Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

Hypertrophic cardiomyopathy (CMP) is a primary myocardial disease characterised by focal (mostly septal) or diffuse LV wall thickening (with or without LV outflow obstruction). Myofibrillar hypertrophy and disarray [20] and myocardial fibrosis have been described histologically [3]. Inadequate capillary density and intimal hyperplasia of intramural coronary arteries, which were also seen in such patients, may contribute to myocardial ischaemia [3]. There are predilection patterns of CE in patients with hypertrophic CMP: more than 80% of patients exhibit patchy fibrosis at the right ventricular insertion points and in the anteroseptal wall in the region of characteristic septal thickening (Figs. 4a and 5a, b) [21, 22]. Myocardial fibrosis, however, is also located in non-hypertrophic segments [23, 24]. As the amount of CE in hypertrophic CMP often corresponds with functional parameters and the frequency of cardiac events, CE-CMR may potentially be useful for risk stratification [25]. However, data regarding the prognostic value of these findings remain scarce; therefore, further research is warranted [26].

Presence and extent of CE following percutaneous transseptal myocardial ablation (by alcohol injection) for the treatment of significant LV outflow tract obstruction indicate the location and extent of therapeutic myocardial tissue destruction [27].

Idiopathic dilated CMP is characterised by dilation and impaired contractility of the left ventricle or both ventricles in the absence of abnormal loading conditions (e.g., arterial hypertension, valvular disease), and/or a CMP with a distinct cause (e.g., ischaemic heart disease; peripartum cardiomyopathy; toxin-, chemotherapy-, or tachycardia-induced cardiomyopathy; certain endocrinopathies) [1]. Histology is nonspecific, and a variety of myocardial tissue alterations may occur or coexist, including myocyte hypertrophy and segmental or diffuse interstitial fibrosis. Current CE-CMR techniques are unlikely to detect diffuse fibrosis due to limited voxel resolution [28]. Myocardial fibrosis in idiopathic dilated CMP is mostly seen in the LV midwall with septal predominance and a linear pattern (Figs. 4b and 5c, d); however, it has occasionally been described at subendocardial and subepicardial locations with a more patchy pattern [23]. Of note, in various studies, the prevalence of myocardial fibrosis varied from 13% to 62% [29, 30]. It has been suggested that the degree of CE may correlate with functional impairment of the LV [31]. There are preliminary data demonstrating that the presence of CE is associated with an unfavourable clinical outcome and may be a predictor of sudden death in patients with idiopathic dilated CMP [29, 32, 33].

The arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by structural and functional abnormalities, with progressive fibrous and fatty infiltration involving variable regions of the right and left ventricular myocardium. This process finally leads to progressive RV failure and ventricular tachyarrhythmia [23]. Diagnosis of this condition remains a challenge, with nonspecific abnormalities on echocardiographic and angiographic examinations. Endomyocardial biopsy has a low sensitivity, as samples are usually taken from the septum, a region that is infrequently involved [23]. Information from CE-CMR may help to guide targeted endomyocardial biopsies. Predilection patterns with midwall CE are found in the basal anterior region (Fig. 4c) and/or the RV outflow tract. These patterns of fibrosis correlate with fibro-fatty replacement of the myocardium at histological assessment and predict induction of ventricular tachycardia during electrophysiological studies. As the presence of ARVC cannot be ruled out based on CMR findings alone, standardised guidelines have been proposed which define major and minor criteria, including morphological, histological, electrocardiographic, functional, and genetic characteristics [34, 35].

Myocarditis is an acute or chronic inflammatory disease of the myocardium, which can be caused by viruses or initiated by post-infectious immune or primarily organ-specific autoimmune responses [36]. Patients generally recover or infrequently develop dilated CMP, sometimes even with life-threatening complications including severe heart failure and malignant arrhythmias [37]. Diagnosis of myocarditis is challenging because of a diverse clinical presentation and a limited sensitivity of endomyocardial biopsies, but may be facilitated by use of CE-CMR or myocardial global relative enhancement CMR [38, 39]. Presence of CE has been reported in 44–95% of patients with myocarditis, [40, 41] indicating areas of myocardial damage with a sensitivity of 100% and a specificity of 90% (compared with histopathology) [40]. In acute myocarditis, CE is frequently located in the lateral wall, originating from the epicardium. The subendocardium is generally not involved, with the exception of eosinophilic myocarditis which frequently involves the endomyocardium (Fig. 6a) [23, 42]. In chronic myocarditis, besides an increased oedema on T2-weighted imaging, an increased global relative enhancement is a common finding as confirmed in immunohistological analyses [38]. CE-CMR identified areas of myocardial damage in 70% of patients with biopsy-proven chronic myocarditis and showed a predilection pattern (LV midwall and/or subepicardial). CE may also help to guide targeted endomyocardial biopsies. In myocarditis, CE may provide additional information that could help to differentiate between viral origins; in the majority of parvovirus B19 patients, CE is found in the lateral free wall, while in patients with HHV6 myocarditis, CE frequently involves the interventricular septal midwall [43]. In addition, we recently studied a limited number of patients with chronic fatigue syndrome and concomitant Ebstein Barr virus or cytomegalovirus myocarditis who showed a certain predilection of the septal region in the presence of CE. Inflammatory activity on T2-weighted imaging and myocardial fibrosis on CE-CMR may have relevant prognostic implications in acute and chronic myocarditis and may ultimately serve as a tool to triage patients [44]. In addition, cardiac function and regression of myocardial changes can be well observed with CMR.

