Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy.

BACKGROUND: The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities. METHODS: Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated. RESULTS: Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients. CONCLUSIONS: Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.

Can strain rate imaging predict recovery of contraction after acute myocardial infarction?

AIMS: To assess whether strain rate imaging (SRI) can serve to evaluate myocardial viability in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In 23 patients with ACS, we measured longitudinal tissue Doppler strain and strain rate values from left ventricular basal, mid, and apical segments (n = 414). These segments were grouped according to their acute end-systolic strain values (S(ES)) into those with normocontraction (S(ES)≤-13%), hypocontraction (S(ES) between -13 and -7%), and severe contraction abnormality (S(ES)>-7%). At 8 months, we evaluated the recovery of contraction: Segments with acutely severe contraction abnormality that improved their strain values to ≤-7% were defined as viable, and those that failed to do so as non-viable. In the acute phase, S(ES), post-systolic strain, as well as systolic, early, and late diastolic strain rate values were significantly better in the viable than in the non-viable segments. Post-systolic strain had the best AUC 0.78, and a cut-off value of -3.8% predicted recovery from severe contraction abnormality with a sensitivity of 85% and specificity of 62%. The transmurality of the infarction, assessed by magnetic resonance imaging with delayed enhancement, was significantly larger in the non-viable than in the viable segments (P = 0.006). Acute global S(ES) and systolic strain rate showed the best correlations with final global S(ES) and global infarction percentage after recovery. CONCLUSION: SRI can serve to evaluate myocardial viability in patients with ACS, and to assess the recovery of segmental as well as global left ventricular function.

Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

Early familial dilated cardiomyopathy: identification with determination of disease state parameter from cine MR image data.

PURPOSE: To characterize early changes in cardiac anatomy and function for lamin A/C gene (LMNA) mutation carriers by using magnetic resonance (MR) imaging and to develop tools to analyze and visualize the findings. MATERIALS AND METHODS: The ethical review board of the institution approved the study, and informed written consent was obtained. The patient group consisted of 12 subjects, seven women (mean age, 36 years; age range, 18-54 years) and five men (mean age, 28 years; age range, 18-39 years) of Finnish origin, who were each heterozygotes with one LMNA mutation that may cause familial dilated cardiomyopathy (DCM). All the subjects were judged to be healthy with transthoracic echocardiography. The control group consisted of 14 healthy subjects, 11 women (mean age, 41 years; range, 23-54 years) and three men (mean age, 45 years; range, 34-57 years), of Finnish origin. Cine steady state free precession MR imaging was performed with a 1.5-T system. The volumes, wall thickness, and wall motion of both left ventricle (LV) and right ventricle were assessed. A method combining multiple MR image parameters was used to generate a global cardiac function index, the disease state parameter (DSP). A visual fingerprint was generated to assess the severity of familial DCM. RESULTS: The mean DSP of the patient group (0.69 +/- 0.15 [standard deviation]) was significantly higher than that of the control group (0.32 +/- 0.13) (P = .00002). One subject had an enlarged LV. CONCLUSION: Subclinical familial DCM was identified by determination of the DSP with MR imaging, and this method might be used to recognize familial DCM at an early stage.

Tissue Doppler strain-mapping in the assessment of the extent of chronic myocardial infarction: validation using magnetic resonance imaging.

AIMS: The distribution of myocardial strain values can be visualized by colour-coded strain images. We examined for the first time if this strain-mapping function can be used to study the extent of prior myocardial infarction. METHODS AND RESULTS: Echocardiography and cardiac magnetic resonance imaging with delayed contrast enhancement were performed in 26 patients with chronic myocardial infarction. Two-dimensional strain images of the left ventricle were obtained in all standard apical views. Myocardial segments (n = 416) were assigned a score ranging from one to four based on the strain-coded colour of the segment, with higher scores representing worse myocardial function. Strain-mapping scores and quantitative strain values averaged, respectively, 1.3 +/- 0.6 and -16.4 +/- 7.6% in segments without infarction, 1.7 +/- 1.0 and -15.0 +/- 8.6% in non-transmural infarctions, and 2.8 +/- 1.2 and -6.5 +/- 8.6% in transmural infarctions. Strain-mapping had a sensitivity of 60% and a specificity of 95% in detecting segments with transmural myocardial infarction. Corresponding values for echocardiographic wall motion analysis were 50 and 96%. Strain-mapping was possible in 80% of the segments and inter-observer agreement was substantial (kappa = 0.63). CONCLUSION: Strain-mapping is a clinically applicable method for the assessment of regional myocardial function in post-myocardial infarction patients. Strain-mapping has reasonable feasibility and is more sensitive in detecting infarction damage than routine wall motion analysis.