Search

Background Duchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far. Methods Sixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day. Results An impaired left ventricular (LV) systolic function (defined as LV-EF

Coronary vasospasm is a severe vasoconstriction of an epicardial coronary artery, which may lead to myocardial ischemia and cause symptoms of angina. The gold-standard for diagnosing coronary vasospasm is to perform an intracoronary provocation test and to demonstrate the epicardial vasoconstriction by coronary angiography. We report the case of a patient with coronary vasospasm in whom we succeeded to non-invasively provoke and subsequently non-invasively demonstrate myocardial ischemia by perfusion cardiovascular magnetic resonance (CMR).

Background Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. Methods Sixty-four MM patients (50 ± 15 years, 44 % male) and 25 matched controls (52 ± 14 years, 36 % male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: a) CPEO/KSS (N = 33); b) MELAS/–like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). Results Among the 64 MM patients, 34 (53 %) had at least one abnormal CMR finding: 18 (28 %) demonstrated an impaired left ventricular ejection-fraction (LV-EF

Cardiac involvement with progressive myocardial fibrosis leading to dilated cardiomyopathy is a major cause of death in muscular dystrophy patients. Extracellular volume fraction (ECV) measurement based on T1-mapping pre- and post-contrast promises the detection of early 'diffuse' myocardial fibrosis that cannot be depicted by conventional con- trast-imaging based on late gadolinium enhancement (LGE). With this study, we evaluated the presence of diffuse myocardial fibrosis in regions of 'normal' (LGE-negative) and 'diseased' (LGE-positive) appearing myocardium as well as its relation to the extent of left ventricular (LV) dysfunction and the occurrence of arrhythmias in Becker muscular dystrophy (BMD) patients. Methods and results Twenty-seven BMD patients (35+ 12 years) and 17 matched male healthy controls (33+ 8 years) underwent cardio- vascular magnetic resonance (CMR) studies including ECV measurement and LGE-imaging. Ambulatory monitoring of arrhythmic events was performed by means of an external event loop recorder. Twenty BMD patients (74%) demon- strated cardiac involvement as detected by typical inferolateral presence of LGE. Twelve patients (44%) had an impaired LV ejection fraction—all being LGE-positive. Global myocardial ECV was significantly higher in the BMD group (29+ 6%) compared with the control group (24+ 2%, P ¼ 0.001). Patients with cardiac involvement demonstrated higher global ECV (31+ 6%) as well as significantly increased regional ECV not only in LGE-positive segments (34+ 6%), but also in LGE-negative segments (28+ 6%) compared with BMD patients without cardiac involvement and to controls, respect- ively (24+ 3 and 24+ 2%, P ¼ 0.005). Global ECV in patients with cardiac involvement substantially correlated to LV ejection fraction (r ¼ 20.629, P ¼ 0.003) and to the number of LGE-positive segments (r ¼ 0.783, P , 0.001). On univariable analysis, global ECV-but not the categorical presence of LGE per se- -was significantly associated with arrhythmic events (OR: 1.97, CI: 32.22-1.21, P ¼ 0.032). Conclusion ECV measurement by CMR is a useful tool in assessing the total extent of myocardial fibrosis as well as in depicting subtle diffuse fibrosis in areas of normal appearing myocardium on LGE-images. Thus, myocardial ECV is a potential additional quantitative tool for accurate detection of cardiac involvement and risk stratification in muscular dystrophy patients.

Background Abnormalities of dystrophin expression cause Duchenne Muscular Dystrophy (D) or Becker Muscular Dystrophy (B). Since widespread use of non-invasive respiratory ventilation, many D patients who previously died in their early 20 s from respiratory failure are now surviving longer and developing cardiomyopathy. In B patients, disease progression is slower, however, development of progressive cardiomyopathy is highly frequent. One previously identified predictor of mortality in cardiomyopathy is myocardial fibrosis as detected by late gadolinium enhacement (LGE) cardiovascular magnetic resonance (CMR) imaging. Furthermore, a high percentage and typical inferolateral pattern of LGE has been previously reported in small numbers of patients with B/D, however, the relationship with left ventricular systolic dysfunction needs to be further evaluated.

Only few data is available regarding a direct comparison of both non-invasive CMR and invasive EMB with respect to conformity of procedure-derived diagnoses in the same patients.