Cardiac involvement in sarcoidosis, a multisystem granulomatous disorder of unknown aetiology, is clinically often asymptomatic (95%) while autopsy revealed cardiac manifestation in up to 60% [50]. Advanced sarcoidosis leads to septal thinning, systolic and diastolic dysfunction, and pericardial effusion, which can easily be detected with echocardiography [4]. Early sarcoidosis, however, is more challenging to diagnose, and CMR can be very useful in this context. During the acute stage of this disease, regions of active inflammation and oedema are visible on T2-weighted images as areas of increased signal intensity. During the chronic stage, CE will typically appear as a midwall or epicardial nonischaemic pattern (Fig. 6b), but occasionally, subendocardial or transmural CE may be observed, mimicking a pattern of post-MI. CE has been found in 50% of all patients diagnosed with sarcoidosis [51]. CE-CMR may also be useful to evaluate the response to therapy. In a CMR study of 16 patients with sarcoidosis, CE was markedly diminished 1 month after the initiation of steroid therapy [51]. CE in sarcoidosis patients may be associated with future adverse events (including cardiac death), but confirmation in larger patient cohorts is required [50].

Both primary and secondary amyloidosis are characterised by extracellular deposition of fibrillar proteins, [1] which may lead to restrictive cardiomyopathy with an initially preserved systolic LV function [52]. In cardiac amyloidosis, CE is commonly found as a result of the expansion of interstitial space and some endomyocardial fibrosis, [53] leading to a usually global and diffuse CE pattern [4]. Although the subendocardium is commonly involved (as in ischaemic heart disease), the distribution of CE is not related to a particular coronary perfusion area (Fig. 6c) [4].

The parasitic protozoan Trypanosoma cruzi causes Chagas’ disease, which is endemic in the Latin American region [4]. During chronic disease, the heart is the most frequently affected organ, and patients present with refractory heart failure, disorders of the conduction system, or ventricular tachycardia [3, 54]. The fundamental pathological processes include an inflammatory response, cellular damage with a broad variation of intensity (minimal alterations up to extensive necrosis), and fibrosis [55]. Early cardiac involvement may be detected by CE-CMR before the onset of symptoms [56]. CE is often seen epicardially or in the LV midwall with an inferolateral predilection pattern (Fig. 6d), but other regions—including the apex—may also sometimes be affected [4].

Pulmonary arterial hypertension, both primary and secondary, is characterised by an increased pulmonary vascular resistance that results in pressure overload on the right ventricle [57]. Cine CMR permits accurate assessment of RV mass and volumes which is often difficult to accomplish with other imaging modalities [3]. Myocardial CE is frequently observed in patients with severe symptomatic pulmonary artery hypertension with predilection patterns involving both right ventricular septal insertion points and the interventricular septum (Fig. 6e). CE in the interventricular septum was found to be associated with septal bowing (on cine CMR), and the extent of CE correlated inversely with right ventricular systolic function [58].

Both Becker and Duchenne muscular dystrophies are progressive X chromosome-linked recessive neuromuscular diseases with myocardial involvement in up to 72% of patients showing a mildly reduced LV function up to severe LV impairment and dilated CMP. Cardiac myocyte dystrophin deficiency leads to necrosis causing replacement of damaged myocardium by connective tissue and fat in both ventricles. On CE-CMR, hyperenhancement is predominantly seen in LV midwall (Fig. 6f) and has been described in 73–100% of patients [59]. Early diagnosis of myocardial involvement as assessed with CE-CMR may permit an earlier treatment of heart failure which could increase life expectancy.

Chloroquine-induced cardiomyopathy is a rare iatrogenic disease that is associated with long-term intake of chloroquine, which is most frequently prescribed for treatment of rheumatoid arthritis and malaria prophylaxis [60]. This CMP is characterised by ineffective lysosomal metabolism because of an increase in pH that leads to accumulation of lysosomal glycosphingolipids and finally thickening of cardiac walls [61]. The time interval between the start of chloroquine therapy and disease manifestation varies greatly, ranging from several months to more than 20 years [60]. CMR may demonstrate the presence of LV hypertrophy with accompanying areas of CE in the basal septum and at the insertion point of the right ventricle (Fig. 6g).

Fabry disease, an X chromosome-linked lysosomal storage disease caused by a deficient activity of the enzyme α-galactosidase A, can also result in the accumulation of glycosphingolipids in multiple organs, including the heart [61, 62]. Fabry disease cardiomyopathy should therefore always be considered in the differential diagnosis of ‘idiopathic’ LV hypertrophy (in the absence of arterial hypertension or valvular disease).