or RV show a moderate to severe degree of dilatation with a severely impaired ejection fraction (e.g. lower than 20%) (Figs. 1 and 3). The volumetric measurement of the ventricles is usually performed in the cardiac short-axis plane (MRI) or using reconstructed images in the cardiac short-axis plane (MDCT). For MDCT evaluation of LV function, end-diastole is usually identified as the image with the maximum diameter (approximately at 85% of RR diameter), while the minimum diameter (about 25% of RR) corresponds to end-systole. Software has been developed to semi-automatically determine ventricular volumes and function, and myocardial mass.
Myocardial contraction abnormalities are invariably present in DCM patients, visible as hypokinetic to dyskinetic wall motion, diminished to absent systolic wall thickening, and a variable degree of ventricular dyssynchrony often with abnormal systolic motion of the interventricular septum and apical rocking (Movie 3). Cine MRI is without any doubt the reference tool for assessing myocardial wall motion and thickening patterns, and has potential in the assessment of ventricular dyssynchrony. Regional abnormalities are usually described using the 17-segment AHA approach.
Myocardial tissue characterisation
Although LGE MRI is able to depict subtle forms of myocardial scarring (<1 g) , this sequence is of limited value in depicting diffuse myocardial fibrosis, probably explaining why most DCM patients in the study by McCrohon et al.  showed normal LGE MRI. Recently, substantial progress has been made with the development of myocardial T1 mapping techniques. Diffuse collagen deposition increases the extracellular space, causing an increased interstitial accumulation of gadolinium at steady state, thus reducing the myocardial T1 relaxation time [26, 29, 30, 49, 50]. Several groups have reported in DCM patients a tight relation between the expansion in extracellular space (reflecting myocardial fibrosis) and the impairment in myocardial blood flow, ventricular dilatation and ventricular dysfunction [29, 50, 51, 52].
It is believed that approximately 5-10% of patients with acute myocarditis progress towards DCM and ultimately will need cardiac transplantation [1, 53]. While the role of MRI in the diagnosis of acute myocarditis is well established, with recently published recommendations by an expert committee (“Lake Louise Criteria”) , the role of MRI in chronic myocarditis is less well defined, but is probably important because patients with DCM secondary to chronic myocarditis may show a favourable response to immunomodulatory therapy. De Cobelli et al.  reported in patients with biopsy-proven chronic myocarditis a similar focal pattern of enhancement as in patients with acute myocarditis in up to 70% of a group of patients with chronic inflammation at endomyocardial biopsy. Moreover, patients with persistent chronic myocarditis frequently showed generalised myocardial oedema and increase in global myocardial enhancement. On the other hand, focal myocardial LGE, probably reflecting myocardial scarring, had low sensitivity and specificity in depicting chronic myocarditis [28, 55]. Finally, Mahrholdt et al.  evaluated patients with acute myocarditis at the 3-month follow-up and reported a significant reduction in the extent of midwall/subepicardial focal myocardial enhancement representing residual inflammation or fibrotic scarring.
Left ventricular non-compaction cardiomyopathy
Myocardial viability assessment
Obstructive CAD may cause myocardial ischaemia and dysfunction, and initiate compensatory ventricular remodelling with progressive dilatation, which ultimately may lead to ischaemic heart failure (Fig. 8). The crucial question to solve in these patients is whether percutaneous or surgical coronary revascularisation will improve function in the dysfunctional regions and ultimately improve patient outcome . As the myocardial substrate underlying the dysfunction in the setting of CAD is heterogeneous, including stunned, ischaemic, hibernating, necrotic and scarred myocardium, the goal of myocardial viability assessment is to determine the ischaemic substrate. It is important to emphasise that different ischaemic substrates can be present within the same coronary perfusion territory [73, 74]. Only the viable substrates may recover function following reperfusion. Even if there are not yet any prospectively controlled studies on the effects of revascularisation, there is a substantial amount of clinical evidence that patients with reversible LV dysfunction may benefit from a revascularisation procedure [75, 76].