Background The T1-mapping MOLLI technique has already proved to be a robust and reproducible technique for myocardial extracellular volume fraction (ECV) estimation in both healthy individuals and patients with different cardiomyopathies. Monozygotic twins share the same DNA information and frequently grow up in a similar environment. However, epigenetic as well as environmental factors may lead to major differences in clinical phenotype, organ function as well as character and behaviour. Therefore, monozygotic twins provide a very interesting and attractive research model regarding specific organ structure, metabolism and function. With this study, we aimed at evaluating possible ECV measurement variations within pairs of healthy monozygotic twins.

Background Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Although BMD patients present milder skeletal muscle involvement, they have been shown to present more advanced cardiomyopathy than DMD. Female DMD/BMD carriers are usually free of skeletal muscle symptoms but they may also develop cardiomyopathy. The present study aimed at characterizing the presence and pattern of cardiac abnormalities in a group of genetically-proven MD-carriers by means of comprehensive CMR studies. Moreover, we wanted to test whether DMD carriers (DMDc) and BMD carriers (BMDc) are differently affected.

Summary Only in patients with elevated levels of cardiac troponin CMR can reliably corroborate the clinical diagnosis of acute myocarditis Background Diagnosis of myocarditis remains a difficult clinical challenge, since the clinical spectrum of myocarditis is multifaceted. As clinical presentation and ECG-changes tend to be non-specific, cardiovascular magnetic resonance (CMR) has proven to be av aluable diagnostic tool regarding non-invasive diagnosis of myocarditis. However, CMR studies are time- and cost-intensive. Hence, further parameters are warranted to identify those individuals in whom a CMR study is likely to add crucial information regarding correct and timely diagnosis of acute myocarditis. The current study sought to elucidate the diagnostic yield of CMR in young patients aged ≤ 40 yrs with clinical diagnosis of myocarditis based on symptoms and ECG in relation to the presence or absence of elevated levels of cardiac troponin as an additional marker of acute myocardial injury. Methods Between 2009 and 2011, young patients aged ≤ 40 yrs presenting with acute or subacute chest pain and significant new-onset ST-segment changes suggestive of myocarditis, prospectively underwent CMR studies after obstructive coronary artery disease (CAD) was ruled out by coronary angiography if risk factors were present. Black-blood T2-weighted turbo-spin-echo (TSE) sequences were obtained to detect myocardial edema. Late gadolinium enhancement (LGE) imaging was performed in order to detect focal areas of contrast enhancement. Studies were performed on a 1.5 Tesla MR-Scanner (Siemens Sonata). Results During the recruitment period, 106 consecutive patients aged 17 to 40 yrs were included. Mean age was 29±7 yrs. In 19 patients additional cardiac catheterization was performed in order to definitely rule out obstructive CAD. LGE was successfully performed in all patients while in one patient T2-weighted edema images could not be obtained due to insufficient image quality. 13 (12%) patients showed significantly elevated levels of cardiac troponin. 15 (14%) patients showed focal late gadolinium enhancement (LGE) indicating myocarditis. All patients (100%) who presented with elevated levels of troponin showed presence of focal LGE. T2-weighted edema imaging showed correlating myocardial edema in 7 of these 13 individuals (54%). However, none of the 2 patients demonstrating LGE in the absence of elevated cardiac enzymes had signs of myocardial edema assessed by T2-weighted edema imaging but both turned out to have anamnestic evidence of subsided myocarditis in the past requiring exclusion of “acute” myocarditis. Moreover, the remaining 91 young patients with an unequivocal clinical diagnosis of myocarditis - but normal troponin levels - demonstrated normal findings by both T2-weighted edema and LGE imaging.

Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

Background Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal α–1,4-glucosidase leading to accumulation of glycogen in target tissues with progressive organ failure. While the early infantile-onset form is characterized by early severe hypertrophic cardiomyopathy with cardiac and respiratory failure, clinically relevant cardiomyopathy seems to be uncommon in patients with late-onset Pompe disease, and the prevalence and nature of myocardial abnormalities are still to be clarified. Methods Seventeen patients with genetically proven late-onset Pompe disease (50 ± 18 years, 11 male) and 18 age- and gender-matched healthy controls (44 ± 10 year, 12 male) underwent comprehensive cardiovascular magnetic resonance (CMR) including conventional and advanced techniques: cine and feature tracking-based strain imaging for depiction of (even subtle) systolic LV dysfunction as well as late gadolinium enhancement (LGE) and myocardial extracellular volume fraction (ECV) quantification for focal and diffuse fibrosis detection. Results All patients had normal left ventricular (LV) and right ventricular (RV) volumes and normal LV and RV ejection fraction. In comparison to healthy controls, neither conventional cine nor advanced feature-tracking based-strain imaging could depict any (subclinical) myocardial systolic dysfunction. Three (18%) of the patients had non-ischemic LGE in the basal inferolateral wall and 21% demonstrated elevated global ECV values suggestive of interstitial myocardial fibrosis. Non-specific abnormalities such as left atrial (LA) dilatation were present in two patients, while LV hypertrophy was seen only in one. Two of the three LGE-positive patients were also hypertensive and demonstrated high global ECV values (>30%) in addition to dilated LA. After a median follow-up of 25 (11–29) months, only one cardiovascular event occurred: one of the LGE-positive patients with a high cardiovascular risk profile suffered an acute coronary syndrome. Conclusion In contrast to the early infantile-onset form of Pompe disease, mild and rather non-specific cardiac abnormalities can be detected by CMR only in a small proportion of patients with late-onset Pompe disease. The observed structural abnormalities seem to result from an interplay between the storage disease and other comorbidities and they did not affect short-term to mid-term prognosis in adult Pompe patients.

Introduction: Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction.

Background Becker-Kiener muscular dystrophy (BMD) represents an X-linked genetic disease associated with myocardial involvement potentially resulting in dilated cardiomyopathy (DCM). Early diagnosis of cardiac involvement may permit earlier institution of heart failure treatment and extend life span in these patients. Both echocardiography and nuclear imaging methods are capable of detecting later stages of cardiac involvement characterised by wall motion abnormalities. Cardiovascular magnetic resonance (CMR) has the potential to detect cardiac involvement by depicting early scar formation that may appear before onset of wall motion abnormalities. Methods In a prospective two-center-study, 15 male patients with BMD (median age 37 years; range 11 years to 56 years) underwent comprehensive neurological and cardiac evaluations including physical examination, echocardiography and CMR. A 16-segment model was applied for evaluation of regional wall motion abnormalities (rWMA). The CMR study included late gadolinium enhancement (LGE) imaging with quantification of myocardial damage. Results Abnormal echocardiographic results were found in eight of 15 (53.3%) patients with all of them demonstrating reduced left ventricular ejection fraction (LVEF) and rWMA. CMR revealed abnormal findings in 12 of 15 (80.0%) patients (p = 0.04) with 10 (66.6%) having reduced LVEF (p = 0.16) and 9 (64.3%) demonstrating rWMA (p = 0.38). Myocardial damage as assessed by LGE-imaging was detected in 11 of 15 (73.3%) patients with a median myocardial damage extent of 13.0% (range 0 to 38.0%), an age-related increase and a typical subepicardial distribution pattern in the inferolateral wall. Ten patients (66.7%) were in need of medical heart failure therapy based on CMR results. However, only 4 patients (26.7%) were already taking medication based on clinical criteria (p = 0.009). Conclusion Cardiac involvement in patients with BMD is underdiagnosed by echocardiographic methods resulting in undertreatment of heart failure. The degree and severity of cardiac involvement in this population is best characterised when state-of-the-art CMR methods are applied. Further studies need to demonstrate whether earlier diagnosis and institution of heart failure therapy will extend the life span of these patients.

Background Recently, we could demonstrate in humans that (ultrasmall) superparamagnetic iron-oxide (U/SPIO)-based contrast agents enable a detailed characterization of myocardial infarct pathology. Considering the multifunctionality of U/SPIO-based nanoparticles (magnetic targeting as well as diagnostic imaging properties) and their superior safety profile compared to gadoliniumbased compounds, we performed ex vivo analyses and evaluated the magnetic navigating/targeting properties of U/SPIO.

Cardiovascular magnetic resonance (CMR) studies in patients with pacemakers or implantable cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. Therefore, in the last years the manufacturers developed not only MR-conditional pacemakers, but also MR-conditional ICDs. However, the clinical experience regarding the feasibility and limitations of MR studies of the heart in patients with ICDs is still limited. In particular, there are hardly any CMR studies in the same patients performed prior to and post ICD implantation allowing a one-to-one comparison of the obtained CMR images. This is the first presentation of a CMR study in a patient with the world’s first and so far only MR-conditional ICD. In our case, a major problem related to the presence of the MR conditional ICD was an image artifact caused by the device’s generator which hampered the visualization of the midventricular and apical anterior and antero-lateral segments in all sequences performed. Considering previous studies, right chest implantation of the ICD could probably have helped in this setting and may be preferred in future ICD implantations. Our case report nicely illustrates the real clinical need for specially designed implantable devices that ensure safe and high-quality imaging in patients in whom serial CMR is required.