As sudden cardiac death due to ventricular arrhythmias may be the first clinical manifestation of DCM, identification of patients at risk who may benefit from implantable cardioverter defibrillator (ICD) implantation or from an ablation procedure is of primordial importance. Several papers have shown that non-ischaemic cardiomyopathy patients with midwall myocardial LGE involving more than 25% of wall thickness are at high risk at inducible ventricular tachycardia and should be referred for definitive anti-arrhythmic device therapy [86, 87, 88, 89]. LGE MRI adds predictive value especially in the DCM patients with a mildly to moderately decreased ejection fraction, those with abnormal myocardial enhancement having potential benefit from prophylactic ICD placement . In a recent study by Hombach et al.  that included 141 DCM patients, midwall myocardial LGE was not an independent prognostic factor, stressing the need for large prospective studies on this topic . Bogun et al. used LGE MRI to plan an appropriate mapping and ablation strategy in a small group of DCM patients . The location of the scar (endocardial versus epicardial) was an important factor in determining the optimal approach to ablation. However, the success of catheter ablation was low in patients with a scar located in the midwall.
Cardiac resynchronisation therapy
In patients with DCM, ventricular dilatation and replacement fibrosis lead to a heterogeneous excitation spread across the LV wall with a delay in intraventricular conduction and a left bundle branch block morphology on the ECG. Segmental wall motion analysis shows hypokinesis to dyskinesis with a variable degree of dyssynchrony [92, 93]. Ventricular dyssynchrony worsens systolic performance, impedes ventricular filling, and causes paradoxical septal motion during early systole. Cardiac resynchronisation therapy (CRT) consists of the implantation of a biventricular pacemaker in order to improve synchronicity of myocardial contraction leading to improved ventricular performance. In properly selected patients, CRT implantation is associated with improvement of symptoms and a decrease in mortality and hospitalisation for heart failure. However, up to 40% of CRT-treated patients show no benefit from CRT, urging the need for better identification of responders to CRT treatment.
MRI is a promising tool for identifying and selecting patients eligible for CRT [93, 94]. MRI has the advantage of integrating functional/dyssynchrony imaging with morphological and tissue characterisation imaging. Novel MRI techniques such as DENSE (displacement encoding with stimulated echoes) and TVM (tissue velocity mapping) are appealing for the quantification of the degree of dyssynchrony throughout the LV. In addition, LGE MRI enables the depiction of myocardial scar presence and extent. The higher the scar burden, the lower the chance of CRT response [95, 96, 97]. Moreover, as reported by Chalil et al.  correct placement of CRT leads is crucial. Positioning of the pacing lead in the scarred myocardium is followed by a lack of CRT response. MRI is currently the best technique for guiding the interventional cardiologist to correctly position CRT leads. The lead should be placed in the myocardium displaying the latest activation. On the other hand, scar stimulation by pacing prevents correct impulse transmission, and consequent inhibition of myocardial contractility.
Coronary artery imaging
As previously mentioned, the ventricular dilatation associated with systolic dysfunction can be due to DCM or secondary to coronary artery disease. In the last two decades, coronary artery imaging by MRI and MDCT has been extensively studied as an alternative to invasive catheter angiography. Despite high initial expectations, it has nowadays become evident that MRI has a limited role in depicting coronary artery plaques . Supported by encouraging results of several single-centre and multicentre trials, MDCT is now considered a reliable method for the detection and, in particular, for the exclusion of CAD [12, 102]. However, it should be emphasised that MDCT still faces many challenges, in particular imaging of heavily calcified plaques and stent imaging, although further improvement can be expected with newer generation equipment .
In the end, the role of an imaging method is to provide accurate information for the clinician, to minimise the degree of uncertainty in the diagnosis and patient management, and to improve patient outcome. MRI is becoming generally accepted as an important imaging technique in patients with DCM offering the clinician not only accurate information regarding the severity of ventricular dilatation and dysfunction but also regarding myocardial tissue composition, which is important in establishing the underlying cause, in predicting the risk of future events, and in selecting eligible candidates for CRT. The fast and continuous progress in MDCT technology has enabled accurate information regarding coronary artery and venous anatomy to be provided, but this technique has the potential to offer a broader cardiac assessment, including tissue characterisation and functional assessment.
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